Staged bilateral total knee arthroplasty is performed increasingly frequently but no data has been published comparing the specific outcome for the first knee replacement to that of the second. Pre-operative and post-operative Oxford Knee Scores (/ 48) were reviewed for each knee in a series of 91 patients undergoing staged bilateral total knee arthroplasty over a 5-year period. Pre-operative scores for the first total knee arthroplasty were significantly worse with a mean of 14.9 in comparison to 17.0 for the second knee (P=0.0083). While there was no significant difference between the mean post-operative scores for the first knee (37.4) and the second knee (36.6) (P=0.195), the mean improvement was significantly less for the second knee (22.6 points versus 19.6 points) (P=0.0045). Our results demonstrate that in patients undergoing staged bilateral knee arthroplasty, the second knee replacement is commonly performed at a lower threshold and functional improvement is less than for the first knee. This data will be important to inform the expectations of patients considering proceeding to bilateral knee arthroplasty after previously having undergone a primary total knee replacement

Introduction and Objective. Platelet-Rich-plasma (PRP) has been used in combination with stem cells, from different sources, with encouraging results both in vitro and in vivo in osteochondral defects management. Adipose-derived Stem Cells (ADSCs) represents an ideal resource for their ease of isolation, abundance, proliferation and differentiation properties into different cell lineages. Furthermore, Stem Cells in the adipose tissue are more numerous than from other sources. Aim of this study was to evaluate the potential of ADSCs in enhancing the effect of arthroscopic mesenchymal stimulation combined with infiltration of PRP. Materials and Methods. The study includes 82 patients. 41 patients were treated with knee arthroscopy, Steadman microfractures technique and intraoperative PRP infiltration, Group A. In the Group B, 41 patients were treated knee arthroscopy, Steadman microfractures and intraoperative infiltration of PRP and ADSCs (Group B). Group A was used as a control group. Inclusion criteria were: Age between 40 and 65 years, Outerbridge grade III-IV chondral lesions, Kellegren-Lawrence Grade I-II. Patient-reported outcome measures (PROMs) evaluated with KOOS, IKDC, VAS, SF-12 were assessed pre-operatively and at 3 weeks, 6 months, 1-year post-operative. 2 patients of Group A and 3 patients of Group B, with indication of Puddu plate removal after high tibial osteotomy (HTO), underwent an arthroscopic second look, after specific informed consent obtained. On this occasion, a bioptic sample was taken from the repair tissue of the chondral lesion previously treated with Steadman microfractures. Results. PROMs showed statistically significant improvement (p <0.05) with comparable results in both groups. The histological examination of the bioptic samples in Group B showed a repair tissue similar to hyaline cartilage, according to the International Cartilage Repair Society (ICRS) Visual Histological Assessment Scale. In Group A, the repair tissue was fibrocartilaginous. Conclusions. According to the PROMs and the histological results, showing repair tissue after Steadman microfractures qualitatively similar to hyaline cartilage, the combination of ADSCs and PRP could represent an excellent support to the arthroscopic treatment of focal chondral lesions and mild to moderate osteoarthritis

Introduction. The purpose of this study was to evaluate the functional and radiographical mid-term follow-up results of a second generation metal-on-metal cementless total hip arthroplasty for the treatment of osteonecrosis of the femoral head in patients younger than 50 years. Methods. Twenty eight patients (35 hips) who underwent total hip arthroplasty with second generation metal-on-metal bearings for osteonecrosis of the femoral head at a minimum 5-year follow-up were included in this study. There were 5 women (6 hips) and 23 men (29 hips) who had a mean age of 40 years (range, 23 to 49 years) and a mean follow-up of 7 years. We used a Fitmore (Zimmer) cup and a 28mm Metasul femoral head in all cases. A CLS (Protek AG/Zimmer) femoral stem was used in 30 hips and a Cone prosthesis¯ (Protek AG) was used in 5 hips. Functional results were measured by Harris hip (HHS) and WOMAC scores. Radiographic evaluations were used to assess loosening and osteolysis according to Gruen and Delee and Charnley criteria. Results. The mean Harris hip score improved from 58 points (range, 35 to 67 points) pre-operatively to 92 points (range, 84 to 99 points) post-operatively, and the mean WOMAC score improved from 73 points (range, 63 to 89 points) to 30 points (range, 24 to 41 points). On radiological evaluation, all femoral and acetabular components were well-fixed without loosening or subsidence. Osteolysis was observed in 5 hips (14%) (acetabular osteolysis in 2 cases-Zone 2; 1, Zone 3; 1, femoral osteolysis in 3 cases- Zone 1; 2, Zone 7; 1). There were no complications including immediate post-operative deep infection, delayed infection, or recurrent dislocation. There was no case of revision for aseptic loosening. Conclusion. Second generation metal-on-metal cementless total hip arthroplasty for the treatment of osteonecrosis of the femoral head in patients younger than 50 years showed favorable functional and radiographic results

A tendon is a fibrous connective tissue that acts to transmit tensile forces between muscles and bones. It mainly consists of soluble substance, collagen and small volume of elastic fibres, which are produced by tenoblasts and tenocytes. The Achilles tendon is the thickest tendon in the human body that subjects to some of the highest tensile force, thus disorders and ruptures commonly happen. As the insoluble fibrous components in Achilles tendons, the collagen fibrils and elastic fibres have unique spatial structure that plays important functional roles. Despite this, the understanding of relationship between them is still limited due to the lack of imaging evidence. Using confocal and second harmonic generation microscopy, this study aims to comprehensively investigate the spatial relationship of collagen, elastic fibres and tenocytes in hydrated tendons. Longitudinal sections of 50 µm thick and transverse sections of 20 µm thick were cryo-sectioned respectively from the mid-portion of ten rabbit Achilles tendons. Sections were stained with 0.03g/L Acridine Orange (AO) and 1mg/ml Sulforhodamine B (SRB) solution respectively for labelling the nucleus and elastic fibres. The Leica TCS SP2 multiphoton microscopy containing second harmonic generation microscopy can image collagen without labelling. The sections were scanned by the multiphoton microscopy, and images were processed and reconstructed into 3D images to study the spatial structure of collagen, elastic fibres and cells in Achilles tendons. A rabbit Achilles tendon consists of three sub-tendons named flexor digitorum superficialis tendon, medial gastrocnemius tendon and lateral gastrocnemius tendon. Loose connective tissue connects the three sub-tendons and ensures efficient sliding between sub-tendons. The 3D network shows that the mid-portion of Achilles tendons is composed of longitudinal collagen and elastic fibres, while spindle tenocytes rest along the collagen and elastic fibres. Tenocytes appear to have a closer microstructural relationship with the elastic fibres. In comparison with the collagen, tenocytes and elastic fibres only occupy a very small volume in the 3D network. The elastic fibres exist in both tendon proper and endotenons. The tendon sheath and loose connective tissue have a higher cell density, and the cells are large and round while compared with tenocytes. As a component of the extracellular matrix (ECM) in Achilles tendons that closely mediates with the tenocytes, the elastin may participate in the force transition and interaction between tenocytes and the ECM. The elastic fibres may also endow Achilles tendons with unique mechanical properties to stand for tensile force

Summary. Objective assessment of tendon histomorphology, particularly in the context of tissue repair, requires comprehensive analyses of both cellular distribution and matrix architecture. Fourier Transform analyses of histological images collected with second harmonic generation (SHG-FT) technique provide objective, quantitative assessment of collagen fiber organization with high specificity. Concurrent nuclear staining allows simultaneous analyses of cell morphology and distribution. Introduction. Tendon injuries can be career-limiting in human and equine athletes, since the architectural organization of the tissues are lost in the course of fibrotic repair. Objective assessment of tendon repair is problematical, particularly in research addressing potential therapies. Fourier Transform analyses of histological images collected with second harmonic generation (SHG-FT) technique can provide objective, quantitative assessments of collagen fiber organization with high specificity. This study describes the use of SHG-FT with fluorescently-labelled tendon-derived cells (TDC) in an in-vivo model of equine tendinitis to assess the temporal and spatial effects of cell delivery on collagen fiber organization. Materials and methods. Collagenase-induced tendinitis was created in the mid-metatarsal region of one hindlimb superficial digital flexor tendons (SDFT) in two horses. SDFTs from two clinically normal adult horses and were also used as controls. Autogenous TDCs were isolated from the lateral digital extensor tendon of the contralateral hind limb. Four weeks post-collagenase injection, 10×10. 6. DiI-labeled TDCs were injected into the tendon lesions. Tendon samples were obtained for histologic evaluation following euthanasia, 2-weeks after cell injections. Tendon samples were cryo-sectioned to 25–30μ exposed to nuclear counter stains (DAPI and PI) and imaged immediately through a confocal microscope (Zeiss LSM 710) with a 2-photon laser source, to obtain backward SHG (bSHG) and forward SHG (fSHG) images. In addition, images with DiI and DAPI fluorescence were acquired using 500–550 nm (green) or 565–615 nm (orange) emission filters, respectively. Fourier analysis of the SHG images was carried out using imageJ software. Results. DiI-labeled TDCs could be imaged successfully under two-photon fluorescence concurrently with SHG imaging. This was possible because the excitation wavelength of the two-photon laser (780nm) and detection of emissions above 565nm do not interfere with the bSHG band (380–400nm). Images collected with bSHG included signals from DAPI-stained nuclei. In contrast, emissions from PI-labeled nuclei were acquired independently of SHG signals. The contrast generated by individual collagen fibers was higher in images collected with fSHG than bSHG. SHG-FT of fSHG images provided accurate assessment of collagen fiber orientation in repair tissue and normal tendon. Discussion/Conclusions. Objective assessment of collagen orientation, along with spatial distribution of cells within healing tendon serves as useful indices of healing. Injected DiI-labeled TDCs could be imaged successfully under two-photon fluorescence concurrently with SHG imaging. However, DiI fluorescence is susceptible to photo-bleaching during SHG acquisition. Use of an alternative nuclear counter stains, such as PI, that do not emit along with SHG signal should be considered to optimise data acquisition and support simultaneous analyses of collagen structure, cellular morphology and cell distribution. SHG-FT histologic analysis along with biochemical and biomechanical indices collectively provide comprehensive assessment of therapies for tendon repair

Summary Statement

This study assesses oxidation, mechanical behavior and revision reasons of 2^nd generation HXLPE used in total hip and knee arthroplasty. While oxidation was low for both X3 and E1 HXLPEs, oxidative regional variations were detected in the sequentially annealed cohort.

Infections represent a devastating complication in orthopedic and traumatological surgery, with high rates of morbidity and mortality. An early intervention is essential, and it includes a radical surgical approach supported by targeted intravenous antimicrobial therapy. The availability of parenteral antibiotics at the site of infection is usually poor, so it is crucial to maximize local antibiotic concentration using local carriers. Our work aims to describe the uses of one of these systems, Stimulan®, for the management and prevention of infections at our Institution. Analysing the reported uses of Stimulan®, we identified two major groups: bone substitute and carrier material for local antibiotic therapy. The first group includes its application as a filler of dead spaces within bone or soft tissues resulting from traumatic events or previous surgery. The second group comprehends the use of Stimulan® for the treatment of osteomyelitis, post-traumatic septic events, periprosthetic joint infections, arthroplasty revision surgery, prevention in open fractures, surgery of the diabetic foot, oncological surgery and for all those patients susceptible to a high risk of infection. We used Stimulan® in several complex clinical situations: in PJIs, in DAPRI procedure and both during the first and the second stage of a 2-stage revision surgery; furthermore, we started to exploit this antibiotic carrier also in prophylaxis of surgical site infections, as it happens in open fractures, and when a surgical site remediation is required, like in osteomyelitis following ORIF. Stimulan® is an extremely versatile and polyhedric material, available in the form of beads or paste, and can be mixed to a very broad range of antibiotics to better adapt to different bacteria and their antibiograms, and to surgeon's needs. These properties make it a very useful adjuvant for the management of complex cases of infection, and for their prevention, as well

Cells typically respond to a variety of geometrical cues in their environment, ranging from nanoscale surface topography to mesoscale surface curvature. The ability to control cellular organisation and fate by engineering the shape of the extracellular milieu offers exciting opportunities within tissue engineering. Despite great progress, however, many questions regarding geometry-driven tissue growth remain unanswered. Here, we combine mathematical surface design, high-resolution microfabrication, in vitro cell culture, and image-based characterization to study spatiotemporal cell patterning and bone tissue formation in geometrically complex environments. Using concepts from differential geometry, we rationally designed a library of complex mesostructured substrates (10. 1. -10. 3. µm). These substrates were accurately fabricated using a combination of two-photon polymerisation and replica moulding, followed by surface functionalisation. Subsequently, different cell types (preosteoblasts, fibroblasts, mesenchymal stromal cells) were cultured on the substrates for varying times and under varying osteogenic conditions. Using imaging-based methods, such as fluorescent confocal microscopy and second harmonic generation imaging, as well as quantitative image processing, we were able to study early-stage spatiotemporal cell patterning and late-stage extracellular matrix organisation. Our results demonstrate clear geometry-dependent cell patterning, with cells generally avoiding convex regions in favour of concave domains. Moreover, the formation of multicellular bridges and collective curvature-dependent cell orientation could be observed. At longer time points, we found clear and robust geometry-driven orientation of the collagenous extracellular matrix, which became apparent with second harmonic generation imaging after ∼2 weeks of culture. Our results highlight a key role for geometry as a cue to guide spatiotemporal cell and tissue organisation, which is relevant for scaffold design in tissue engineering applications. Our ongoing work aims at understanding the underlying principles of geometry-driven tissue growth, with a focus on the interactions between substrate geometry and mechanical forces

Herein we address, hyaline cartilage regeneration issue by engineering a synthetic biocompatible hydrogel scaffold capable to promote chondrogenic differentiation. In this study, the chemically crosslinked hydrogels consisting of synthetic peptides that have the collagen-like sequence Cys-Gly-(Pro-Lys-Gly)4 (Pro-Hyp-Gly)4 (Asp-Hyp-Gly)4- conjugated with RGD sequence (CLP-RGD) and crosslinked hydrogels of type I collagen (CA) were used. For cartilage formation, we used human skeletal muscle-derived stem/progenitor cells (hMDSPCs) set for differentiation towards a chondrogenic lineage by BMP-7 and TGF-ß3 growth factors. Initially 150, 100 and 75 ng of BMP-7and TGF-ß3 growth factors were inserted in each scaffold and amount of growth factors diffusing out of the scaffolds was observed by ELISA assays. In vitro experiments were performed by seeding hMDSPCs onto hydrogels loaded with growth factors (75ng/scaffold) and cultured for 28 days. Cartilage formation was monitored by ELISA and RT-PCR assays. All experiments were performed in triplicates or quadruplicates. Growth factors incorporation strategy allowed a sustained release of TGF-ß3 growth factor, 6.00.3% of the initially loaded amount diffused out after 4 h and 2.70.5% already at the second time point (24h) from CA and CLP-RGD substrates. For the BMP-7 growth factor, 13.12.3% and 15.751.6% of the initially loaded amount diffused out after 4 h, 1.70.2% and 2.450.3% at the second time point (24 h) from CA and CLP-RGD respectively. In vitro experiments shown that scaffolds with immobilized growth factors resulted in higher collagen type II accumulation when compared to the scaffolds alone. The gene expression on CLP-RGD hydrogels with growth factors has shown lower collagen type I expression and higher aggrecan expression compared to day 0. However, we also report increased collagen X gene expression on CA hydrogels (with growth factors). Our results support the potential of the strategy of combining hydrogels functionalized with differentiation factors toward improving cartilage repair

Introduction. As per national guidelines for Ankle fractures in the United Kingdom, fractures considered stable can be treated with analgesia, splinting and allowed to weight bear as tolerated. The guidelines also suggest further follow-up not mandatory. This study was aimed at evaluating the current clinical practice of managing stable ankle fractures at a university hospital against national guidelines. Method. The study was undertaken using retrospectively collected data, the inclusion criteria being all adults with stable ankle fracture pattern treated non-operatively between December 2022 and April 2023. Collected data included age of patient, date of injury, type of immobilization, number of clinical visits and any complications. Results. 41 cases were identified and analyzed. The mean age of the cohort was 49.8 years (Standard deviation 20.01). Twelve percent (n = 5) were reviewed in clinic, treated and discharged as stable Weber B type fracture pattern as per national guidelines after the first visit. About 52% (n = 21) were seen in clinic twice before discharge, first visit between 1-2 weeks and the last clinic visit between 5-7 weeks. About a third of patients (30%, n = 12) were seen in clinic on more than two occasions. At the first clinic visit 87% (n = 36) were given a boot and allowed to weight bear as tolerated. Two patients were diagnosed with deep vein thrombosis/pulmonary embolism during the treatment duration. Three patients had extended duration of follow up for ongoing symptoms. None discharged after first or second visit needed surgery for displaced or malunited fracture. Conclusion. Patients discharged from clinic after first or second visit did not need any further surgery. As per national guidelines, patients deemed stable weber B lateral malleolus fracture pattern after weight bearing radiograph can be treated safely with a weight bearing walking boot with no further follow up

It is known that Osteoporosis is the pathology of bone mass and tissue loss resulting in an increase of fragility, risk of fracture occurrence, and risk of fracture recurrence. We noted there was no definitive pathway in our last audit, therefore recommended: availability of the Osteoporosis clinic referral form in an accessible place, the form be filled by the doctor reviewing the patient in the first fracture clinic, and a liaison nurse to ensure these forms were filled and sent to the Osteoporosis clinic. This second audit analyses our Trust's response to these recommendations and effect achieved in Osteoporosis care. We reviewed our local data base from the 7/27/2020 – 10/2/2021 retrospectively for distal radius fractures who were seen in fracture clinic. We analysed a sample size of 59 patients, excluding patients who had already commenced bone protection medications. 67.7% of our patients had neither been on bone protection medications nor recorded referrals and 13.5% were already on bone protection medications when they sustained the fragility fracture. Ten out of the 51 patients were offered referral to the osteoporosis clinic, and one refused. This makes 20% (10 out of 50) of the patients had completed referrals. In comparison, in our first audit, 11% had already been on bone protection medications and 18% had completed referrals. The second cycle showed a slight increase in compliance. Majority of the referrals were completed by Orthopaedic Consultants in both audits and ana awareness increase noted among non-consultants in starting the referral process. Based on our analysis, our Trust has a slight improvement in commencing bone protection medications, associated with slight improvement in completing referrals to the Osteoporosis clinic. Despite our recommendations in the first audit, there is still no easily accessible definitive pathway to ensure our Trust's patients have timely access to bone protection and continued care at the Osteoporosis clinic. We recommend streamlining our recommendations to have a more effective approach in ensuring our Trust meets national guidelines. We will implement a Yes or No question assessment for patients visiting clinic in our electronic database which should assist in referral completions

This edition of the Cochrane Corner looks at the three reviews that were published in the second half of 2023: surgical versus non-surgical interventions for displaced intra-articular calcaneal fractures; cryotherapy following total knee arthroplasty; and physical activity and education about physical activity for chronic musculoskeletal pain in children and adolescents

Aim of this study was the development of a dynamic FE-framework to identify worst-case size combinations and kinematics in a virtual wear simulator setup covering five daily activities and high, dynamic loads. Two cruciate sacrificing knee designs (D1 & D2) were tested physically on a wear-testing machine prior the model development using a high demanding, daily activity protocol (HDA) [1]. A simplified FE-setup was generated, reduced to the 3D geometries of the assembly whereas the representation of the mechanical wear simulator conditions and the load transmission was achieved by joint elements. Inertial and other time-related effects of the physical situation were compensated by a system of spring- and damper elements. Using a time-series signal optimization approach on the anterior-posterior translation and the internal-external rotation results for each activity, 38 variable parameters were varied in between pre-defined limits in a semiautomatic workflow. For each design, two consecutive cycles of a single activity were analysed and the results of the second cycle were used for the optimization. Based on the determined values, a single set of averaged parameter settings was identified that covers all activity cycles sufficiently. A total of 1010 dynamic analyses were carried out in order to find a sharable set of parameter values. In this study, an efficient simulation workflow for design evaluation was developed. Therefore, a HDA wear-testing machine was simplified to boundary conditions and stabilizing elements, using a single set of parameters for all activities. The calculated kinematics were in a comparable range to the machine output. Further applications of the method were found in systematic analyses of entire implant systems to achieve consistent kinematics over the size compatibility range in the design process of new implant systems

The objective of this study was to investigate how a new customizable light-curable osteosynthesis method (AdFix) compared to traditional metal hardware when loaded in torsion in an ovine phalanx model. Twenty-one ovine proximal phalanges were given a 3mm transverse osteotomy and four 1.5mm cortex screws were inserted bicortically on either side of the gap. The light-curable polymer composite was then applied using the method developed by Hutchinson [1] to create osteosyntheses in two groups, having either a narrow (6mm, N=9) or a wide (10mm, N=9) fixation patch. A final group (N=3) was fixated with conventional metal plates. The constructs were loaded in torsion at a rate of 6°/second until failure or 45° of rotation was reached. Torque and angular displacement were measured, torsional stiffness was calculated as the slope of the Torque-Displacement curve, and maximum torque was queried for each specimen. The torsional stiffnesses of the narrow, wide, and metal plate constructs were 39.1 ± 6.2, 54.4 ± 6.3, and 16.2 ± 3.0 Nmm/° respectively. All groups were statistically different from each other (p<0.001). The maximum torques of the narrow, wide, and metal plate constructs were 424 ± 72, 600 ± 120, and 579 ± 20 Nmm respectively. The narrow constructs were statistically different from the other two (p<0.05), while the wide and metal constructs were not statistically different from each other (p=0.76). This work demonstrated that the torsional performance of the novel solution is comparable to metal fixators. As a measure of the functional range, the torsional stiffness in the AdhFix exceeded that of the metal plate. Furthermore, the wide patches were able to sustain a similar maximum toque as the metal plates. These results suggest AdhFix to be a viable, customizable alternative to metal implants for fracture fixation in the hand

Surgical education of fracture fixation biomechanics relies mainly on simplified illustrations to distill the essence of the underlying principles. These mostly consist of textbook drawings or hands-on exercises during courses, both with unique advantages such as broad availability and haptics, respectively. Computer simulations are suited to bridge these two approaches; however, the validity of such simulations must be guaranteed to teach the correct aspects. Therefore, the aim of this study was to validate finite element (FE) simulations of bone-plate constructs to be used in surgical education in terms of fracture gap movement and implant surface strain. The validation procedure was conducted in a systematic and hierarchical manner with increasing complexity. First, the material properties of the isolated implant components were determined via four-point bending of the plate and three-point bending of the screw. Second, stiffness of the screw-plate interface was evaluated by means of cantilever bending to determine the properties of the locking mechanism. Third, implant surface strain and fracture gap motion were measured by testing various configurations of entire fixation constructs on artificial bone (Canevasit) in axial compression. The determined properties of the materials and interfaces assessed in these experiments were then implemented into FE models of entire fixation constructs with different fracture width and screw configurations. The FE-predicted implant surface strains and fracture gap motions were compared with the experimental results. The simulated results of the different construct configurations correlated strongly with the experimentally measured fracture gap motions (R. 2. >0.99) and plate surface strains (R. 2. >0.95). In a systematic approach, FE model validation was achieved successfully in terms of fracture gap motion and implant deformation, confirming trustworthiness for surgical education. These validated models are used in a novel online education tool OSapp (. https://osapp.ch/. ) to illustrate and explain the biomechanical principles of fracture fixations in an interactive manner

In chronically infected fracture non-unions, treatment requires extensive debridement to remove necrotic and infected bone, often resulting in large defects requiring elaborate and prolonged bone reconstruction. One approach includes the induced membrane technique (IMT), although the differences in outcome between infected and non-infectious aetiologies remain unclear. Here we present a new rabbit humerus model for IMT secondary to infection, and, furthermore, we compare bone healing in rabbits with a chronically infected non-union compared to non-infected equivalents. A 5 mm defect was created in the humerus and filled with a polymethylmethacrylate (PMMA) spacer or left empty (n=6 per group). After 3 weeks, the PMMA spacer was replaced with a beta-tricalcium phosphate (chronOs, Synthes) scaffold, which was placed within the induced membrane and observed for a further 10 weeks. The same protocol was followed for the infected group, except that four week prior to treatment, the wound was inoculated with Staphylococcus aureus (4×10. 6. CFU/animal) and the PMMA spacer was loaded with gentamicin, and systemic therapy was applied for 4 weeks prior to chronOs application. All the animals from the infected group were culture positive during the first revision surgery (mean 3×10. 5. CFU/animal, n= 12), while at the second revision, after antibiotic therapy, all the animals were culture negative. The differences in bone healing between the non-infected and infected groups were evaluated by radiography and histology. The initially infected animals showed impaired bone healing at euthanasia, and some remnants of bacteria in histology. The non-infected animals reached bone bridging in both empty and chronOs conditions. We developed a preclinical in vivo model to investigate how bacterial infection influence bone healing in large defects with the future aim to explore new treatment concepts of infected non-union

Virtual mechanical testing is a method for measuring bone healing using finite element models built from computed tomography (CT) scans. Previously, we validated a dual-zone material model for ovine fracture callus that differentiates between mineralized woven bone and soft tissue based on radiodensity. 1. The objective of this study was to translate the dual-zone material model from sheep to two important clinical scenarios: human tibial fractures in early-stage healing and late-stage nonunions. CT scans for N = 19 tibial shaft fractures were obtained prospectively at 12 weeks post-op. A second group of N = 33 tibial nonunions with CT scans were retrospectively identified. The modeling techniques were based on our published method. 2. The dual-zone material model was implemented for humans by performing a cutoff sweep for both the 12-week and nonunion groups. Virtual torsional rigidity (VTR) was calculated as VTR = ML/φ [N-m. 2. /°], where M is the moment reaction, L is the diaphyseal segment length, and φ is the angle of twist. As the soft tissue cutoff was increased, the rigidity of the clinical fractures decreased and soft tissue located within the fracture gaps produced higher strains that are not predicted without the dual zone approach. The structural integrity of the nonunions varied, ranging from very low rigidities in atrophic cases to very high rigidities in highly calcified hypertrophic cases, even with dual-zone material modeling. Human fracture calluses are heterogeneous, comprising of woven bone and interstitial soft tissue. Use of a dual-zone callus material model may be instrumental in identifying delayed unions during early healing when callus formation is minimal and/or predominantly fibrous with little mineralization. ACKNOWLEDGEMENTS:. This work was supported by the National Science Foundation (NSF) grant CMMI-1943287

Successful application of patient derived cells to engineer vascularized bone grafts is often hampered by low cell numbers and lengthy in vitro expansion. With sound induced morphogenesis (SIM), local cell density enhancement was shown to improve microvasculature formation at lower cell concentration than conventional methods [1]. SIM takes advantage of hydrodynamic forces that act on cells to arrange them within a hydrogel. Following, we are evaluating the potential of cell-hydrogel biografts with high local cell density to improve the therapeutic efficacy in clinical scenarios such as anastomosis or bone formation within non-union fractures. To assess anastomosis, human umbilical vein endothelial cells (HUVEC) and human mesenchymal stromal cells (MSC) were mixed at a 1:1 ratio in PEG-based or Dextran-based hydrogels at a final concentration of 2×10. 6. cells×mL. -1. For ectopic bone formation, MSC were resuspended in PEG-based hydrogels at 2×10. 6. or 5×10. 6. cells×mL. -1. , with or without BMP-2. Cells were assembled into distinct patterns at a frequency of 60 Hz. Four biografts of 4 × 9 mm. 2. were implanted at the back of nude mice (total of 7 animals) and harvested after 2 or 8 weeks. Explants were fixed and imaged as whole constructs or embedded in paraffin for histological analysis. Upon explantation, microscopic evaluation indicated that HUVEC were retained within the PEG-hydrogel after 2 weeks and formed a pre-vascular network. In the second study, ectopic bone formation was more pronounced in areas of higher local cell density based on visual inspection. Ongoing experiments are further characterizing bone formation by micro-CT and histological evaluation. Our results indicate that local cell density enhancement by sound requires a lower initial cell concentration than conventional, static seeding methods to achieve comparable microvasculature structures or local osteogenesis

Treatment of bone infection often includes a burdensome two-stage revision. After debridement, contaminated implants are removed and replaced with a non-absorbable cement spacer loaded with antibiotics. Weeks later, the spacer is exchanged with a bone graft aiding bone healing. However, even with this two-stage approach infection persists. In this study, we investigated whether a novel 3D-printed, antibiotic-loaded, osteoinductive calcium phosphate scaffold (CPS) is effective in single-stage revision of an infected non-union with segmental bone loss in rabbits. A 5 mm defect was created in the radius of female New Zealand White rabbits. The bone fragment was replaced, stabilized with cerclage wire and inoculated with Staphylococcus aureus (MSSA). After 4 weeks, the infected bone fragment was removed, the site debrided and a spacer implanted. Depending on group allocation, rabbits received: 1) PMMA spacer with gentamycin; 2) CPS loaded with rifampin and vancomycin and 3) Non-loaded CPS. These groups received systemic cefazolin for 4 weeks after revision. Group 4 received a loaded CPS without any adjunctive systemic therapy (n=12 group1-3, n=11 group 4). All animals were euthanized 8 weeks after revision and assessed by quantitative bacteriology or histology. Covariance analysis (ANCOVA) and multiple regression were performed. All animals were culture positive at revision surgery. Half of the animals in all groups had eliminated the infection by end of study. In a historical control group with empty defect and no systemic antibiotic treatment, all animals were infected at euthanasia. There was no significant difference in CFU counts between groups at euthanasia. Our results show that treating an osteomyelitis with segmental bone loss either with CPS or PMMA has a similar cure rate of infection. However, by not requiring a second surgery, the use of CPS may offer advantages over non-resorbable equivalents such as PMMA

No proven long-term joint-preserving treatment options exist for patients with irreparable meniscal damage. This study aimed to assess gait kinematics and contact pressures of novel fibre-matrix reinforced polyvinyl alcohol-polyethylene glycol (PVA-PEG) hydrogel meniscus implanted ovine stifle joints against intact stifles in a gait simulator. The gait simulator controlled femoral flexion-extension and applied a 980N axial contact force to the distal end of the tibia, whose movement was guided by the joint natural ligaments (Bartolo; ORS 2021;p1657- LB). Five right stifle joints from sheep aged >2 years were implanted with a PVA-PEG total medial meniscus replacement, fixed to the tibia via transosseous tunnels and interference screws. Implanted stifle joint contact pressures and kinematics in the simulator were recorded and compared to the intact group. Contact pressures on the medial and lateral condyles were measured at 55° flexion using Fujifilm Prescale Low Pressure film inserted under the menisci. 3D kinematics were measured across two 30 second captures using the Optotrak Certus motion-tracking system (Northern Digital Inc.). Medial peak pressures were not significantly different between the implanted and intact groups (p>0.4), while lateral peak pressures were significantly higher in the implanted group (p<0.01). Implanted stifle joint kinematics in the simulator did not differ significantly from the intact baseline (p>0.01), except for in distraction-compression (p<0.01). Our findings show that the fibre-matrix reinforced PVA-PEG hydrogel meniscal replacement restored the medial peak contact pressures. Similar to published literature (Fischenich; ABE 2018;46(11):1–12), the lateral peak pressures in the implanted group were higher than the intact. Joint kinematics were similar across groups, with slightly increased internal-external rotation in the implanted group. These findings highlight the effectiveness of the proposed approach and motivate future work on the development of a total meniscal replacement