Introduction and Objective. Bone is a tissue which continually regenerates and also having the ability to heal after injuries however, healing of large defects requires intensive surgical treatment. Bioactive glasses are unique materials that can be utilized in both bone and skin regeneration and repair. They are degradable in physiological fluids and have osteoconductive, osteoinductive and osteostimulative properties. Osteoinductive growth factors such as Bone Morphogenetic Proteins (BMP), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), Transforming Growth Factor (TGF) are well known to stimulate new bone formation and regeneration. Unfortunately, the synthesis of these factors is not cost- effective and, the broad application of growth factors is limited by their poor stability in the scaffolds. Instead, it is wise to incorporate osteoinductive nanomaterials such as graphene nanoplatelets into the structures of synthetic scaffolds. In this study, borate-based 13-93B3 bioactive glass scaffolds were prepared by polymer foam replication method and they were coated with graphene-containing poly (ε-caprolactone) layer to support the bone repair and regeneration. Materials and Methods. Effects of graphene concentration (1, 3, 5, 10 wt%) on the healing of rat segmental femur defects were investigated in vivo using male Sprague–Dawley rats. Fabricated porous bioactive glass scaffolds were coated by graphene- containing polycaprolactone solution using dip coating method. The prepared 0, 1, 3, 5 and 10 wt% graphene nanoparticle-containing PCL-coated composite scaffolds were designated as BG, 1G-P-BG, 3G-P-BG, 5G-P-BG and 10G-P-BG, for each group (n: 4) respectively. Histopathological and immunohistochemical (bone morphogenetic protein, BMP-2; smooth muscle actin, SMA and alkaline phosphatase, ALP) examinations were made after 4 and 8 weeks of implantation. Results. Results showed that after 8-weeks of implantation both cartilage and bone formation were observed in all animal groups. After 4 and 8 weeks of implantation the both osteoblast and osteoclast numbers were significantly higher in the group 4 compared to the control group. Bone formation was significant starting from 1 wt% graphene-coated bioactive glass implanted group and highest amount of bone formation was obtained in group containing 10 wt% graphene (p<0.001). Newly formed vessels expressed this marker and increased vascularization was observed in 8- weeks period compared to the 4-weeks period. In addition, an increase in new vessel formation were observed in graphene-coated scaffold implanted groups compared to the control group. While cartilage tissue was observed in control group, bone formation percentages were significant in graphene-coated scaffold implanted groups. Highest amount of bone formation occurred in group 4 (10 % wt G-C). Conclusions. Additionally, the presence of graphene nanoplatelets enhanced the BMP-2, SMA and ALP levels compared to the bare bioactive glass scaffolds. It was concluded that pristine graphene-coated bioactive glass scaffolds improve osteointegration and bone formation in rat femur defect when compared to bare bioglass scaffolds

Aims. Custom-made partial pelvis replacements (PPRs) are increasingly used in the reconstruction of large acetabular defects and have mainly been designed using a triflange approach, requiring extensive soft-tissue dissection. The monoflange design, where primary intramedullary fixation within the ilium combined with a monoflange for rotational stability, was anticipated to overcome this obstacle. The aim of this study was to evaluate the design with regard to functional outcome, complications, and acetabular reconstruction. Methods. Between 2014 and 2023, 79 patients with a mean follow-up of 33 months (SD 22; 9 to 103) were included. Functional outcome was measured using the Harris Hip Score and EuroQol five-dimension questionnaire (EQ-5D). PPR revisions were defined as an endpoint, and subgroups were analyzed to determine risk factors. Results. Implantation was possible in all cases with a 2D centre of rotation deviation of 10 mm (SD 5.8; 1 to 29). PPR revision was necessary in eight (10%) patients. HHS increased significantly from 33 to 72 postoperatively, with a mean increase of 39 points (p < 0.001). Postoperative EQ-5D score was 0.7 (SD 0.3; -0.3 to 1). Risk factor analysis showed significant revision rates for septic indications (p ≤ 0.001) as well as femoral defect size (p = 0.001). Conclusion. Since large acetabular defects are being treated surgically more often, custom-made PPR should be integrated as an option in treatment algorithms. Monoflange PPR, with primary iliac fixation, offers a viable treatment option for Paprosky III defects with promising functional results, while requiring less soft-tissue exposure and allowing immediate full weightbearing. Cite this article: Bone Jt Open 2024;5(8):688–696

Background. Despite promising results have shown by osteogenic cell-based demineralized bone matrix composites, they need to be optimized for grafts that act as structural frameworks in load-bearing defects. The purpose of this experiment is to determine the effect of bone marrow mesenchymal stem cells seeding on partially demineralized laser-perforated structural allografts that have been implanted in critical femoral defects. Materials and Methods. Thirty-two wistar rats were divided into four groups according to the type of structural bone allograft; the first: partially demineralized only (Donly), the second: partially demineralized stem cell seeded (DST), the third: partially demineralized laser-perforated (DLP), and the fourth: partially demineralized laser-perforated and stem cell seeded (DLPST). Trans-cortical holes were achieved in four rows of three holes approximated cylindrical holes 0.5 mm in diameter, with centres 2.5 mm apart. P3 MSCs were used for graft seeding. Histologic and histomorphometric analysis were performed at 12 weeks. Results. DLP grafts had the highest woven bone formation, where most parts of laser pores were completely healed by woven bone. DST and DLPST grafts surfaces had extra vessel-ingrowth-like porosities. Furthermore, in the DLPST grafts, a distinct bone formation at the interfaces was noted. Conclusion. This study indicated that surface changes induced by laser perforation, accelerated angiogenesis induction by MSCs, which resulted in endochondral bone formation at the interface. Despite non-optimal results, stem cells showed a tendency to improve osteochondrogenesis, and the process might have improved, if they could have been supplemented with the proper stipulations

Introduction

what size of defect is optimal for creating an atrophic nonunion animal model has not been well defined. Our aim in this study was to establish a clinically relevant model of atrophic nonunion in rat femur by creation of a bone defect to research fracture healing and nonunion.

Revision total hip arthroplasty (rTHA) in the presence of femoral defects can be technically challenging. Reconstruction with long stems is widely accepted as the standard. However long stems can be difficult to insert and can compromise distal bone stock for future revisions. The aims of this study were to identify whether there was a difference in survival and outcomes following rTHA using a long versus standard or short femoral stem. A comprehensive systematic review was performed according to PRISMA guidelines using the MEDLINE, EMBASE, Chochrane Library and Web of Science databases. Inclusion criteria were (i) adult patients >18 years; (ii) randomised controlled trials, joint registry, or cohort studies; (iii) single or staged rTHA for Paprosky 1–3B femoral defects. Exclusion criteria were (i) mixed reporting without subgroup analysis for revision stem length; (ii) ex-vivo studies. Screening for eligibility and assessment of studies was performed by the authors. Out of 341 records, 9 studies met criteria for analysis (including 1 study utilising joint registry data and 1 randomised controlled trial). Across studies there were 3102 rTHAs performed in 2982 patients with a mean age of 67.4 years and a male: female ratio of 0.93. Revision prostheses were long-stemmed in 1727 cases and short or standard in 1375 cases with a mean follow up of 5 years (range, 0-15 years). On subgroup analysis the use of a long cemented stem compared to a long cementless prosthesis was associated with fewer complications and periprosthetic fracture in older patients. Survivorship was 95% with short stems compared to 84% with long stems at 5 years. Moderate quality evidence suggests that in rTHA with Paprosky type 1-3B femoral defects, the use of a short or standard stem can achieve comparable outcomes to long stems with fewer significant complications and revisions. Using a shorter stem may yield a more straightforward surgical technique and can preserve distal bone stock for future revision

Despite the major advances in osteosynthesis after trauma, there remains a small proportion of patients (<10%) who exhibit delayed healing and/or eventual progression to non-union. While known risk factors exist, e.g. advanced age or diabetes, the exact molecular mechanism underlying the impaired healing is largely unknown and identifying which specific patient will develop healing complications is still not possible in clinical practice. The talk will cover our novel multimodal approaches in small animals, which have the potential to precisely capture and understand biological changes during fracture healing on an individual basis. Via combining emerging omics technologies with our recently developed femur defect loading equipment in mice, we provide a platform to precisely link mechanical and molecular analyses during fracture healing

The ability of the body to constantly maintain metabolism homeostasis while fulling the heightened energy and macromolecule demand is crucial to ensure successful tissue healing outcomes. Studies investigating the local metabolic environment during healing are scarce to date. Here, using Type 2 Diabetes (T2D) as a study model, we investigate the impact of metabolism dysregulation on scaffold-guided large-volume bone regeneration. Our study treated wild-type or T2D rats with 5 mm critical-sized femoral defects with 3D-printed polycaprolactone (PCL) scaffolds with 70% porosity. Metabolomics was leveraged for a holistic view of metabolism alteration as healing progress and correlated to regenerated bone tissue volume and quality assessed using micro-computed tomography (µ-CT), histology, and immunohistology. Semi-targeted metabolomics analysis indicated dysregulation in the glycolysis and TCA cycle – the main energy production pathways, in T2D compared to healthy animals. The abundance of metabolites substrates, i.e., amino acids – for protein/ extracellular matrix synthesis was also affected in T2D. Tissue-level metabolites observations aligned with morphological observation with less newly formed bone observed in T2D than wild-type rats. This study enlightens the metabolism landscape during scaffold-guided large-volume bone regeneration in wild-type vs. T2D to further guide the personalization of the scaffold to drive successful regeneration

Bone defects require implantable graft substitutes, especially porous and biodegradable biomaterial for tissue regeneration. The aim of this study was to fabricate and assess a 3D-printed biodegradable hydroxyapatite/calcium carbonate scaffold for bone regeneration. Materials and methods:. A 3D-printed biodegradable biomaterial containing calcium phosphate and aragonite (calcium carbonate) was fabricated using a Bioplotter. The physicochemical properties of the material were characterised. The materials were assessed in vitro for cytotoxicity and ostegenic potential and in vivo in rat intercondylar Φ3mm bone defect model for 3 months and Φ5mm of mini pig femoral bone defects for 6 months. The results showed that the materials contained hydroxyapatite and calcium carbonate, with the compression strength of 2.49± 0.2 MPa, pore size of 300.00 ± 41mm, and porosity of 40.±3%. The hydroxyapatite/aragonite was not cytotoxic and it promoted osteogenic differentiation of human umbilical cord matrix mesenchymal stem cells in vitro. After implantation, the bone defects were healed in the treatment group whereas the defect of controlled group with gelatin sponge implantation remained non-union. hydroxyapatite/aragonite fully integrated with host bone tissue and bridged the defects in 2 months, and significant biodegradation was followed by host new bone formation. After implantation into Φ5mm femoral defects in mini pigs hydroxyapatite/aragonite were completed degraded in 6 months and fully replaced by host bone formation, which matched the healing and degradation of porcine allogenic bone graft. In conclusion, hydroxyapatite/aragonite is a suitable new scaffold for bone regeneration. The calcium carbonate in the materials may have played an important role in osteogenesis and material biodegradation

Femoroacetabular impingement is a prearthritic deformity frequently associated with early chondral damage. Several techniques exist for restoring larger cartilage defects. While AMIC proved to be an effective treatment in knee and ankle, there are only short-term data available in hip. This study aimed to investigate the mid-term clinical outcome of patients with chondral lesions treated by AMIC and evaluate the quality of repair tissue via MRI. This retrospective, single center study includes 18 patients undergoing surgical hip dislocation for FAI between 2013 and 2016. Inclusion criteria were: cam or pincer-type FAI, femoral or acetabular chondral lesions > 1 cm. 2. , (IRCS III-IV). Due to exclusion criteria and loss-to-follow-up 9 patients (10 hips) could be included. Patient reported outcome measures included Oxford Hip Score (OHS) & Core Outcome Measure Index (COMI)). MRIs were evaluated using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. None of the patients underwent revision surgery except screw removals from the greater trochanter. Followup data indicate a satisfactory to good hip function at 5 years: PROMS improved from pre- to postop at 5 years: OHS from 38.1 to 43.4, COMI from to 1.8 and UCLA from 4 to 8.1 respectively. MOCART score was 67.5 postoperatively. Subgrouping showed slightly better results for acetabular defects (Ø 69.4) compared femoral defects (Ø 60). Based on the reported mid-term results, we consider AMIC as a valuable treatment option for larger chondral defects of the hip

Although bone morphogenetic protein 2 (BMP-2) has been FDA-approved for spinal fusion for decades, its disadvantages of promoting osteoclast-based bone resorption and suboptimal carrier (absorbable collagen sponge) leading to premature release of the protein limit its clinical applications. Our recent study showed an excellent effect on bone regeneration when BMP-2 and zoledronic acid (ZA) were co-delivered based on a calcium sulphate/hydroxyapatite (CaS/HA) scaffold in a rat critical-size femoral defect model. Therefore, the aim of this study was to evaluate whether local application of BMP-2 and ZA released from a CaS/HA scaffold is favorable for spinal fusion. We hypothesized that CaS/HA mediated controlled co-delivery of rhBMP-2 and ZA could show an improved effect in spinal fusion over BMP-2 alone. 120, 8-week-old male Wistar rats (protocol no. 25-5131/474/38) were randomly divided into six groups in this study (CaS/HA, CaS/HA + BMP-2, CaS/HA + systemic ZA, CaS/HA + local ZA, CaS/HA + BMP-2 + systemic ZA, CaS/HA + BMP-2 + local ZA). A posterolateral spinal fusion at L4 to L5 was performed bilaterally by implanting group-dependent scaffolds. At 3 weeks and 6 weeks, 10 animals per group were euthanized for µCT, histological staining, or mechanical testing. µCT and histological results showed that the CaS/HA + BMP-2 + local ZA group significantly promoted bone regeneration than other treated groups. Biomechanical testing showed breaking force in CaS/HA + BMP + local ZA group was significantly higher than other groups at 6 weeks. In conclusion, the CaS/HA-based biomaterial functionalized with bioactive molecules rhBMP-2 and ZA enhanced bone formation and concomitant spinal fusion outcome. Acknowledgements: Many thanks to Ulrike Heide, Anna-Maria Placht (assistance with surgeries) as well as Suzanne Manthey & Annett Wenke (histology)

Principles of bone preservation and restoration of biomechanical alignment should be followed during revision total hip arthroplasty (THA). Where possible, conservative femoral revision techniques and even reconstructive de-escalation involving using primary stems should be considered. This study aims to investigate the outcome of patients who have undergone conservative femoral revision THA in our Institution. We retrospectively identified patients from our Institution's revision arthroplasty database who had cemented, or un-cemented primary stems implanted during revision THA of a previous stemmed femoral implant. Our primary outcome measure was all-cause re-revision THA with a secondary outcome measure of improvement in Oxford hip score (OHS). Radiographic evidence of stem loosening and post-op complications were recorded. Between 02/12/2014 to 12/12/2019, there were 226 patients identified with a mean follow up of 2 years (1–5 years). The majority of cases were represented by Paprosky type 1 (63%) and type 2 (25%) femoral defects. There were 45 patients (20%) who underwent impaction bone grafting (IBG) and 43 patients (19%) who had a cement in cement (CinC) femoral revision and cemented primary stem in 137 (60%), 1 uncemented stem with no IBG or CinC revision. Kaplan Meier survival for all-cause re-revision THA was 93.7% (95% CI: 88.3 – 100) at 3 years. The reasons for re-revision included 4 periprosthetic fractures, 4 dislocations, 1 deep infection, 1 loosening of femoral component and 1 loosening of acetabular component. Pre- and post-operative OHS scores were available in 137 hips (60%) with a mean improvement of 13. Radiographic review revealed 7% of cases with evidence of loosening in 1 or more Gruen zones. Our early results support the use of conservative femoral revision THA techniques where appropriate, with low complication and re-revision rates. Revisions using primary femoral components, where appropriate, should be considered in surgical planning to avoid unnecessary reconstructive escalation

Background. We have reported an injectable L-pNIPAM-co-DMAc hydrogel with hydroxyaptite nanoparticles (HAPna) which promotes mesenchymal stem cell (MSC) differentiation to bone cells without the need for growth factors. This hydrogel could potentially be used as an osteogenic and osteoconductive bone filler of spinal cages to improve vertebral body fusion. Here we investigated the biocompatibility and efficacy of the hydrogel in vivo using a proof of concept femur defect model. Methods. Rat sub-cut analysis was performed to investigate safety in vivo. A rat femur defect model was performed to evaluate efficacy. Four groups were investigated: sham operated controls; acellular L-pNIPAM-co-DMAc hydrogel; acellular L-pNIPAM-co-DMAc hydrogel with HAPna; L-pNIPAM-co-DMAc hydrogel with rat MSCs and HAPna. Following 4 weeks, defect site and organs were histologically examined to determine integration, repair and inflammatory response, as well as Micro-CT to assess mineralisation. Results. No inflammatory reactions or toxicity were seen in any animal. Enhanced bone healing was observed in aged exbreeder female rats where hydrogel was injected with increased deposition of collagen type I. Integration of the hydrogel with surrounding bone was observed without the need for delivered MSCs; native cell infiltration was also seen and bone formation was observed within all hydrogel systems investigated. Conclusion. This novel hydrogel is biocompatible, facilitates migration of cells, promotes increased bone formation and integrates with surrounding bone. This system could be injected to fill spaces within and surrounding spinal cages to aid in cage fixation and spinal fusion without the need for harvesting of bone autografts, thus reducing operative risk and surgical cost. Conflicts of Interest: None. Source of Funding: BMRC, MERI Sheffield Hallam University

An ex vivo biomechanical test model for evaluating a novel bone adhesive has been developed. However, at day 1 in the in vivo pilot, high blood flow forced the study to halt until the solution presented here was developed. The profuse bleeding after bone core removal affected the bond strength and was reflected in the lower mean peak value 1.53N. After considering several options, we were successful in sealing the source of blood flow by pressing adhesive into place after bone core removal. After the initial adhesive had cured additional adhesive was used to secure the bone core in place. The animals were sacrificed after 24 h and a tensile test was undertaken on the bone core to failure. The ex vivo study produced mean peak tensile loads of 7.63N SD 2.39N (n=8, 4 rats 8 femurs). Whilst the mean peak tensile loads in the day 1 in vivo pilot were significantly lower 1.53N SD1.57 (n=8, 6 rats 8 femurs − 4 used for other tests). The subsequent layered adhesive bone cores showed a mean peak tensile force of 6.79N SD =3.13 (n=8, 4 rats 8 femurs). 7/8 failed at the bone to glue interface. This is the first successful demonstration of bonding bone in vivo for this class of adhesives. The development of a double adhesive method of fixing a bone core in the distal femur enabled mean peak tensile forces to be achieved in vivo at 24 hours that were comparable with the ex vivo results previously demonstrated. This method supports application in further animal series and over longer time scales. Biomaterials researchers that intend to use gel or paste like preparations in distal femur defects in the rat should be aware of the risks of biomaterial displacement by local blood flow

Staged revision arthroplasty for the periprosthetic hip infection is the accepted mode of treatment. Unfortunately, the first stage revision compromises the patient’s function secondary to inability to weight-bear. Pros-theses coated with antibiotic-loaded cement have been adapted to improve function but have failed in larger femoral defects. This implant and technique described improves patient mobility and decreases morbidity as compared to conventional techniques. The purpose of this study was to find an implant to accommodate most femoral defects and to be readily available for managing periprosthetic hip infections. A prospective study was performed comparing the PROSTALAC(DePuy, IN) implant (Group I) to a Solution(DePuy, IN) implant (Group II) covered in antibiotics for management of the first stage. All patients had a confirmed pyogenic gram positive or gram negative infection. Fifty-two patients were compared with each group being matched by their femoral defect type (Paprosky: Type I and II: 24, Type III:20, Type IV: 8). Follow-up was for a minimum of thirty-six months. All patients were encouraged to weight bear as tolerated. One recurrence of infection occurred after a second stage revision in Group I. Cost of the implant averaged $700 cheaper in Group II. More significant was the fact that the average length of hospital stay was decreased in Group II by seven days and forty-seven days for the Type III and Type IV femurs respectively. All patients in Group I received a second stage revision. Five of the Group II patients refused a second stage revision secondary to their satisfactory function and had better post-op function. An alternative treatment for staged periprosthetic hip infections is proposed which can decrease hospital stay, improve function, and allow routine implant use for its implementation

Revision hip surgery is about simplification. As such, a single revision stem makes sense. The most important advantage of Tapered Conical Revision (TCR) stem is versatility - managing ALL levels of femoral bone loss (present before revision or created during revision). The surgeon and team quickly gain familiarity with the techniques and instruments for preparation and implantation and subsequently master its use for a variety of situations. This ability to use the stem in a variety of bone loss situations eliminates intraoperative shuffle (changes in the surgical plan resulting in more instruments being opened), as bone loss can be significantly underestimated preoperatively or may change intraoperatively. Furthermore, distal fixation can be obtained simply and reliably. Paprosky 1 femoral defects can be treated with a primary-type stem for the most part. All other femoral defects can be treated with a TCR stem. Fully porous coated stems also work for many revisions but why have two different revision stem choices available when the TCR stems work for ALL defects?. TCR stems can be modular or monolithic but there are common keys to success. First and foremost, proper exposure is essential to assess bone defects and to safely prepare the femur. An extended osteotomy is often useful. Reaming distally to prepare a cone for fixation of the conical stem is a critical requirement to prevent subsidence (true for all revision stems). Restoration of hip mechanics (offset, leg length and stability) is fundamental to the clinical result. TCR stems have instrumentation and techniques that ensure this happens, since all this occurs AFTER distal stability is achieved. Modular TCR versions have some advantages. The proximal body size and length can be adjusted AFTER stem insertion if the stem goes deeper than the trial. Any proximal/distal bone size mismatch can be accommodated. If the surgeon believes that proximal bone ingrowth is important to facilitate proximal bone remodeling, modular TCR stems can more easily accomplish this. Further, proximal bone contact and osseointegration will protect the modular junction from stress and possible risk of fracture. Monolithic TCR versions also have some advantages. Modular junction mechanical integrity cannot accommodate smaller bone sizes. Shorter stem lengths are not available in modular versions, and shorter TCR stems are an option in many revision cases. The possibility of modular junction corrosion is eliminated and fracture of the stem at that junction, of course, is not possible. The monolithic stem option is less expensive as well. Consider Modular TCR stems in your learning curve, if you feel proximal bone osseointegration is important and if proximal/distal size mismatch is present. Consider Monolithic TCR stems after your learning curve to reduce cost, when a short stem works, and if a small stem is needed. Both Modular and Monolithic stems can be used for ALL cases with equal quality of result

Objectives. Recent studies have shown that modulating inflammation-related lipid signalling after a bone fracture can accelerate healing in animal models. Specifically, decreasing 5-lipoxygenase (5-LO) activity during fracture healing increases cyclooxygenase-2 (COX-2) expression in the fracture callus, accelerates chondrogenesis and decreases healing time. In this study, we test the hypothesis that 5-LO inhibition will increase direct osteogenesis. Methods. Bilateral, unicortical femoral defects were used in rats to measure the effects of local 5-LO inhibition on direct osteogenesis. The defect sites were filled with a polycaprolactone (PCL) scaffold containing 5-LO inhibitor (A-79175) at three dose levels, scaffold with drug carrier, or scaffold only. Drug release was assessed in vitro. Osteogenesis was assessed by micro-CT and histology at two endpoints of ten and 30 days. Results. Using micro-CT, we found that A-79175, a 5-LO inhibitor, increased bone formation in an apparent dose-related manner. Conclusions. These results indicate that 5-LO inhibition could be used therapeutically to enhance treatments that require the direct formation of bone

Modern modular revision stems employ tapered conical (TCR) distal stems designed for immediate axial and rotational stability with subsequent osseo-integration of the stem. Modular proximal segments allow the surgeon to achieve bone contact proximally with eventual ingrowth that protects the modular junction. The independent sizing of the proximal body and distal stem allows for each portion to obtain intimate bony contact and gives the surgeon the ability precisely control the femoral head center of rotation, offset, version, leg length, and overall stability. The most important advantage of modular revision stems is versatility - the ability to manage ALL levels of femoral bone loss (present before revision or created during revision). Used routinely, this allows the surgeon to quickly gain familiarity with the techniques and instruments for preparation and implantation and subsequently master the use for all variety of situations. This also allows the operating room staff to become comfortable with the instrumentation and components. Additionally, the ability to use the stem in all bone loss situations eliminates intra-operative shuffle (changes in the surgical plan resulting in more instruments being opened), as bone loss can be significantly under-estimated pre-operatively or may change intra-operatively. Furthermore, distal fixation can be obtained simply and reliably. Paprosky 1 femoral defects can be treated with a primary-type stem for the most part. All other femoral defects can be treated with a TCR stem. Fully porous coated stems also work for many revisions but why have two different revision stem choices available when the TCR stems work for ALL defects?. The most critical advantage is the ability to separate completely the critical task of fixation from other important tasks of restoring offset, leg length, and stability. Once fixation is secured, the surgeon can concentrate on hip stability and on optimization of hip mechanics (leg length and offset). The ability to do this allows the surgeon to maximise patient functionality post-operatively. Modular tapered stems have TWO specific advantages over monolithic stems in this important surgical task. The proximal body size and length can be adjusted AFTER stem insertion if the stem goes deeper than the trial. Further, proximal/distal bone size mismatch can be accommodated. The surgeon can control the diameter of the proximal body to ensure proper bony apposition independent of distal fitting needs. If the surgeon believes that proximal bone ingrowth is important to facilitate proximal bone remodeling, modular TCR stems can more easily accomplish this. The most under-appreciated advantage is the straightforward instrumentation system that makes the operation easier for the staff and the surgeon, while enhancing the operating room efficiency and reducing cost. Also, although the implant itself may result in more cost, most modular systems allow for a decrease in inventory requirements, which make up the cost differential. One theoretical disadvantage of modular revision stems is modular junction fracture, which can happen if the junction itself is not protected by bone. Ensuring proximal bone support can minimise this problem. Once porous ingrowth occurs proximally, the risk of junction fracture is eliminated. Even NON-modular stems fracture when proximal bone support is missing. Another theoretical issue is modular junction corrosion but this not a clinical one, since both components are titanium. One can also fail to connect properly the two parts during surgery

Despite the increasing availability of bone grafting materials, the regeneration of large bone defects remains a challenge. Especially infection prevention while fostering regeneration is a crucial issue. Therefore, loading of grafting material with antibiotics for direct delivery to the site of need is desired. This study evaluates the concept of local delivery using in vitro and in vivo investigations. We aim at verifying safety and reliability of a perioperative enrichment procedure of demineralized bone matrix (DBM) with gentamicin. DBM (DBMputty, DIZG, Germany) was mixed with antibiotic using a syringe with an integrated mixing propeller (Medmix Systems, Switzerland). Gentamicin, as powder or solution, was mixed with DBM at different concentrations (25 −100 mg/g DBM), release and cytotoxicity was analyzed. For in vivo analysis, sterile drill hole defects (diameter: 6 mm, depth: 15 mm) were created in diaphyseal and metaphyseal bones of sheep (Pobloth et al. 2016). Defects (6 – 8 per group and time point) were filled with DBM or DBM enriched with gentamicin (50 mg/g DBM) or left untreated. After three and nine weeks, defect regeneration was analyzed by µCT and histology. The release experiments revealed a burst release of gentamicin from DBM independent of the used amount, the sampling strategy, or the formulation (powder or solution). Gentamicin was almost completely released after three days in all set-ups. Eluates showed an antimicrobial activity against S. aureus over at least three days. Eluates had no negative effect on viability and alkaline phosphatase activity of osteoblast-like cells (partially published Bormann et al. 2014). µCT and histology of the drill hole defects revealed a reduced bone formation with gentamicin loaded DBM. After nine weeks significantly less mineralized tissue was detectable in metaphyseal defects of the gentamicin group. Histological evaluation revealed new bone formation starting at the edges of the drill holes and growing into the center over time. The amount of DBM decreased over time due to the active removal by osteoclasts while osteoblasts formed new bone. Using this mixing procedure, loading of DBM was fast, reliable and possible during surgical setting. In vitro experiments revealed a burst and almost complete release after three days, antimicrobial activity and good biocompatibility of the eluates. Gentamicin/DBM concentration was in the range of clinically used antibiotic-loaded-cement for prophylaxis and treatment in joint replacement (Jiranek et al. 2006). The delayed healing seen in vivo was unexpected due to the good biocompatibility found in vitro. A reduced healing was also seen in spinal fusion where DBM was mixed with vancomycin (Shields et al. 2017), whereas DBM with gentamicin or DBM/bioactive glass with tobramycin had no negative effect on osteoinductivity or femur defect healing, respectively (Lewis et al. 2010, Shields et al. 2016). In conclusion, loading of DBM with gentamicin showed a proper antibiotic delivery over several days, covering the critical phase shortly after surgery. Due to the faster and complete release of the antibiotic compared to antibiotic loaded cement, the amount of antibiotic should be much lower in the DBM compared to cement

The potential of piezoelectric biomaterials for bone tissue engineering is demonstrated. This work proves that the use of piezoelectric poly(vinylidene fluoride) (PVDF), able to provide electrical stimuli upon mechanical solicitation to the growing bone cells, enhances the bone regeneration in vivo. Poled and non-poled PVDF films, with and without macroscopic piezoelectric response, respectively and randomly oriented piezoelectric electrospun fiber mats have been used as substitutes for bone to test their osteogenic properties in Wistar rats by analyzing new bone formation in 3 mm bilateral femur defects in vivo. After 4 weeks, the qualification of the regenerated bone was performed according the H&E staining. Defect implanted with poled PVDF films demonstrated significantly more defect closure and bone remodeling, showing the large potential of piezoelectric biomaterials for bone repair, as well as for other electromechanical responsive tissues such as muscle and tendon

Bone has a remarkable capacity to heal. However, in some instances the amount of bone which is needed to heal exceeds its healing capacity. Due to reported issues with current treatments there is continued research into alternative approaches with a view to producing an off the shelf alternative to the gold standard autologous bone transplants. The current investigated the use of a chitosan/hydroxyapatite scaffold, which was used to covalently bone morphogenetic protein and vascular endothelial growth factor using a UV crosslinking process. Results indicate that the incorporation of hydroxyapatite increased the mechanical properties of the scaffold compared to chitosan alone. Furthermore, crosslinking was confirmed using swelling studies and FTIR analysis. Elisa indicated that physiological doses of BMP were released after 10 days while in vitro testing did not indicate a cytotoxic response to the scaffold. In vivo testing in a rat femoral defect model indicated the efficacy of the treatment with scaffolds containing BMP and VEGF in combination resulting in more bone in the defect compared to the scaffold alone 8 weeks post-surgery