Aim: The aim of the study was to investigate the influence of bone density of the greater tuberosity on mechanical strength of different bone anchors for rotator cuff surgery. Especially in osteopenic bone the metal bone anchors and transosseus sutures are still the “gold-standard” in rotator cuff surgery. Material and Methods: Four bone anchors, each standing for a specific group of bone anchor, and two suture materials were tested. One of them was the metallic Super Revo screw 5.0 (Linvatec), the absorbable screw Spiralok 5.0 (Mitek), the absorbable press-fit anchor Bioknotless RC (Mitek) and the absorbable Ultrasorb RC (Linvatec). The suture materials tested was the well known V-37 (Ethicon) and the new Orthocord (Mitek) both USP 2. All fixations systems were tested on a) 6 pairs of fresh-frozen human shoulders from young adults (range 20–50 yrs.) and b) 6 pairs of fresh frozen human shoulders from elderly (range 60–93 yrs.). Cyclic loading was performed, as it was considered the best way to simulate the postoperative conditions in a manner similar to those used in prior studies until the system failed. The maximum tensile strength, the failure mode, and the displacement of the fixation device (system displacement) under load at the first cycle at 75 N and at the maximum tensile strength were recorded. Results: The absorbable Spiralok 5 mm screw anchor showed the highest failure load with a mean of 171 N in osteopenic bone. The suture material Orthocord and V-37 had the lowest mechanical strength in osteopenic bone with a mean of 125 N resp. 114 N. The remaining anchors had an almost identical failure load with means of 150 N (Super Revo 5 mm and Bioknotless RC) and 151 N (Ultrasorb RC). No statistical significance was found though. Comparing the mechanical strength of each fixation system in healthy and osteopenic bone no statistical significant difference was found except for the V-37 suture. In healthy bone the failure load of V-37 suture had a mean of 204 N and in osteopenic bone of 114 N. Discussion: The absorbable Spiralok 5 mm screw showed a good performance in healthy and osteopenic bone when compared with standard bone anchor like the titan Super Revo 5 mm screw or transosseous sutures. Absorbable anchors have certain advantages, besides that usually they are more expensive. They can easily be overdrilled in case of rupture of the suture material, and they do not interfere during later revision surgery or for imaging studies such as magnetic resonance imaging

Background: The stability of fracture fixation is influenced by the type of fixation, densitometric and geometric structure of the bone. DXA measures the integral mass of trabecular and cortical bone mineral but cannot discriminate between the structurally and mechanically separate constitutes. Distribution and organisation of bone mass (the geometric structure) has the final determination of the mechanical properties of bone. Pq CT scan is able to measure densitometric and geometric parameters of bone structure. However, there are no reports in the literature on the relationship between these measurements and the strength of fracture fixation. Our aim is to study the correlation between geometric and densitometric measurements of Pq CT scan, with the strength of fixation of bicondylar tibial plateau fractures and to assess the role of both trabecular and cancellous bone in that strength. Method: Eight Fresh frozen human cadaveric tibias were collected from subjects without a medical history of skeletal pathology. The proximal 10% of the tibia was scanned in a peripheral quantitative computer tomography scanner 1mm thick transverse slides, the cancellous and cortical bone mineral density of the proximal tibia were measured. The geometrical parameters: cortical area, trabecular area, bone strength index (BSI) and the Stress strain index (SSI) as non invasive indicators of the mechanical strength of the bone, were also calculated. A bicondylar tibial plateau fracture was simulated, stabilised, and then tested. All tibias were fixed with Dual buttress plating using a standard AO technique. Cyclic axial compression tests were performed. Inter-fragmentary shear displacements were measured using four extensometers. Failure was defined as over 3mm displacement. Results: Except for the cortical density, there was a strong correlation between failure load and geometric and densitometric parameters. The trabecular density was the best predictor of fixation strength of tibial plateau fracture. Discussion: Trabecular density is a more reliable parameter to measure than the cortical density. Therefore, the fixation strength of tibial plateau fracture is dominantly influenced by the mechanical properties of cancelous bone. Cortical bone has a secondary role. These results highlight the importance of fixation techniques that rely on cancellous bone anchoring such as tensioned fine wire fixation in tibial plateau fractures

Aim: Retears after rotator cuff surgery occur frequently and may compromise the functional results. Failure of bone anchors and sutures may influence the results to a great part. The goals of this in vitro investigation were to determine the mechanical strength and stiffness of different bone anchors frequently used in arthroscopic rotator cuff surgery. Focus was put a material and design of the anchors. Material und Methods: Four bone anchors were tested, each standing for a specific group of bone anchor. The metallic Super Revo screw 5.0 (Linvatec), the absorbable screw Spiralok 5.0 (Mitek), the absorbable press-fit anchor Bioknotless RC (Mitek) and the absorbable Ultra-sorb RC (Linvatec). The anchors were tested on 12 pairs of fresh-frozen human shoulders. The mean age at the time of death was fifty-seven years (range 27–93 yrs.). Cyclic loading was performed, as it was considered the best way to simulate the postoperative conditions. The maximum tensile strength, the failure mode, and the displacement of the fixation device (system displacement) under load at the first cycle of 75 N and at the maximum tensile strength were recorded. Results: As reported before the most frequent failure mode for the titan anchor Super Revo 5 mm was a rupture of the threads at the eyelet. The absorbable Spiralok 5 mm screw anchor showed the highest failure load with a mean of 223 N. The failure loads of the remaining anchors were similar and ranged from a mean of 169 N for the Super Revo 5 mm, over a mean of 173 N for the Ultrasorb RC anchor to a mean of 188 N for the Bioknotless anchor. Among these anchors the differences were not significant. Only the Spiralok 5 mm screw showed a significantly higher failure load when compared with the Super Revo 5 mm screw. The displacement of the various systems showed significant differences. The displacement of the Bioknotless anchor showed after the cycle with a tensile strength of 75 N a mean displacement of 13.8 mm, which was significant when compared with the remaining anchors. Discussion: Our study shows that there is no advantage in using titan anchors with regards to primary stability in arthroscopic rotator cuff repair. We could even detect a significantly higher failure load for the absorbable Spiralok 5 mm screw anchor compared to the Super Revo 5 mm titan screw. Stability and system displacement depend not only on the anchor material but on the design of the anchor. We found that the absorbable Bioknotless RC anchor showed a significantly higher system displacement during the first cyclic loading (75 N) while all other anchors tested had a similar system displacement

Antibiotic-laden bone cement is an important strategy of treatment for an established bone infection. It was aimed to find the safe antibiotic dose intervals of the antibiotic cements soaked in Phosphate Buffered Saline solution and to determine whether there was a difference in terms of mechanical strength between the prepared samples. This study was done in our institute Microbiology and Metallurgy laboratories. All samples were prepared using manual mixing technique using 40 g radiopaque Biomet® Bone cement (Zimmer Biomet, Indiana, USA) under sterile conditions at 19 ± 2 ºC. In this study, vancomycin (4 groups − 0.5, 2, 4, 6 g), teicoplanin (4 groups − 0.8, 1.2, 2, 2.4 g), daptomycin (4 groups − 1, 2, 2.5, 3 g), piperacillin-tazobactam (4 groups − 0.125, 0.5, 1, 2 g) and meropenem (4 groups − 0.5, 2, 4, 6 g) were measured in a assay balance and added to the cement powder. Antibiotic levels ranged from the lowest 0.625% to the highest 15%. 80×10×4 mm rectangle prism-shaped sample for mechanical measurements in accordance to ISO 5833 standart and 12×6×1 mm disc-shaped samples for microbiological assesments were used. Four sample for each antibiotic dose and control group was made. Prepared samples were evaluated macroscopically and faulty samples were excluded from the study. Prepared samples were kept in Phosphate Buffered Saline solution renewed every 24 hours at 37 ºC. At the end of 6 weeks, all samples were tested with Instron ® 3369 (Norwood Massachusetts, USA) four point bending test. Staphylococcus aureus (ATCC 29213) strain was used for samples of antibiotics containing vancomycin, teicoplanin and daptomycin after the samples prepared for antibiotic release were maintained under sterile conditions and kept in Phosphate Buffered Saline solution as appropriate. For samples containing meropenem and piperacillin - tazobactam antibiotics, Pseudomonas aeruginosa (ATCC 27853) strain was used. The addition of more than 5% antibiotics to the cement powder was significantly reduced mechanical strength in all groups(p <0.05) however the power of significance was changed depending on the type of antibiotic. In general, adding antibiotics with 2.5% and less for cement amount was not cause significant changes in mechanical measurements. There was a negative correlation between the increase in the amount of antibiotics mixed with cement and the durability of the cement (p: <0.001, r: −0.883 to 0.914). In this study, especially the antibacterial effects of piperacillin-tazobactam, containing 0.25 gr and 0.5 gr antibiotic doses, were found to be low. There was no bacterial growth in all other groups for 21 days. Considering the mechanical properties of groups containing meropenem, vancomycin, daptomycin and teicoplanin, it was observed that all antibiotic cements remained above the limit value of 50 MPa in the bending test at concentrations containing 2.5% and less antibiotics. This was not achieved for the piperacillin-tazobactam group. The findings of the study showed that each antibiotic has different MPa values at different doses. Therefore, it could be concluded that not only the antibiotic dose but also the type oould change the mechanical properties. In the light of these findings, mixing more than 2.5% antibiotics in cement for the antibiotic types included in the study was ineffective in terms of antibacterial effect and mechanically reduces the durability of cement below the standard value of 50 MPa

Osteoporosis accounts for a leading cause of degenerative skeletal disease in the elderly. Osteoblast dysfunction is a prominent feature of age-induced bone loss. While microRNAs regulate osteogenic cell behavior and bone mineral acquisition, however, their function to osteoblast senescence during age-mediated osteoporosis remains elusive. This study aims to utilize osteoblast-specific microRNA-29a (miR-29a) transgenic mice to characterize its role in bone cell aging and bone mass.

Young (3 months old) and aged (9 months old) transgenic mice overexpressing miR-29a (miR-29aTg) driven by osteocalcin promoter and wild-type (WT) mice were bred for study. Bone mineral density, trabecular morphometry, and biomechanical properties were quantified using μCT imaging, material testing system and histomorphometry. Aged osteoblasts and senescence markers were probed using immunofluorescence, flow cytometry for apoptotic maker annexin V, and RT-PCR.

Significantly decreased bone mineral density, sparse trabecular morphometry (trabecular volume, thickness, and number), and poor biomechanical properties (maximum force and breaking force) along with low miR-29a expression occurred in aged WT mice. Aging significantly upregulated the expression of senescence markers p16INK4a, p21Waf/Cip1, and p53 in osteoporotic bone in WT mice. Of note, the severity of bone mass and biomechanical strength loss, as well as bone cell senescence, was remarkably compromised in aged miR-29aTg mice. In vitro, knocking down miR-29a accelerated senescent (β-galactosidase activity and senescence markers) and apoptotic reactions (capsas3 activation and TUNEL staining), but reduced mineralized matrix accumulation in osteoblasts. Forced miR-29a expression attenuated inflammatory cytokine-induced aging process and retained osteogenic differentiation capacity. Mechanistically, miR-29a dragged osteoblast senescence through targeting 3′-untranslated region of anti-aging regulator FoxO3 to upregulate that of expression as evident from luciferase activity assessment.

Low miR-29a signaling speeds up aging-induced osteoblast dysfunction and osteoporosis development. Gain of miR-29a function interrupts osteoblast senescence and shields bone tissue from age-induced osteoporosis. The robust analysis sheds light to the protective actions of miR-29a to skeletal metabolism and conveys a perspective of miR-29a signaling enhancement beneficial for aged skeletons.

We have studied the mechanical properties of several current techniques of tendon-to-bone suture employed in rotator-cuff repair. Non-absorbable braided polyester and absorbable polyglactin and polyglycolic acid sutures best combined ultimate tensile strength and stiffness. Polyglyconate and polydioxanone sutures failed only at high loads, but elongated considerably under moderate loads. We then compared the mechanical properties of nine different techniques of tendon grasping, using 159 normal infraspinatus tendons from sheep. The most commonly used simple stitch was mechanically poor: repairs with two or four such stitches failed at 184 N and 208 N respectively. A new modification of the Mason-Allen suture technique improved the ultimate tensile strength to 359 N for two stitches. Finally, we studied the mechanical properties of several methods of anchorage to bone using typically osteoporotic specimens. Single and even double transosseous sutures and suture anchor fixation both failed at low tensile loads (about 140 N). The use of a 2 mm thick, plate-like augmentation device improved the failure strength to 329 N. The mechanical properties of many current repair techniques are poor and can be greatly improved by using good materials, an improved tendon-grasping suture, and augmentation at the bone attachment.

Summary Statement

A population based finite element study that accounts for subject-specific morphology, density and load variations, suggests that osteoporosis does not markedly lower the mechanical compliance of the proximal femur to routine loads.

Comparison of two cementing techniques: femoral component insertion into early-cure stage cement and insertion into late-cure stage cement in an in vivo model to identify if cement cure stage affects the strength of the bone cement interface.

Bilateral arthroplasties – using only the femoral component - were performed in vivo on paired porcine femora. The femora were harvested and cross-sectioned in preparation for strength testing. Performance was measured by peak load required to push the femoral prosthesis and surrounding cement mantle free of the cancellous bone.

The mean failure load for prostheses inserted into late cure stage cement was 908 N +/− SD 420, whereas the mean failure load for the conjugate early cure stage cement was 503 N +/− SD 342. A paired t-test indicated significantly higher load failure rates in the late cure stage cement versus the early cure stage samples (t=2.37, p< 0.049).

Femoral component insertion into late cure stage cement required statistically significant higher loads for push-out when compared to femoral component insertion into early cure stage cement.

Purpose of Study: To compare the mechanical performance of two commonly used arthroscopic slip knots with that of a hand tied control.

Methods: The arthroscopic slip knots assessed were the Duncan Loop (DL) and the Tautline Hitch (TLH), both of which were tied with arthroscopic knot pushers and secured with Three Reversing Hitches on Alternating Posts (RHAPs). These were compared with four hand tied throws of a squre knot. All three knots were tied using three different materials: number two Ethibond, number one PDS and number two Fiberwire. All knots were tied in a close loop configuration between two metal bars mounted on an Instron materials testing device and pulled apart to both clinical and ultimate failure. Clinical failure was defined as the force in Newtons (N) required to increase loop length by three millimetres, which equtes in vivo with a critical loss in apposition of repaired tissues. Ultimate failure was defined as the force in N resulting in complete slippage or breakage of the knot being tested. This study was different than those before it in that a much larger number of each knot/suture permutation was tested (thirty in each case) to give the study sufficient power to detect significant differences between the knots tested.

Results and Conclusion: Based on the findings of this study, it is our recommendation that an arthroscopic TLH slip knot secured with three RHAPs and tied using a number two Fiberwire suture be used to produce shoulder repairs that are equivalent if not superior to those achieved using open hand tied methods.

The use of fresh morsellised allograft in impaction bone grafting for revision hip surgery remains the gold standard. Bone marrow contains osteogenic progenitor cells that arise from multipotent mesenchymal stem cells and we propose that in combination with allograft will produce a living composite with biological and mechanical potential. This study aimed to determine if human bone marrow stromal cells (HBMSC) seeded onto highly washed morsellised allograft could survive the impaction process, differentiate and proliferate along the osteogenic lineage and confer biomechanical advantage in comparison to impacted allograft alone. Future work into the development of a bioreactor is planned for the potential safe translation of such a technique into clinical practice.

Methods: HBMSC were isolated and culture expanded in vitro under osteogenic conditions. Cells were seeded onto prepared morsellised allograft and impacted with a force equivalent to a standard femoral impaction (474J/m2). Samples were incubated for either two or four week periods under osteogenic conditions and analysed for cell viability, histology, immunocytochemistry, and biochemical analysis of cell number and osteogenic enzyme activity. Mechanical shear testing, using a Cam shear tester was performed, under three physiological compressive stresses (50N, 150N, 250N) from which the shear strength, internal friction angle and particle interlocking values were derived.

Results: HBMSC survival post impaction, as evidenced by cell tracker green staining, was seen throughout the samples. There was a significant increase in DNA content (P< 0.05) and specific alkaline phosphatase activity (P< 0.05) compared to impacted seeded allograft samples. Immunocytochemistry staining for type I collagen confirmed cell differentiation along the osteogenic lineage. There was no statistical difference in the shear strength, internal friction angle and particulate cohesion between the two groups at 2 and 4 weeks.

Conclusion: HBMSC seeded onto allograft resulted in the formation of a living composite capable of withstanding the forces equivalent to a standard femoral impaction and, under osteogenic conditions, differentiate and proliferate along the osteogenic lineage. In addition, there was no reduction in aggregate shear strength and longer term studies are warranted to examine the biomechanical advantage of a living composite. The therapeutic implications of such composites auger well for orthopaedic applications.

Introduction

Total leg muscle function in hip OA patients is not well studied. We used a test-retest protocol to evaluate the reproducibility of single- and multi-joint peak muscle torque and rapid torque development in a group of 40–65 yr old hip patients. Both peak torque and torque development are outcome measures associated with functional performance during activities of daily living.

Aims. Orthopaedic surgery requires grafts with sufficient mechanical strength. For this purpose, decellularized tissue is an available option that lacks the complications of autologous tissue. However, it is not widely used in orthopaedic surgeries. This study investigated clinical trials of the use of decellularized tissue grafts in orthopaedic surgery. Methods. Using the ClinicalTrials.gov (CTG) and the International Clinical Trials Registry Platform (ICTRP) databases, we comprehensively surveyed clinical trials of decellularized tissue use in orthopaedic surgeries registered before 1 September 2022. We evaluated the clinical results, tissue processing methods, and commercial availability of the identified products using academic literature databases and manufacturers’ websites. Results. We initially identified 4,402 clinical trials, 27 of which were eligible for inclusion and analysis, including nine shoulder surgery trials, eight knee surgery trials, two ankle surgery trials, two hand surgery trials, and six peripheral nerve graft trials. Nine of the trials were completed. We identified only one product that will be commercially available for use in knee surgery with significant mechanical load resistance. Peracetic acid and gamma irradiation were frequently used for sterilization. Conclusion. Despite the demand for decellularized tissue, few decellularized tissue products are currently commercially available, particularly for the knee joint. To be viable in orthopaedic surgery, decellularized tissue must exhibit biocompatibility and mechanical strength, and these requirements are challenging for the clinical application of decellularized tissue. However, the variety of available decellularized products has recently increased. Therefore, decellularized grafts may become a promising option in orthopaedic surgery. Cite this article: Bone Joint Res 2023;12(3):179–188

Aims. To develop an early implant instability murine model and explore the use of intermittent parathyroid hormone (iPTH) treatment for initially unstable implants. Methods. 3D-printed titanium implants were inserted into an oversized drill-hole in the tibiae of C57Bl/6 mice (n = 54). After implantation, the mice were randomly divided into three treatment groups (phosphate buffered saline (PBS)-control, iPTH, and delayed iPTH). Radiological analysis, micro-CT (µCT), and biomechanical pull-out testing were performed to assess implant loosening, bone formation, and osseointegration. Peri-implant tissue formation and cellular composition were evaluated by histology. Results. iPTH reduced radiological signs of loosening and led to an increase in peri-implant bone formation over the course of four weeks (timepoints: one week, two weeks, and four weeks). Observational histological analysis shows that iPTH prohibits the progression of fibrosis. Delaying iPTH treatment until after onset of peri-implant fibrosis still resulted in enhanced osseointegration and implant stability. Despite initial instability, iPTH increased the mean pull-out strength of the implant from 8.41 N (SD 8.15) in the PBS-control group to 21.49 N (SD 10.45) and 23.68 N (SD 8.99) in the immediate and delayed iPTH groups, respectively. Immediate and delayed iPTH increased mean peri-implant bone volume fraction (BV/TV) to 0.46 (SD 0.07) and 0.34 (SD 0.10), respectively, compared to PBS-control mean BV/TV of 0.23 (SD 0.03) (PBS-control vs immediate iPTH, p < 0.001; PBS-control vs delayed iPTH, p = 0.048; immediate iPTH vs delayed iPTH, p = 0.111). Conclusion. iPTH treatment mediated successful osseointegration and increased bone mechanical strength, despite initial implant instability. Clinically, this suggests that initially unstable implants may be osseointegrated with iPTH treatment. Cite this article: Bone Joint Res 2022;11(5):260–269

To address the current challenge of anterior cruciate ligament (ACL) reconstruction, this study is the first to fabricate a braided collagen rope (BCR) which mimics native hamstring for ACL reconstruction. The study aims to evaluate the biological and biomechanical properties of BCR both in vivo and vitro. Rabbit ACL reconstruction model using collagen rope and autograft (hamstring tendon) was conducted. The histological and biomechanical evaluations were conducted at 6-, 12-, 18, 26-week post-operation. In vitro study included cell morphology analysis, cell function evaluation and RNA sequencing of the tenocytes cultured on BCR. A cadaver study was also conducted to verify the feasibility of BCR for ACL reconstruction. BCR displays satisfactory mechanical strength similar to hamstring graft for ACL reconstruction in rabbit. Histological assessment showed BCR restore ACL morphology at 26 weeks similar to native ACL. The superior dynamic ligamentization in BCR over autograft group was evidenced by assessment of cell and collagen morphology and orientation. The in vitro study showed that the natural collagen fibres within BCR enables to signal the morphology adaptation and orientation of human tenocytes in bioreactor. BCR enables to enhance cell proliferation and tenogenic expression of tenocytes as compared to hydrolysed collagen. We performed an RNA-Sequencing (RNA-seq) experiment where RNA was extracted from tenocyte seeded with BCR. Analysis of enriched pathways of the up-regulated genes revealed that the most enriched pathways were the Hypoxia-inducible factor 1-alpha (HIF1A) regulated networks, implicating the possible mechanism BCR induced ACL regeneration. The subsequent cadaver study was conducted to proof the feasibility of BCR for ACL reconstruction. This study demonstrated the proof-of-concept of bio-textile braided collagen rope for ACL reconstruction, and the mechanism by which BCR induces natural collagen fibres that positively regulate morphology and function of tenocytes

A spine compression fracture is a very common form of fracture in elderly with osteoporosis. Injection of polymethyl methacrylate (PMMA) to fracture sites is a minimally invasive surgical treatment, but PMMA has considerable clinical risks. We develop a novel type thermoplastic injectable bone substitute contains the proprietary composites of synthetic ceramic bone substitute and absorbable thermoplastic polymer. We used thermoplastic biocompatible polymers Polycaproactone (PCL) to encapsulate calcium-based bone substitutes hydroxyapatite (Ca10(PO4)6(OH)2, HA) and tricalcium phosphate (TCP) to form a biodegradable injectable bone composite material. The space occupation ration PCL:HA/TCP is 1:9. After heating process, it can be injected to fracture site by specific instrument and then self-setting to immediate reinforce the vertebral body. The thermoplastic injection bone substitute can obtain good injection properties after being heated by a heater at 90˚C for three minutes, and has good anti-washout property when injected into normal saline at 37˚C. After three minutes, solidification is achieved. Mechanical properties were assessed using the material compression test system and the mechanical support close to the vertebral spongy bone. In vitro cytotoxicity MTT assay (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was performed and no cell cytotoxicity was observed. In vivo study with three New Zealand rabbits was performed, well bone growth into bone substitute was observed and can maintain good mechanical support after three months implantation. The novel type thermoplastic injection bone substitute can achieve (a) adequate injectability and viscosity without the risk of cement leakage; (b) adequate mechanical strength for immediate reinforcement and prevent adjacent fracture; (c) adequate porosity for new bone ingrowth; (e) biodegradability. It could be developed as a new option for treating vertebral compression fractures

In 2021 the bone grafting market was worth €2.72 billion globally. As allograft bone has a limited supply and risk of disease transmission, the demand for synthetic grafting substitutes (BGS) continues to grow while allograft bone grafts steadily decrease. Synthetic BGS are low in mechanical strength and bioactivity, inspiring the development of novel grafting materials, a traditionally laborious and expensive process. Here a novel BGS derived from sustainably grown coral was evaluated. Coral-derived scaffolds are a natural calcium carbonate bio-ceramic, which induces osteogenesis in bone marrow mesenchymal stem cells (MSCs), the cells responsible for maintaining bone homeostasis and orchestrating fracture repair. By 3D printing MSCs in coral-laden bioinks we utilise high throughput (HT) fabrication and evaluation of osteogenesis, overcoming the limitations of traditional screening methods. MSC and coral-laden GelXA (CELLINK) bioinks were 3D printed in square bottom 96 well plates using a CELLINK BIO X printer with pneumatic adapter Samples were non-destructively monitored during the culture period, evaluating both the sample and the culture media for metabolism (PrestoBlue), cytotoxicity (lactose dehydrogenase (LDH)) and osteogenic differentiation (alkaline phosphatase (ALP)). Endpoint, destructive assays used included qRT-PCR and SEM imaging. The inclusion of coral in the printed bioink was biocompatable with the MSCs, as reflected by maintained metabolism and low LDH release. The inclusion of coral induced osteogenic differentiation in the MSCs as seen by ALP secretion and increased RUNX2, collagen I and osteocalcin transcription. Sustainably grown coral was successfully incorporated into bioinks, reproducibly 3D printed, non-destructively monitored throughout culture and induced osteogenic differentiation in MSCs. This HT fabrication and monitoring workflow offers a faster, less labour-intensive system for the translation of bone substitute materials to clinic. Acknowledgements: This work was co-funded by Enterprise Ireland and Zoan Biomed through Innovation Partnership IP20221024

Residual tumor cells left in the bone defect after malignant bone tumor resection can result in local tumor recurrence and high mortality. Therefore, ideal bone filling materials should not only aid bone reconstruction or regeneration, but also exert local chemotherapeutic efficacy. However, common bone substitutes used in clinics are barely studied in research for local delivery of chemotherapeutic drugs. Here, we aimed to use facile manufacturing methods to render polymethylmethacrylate (PMMA) cement and ceramic granules suitable for local delivery of cisplatin to limit bone tumor recurrence. Porosity was introduced into PMMA cement by adding 1-4% carboxymethylcellulose (CMC) containing cisplatin, and chemotherapeutic activity was rendered to two types of granules via adsorption. Then, mechanical properties, porosity, morphology, drug release kinetics, ex vivo reconstructive properties of porous PMMA and in vitro anti-cancer efficacy against osteosarcoma cells were assessed. Morphologies, molecular structures, drug release profiles and in vitro cytostatic effects of two different drug-loaded granules on the proliferation of metastatic bone tumor cells were investigated. The mechanical strengths of PMMA-based cements were sufficient for tibia reconstruction at CMC contents lower than 4% (≤3%). The concentrations of released cisplatin (12.1% and 16.6% from PMMA with 3% and 4% CMC, respectively) were sufficient for killing of osteosarcoma cells, and the fraction of dead cells increased to 91.3% within 7 days. Functionalized xenogeneic granules released 29.5% of cisplatin, but synthetic CaP granules only released 1.4% of cisplatin over 28 days. The immobilized and released cisplatin retained its anti-cancer efficacy and showed dose-dependent cytostatic effects on the viability of metastatic bone tumor cells. Bone substitutes can be rendered therapeutically active for anticancer efficacy by functionalization with cisplatin. As such, our data suggest that multi-functional PMMA-based cements and cisplatin-loaded granules represent viable treatment options for filling bone defects after bone tumor resection

We developed a novel silorane-based biomaterial (SBB) for use as an orthopedic cement. SBB is comprised of non-toxic silicon-based monomers, undergoes non-exothermic polymerization, and has weight-bearing strength required of orthopedic cements. We sought to compare the antibiotic release kinetics of this new cement to that of commercially available PMMA bone cement. We also evaluated each material's inherent propensity to support the attachment of bacteria under both static and dynamic conditions. One gram of either rifampin or vancomycin was added to 40g batches of PMMA and SBB. Pellets were individually soaked in PBS. Eluate was collected and tested daily for 14 days using HPLC. Compressive strength and modulus were tested over 21 days. Bioassays were used to confirm the bioactivity of the antibiotics eluted. We measured the growth and maturation of staphylococcus aureus (SA) biofilm on the surface of both PMMA and SBB disks over the course of 72 hours in a static well plate and in a dynamic biofilm reactor (CDC Biofilm Reactor). N=4 at 24, 48, and 72 hours. A luminescent strain of SA (Xen 29) was employed allowing imaging of bacteria on the discs. SBB eluted higher concentrations of vancomycin than did PMMA over the course of 14 days (p<0.001). A significant 55.1% greater day 1 elution was observed from SBB. Silorane cement was able to deliver rifampin in clinically favorable concentrations over 14 days. On the contrary, PMMA was unable to deliver rifampin past day 1. The incorporation of rifampin into PMMA severely reduced its mechanical strength (p<0.001) and modulus (p<0.001). Surface bacterial radiance of PMMA specimens was significantly greater than that of SBB specimens at all time points (p<0.05). The novel silorane-based cement demonstrated superior antibiotic release and, even without antibiotic incorporation, demonstrated an innate inhabitation to bacterial attachment and biofilm

Aim. Prosthetic joint infections pose a major clinical challenge. Developing novel material surface technologies for orthopedic implants that prevent bacterial adhesion and biofilm formation is essential. Antimicrobial coatings applicable to articulating implant surfaces are limited, due to the articulation mechanics inducing wear, coating degradation, and toxic particle release. Noble metals are known for their antimicrobial activity and high mechanical strength and could be a viable coating alternative for orthopaedic implants [1]. In this study, the potential of thin platinum-based metal alloy coatings was developed, characterized, and tested on cytotoxicity and antibacterial properties. Method. Three platinum-based metal alloy coatings were sputter-coated on medical-grade polished titanium discs. The coatings were characterized using optical topography and scanning electron microscopy with energy dispersive spectroscopy (SEM/EDS). Ion release was measured using inductively coupled plasma optical emission spectrometry (ICP-OES). Cytotoxicity was tested according to ISO10993-5 using mouse fibroblasts (cell lines L929 and 3T3). Antibacterial surface activity, bacterial adhesion, bacterial proliferation, and biofilm formation were tested with gram-positive Staphylococcus aureus ATCC 25923 and gram-negative Escherichia coli ATCC 25922. Colony forming unit (CFU) counts, live-dead fluorescence staining, and SEM-EDS images were used to assess antibacterial activity. Results. Three different platinum-based metal alloys consisting of platinum-iridium, platinum-copper, and platinum-zirconium. The coatings were found 80 nm thick, smooth (roughness average < 60 nm), and non-toxic. The platinum-copper coating showed a CFU reduction larger than one logarithm in adherent bacteria compared to uncoated titanium. The other coatings showed a smaller reduction. This data was confirmed by SEM and live-dead fluorescence images, and accordingly, ICP-OES measurements showed low levels of metal ion release from the coatings. Conclusions. The platinum-copper coating showed low anti-adhesion properties, even with extremely low metal ions released. These platinum-based metal alloy coatings cannot be classified as antimicrobial yet. Further optimization of the coating composition to induce a higher ion release based on the galvanic principle is required and copper looks most promising as the antimicrobial compound of choice. Acknowledgments. This publication is supported by the DARTBAC project (with project number NWA.1292.19.354) of the research program NWA-ORC which is (partly) financed by the Dutch Research Council (NWO); and the AMBITION project (with project number NSP20–1-302), co-funded by the PPP Allowance made available by Health-Holland, Top Sector Life Sciences & Health to ReumaNederland

Objectives. The objective of this study was to characterize the effect of rifampin incorporation into poly(methyl methacrylate) (PMMA) bone cement. While incompatibilities between the two materials have been previously noted, we sought to identify and quantify the cause of rifampin’s effects, including alterations in curing properties, mechanical strength, and residual monomer content. Methods. Four cement groups were prepared using commercial PMMA bone cement: a control; one with 1 g of rifampin; and one each with equimolar amounts of ascorbic acid or hydroquinone relative to the amount of rifampin added. The handling properties, setting time, exothermic output, and monomer loss were measured throughout curing. The mechanical strength of each group was tested over 14 days. A radical scavenging assay was used to assess the scavenging abilities of rifampin and its individual moieties. Results. Compared with control, the rifampin-incorporated cement had a prolonged setting time and a reduction in exothermic output during polymerization. The rifampin cement showed significantly reduced strength and was below the orthopaedic weight-bearing threshold of 70 MPa. Based on the radical scavenging assay and strength tests, the hydroquinone structure within rifampin was identified as the polymerization inhibitor. Conclusion. The incorporation of rifampin into PMMA bone cement interferes with the cement’s radical polymerization. This interference is due to the hydroquinone moiety within rifampin. This combination alters the cement’s handling and curing properties, and lowers the strength below the threshold for weight-bearing applications. Additionally, the incomplete polymerization leads to increased toxic monomer output, which discourages its use even in non-weight-bearing applications. Cite this article: G. A. Funk, E. M. Menuey, K. A. Cole, T. P. Schuman, K. V. Kilway, T. E. McIff. Radical scavenging of poly(methyl methacrylate) bone cement by rifampin and clinically relevant properties of the rifampin-loaded cement. Bone Joint Res 2019;8:81–89. DOI: 10.1302/2046-3758.82.BJR-2018-0170.R2

Varus malalignment increases the susceptibility of cartilage to mechanical overloading, which stimulates catabolic metabolism to break down the extracellular matrix and lead to osteoarthritis (OA). The altered mechanical axis from the hip, knee to ankle leads to knee joint pain and ensuing cartilage wear and deterioration, which impact millions of the aged population. Stabilization of the remaining damaged cartilage, and prevention of further deterioration, could provide immense clinical utility and prolong joint function. Our previous work showed that high tibial osteotomy (HTO) could shift the mechanical stress from an imbalanced status to a neutral alignment. However, the underlying mechanisms of endogenous cartilage stabilization after HTO remain unclear. We hypothesize that cartilage-resident mesenchymal stem cells (MSCs) dampen damaged cartilage injury and promote endogenous repair in a varus malaligned knee. The goal of this study is to further examine whether HTO-mediated off-loading would affect human cartilage-resident MSCs' anabolic and catabolic metabolism. This study was approved by IACUC at Xi'an Jiaotong University. Patients with medial compartment OA (52.75±6.85 yrs, left knee 18, right knee 20) underwent open-wedge HTO by the same surgeons at one single academic sports medicine center. Clinical data was documented by the Epic HIS between the dates of April 2019 and April 2022 and radiographic images were collected with a minimum of 12 months of follow-up. Medial compartment OA with/without medial meniscus injury patients with unilateral Kellgren /Lawrence grade 3–4 was confirmed by X-ray. All incisions of the lower extremity healed well after the HTO operation without incision infection. Joint space width (JSW) was measured by uploading to ImageJ software. The Knee injury and Osteoarthritis Outcome Score (KOOS) toolkit was applied to assess the pain level. Outerbridge scores were obtained from a second-look arthroscopic examination. RNA was extracted to quantify catabolic targets and pro-inflammatory genes (QiaGen). Student's t test for two group comparisons and ANOVA analysis for differences between more than 2 groups were utilized. To understand the role of mechanical loading-induced cartilage repair, we measured the serial changes of joint space width (JSW) after HTO for assessing the state of the cartilage stabilization. Our data showed that HTO increased the JSW, decreased the VAS score and improved the KOOS score significantly. We further scored cartilage lesion severity using the Outerbridge classification under a second-look arthroscopic examination while removing the HTO plate. It showed the cartilage lesion area decreased significantly, the full thickness of cartilage increased and mechanical strength was better compared to the pre-HTO baseline. HTO dampened medial tibiofemoral cartilage degeneration and accelerate cartilage repair from Outerbridge grade 2 to 3 to Outerbridge 0 to 1 compared to untreated varus OA. It suggested that physical loading was involved in HTO-induced cartilage regeneration. Given that HTO surgery increases joint space width and creates a physical loading environment, we hypothesize that HTO could increase cartilage composition and collagen accumulation. Consistent with our observation, a group of cartilage-resident MSCs was identified. Our data further showed decreased expression of RUNX2, COL10 and increased SOX9 in MSCs at the RNA level, indicating that catabolic activities were halted during mechanical off-loading. To understand the role of cartilage-resident MSCs in cartilage repair in a biophysical environment, we investigated the differentiation potential of MSCs under 3-dimensional mechanical loading conditions. The physical loading inhibited catabolic markers (IL-1 and IL-6) and increased anabolic markers (SOX9, COL2). Knee-preserved HTO intervention alleviates varus malalignment-related knee joint pain, improves daily and recreation function, and repairs degenerated cartilage of medial compartment OA. The off-loading effect of HTO may allow the mechanoregulation of cartilage repair through the differentiation of endogenous cartilage-derived MSCs

Anterior cruciate ligament (ACL) reconstruction is the current standard of care for ACL tears. However, the results are not consistently successful, autografts or allografts have certain disadvantages, and synthetic grafts have had poor clinical results. The aim of this study was to determine the efficacy of tissue engineering decellularized tibialis tendons by recellularization and culture in a dynamic tissue bioreactor. To determine if recellularization of decellularized tendons combined with mechanical stimulation in a bioreactor could replicate the mechanical properties of the native ACL and be successfully used for ACL reconstruction in vivo. Porcine tibialis tendons were decellularized and then recellularized with human adult bone marrow-derived stem cells. Tendons were cultured in a tissue bioreactor that provided biaxial cyclic loading for up to 7 days. To reproduce mechanical stresses similar to hose experienced by the ACL within the knee joint, the tendons were subjected to simultaneous tension and torsion in the bioreactor. Expression of tendon-specific genes, and newly synthesized collagen and glycosaminoglycan (GAG) were used to quantify the efficacy of recellularization and dynamic bioreactor culture. The mechanical strength of recellularized constructs was measured after dynamic stimulation. Finally, the tissue-engineered tendons were used to reconstruct the ACL in mini-pigs and mechanical strength was assessed after three months. Dynamic bioreactor culture significantly increased the expression of tendon-specific genes, the quantity of newly synthesized collagen and GAG, and the tensile strength of recellularized tendons. After in vivo reconstruction, the tensile strength of the tissue-engineered tendons increased significantly up to 3 months after surgery and were within 80% of the native strength of the ACL. Our translational study indicates that the recellularization and dynamic mechanical stimuli can significantly enhance matrix synthesis and mechanical strength of decellularized porcine tibialis tendons. This approach to tissue engineering can be very useful for ACL reconstruction and may overcome some of the disadvantages of autografts and allografts

Background. Tigecycline, the first member of glycylcycline family, has effective antimicrobial activity against resistant and implant associated infectious organisms. The objectives of this study are to assess the compressive and tensile mechanical strength characteristics of tigecycline loaded bone cement and to compare them with vancomycin and daptomycin loaded bone cements which are used in prosthetic joint infections with resistant microorganisms. Methods. A control group without antibiotics and three antibiotic loaded bone cement groups with varying concentrations (1g, 2g and 3g vancomycin, 0.5g, 1g and 1.5g daptomycin and 50mg, 100mg and 150mg tigecycline) were prepared and tested according to ASTM F451 and ISO 5833 standards. Statistical analysis of the obtained data done by using LSD (least significant difference) and Bonferroni corrected Mann Whitney tests. Results. Both compression and tension tests showed that all determined antibiotic concentrations resulted in significant decrease when compared to the control group. Despite heterogenous statistical results, it was seen that the mechanical strength of tigecycline loaded bone cement was not significantly lower (even higher in some comparisons) when compared to vancomycin and daptomycin loaded bone cements. Conclusion. When used at defined concentrations, tigecycline loaded bone cement does not have mechanical disadvantage compared to vancomycin and daptomycin loaded bone cements. Thus, it should be kept in mind as an option in appropriate clinical situations

Objective: The purpose of the present study was to assess whether clinicians are actually able to evaluate the mechanical status of lengthening callus from plain radiographs. Materials and Methods: 36 rats were employed in this study. Their left femurs were lengthened by 6 mm as a bone lengthening model. Rats were euthanized at 4 8 12 and 16 weeks after lengthening. Both femora were X-rayed and then bone density parameters (bone mineral content, bone mineral density and bone area) of lengthening callus were measured using pQCT. Three-point bending test was performed to determine the mechanical strength of the both bones. We defined the ratio of the strength of lengthening side to control side as estimated strength recovery rate (%). Then 20 orthopaedic surgeons evaluated only the X-ray photographs and tried to estimate the relative mechanical strength (%) of the affected side compared to the control side. Results: Between the recovery percentage of mechanical strength and bone mineral content, a positive simple correlation (R2=0.11, p< 0.05) was seen. No significant correlation was seen between the recovery percentage of mechanical strength estimated by orthopaedists and the mechanical strength measured by three-point bending test (qualified doctors: R2=0.0793 p=0.291 unqualified doctors: R2=0.0523 p=0.394). Discussion and conclusion: It became obvious that to estimate the strength of lengthening callus from plain radiographs alone is quite difficult as compared with the studies of the simple fracture model that have been reported until now

Current strategy for orthopedic tissue engineering mainly focusses on the regeneration of the damaged tissue using cell-seeded three-dimensional scaffolds. Biocompatible scaffolds with controllable degradation and suitable mechanical property are required to support new tissue in-growth and regeneration . [1]. Porous composite scaffolds made from organic and inorganic materials are highly preferred, which can mimic the natural bone in their composition as well can enhance tissue repair . [2]. Scaffolds with optimum mechanical strength in both dry and wet state are more suitable for in vivo orthopedic application. Biphasic calcium phosphate (BCP), a biocompatible ceramic and carboxymethyl cellulose (CMC), a semi-natural polymer are used in the study to prepare composite scaffolds. Citric acid is used as a crosslinking agent for the polymer to improve its stability . [3]. Stability, mechanical property in dry and wet conditions and cytocompatibility of the scaffolds were investigated. Cellulose-BCP (BC25) and crosslinked cellulose-BCP (BC25CA) scaffolds are fabricated by freeze-drying method. The stability of the scaffolds was assessed in phosphate buffered saline (PBS) and compressive modulus was measured in dry and wet condition. Cytocompatibility was assessed by culturing pre-osteoblast cells at a density of 2.5×10. 4. on crosslinked scaffold and cell proliferation was measured by performing MTT assay on day 4 and 7. Crosslinked scaffold was more stable than non-crosslinked scaffold in aqueous environment as the latter disintegrated within few hours in the solution. Non-crosslinked scaffold showed higher compressive modulus of 116.3±14.8 kPa in dry condition but is reduced to 1.2±0.7 kPa in hydrated state. Though the crosslinked scaffold shows low compressive modulus of 37.67±6.7 kPa in dry state, it exhibited appreciable compressive moduli of 17.15±1.3 kPa in hydrated state. Thus, the crosslinking of the scaffolds improved the stability as well as the mechanical strength in wet condition. Cytocompatibility was assessed by culturing pre-osteoblast cells and from the MTT assay, it is shown that the cells are proliferating on the crosslinked scaffolds with time which indicates that the scaffolds are non-toxic and cytocompatible. Stability and optimum mechanical property for scaffold in aqueous environment are highly crucial for in vivo hard tissue regeneration. This study demonstrated the preparation of crosslinked scaffolds which exhibited good stability and mechanical strength in wet condition along with a porous architecture, controlled degradability and cytocompatibility, hence, crosslinked cellulose-BCP scaffold can be used for orthopedic application

Objectives. The objective of this study was to determine if combining variations in mixing technique of antibiotic-impregnated polymethylmethacrylate (PMMA) cement with low frequency ultrasound (LFUS) improves antibiotic elution during the initial high phase (Phase I) and subsequent low phase (Phase II) while not diminishing mechanical strength. Methods. Three batches of vancomycin-loaded PMMA were prepared with different mixing techniques: a standard technique; a delayed technique; and a control without antibiotic. Daily elution samples were analysed using flow injection analysis (FIA). Beginning in Phase II, samples from each mix group were selected randomly to undergo either five, 15, 45, or 0 minutes of LFUS treatment. Elution amounts between LFUS treatments were analysed. Following Phase II, compression testing was done to quantify strength. A-priorit-tests and univariate ANOVAs were used to compare elution and mechanical test results between the two mix groups and the control group. Results. The delayed technique showed a significant increase in elution on day one compared with the standard mix technique (p < 0.001). The transition point from Phase I to Phase II occurred on day ten. LFUS treatments significantly increased elution amounts for all groups above control. Delayed technique resulted in significantly higher elution amounts for the five-minute- (p = 0.004) and 45-minute- (p < 0.001) duration groups compared with standard technique. Additionally, the correlations between LFUS duration and total elution amount for both mix techniques were significant (p = 0.03). Both antibiotic-impregnated groups exhibited a significant decrease in offset yield stress compared with the control group (p < 0.001), however, their lower 95% confidence intervals were all above the 70 MPa limit defined by International Standards Organization (ISO) 5833-2 reference standard for acrylic bone cement. Conclusion. The combination of a delayed mix technique with LFUS treatments provides a reasonable means for increasing both short- and long-term antibiotic elution without affecting mechanical strength. Cite this article: Dr. T. McIff. Combination of modified mixing technique and low frequency ultrasound to control the elution profile of vancomycin-loaded acrylic bone cement. Bone Joint Res 2016;5:26–32. doi: 10.1302/2046-3758.52.2000412

As compared to magnesium (Mg) and iron (Fe), solid zinc (Zn)-based absorbable implants show better degradation rates. An ideal bone substitute should provide sufficient mechanical support, but pure Zn itself is not strong enough for load-bearing medical applications. Modern processing techniques, like additive manufacturing (AM), can improve mechanical strength of Zn. To better mimic the in vivo situation in the human body, we evaluated the degradation behavior of porous Zn implants in vitro under dynamic conditions. Our study applied selective laser melting (SLM) to build topographically ordered absorbable Zn implants with superior mechanical properties. Specimens were fabricated from pure Zn powder using SLM and diamond unit cell topological design. In vitro degradation was performed under both static and dynamic conditions in a custom-built set-up under cell culture conditions (37 °C, 20% O2 and 5% CO2) for up to 28 days. Mechanical properties of the porous structures were determined according to ISO 13314: 2011 at different immersion time points. Modified ISO 10993 standards were used to evaluate biocompatibility through direct cell seeding and indirect extract-based cytotoxicity tests (MTS assay, Promega) against identically designed porous titanium (Ti-6Al-4V) specimens as reference material. Twenty-four hours after cell seeding, its efficacy was evaluated by Live-Dead staining (Abcam) and further analyzed using dual channel fluorescent optical imaging (FOI) and subsequent flow cytometric quantification. Porous Zn implants were successfully produced by means of SLM with a yield strength and Young's modulus in the range of 3.9–9.6 MPa and 265–570 MPa, respectively. Dynamic flow significantly increased the degradation rate of AM porous Zn after 28 days. Results from Zn extracts were similar to Ti-6Al-4V with >95% of cellular activity at all tested time points, confirming level 0 cytotoxicity (i.e., This study clearly shows the great potential of AM porous Zn as a bone substituting material. Moreover, we demonstrate that complex topological design permits control of mechanical properties and degradation behavior

After anterior cruciate ligament (ACL) rupture, reconstructive surgery with a hamstring tendon autograft is often performed. Despite overall good results, ACL re-rupture occurs in up to 10% of the patient population, increasing to 30% of the cases for patients aged under 20 years. This can be related to tissue remodelling in the first months to years after surgery, which compromises the graft's mechanical strength. Resident graft fibroblasts secrete matrix metalloproteinases (MMPs), which break down the collagen I extracellular matrix. After necrosis of these fibroblasts, myofibroblasts repopulate the graft, and deposit more collagen III rather than collagen I. Eventually, the cellular and matrix properties converge towards those of the native ACL, but full restoration of the ACL properties is not achieved. It is unknown how inter-patient differences in tissue remodelling capacity contribute to ACL graft rupture risk. This research measured patient-specific tissue remodelling-related properties of human hamstring tendon-derived cells in an in vitro micro-tissue platform, in order to identify potential biological predictors for graft rupture. Human hamstring tendon-derived cells were obtained from remnant autograft tissue after ACL reconstructions. These cells were seeded in collagen I gels on a micro-tissue platform to assess inter-patient cellular differences in tissue remodelling capacity. Remodelling was induced by removing the outermost micro-posts, and micro-tissue compaction over time was assessed using transmitted light microscopy. Protein expression of tendon marker tenomodulin and myofibroblast marker α-smooth muscle actin (αSMA) were measured using Western blot. Expression and activity of remodelling marker MMP2 were determined using gelatin zymography. Cells were obtained from 12 patients (aged 12–51 years). Patient-specific variations in micro-tissue compaction speed or magnitude were observed. Up to 50-fold differences in αSMA expression were found between patients, although these did not correlate with faster or stronger compaction. Surprisingly, tenomodulin was only detected in samples obtained from two patients. Total MMP2 expression varied between patients, but no large differences in active fractions were found. No correlation of patient age with any of the remodelling-related factors was detected. Remodelling-related biological differences between patient tendon-derived cells could be assessed with the presented micro-tissue platform, and did not correlate with age. This demonstrates the need to compare this biological variation in vitro - especially cells with extreme properties - to clinical outcome. Sample size is currently increased, and patient outcome will be determined. Combined with results obtained from the in vitro platform, this could lead to a predictive tool to identify patients at risk for graft rupture

Introduction: Since Albright first proposed the concept of diabetic osteopenia, many studies have investigated the levels of mineral bone density (BMD) and risk of osteoporosis. In this study we investigate the effect of exercise, alfacalcidol and parathyroid hormone (1–34) on bone marker, BMD and bone mechanical properties in spontaneously diabetic GK/Jcl rats. Methods: 18 week-old male GK/Jcl rats were divided into 4 groups; no treatment (NT), exercise (Ex), alfacalcidol (ALF), and parathyroid hormone (PTH). The bone mineral density (BMD) of the lumbar vertebrae (L2-L4) and the left femur was measured by dual energy X-ray absorptiometry (DXA). Serum calcium (Ca), inorganic phosphorus (Pi) and osteocalcin (OC) were measured. Urinary Ca, Po, and creatinine (Cre) were measured. Urinary deoxypyridinoline (D-Pyr) was measured and the data were corrected for urinary Cre concentration. Mechanical strength of L5 was measured by the compression test. The mechanical strength of the right femur was measured by the three-point bending test. Results: The serum Oc levels in Ex and ALF group slightly increased (mean 5%). The serum Oc in PTH group increased significantly compared with that in the NT group (mean 70%). The urinary D-Pyr/Cre in the Ex group decreased compared with that in the NT group (mean 9 %). The urinary D-Pyr/Cre in the groups treated with ALF for 3 months were significantly decreased compared with that in the NT group (mean 20%). The urinary D-Pyr/Cre in the PTH group significantly increased compared with that in the NT group (mean 10%). The BMD of the L2–L4 in ALF group increased compared with NT group (mean 12%). The BMD of the L2–L4 in PTH group significantly increased compared with NT group (mean 10%). In the ALF group, however, the mechanical strength of the lumber vertebra was significantly higher (mean 25%) than that in the NT group. In the PTH group, the compressive load of the lumber vertebra (mean 70%) and breaking strength of the femur (mean 9%) was significantly higher than that in the NT group. Discussion: Treatment of osteoporosis has so far mainly utilized anti-resorptive agents such as estrogen, calcitonin and bisphosphonate, and bone anabolic agents stimulating bone resorption would be useful especially in low-turnover type of osteoporosis such as diabetic osteopenia. ALF treatment suppressed osteoclastic bone resorption while maintaining or even stimulating bone formation, and consequently increased bone mass with a parallel improvement in the mechanical strength of bone. PTH (1–34) had strong effects for improve the mechanical strength of the spine. In conclusion, it was demonstrated that ALF and PTH differed in their potency for improving the strength of the spine. Our results of biochemical parameter analysis demonstrated that ALF caused a significant suppression of bone resorption and maintained formation. The other hand, PTH had a strong effect on stimulating the bone turnover and bone strength, whereas it could affect the bone quality and reduce the risk of the spine fracture. These results provide important clues in understanding the action mechanisms of these agents on bone metabolism in the treatment of diabetic osteopenia

Aims. To determine whether half-threaded screw holes in a new titanium locking plate design can substantially decrease the notch effects of the threads and increase the plate fatigue life. Methods. Three types (I to III) of titanium locking plates were fabricated to simulate plates used in the femur, tibia, and forearm. Two copies of each were fabricated using full- and half-threaded screw holes (called A and B, respectively). The mechanical strengths of the plates were evaluated according to the American Society for Testing and Materials (ASTM) F382-14, and the screw stability was assessed by measuring the screw removal torque and bending strength. Results. The B plates had fatigue lives 11- to 16-times higher than those of the A plates. Before cyclic loading, the screw removal torques were all higher than the insertion torques. However, after cyclic loading, the removal torques were similar to or slightly lower than the insertion torques (0% to 17.3%), although those of the B plates were higher than those of the A plates for all except the type III plates (101%, 109.8%, and 93.8% for types I, II, and III, respectively). The bending strengths of the screws were not significantly different between the A and B plates for any of the types. Conclusion. Removing half of the threads from the screw holes markedly increased the fatigue life of the locking plates while preserving the tightness of the screw heads and the bending strength of the locking screws. However, future work is necessary to determine the relationship between the notch sensitivity properties and titanium plate design. Cite this article: Bone Joint Res 2020;9(10):645–652

Background. Antibiotic-loaded cement has been used over decades as a local antibiotic delivery for the treatment of bone and joint infections. However, there were some disadvantages such as unpredictable elution, insufficient local concentration and reduced mechanical strength. We developed hydrophilized bone cement and investigated whether it can improve consistent antibiotic release for extended periods to be effective in eradicating joint infection without any changes of mechanical strength. Methods. The experiments consists of preparation of the hydrophilized, vancomycin-loaded bone cement, In vitro test including drug release behavior, mechanical properties by compression test, cytotoxicity, antibacterial effect and animal study. In animal study, Antibiotic cement rod was implanted in the femur of rat osteomyelitis model. Sign of infections were assessed by gross observation, Micro CT and blood analysis at indicated period. Results. The hydrophilized Vancomycin-loaded bone cements showed that continuous release of Vancomycin even over 6 weeks in the drug release test, sufficient mechanical strengths in the compression test and also better anti-bacterial effect compared to other commercially available bone cement. The animal study demonstrated that it has superior inhibition of bacterial proliferation according to imaging and blood analysis compared to control group. Conclusion:. As a results from both in vitro test and animal study, hydrophilized antibiotic bone cement may provide favorable environment to control bone and joint infection by continuous antibiotic release for extended period

Treatment of tendon and ligament injuries remains challenging; the aim is to find a biocompatible substance with mechanical and structural properties that replicate those of normal tendon and ligament. We examined the mechanical properties of Demineralised Cortical Bone (DCB) after gamma irradiation (GI) and freeze drying (FD). We also used different techniques for repairing bone-tendon-bone with DCB in order to measure the mechanical performance of the construct. DCB specimens were allocated into 4 groups; FD, GI, combination of both or none. The maximum tensile forces and stresses were measured. 4 cadaveric models of repair of 1cm patellar tendon defect using DCB were designed; model-1 using one bone anchor, Model-2 using 2 bone anchors, Model-3 off-loading by continuous thread looped twice through bony tunnels, Model-4 off-loading with 3 hand braided threads. Force to failure and mode were recorded for each sample. FD groups results were statistically higher (p=<0.05) compared to non-FD groups, while there was no statistical difference between GI and non-GI groups. The median failure force for model-1: 250N, model-2: 290N, model-3: 767N and model-4: 934N. There was no statistical significance between model-1 and model-2 (p=0.249), however statistical significance was found between other models (p=<0.006). GI has no significant effect on mechanical strength of the CDB while FD may have positive effect on its mechanical strength. Our study shows that a tendon rupture can be successfully augmented with CDB giving initial appropriate mechanical strength suitable for in vivo use providing the biological reactions to the graft are favourable

Background. External fixation is a method of osteosynthesis currently required in traumatology and orthopaedic surgery. Pin tract infection is a common problem in clinical practice. Infection occurs after a bacterial colonisation of the pin due to its contact with skin and local environment. To prevent such local contamination, one way to handle this issue is to create a specific coating using method which could be applied in the medical field. In this work we develop a surface coating for external fixator pins based on photocatalytic TiOα properties, producing a bactericidal effect with sufficient mechanical strength to be compatible with surgical use. Method. The morphology and structure of the sol-gel coating layers were characterised using, respectively, scanning electron microscopy and X-ray diffraction. Resistance properties of the coating were investigated by mechanical testing. Photo-degradation of acid orange 7 in aqueous solution was used as a probe, to assess the photo-catalytic activity of titanium dioxide layers under UV irradiation. The bactericidal effect induced by the process was evaluated against 2 strains: a Staphylococcus aureus and a multiresistant Staphylococcus epidermidis. Results. The coated pins showed good mechanical strength and efficient antibacterial effect after 1 hour of UV irradiation. Conclusion. Our study allowed to develop an antibacterial coating for stainless steel commonly used in surgical practice. The process using photoactive TiO2 exposed to UV irradiation is actually well known and applied in many disinfection fields, and exhibited efficiency against the two main bactericidal strains involved in pin tract infections. Mechanical tests confirmed the coating's ability to resist to important stresses. Moreover, this kind of coating created by sol-gel dip-coating techniques is not expensive and quite easy to do. As a consequence, we can hope that this new option would treat preventively pin tract infection, even if there is an important optimisation task to be done in order to amplify bactericidal properties. Level of evidence. II

Introduction: Impaction allografting allows an initial stable function of revision hip replacements and a method of reconstituting the bone stock. A previous in-vivo ovine study has found that the density of impacted morsellised allograft reduces after six weeks but recovers by twelve weeks. This reduction in density during remodelling may also correspond with a reduced mechanical strength. A probable cause of the low density is osteoclastic bone resorption prior to vascular in growth and the formation of new bone by osteoblasts. BoneSave is a 4–6mm porous granules of hydroxyapatite and tricalcium phosphate, and is designed as be used as a 50:50 mix with morsellised allograft. Bonesave takes a long time to be resorbed and replaced with bone compared with allograft. We hypothesised that the inclusion of BoneSave could slow resorption down and hence maintain the mechanical strength of the graft during remodelling. This study investigated the mechanical strength of BoneSave mixed with allograft at six and twelve weeks after insertion into a defect, with pure allograft as a control. Methods: Twelve yews were used in this study, half were terminated at six weeks the remainder at twelve. The test site was a 15mm diameter hole, approximately 10mm deep, in the medial femoral condyle. Both femurs were operated on consecutively, with allograft on one side and a BoneSave/allograft mix on the other. After euthanasia the distal femurs were removed and CT scans performed to evaluate density. Sixteen millimetre discs were cut from each femur, exposing the test site 4 mm from its proximal end. These graft site was then subjected to non-destructive compression tests in Zwick loading machine. Bone remodelling in the graft was determined using histology. Results: Wilcoxon paired test were used to compare densities of the allograft group with the BoneSave group at 6 and 12 weeks, at both time points there was a significant difference between the groups (p< 0.05). There was no statistical difference in the density of the allograft groups between 6 and 12 weeks, or the Bonesave groups between 6 and 12 weeks using the Mann-Whitney U test (p> 0.05). There was no significant difference between the stiffness of the two groups at both time points using the Mann Whitney U test (p> 0.05). Discussion and Conclusion: This result was unexpected in the allograft group because in a previous study looking at different sized allograft chips there was a significant difference between the density at 6 and 12 weeks. The most likely cause for this is that lower forces were used to impact the graft in this experiment compared with the graft size study. This would have resulted in lower density at time zero, so perhaps this lower density didn’t invoke such a large resorption response. Bone-Save is able to maintain mechanical strength during remodelling when used as a bone graft extender

Summary Statement. We evaluated the mechanical strength of two cortical suspension devices by reproducing clinical situation for ACL reconstruction. A most important factor affecting the displacement during cyclic load was the length of the tendon rather than the length of the device. Introduction. A definite consensus for the optimal graft fixation technique to the femur in an anterior cruciate ligament (ACL) reconstruction has not been reached, although there have been several fixation techniques such as cortical suspension devices, transfixation devices, and interference screws. The purpose of this study was to evaluate the mechanical strength of two cortical suspension devices by reproducing actual clinical situation for ACL reconstruction in order to compare the TightRope. TM. as a new adjustable-length loop device and the EndoButton. TM. as a well-known fixed-length loop device under the consistent conditions. Methods. Two cortical suspension devices were tested under cyclic and pull-to-failure loading conditions in both an isolated device setup and a specimen setup to make a complete bone-device-tendon construct in porcine femurs and bovine flexor tendons using a tensile testing machine. Especially to examine the influence of the length of the tendon and the device, a total length of the bone tunnel was fixed to 35 mm, and an effective length of tendon in the bone tunnel was adjusted to 15 mm for the EndoButton group (EB), the TightRope 15 group (TR15) and 21 mm for the TightRope 21 group (TR21). Results. In the isolated device testing, the ultimate tensile strength of the EB (1430 ± 148 N) had significantly higher than that of the TR (866 ± 53 N), and also had significant difference in the specimen testing. The displacement in the isolated device testing after preloading for the EB (1.09 ± 0.29 mm) showed statistically lower than that for the TR (2.57 ± 1.19 mm), and had a significant difference after the cyclic load. In the specimen testing, on the other hand, the displacement after preloading showed no statistical difference between the EB (1.06 ± 0.30 mm), the TR21 (1.76 ± 2.28 mm) and the TR15 (1.51 ± 1.78 mm). But limiting only to the displacement from 1000 to 2000 cycles, the TR21 (0.92 ± 0.44 mm) showed statistically higher than the TR15 (0.49 ± 0.22 mm). Discussion. Although current results indicated that the EB had greater mechanical strength than the TR, both devices are presumed to provide sufficient fixation strength under clinical conditions. An important new finding from the current study was the measurement of initial displacement from the state of initial fixation until loading began and 50 N of tension was applied. In isolated device testing, the TR had significantly more displacement than the EB during pre-loading. This may reflect the TR's loops stretch until a certain amount of tension is applied. In the comparison of the TR21 and the TR15, the TR21 had a significantly larger displacement with a cyclic load from 1000 to 2000 cycles. This result indicated that a most important factor affecting the displacement during cyclic load was the length of the tendon rather than the length of the device. Thus, we should decide the length of the tendon in the bone tunnel to avoid the displacement of the graft

We studied the calcium content and mechanical strength of cortical bone from rats and dogs after different periods of demineralisation, showing that the rate of demineralisation differed considerably between the species. Specimens from the rat were further treated by chemical extraction and autolysis and tested for osteoinductive properties. We showed that partially demineralised cortical bone retained adequate mechanical strength, while retaining the biological effects of completely demineralised bone. This shows that it is possible to prepare allografts which have adequate mechanical strength and still retain osteo-inductive properties

Adult articular cartilage mechanical functionality is dependent on the unique zonal organization of its tissue. Current mesenchymal stem cell (MSC)-based treatment has resulted in sub-optimal cartilage repair, with inferior quality of cartilage generated from MSCs in terms of the biochemical content, zonal architecture and mechanical strength when compared to normal cartilage. The phenotype of cartilage derived from MSCs has been reported to be influenced by the microenvironmental biophysical cues, such as the surface topography and substrate stiffness. In this study, the effect of nano-topographic surfaces to direct MSC chondrogenic differentiation to chondrocytes of different phenotypes was investigated, and the application of these pre-differentiated cells for cartilage repair was explored. Specific nano-topographic patterns on the polymeric substrate were generated by nano-thermal imprinting on the PCL, PGA and PLA surfaces respectively. Human bone marrow MSCs seeded on these surfaces were subjected to chondrogenic differentiation and the phenotypic outcome of the differentiated cells was analyzed by real time PCR, matrix quantification and immunohistological staining. The influence of substrate stiffness of the nano-topographic patterns on MSC chondrogenesis was further evaluated. The ability of these pre-differentiated MSCs on different nano-topographic surfaces to form zonal cartilage was verified in in vitro 3D hydrogel culture. These pre-differentiated cells were then implanted as bilayered hydrogel constructs composed of superficial zone-like chondro-progenitors overlaying the middle/deep zone-like chondro-progenitors, was compared to undifferentiated MSCs and non-specifically pre-differentiated MSCs in a osteochondral defect rabbit model. Nano-topographical patterns triggered MSC morphology and cytoskeletal structure changes, and cellular aggregation resulting in specific chondrogenic differentiation outcomes. MSC chondrogenesis on nano-pillar topography facilitated robust hyaline-like cartilage formation, while MSCs on nano-grill topography were induced to form fibro/superficial zone cartilage-like tissue. These phenotypic outcomes were further diversified and controlled by manipulation of the material stiffness. Hyaline cartilage with middle/deep zone cartilage characteristics was derived on softer nano-pillar surfaces, and superficial zone-like cartilage resulted on softer nano-grill surfaces. MSCs on stiffer nano-pillar and stiffer nano-grill resulted in mixed fibro/hyaline/hypertrophic cartilage and non-cartilage tissue, respectively. Further, the nano-topography pre-differentiated cells possessed phenotypic memory, forming phenotypically distinct cartilage in subsequent 3D hydrogel culture. Lastly, implantation of the bilayered hydrogel construct of superficial zone-like chondro-progenitors and middle/deep zone-like chondro-progenitors resulted in regeneration of phenotypically better cartilage tissue with higher mechanical function. Our results demonstrate the potential of nano-topographic cues, coupled with substrate stiffness, in guiding the differentiation of MSCs to chondrocytes of a specific phenotype. Implantation of these chondrocytes in a bilayered hydrogel construct yielded cartilage with more normal architecture and mechanical function. Our approach provides a potential translatable strategy for improved articular cartilage regeneration using MSCs

Patellar fractures account for approximately 1% of all fractures. Open reduction and internal fixation is recommended to restore extensor continuity and articular congruity. However, complications such as nonunion and symptomatic hardware, still exist. Furthermore, there is a risk of re-fracturing of the healed bone during the removal of the implants. Magnesium (Mg), a biodegradable metal, has elastic moduli and compressive yield strength that are comparable to those of natural bone. Our previous study showed that released Mg ions enhanced fracture healing. However, Mg-based implants degrade rapidly after implantation and lead to insufficient mechanical strength to support the fracture. Microarc oxidation (MAO) is a metal surface coating that reduces corrosion. We hypothesized that Mg pins, with or without MAO, would enhance fracture healing radiologically, mechanically, and histologically, while MAO would decrease degradation of Mg pins. Patellar fracture was performed on forty-eight 18-week-old female New Zealand White rabbits according to established protocol. Briefly, the patella is osteotomized transversely and a tunnel (1.1mm) was drilled longitudinally through the two bone fragments. A pin (1 mm, stainless steel, Mg, or MAO-Mg) was inserted into the tunnel. The reduced construct was stabilized with a figure-of-eight band wire (⊘ 0.6 mm stainless steel wire). Cast immobilization was applied for 6 weeks. The rabbits were euthanized at week 8 and 12 post-operation. Microarchitecture and mechanical properties of the repaired patella were analyzed with microCT and tensile testing respectively. Histological sections of the repaired patella were stained. To evaluate the effect of the MAO treatment on degradation rate of Mg pin, the volume of the Mg pins in the patella was measured with microCT. At week 8, both Mg and Mg-MAO showed higher ratio of bone volume to tissue volume (BV/TV) than the control while there was no significant different between Mg and Mg-MAO. At week 12, Control, Mg, and Mg-MAO groups showed enlarged patella when compared to the normal patella. Tissue volume (TV) and bone volume (BV) of the patella in Mg and Mg-MAO were larger than those in the Control group. However, the Control had higher ratio of bone volume to tissue volume (BV/TV), TV density, and BV density than Mg and Mg-MAO. Tensile testing showed that the mechanical properties of the repaired patella (failure load, stiffness, ultimate strength, and energy-to-failure) of Mg and Mg-MAO were higher than that of the control at both week 8 and week 12. Histological analysis showed that there was significant new bone formation in the Mg and Mg-MAO group compared with the Control group at week 8 and 12. The degradation rate of the MAO-coated Mg pins was significantly slower than those without MAO at week 8 but no significant difference was detected at week 12. Mechanical, microarchitectural, and histological assessments showed that Mg pins, with or without MAO, enhanced fracture healing of the repaired patella compared to the Control. MAO treatment enhanced the corrosion resistance of the Mg pins at the early time point

Introduction The AO/ASIF 3.5 mm STS is increasingly used for internal fixation of large bones with the recent introduction of the 3.5 mm periarticular plating system. Our study aims to compare the insertion torque and mechanical properties of the screw after insertion into bovine femora using non tapped and pretapped methods. Methods Three groups of ten 3.5 mm AO/ASIF STSs of variable lengths were used. One group was put aside as the control. One group was inserted into fresh bovine femora using pre-tapped drill holes and the final group using non-tapped drill holes. The insetion torques were measured and compared using an analogue torque screw driver. All screws were removed. The three groups were then tested for mechanical strength. The results of the groups were compared we found the insertion torque to be six times greater in the non tapped group compared to the pre tapped group. We noted the non tapped group failed later than the pre-tapped group, this was statistically not significant however. The mechanical strength of the screw was not statistically altered. Conclusions We conclude that the 3.5 mm STS is easier to insert when pre tapped. However pre tapping is not necessary to preserve the mechanical strength of the screw

Introduction. Total Elbow Arthroplasty (TEA) is recognized as an effective treatment solution for patients with rheumatoid arthritis or for traumatic conditions. Current total elbow devices can be divided into linked or unlinked design. The first design usually presents a linking element (i.e. an axle) to link together the ulnar and humeral components to stabilize the joint; the second one does not present any linkage and the stability is provided by both intrinsic design constraints and the soft tissues. Convertible modular solutions allow for an intraoperative decision to link or unlink the prosthesis; the modular connections introduce however additional risks in terms of both mechanical strength and potential fatigue and fretting phenomena that may arise not only due to low demand activities loads, but also high demand (HD) ones that could be even more detrimental. The aim of this study was to assess the strength of the modular connection between the axle and the ulnar component in a novel convertible elbow prosthesis design under simulated HD and activities of daily living (ADLs) loading. Methods. A novel convertible total elbow prosthesis (LimaCorporate, IT) comprising both ulnar and humeral components that can be linked together by means of an axle, was used. Both typical ADLs and HD torques to be applied to the axle were determined based on finite element analysis (FEA); the boundary load conditions for the FEA were determined based on kinematics analysis on real patients in previous studies. The FEA resultant moment acting on the axle junction during typical ADLs (i.e. feeding with 7.2lbs weight in hand) was 3.2Nm while for HD loads (i.e. sit to stand) was 5.7 Nm. In the experimental setup, 5 axle specimens coupled with 5 ulnar bodies through a tapered connection (5 Nm assembly torque) were fixed to a torque actuator (MTS Bionix) and submerged in a saline solution (9g/l). A moment of 3.2 Nm was applied to the axle for 5M cycles through a fixture to test it under ADLs loading. After 5M cycles, the axles were analyzed with regards to fretting behavior and then re-assembled to test them against HD loading by applying 5.7 Nm for 200K cycles (corresponding to 20 years function). Results. All 5 samples withstood all 5.2M loading cycles without any mechanical failure. At the end of 5M cycles, each axle was still stable as the measured disassembly torque was 3.96 +/−0.18 Nm. Slight signs of fretting were detected on the tapered connection after 5M cycles, however they did not compromise the mechanical connection nor the stability. Discussion and Conclusions. Currently there are no reference standards that properly define protocols for biomechanical testing of elbow prostheses. In the present study, a test to mechanically assess the strength of an axle connection under both typical ADLs and HD loads was set. The connection was able to withstand the imposed conditions. In general, testing of TEA devices should include not only standard ADLs loads but also HD loads, which could be more detrimental for the long-term survivorship. For any figures or tables, please contact authors directly

Objectives. Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls. Methods. Trabecular bone from hip fracture patients treated with BP (n = 10) was compared with naïve fractured (n = 14) and non-fractured controls (n = 6). Trabecular cores were synchrotron scanned and micro-CT scanned for microstructural analysis, including quantification of bone volume fraction, microarchitecture and microcracks. The specimens were then mechanically tested in compression. Results. BP bone was 28% lower in strength than untreated hip fracture bone, and 48% lower in strength than non-fractured control bone (4.6 MPa vs 6.4 MPa vs 8.9 MPa). BP-treated bone had 24% more microcracks than naïve fractured bone and 51% more than non-fractured control (8.12/cm. 2. vs 6.55/cm. 2. vs 5.25/cm. 2. ). BP and naïve fracture bone exhibited similar trabecular microarchitecture, with significantly lower bone volume fraction and connectivity than non-fractured controls. Conclusion. BP therapy had no detectable mechanical benefit in the specimens examined. Instead, its use was associated with substantially reduced bone strength. This low strength may be due to the greater accumulation of microcracks and a lack of any discernible improvement in bone volume or microarchitecture. This preliminary study suggests that the clinical impact of BP-induced microcrack accumulation may be significant. Cite this article: A. Jin, J. Cobb, U. Hansen, R. Bhattacharya, C. Reinhard, N. Vo, R. Atwood, J. Li, A. Karunaratne, C. Wiles, R. Abel. The effect of long-term bisphosphonate therapy on trabecular bone strength and microcrack density. Bone Joint Res 2017;6:602–609. DOI: 10.1302/2046-3758.610.BJR-2016-0321.R1

Biometals like Magnesium (Mg) and Zinc (Zn) are essential for life. Mg/Zn-deficiency has been linked to numerous diseases including cardiovascular, bone, diabetics, neurological and neurodegenerative disorders. Moreover, Mg/Zn-based biomaterials have recently emerged as innovative degradable medical implants, typically for cardiovascular and orthopedic application. We study the pathophysiological role of Mg. 2+. /Zn. 2+. ion in vascular and bone diseases, as well as metallic Mg/Zn alloys for stent and bone implant applications. We demonstrated some interesting role and mechanism of Mg. 2+. /Zn. 2+. ion in controlling cellular functions. Also, metallic Mg/Zn-based medical implants exhibited strong potential as stent and bone fixation device. They have sufficient mechanical strength, promotes tissue regeneration, and are fully bioresorbable with minimal toxicity. The beneficial or therapeutic role of biometals Mg/Zn in medicine and biomaterial applications is still not fully explored, our research aims to answer some fundamental questions and to inspire more future studies related to biometals in health

In order to evaluate the feasibility of zinc alloys as future biodegradable bone implant materials, the mechanical properties, corrosion resistance, hemocompatibility, cell activity, proliferation and adhesion, in vivo animal implantation experiments have been employed. The experimental results show that the alloying element magnesium, calcium and strontium can significantly improve the mechanical properties of pure zinc, and further deformation processes can further improve the mechanical properties of zinc alloys. Alloying elements can effectively control the corrosion rates of zinc alloys, which are between the rates of magnesium alloys and iron alloys. Zinc and zinc alloys exhibit excellent hemocompatibility and the hemolysis rate is far lower than 5%. After adding alloying elements Mg, Ca and Sr, MG63 and ECV304 cell proliferation rate and activity increased significantly, while for VSMC cell, the influence of alloying elements effect is not obvious. Zinc alloy intramedullary pins can effectively promote the new bone formation, and after 2 months implanted in mice femur, they still maintained a relatively complete structure, indicating that they are able to provide enough mechanical strength and thus more conducive to bone tissue repair and healing

Biomechanical analysis is important to evaluate the effect of orthopaedic surgeries. CT-image based finite element method (CT-FEM) is one of the most important techniques in the computational biomechanics field. We have been applied CT-FEM to evaluate resorptive bone remodeling, secondary to stress shielding, after total hip arthroplasty (THA). We compared the equivalent stress and strain energy density to postoperative BMD (bone mineral density) change in the femur after THA, and a significant correlation was observed between the rate of changes in BMD after THA and equivalent stress. For periacetabular osteotomy cases, we investigated mechanical stress in the hip joint before and after surgery. Mechanical stress in the hip joint decreased significantly after osteotomy and correlated with the degree of the acetabular coverage. For arthroscopic osteochondroplasty cases, we examined mechanical strength of the proximal femur after cam resection using CT-FEM. The results suggested that both the depth and area of the resection at the distal part of femoral head-neck junction correlated strongly with fracture risk after osteochondroplasty. This talk consists of our results of clinical application studies using CT-FEM, and importance of application of CT-FEM to biomechanical studies to assess the effect of orthopaedic surgeries

Summary Statement. This study describes the design and preliminary in vitro testing of a novel patch for the repair of rotator cuff tendon tears. The laminated design incorporates woven and electrospun components. The woven element provides the patch with excellent mechanical strength and the electrospun layer improves cell attachment and promotes cell orientation and diferentiation. Introduction. Aligned nanofibrous electrospun scaffolds have been previously proposed as ideal scaffolds for tendon repair, replicating the anisotropy of tendon and providing a biomimetic design to encourage tissue regeneration (Hakimi et al., 2012). However, such scaffolds are still limited in terms of mechanical properties. This paper presents the design of a novel patch for rotator cuff repair in which the electrospun scaffold is supported by a woven component. Patients & Methods. Aligned polydioxanone (PDO) electrospun scaffolds were produced using a single nozzle electrospinning set-up with a rotating collector. The woven component was created by weaving PDO monofilaments with a manual loom. The woven and non-woven constituents were bound by a non-destructive method which preserves the surface morphology of the electrospun material. For each type of scaffold, a minimum of 3 specimens were tested to failure in tension using Zwick machine at rate of 0.3 mm/min until failure. For in vitro work, human-derived tendon cells were extracted from rotator cuff tendon tissue obtained during surgical repair, with appropriate ethical approval. Cells were cultured on the scaffolds for at least 14 days. Results. The contribution of the woven component to the tensile strength of the assembled patch is about 20 times more when compared to the electrospun scaffold. In vitro work shows that human tenocytes grown on the nanofibrous non-woven electrospun component align in the direction of the fibre orientation. The appearance of the woven component is shown. Discussion/Conclusion. While the woven component provides most of the mechanical strength, the aligned electrospun fibres enable cell orientation along the axis of the patch. These cells display a similar morphology to tenocytes in native tendons. With the combination of biomimetic features and good mechanical properties, this novel PDO patch is an excellent candidate material to support tendon repair

Collagen is a key component of the extracellular matrix in a variety of tissues and hence is widely used in tissue engineering research, yet collagen has had limited uptake in the field of 3D printing. In this study we successfully adapted an existing electronic printing method, aerosol jet printing (AJP), to print high resolution 3D constructs of recombinant collagen type III (RHCIII). Circular samples with a diameter of 4.5mm and 288 layers thick, or a diameter of 6.5mm and 400 layers thick were printed on glass cover slips with print lines of 60µm. Attenuated Total Reflectance Fourier-Transorm Infa-red (ATR-FTIR) spectroscopy performed on the 4 of the printed samples and dried non-printed RHCIII samples showed that no denaturation had occurred due to the printing process. Printed samples were crosslinked using EDC [N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, Sigma Aldrich] to improve their stability and mechanical strength. Differential scanning calorimetry (DSC) performed showed a marked difference in the denaturation temperature between crosslinked printed samples and fibrillar non-printed samples and nano-indentation showed that the construct was relatively stiff. Previous results with similar samples have shown that mesenchymal stem cells (MSCs) align with and travel parallel to print direction. Results obtained from these samples show signs that they might be applied in other areas such as bone tissue engineering

Scaffold-based bone tissue engineering holds great promise for the future of osseous defects therapies. Prepare the suitable scaffold properties are physiochemical modifications in terms of porosity, mechanical strength, cell adhesion, biocompatibility, cell proliferation, mineralization and osteogenic differentiation are required. We produce various bone tissue scaffolds with different techniques such as lyophilization, 3D printing and electrospinning. We wish to overview all the different novel scaffold methods and materials. To improve scaffolds poor mechanical properties, while preserving the porous structure, it is possible to coat the scaffold with synthetic or natural polymers. An increasing interest in developing materials in bone tissue engineering is directed to the organic/inorganic composites that mimic natural bone. Specifically, bone tissue is a composite of an organic and inorganic matrix. Using PLLA, loofah, chitin and cellulose biomaterials we produced bone tissue scaffold with lyophilization technique. Also, using fish scale powder and wet electrospun Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) a sponge structure had created. Using MRI image data and 3D printer method, a bone tissue scaffold is created by PLA filament. Their mechanical properties had analysed with compression tests and their biocompatibilities had investigated. In order to provide novel strategies for future treatment of bone tumours, the properties of the scaffold, including its in vitro extended-release properties, the inhibition effects of chemotherapeutic agent on the bone tumours and its bone repair capacities were investigated in vitro by using MG63 cells. To develop chemotherapeutic agent-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles in a porous nano-hydroxyapatite scaffold we aimed to use double emulsion method

Balloon kyphoplasty (BKP) is a minimally invasive surgical technique used to correct kyphosis and vertebral compression fractures. BKP uses cement to fill a void created by the inflation of a balloon in a vertebra, it can be used as an alternative to vertebroplasty to reduce cement extravasation. Issues such as poor inter digitisation of the cement and the trabecular bone can arise with the BKP method. This can be due to a compacted layer created during the procedure which can cause complications post-surgery. The primary aim of this study was to investigate alternative cement application methods which could improve the mechanical strength of the bone-cement interface. Three alternative methods were investigated, and cylindrical bone-cement specimens were created for all methods (BKP and three alternatives). An important part of this study was to replicate the compacted layer created by the inflation of the balloon tamp in BKP. Synthetic trabecular bone specimens (Sawbones®, Pacific Research Laboratories, Vashon Island, Washington, USA) were pre-loaded in compression and the resultant compacted layers were found to replicate the compacted layers found in surgery. Mechanical testing was carried out with an MTS Model 858 Bionix. ®. Servohydraulic load frame using static tensile and torsion loads. Static tests revealed that two of the three alternative methods were an improvement on BKP, with a high statistical significance in relation to the mechanical performance of the bone-cement interface (P < 0.001). This data illustrates the potential to improve the standard BKP technique, in terms of bone-cement interface performance

The effect of bisphosphonates on the mechanical properties of the uninjured contra-lateral cortical bone during fracture healing is poorly reported. There remains conflicting evidence with regards the effect of bisphosphonate therapy on cortical bone strength. We assessed the effect of nine weeks of Ibandronate therapy, in a dose known to preserve cancellous bone BMD and strength, on the mechanical properties of the uninjured rat tibial diaphyses using a standardised model of tibial osteotomy and plate fixation. Skeletally mature ex-breeder rats were used. Stress at failure of the tibial diaphyses was measured by a four-point bending test using a custom made jig for rat tibiae. The mechanical strength was compared with radiographic measurements of bone density. Animals received daily subcutaneous injections. 11 rats received 1μg/kg Ibandronate (IBAN) daily and 17 rats received 1ml 0.9% Sodium Chloride (CONTROL) daily. The IBAN group had a statistically significant, p=0.024, higher stress at failure 212.7 (±42.04) MPa compared to the CONTROL group 171.7 (±46.13)MPa. There was a positive correlation between the mechanical strength of bone and the radiological measure of bone density. Osteopenia is known to occur following a fracture even in the contra-lateral limb. This study demonstrates that ibandronate therapy has no detrimental effect and may even increase the strength of uninjured cortical bone during the fracture healing process. The longer term effect of ibandronate on cortical bone especially in relation to the accumulation of mico-damage requires further study. Bisphosphonate effect on the uninjured limb needs to be considered when reporting proportional strength of fracture repair compared to the uninjured limb

Summary. Our results prove that Demineralised Cortical Bone (DCB) can be used as biological tendon graft substitute, combined with correct surgical technique and the use of suture bone anchor early mobilisation can be achieved. Introduction. Surgical repair of tendon injuries aims to restore length, mechanical strength and function. In severe injuries with loss of tendon substance a tendon graft or a substitute is usually used to restore functional length. This is usually associated with donor site morbidity, host tissue reactions and lack of remodelling of the synthetic substitutes which may result in suboptimal outcome. In this study we hypothesise that DCB present in biological tendon environment with early mobilisation and appropriate tension will result in remodelling of the DCB into ligament tissue rather that ossification of the DCB at traditional expected. Our preparatory cadaveric study (abstract submitted to CORS 2013) showed that the repair model used in this animal study has sufficient mechanical strength needed for this animal study. Methods. 6 mature female sheep undergone surgical resection of the distal 1 cm of the right patellar tendon and osteotomy of patellar tendon attachment at the tibial tuberosity under general anaesthesia. Repair was done using DCB with 2 suture bone anchor. Animals were allowed immediate mobilisation after surgery and were sacrificed at 12 weeks. The force passing through the operated and non-operated legs was assessed preoperatively and at week 3, week 6, week 9 and week 12 bay walking the animals over a force plate. Radiographs were taken immediately after euthanasia, the Patella-Tendon-tibia constructs were retrieved and pQCT scan was done. Histological analysis included tenocytes and chondrocytes cell counts, semi-quantitative scoring of the neo-enthesis and polarised microscopy. Result. In this study, none of the retrieved specimens showed any evidence of ossification of the DCB as proved by the pQCT analysis. One animal failed to show satisfactory progress after week 3, X-rays showed patella alta, on specimen retrieval no damage to the DCB was found, sutures and stitches were intact and no evidence of anchor pullout was found. Force plate analysis of the other 5 animals showed satisfactory progression over time with 44% functional weight bearing at week 3 progressing to 79% at week 12. There was full range of movement of the stifle joint after 12 weeks. Histological analysis proved formation of neo-enthesis with evidence of cellulisation, vascularisation and remodelling of the collagen leading to ligamentisation of the DCB. Discussion. Surgical reconstruction of damaged tendons is technically challenging, patellar tendon injuries presents even more challenging situation as it involves weight bearing joint. It is generally accepted that a period of immobilisation with passive range of movement exercises and protected weight bearing for up to 6 weeks post operatively is usually advised. Some surgeons use offloading metal wire to protect the repair for 6 weeks involving second surgical procedure to remove the wire. Demineralised bone is usually used in orthopaedics to utilise its osteogenic properties as bone graft substitute and to enhance osteogenesis in load bearing situations. In our study we explored a potential new use of the demineralised bone as tendon graft substitute, it acts as collagen scaffold allowing host cells to remodel its fibres into ligament like structure