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.

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.

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

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