Rotator cuff tears are common in middle-aged and elderly patients. Despite advances in the surgical repair of rotator cuff tears, the rates of recurrent tear remain high. This may be due to the complexity of the tendons of the rotator cuff, which contributes to an inherently hostile healing environment. During the past 20 years, there has been an increased interest in the use of biologics to complement the healing environment in the shoulder, in order to improve rotator cuff healing and reduce the rate of recurrent tears. The aim of this review is to provide a summary of the current evidence for the use of forms of biological augmentation when repairing rotator cuff tears.

Cite this article: Bone Joint J 2024;106-B(9):978–985.

Introduction. Autologous fat grafting has favourable potential as a regenerative strategy and is the current gold-standard to repair large contour defects, as needed in breast reconstruction after mastectomy and traumatic soft tissue reconstruction. Clinically, there is a limit on the volume of lipoaspirate which can be utilised to repair a soft-tissue defect. Surgical complications are the result of poor structural fidelity of lipoaspirate and graft resorption as a filling material and are hindered further by poor graft vascularisation. This study aims to develop injectable lipoaspirate-derived adipose tissue grafts with enhanced biologically and clinically-admissible structural and functional properties adopting light photocrosslinking of unmodified lipoaspirate. Methods. Patient-derived lipoaspirate was harvested and crosslinked using novel photoinitiator and exposure to visible light (wavelength 450nm) in surgery, establishing bonds between extracellular matrix (ECM) proteins within the material. The degree of crosslinking was tuned (photoinitiator concentration, light exposure, light intensity) and covalent bond formation measured using mass spectrometry. To predict patient response, SWATH-MS was used to identify differences in patient ECM and crosslinked grafts were implanted in vivo using a subcutaneous mouse model. Functional vessel formation and resorption were quantified using micro-CT and tissue-remodelling was assessed via histology. Results. There was an increase in the relative abundance of covalent bonds present with increasing degree of crosslinking. When injected, crosslinked lipoaspirate had better shape fidelity compared with native lipoaspirate – demonstrated by a smaller fibre diameter. Crosslinked lipoaspirate remained viable over long term culture and resulted in more predictable resorption profiles when implanted in vivo. Conclusions. The crosslinking approach described here is tunable and functional across different patient samples. Improving the structural properties of lipoaspirate through minimal manipulation has clinical utility for the delivery of grafts with higher shape fidelity and therefore increased graft survival when implanted

Introduction. Anterior cruciate ligament (ACL) injuries represent a significant burden of disease to the orthopaedic surgeon and often necessitate surgical reconstruction in the presence of instability. The hamstring graft has traditionally been used to reconstruct the ACL but the quadriceps tendon (QT) graft has gained popularity due to its relatively low donor site morbidity. Methods. This is a single centre comparative retrospective analysis of prospectively collected data of patients who had an ACL reconstruction (either with single tendon quadrupled hamstring graft or soft tissue quadriceps tendon graft). All surgeries were performed by a single surgeon using the All-inside technique. For this study, there were 20 patients in each group. All patients received the same post-operative rehabilitation protocol and were added to the National Ligament Registry to monitor their patient related outcome scores (PROM). Results. The average age of patients in the QT group was 29 years (16 males, 4 females) and in the hamstring group was 28 years (18 males, 2 females). The most common mechanism of injury in both groups was a contact twisting injury. There were no statistical differences between the two patient groups in regards to PROMS and need for further revision surgery as analysed on the National Ligament Registry. Conclusions. The all soft tissue QT graft seems to be equivocal to quadrupled hamstring graft in terms of patient function and recovery graft characteristics. Further research may be needed to elucidate the long-term results of the all soft tissue QT graft given its recent increase in use

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

Abstract. Objectives. The patella tendon (PT) is commonly used as a graft material for anterior cruciate ligament reconstruction (ACLR). The function of the graft is to restore the mechanical behaviour of the knee joint. Therefore, it is essential that a robust methodology be developed for the mechanical testing of the PT, as well as for the tissue engineered grafts derived from this tissue. Our objectives were to (1) survey the literature, in order to define the state-of-the-art in mechanical testing of the PT, highlighting the most commonly used testing protocols, and (2) conduct validation studies using porcine PT to compare the mechanical measurements obtained using different methodological approaches. Methods. A PubMed search was performed using a boolean search term to identify publications consisting of PT tensile testing, and limited to records published in the past ten years (2010–2020). This returned a total of 143 publications. A meta-analysis was undertaken to quantify the frequency of commonly used protocol variations (pre-conditioning regime, strain rates, maximum strain, etc.). Validation studies were performed on porcine PT (n=4) using Instron tensile testing apparatus to examine the effect of preconditioning on low-strain (toe-region) mechanical properties. Results. Ramp-to-failure testing was found to be most commonly performed (included in over 90 % of publications), followed by stress relaxation and cyclic testing (∼25 %). Preconditioning was most commonly cyclic (27 %), involving 10–100 cycles. Validation studies show the number of cycles and duration of preconditioning, has no significant effect on toe region transition strain, transition stress, or sensitivity to increasing strain. Conclusions. There is a lack of standardisation in the mechanical testing of PT, which could have implications for the comparison of studies conducted using different protocols. However, variations in preconditioning regime have no effect on low-strain mechanical properties

Blood transfusion, organ and bone marrow transplantation and allogeneic tissue grafting create the potential for significant immunological challenges through the introduction of non-genetically identical major (HLA) and minor histocompatibility antigens (“allo-antigens”) into the body. Strategies to avoid the complications of immune responses against allo-antigens (transfusion reactions, rejection and graft versus host disease) include HLA matching, immunosuppressive therapies and immune tolerance promoting protocols. In the case of allogeneic mesenchymal stem/stromal cells (allo-MSC), it was initially believed that their combined properties of low HLA expression and inherent immune modulatory functions would render them invisible to the host immune system and, therefore, capable of being permanently accepted without further interventions. For clinical indications such as bone and tendon repair, in which permanent engraftment of allo-MSC or MSC-derived tissue constructs is particularly desirable, this model of “immune privilege” seemed almost too good to be true – and indeed, a decade of experimental research in this area has now convincingly demonstrated that allo-MSC typically elicit cellular (T-cell) and humoral (B-cell/antibody) immune responses in immunocompetent hosts – raising concern about their safety and long-term efficacy in human conditions. However, questions related to the immunogenicity of allo-MSC have evolved beyond a simple yes/no scenario to involve interesting observations and concepts about the potency, diversity, duration, functional characteristics and even potential clinical benfits of immunological responses to allo-MSC. In this presentation, I will summarise and critically evaluate current understanding of allo-MSC immunogenicity under experimental and clinical trial conditions with an emphasis on the implications for orthopaedic therapeutics

Collagen materials are extensively used in regenerative medicine. However, they still present limitations such as a mono-domain composition and poor mechanical properties. On the other hand, tissue grafts overcome most of these limitations. In addition, the potential of tissue grafts in musculoskeletal tissue engineering has not been fully investigated. Herein, we ventured to assess the potential of a decellularised porcine peritoneum for musculoskeletal applications by comparing its characteristics with a commercial collagen scaffold employed in tendon. Results indicated that the porcine peritoneum had higher mechanical properties and a lower crosslinking ratio (p < 0.01). Furthermore, it presented a lower resistance to collagenase digestion, which suggests a faster remodelling in vivo of the tissue graft. Immunohistochemistry analysis showed a preserved and multicomponent structure in the porcine peritoneum contrary to the collagen matrix, confirming the multifunctional nature of the tissue graft. Regarding the cell-response assessment, tenocytes and ADSCs were able to grow on both materials, however, proliferation was enhanced by the porcine peritoneum (p<0.01). Immune response by THP-1 showed an acute inflammatory response by macrophages to the collagen matrix, contrary to that observed in the porcine peritoneum which triggered a mild reaction. The in-progress in vivo study in a rabbit tendon model will elucidate the potential of porcine peritoneum for tendon repair applications. The present study shows how the multifunctionality of the porcine peritoneum provides higher cytocompatibility than a mono-domain collagen matrix with human tenocytes and ADSC. Besides, its lower immune response in vitro suggests better remodelling after implantation

Summary. Tissue grafts fail to recapitulate native tendon function, imposing the need for development of functional regeneration strategies. Herein, we describe advancements in tendon repair and regeneration using functionalised natural and synthetic devices and scaffold-free cell-based therapies. Introduction. Tendon and ligament injuries constitute an unmet clinical need with approximately 100,000 new cases annually in US alone. Tissue grafts are considered the gold standard in clinical practice. However, allografts and xenografts can lead to potential disease transmission, whilst the limited supply of autografts in severe injuries and degenerative conditions restricts their use. To this end, scaffold and scaffold-free therapies are under development to address the tissue grafts shortage. Herein, we describe biophysical, biochemical and biological methods to maintain tendon derived cell phenotype and/or differentiation of other cell types towards tenogenic lineage; development of tendon-equivalent facsimiles; and ultimately functional neotendon formation. Materials and Methods. Growth factor supplementation was assessed as means to either maintain tendon derived stem cell phenotype or differentiate them towards tenocytes. The influence of conditioning media was assessed as means to differentiate skin fibroblasts and stem cells towards tenogenic lineage. Biophysical and biochemical/biological features were assessed as means to maintain tendon derived cell phenotype and directional neotissue formation in rat patellar tendon model. Rich in tendon-specific extracellular matrix cell sheets were produced by appropriate modulation of the in vitro microenvironment. Structural, biophysical and biological analyses were subsequently carried out. Discussion & Future Studies. Treatment with 10 and 100 ng/mL of IGF-1 preserved tendon stem cell multipotency for up to 28 days in culture and minimised changes in marker expression and extracellular matrix molecules production enhancing that way the clinical potential of these cells. Hierarchically assembled collagen scaffolds and anisotropically ordered polymeric substrates of rigidity similar to native tendons facilitate tenocyte phenotype maintenance in vitro, whilst in vivo studies are under way to assess the extent of functional tendon regeneration. Appropriate modulation of the in vitro microenvironment of tenocytes with macromolecules enhances tendon specific extracellular matrix deposition within 6 days in culture, facilitating that way the wide acceptance of cell-sheet technology for tendon repair and regeneration

Summary Statement. A biomimetic tissue engineering strategy involving culture on bone scaffolds in perfusion bioreactors allows the construction of stable, viable, patient-specific bone-like substitutes from human induced pluripotent stem cells. Introduction. Tissue engineering of viable bone substitutes represents a promising therapeutic strategy to mitigate the burden of bone deficiencies. Human induced pluripotent stem cells (hiPSCs) have an excellent proliferation and differentiation capacity, and represent an unprecedented resource for engineering of autologous tissue grafts, as well as advanced tissue models for biological studies and drug discovery. A major challenge is to reproducibly expand, differentiate and organize hiPSCs into mature, stable tissue structures. Based on previous studies (1,2,3), we hypothesised that the culture conditions supporting bone tissue formation from adult human mesenchymal stem cells (hMSCs) and human embryonic stem cell (hESC)-derived mesenchymal progenitors could be translated to hiPSC-derived mesenchymal progenitors. Our objectives were to: 1. Derive and characterise mesenchymal progenitors from hiPSC lines. 2. Engineer bone substitutes from progenitor lines exhibiting osteogenic potential in an osteoconductive scaffold – perfusion bioreactor culture model. 3. Assess the molecular changes associated with the culture of hiPSC-progenitors in perfusion bioreactors, and evaluate the stability of engineered bone tissue substitutes in vivo. Methods. hESC and hiPSC lines (derived using retroviral vectors, Sendai virus and episomal vectors) were karyotyped, characterised for pluripotency and induced into the mesenchymal lineage. Mesenchymal progenitors were evaluated for growth potential, expression of surface markers and differentiation potential. Progenitors exhibiting osteogenic potential were cultured on decellularised bovine bone scaffolds in perfusion bioreactors for 5 weeks as previously (3). Global gene expression profiles were evaluated prior and after bioreactor culture. Bone development was investigated using biochemical and histological methods, and by micro-computed tomography (μCT) imaging over the duration of bioreactor culture and after 12-week subcutaneous implantation in immunodeficient mice. Results. Progenitors with high proliferation potential, expressing typical mesenchymal surface antigens were successfully derived from three hiPSC lines. Differences in mesenchymal surface antigens expression and global gene expression profiles of progenitors from different lines corresponded to their differentiation abilities toward the osteogenic, chondrogenic and adipogenic lineages. Bioreactor culture yielded constructs with significantly higher cellularity, AP activity and osteopontin release into the culture medium as compared to static culture. Dense bone matrix formation was evidenced by the positive staining of collagen, osteopontin, bone sialoprotein and osteocalcin. In comparison, static culture yielded constructs with uniformly distributed cells, however tissue formation was scarce. μCT revealed a significant increase in bone structural parameters, evidencing mineralization of the deposited bone tissue during the 5-week culture in bioreactors. Osteogenesis and bone tissue formation were comparable between hESCs, hiPSCs and hMSCs (3). Bioreactor cultivation resulted in repression of genes involved in proliferation and tumorigenesis, and upregulation of genes associated with osteogenesis and bone development. Engineered bone tissue displayed stable phenotype after 12-week implantation in vivo, with cells of human origin, ingrowing vasculature and osteoclasts, suggesting an initiation of tissue remodeling. Discussion/Conclusion. Our biomimetic strategy opens the possibility to construct an unlimited quantity of patient-specific bone grafts for personalised applications, and to generate qualified experimental models to study bone biology under normal and pathological conditions, as well as test new drugs using selected pools of hiPSC lines

We investigated whether strontium-enriched calcium phosphate cement (Sr-CPC)-treated soft-tissue tendon graft results in accelerated healing within the bone tunnel in reconstruction of the anterior cruciate ligament (ACL). A total of 30 single-bundle ACL reconstructions using tendo Achillis allograft were performed in 15 rabbits. The graft on the tested limb was treated with Sr-CPC, whereas that on the contralateral limb was untreated and served as a control. At timepoints three, six, nine, 12 and 24 weeks after surgery, three animals were killed for histological examination. At six weeks, the graft–bone interface in the control group was filled in with fibrovascular tissue. However, the gap in the Sr-CPC group had already been completely filled in with new bone, and there was evidence of the early formation of Sharpey fibres. At 24 weeks, remodelling into a normal ACL–bone-like insertion was found in the Sr-CPC group. Coating of Sr-CPC on soft tissue tendon allograft leads to accelerated graft healing within the bone tunnel in a rabbit model of ACL reconstruction using Achilles tendon allograft.

Cite this article: Bone Joint J 2013;95-B:923–8.

Anterior cruciate ligament (ACL) injuries are being seen with increasing frequency in children. Treatment of the ACL deficient knee in skeletally immature patients is controversial. To determine the outcome of anatomic transphyseal ACL reconstruction in tanner stage 1 and 2 patients with open growth plates at a minimum of 2 years after surgery. Between 2007–2008, 16 prepubescent skeletally immature patients underwent anatomic transphyseal ACL reconstruction using soft tissue grafts. All patients were tanner stage 1 and 2 and all had open growth plates. Outcomes were assessed at a minimum of 2 years after surgery and included: limb alignment, limb length, instrumented testing with KT-1000 and International Knee Documentation Committee (IKDC) score. Mean age at the time of surgery was 12 years (8–14). Graft choices included: living-related donor hamstring tendon allograft (n=14), hamstring tendon autograft (n=1) and fresh frozen allograft (n=1). Mean IKDC subjective score was 96 (84–100). Sixty-two percent of patients had <3mm side-to-side difference on instrumented KT-1000 testing and 88% had a negative pivot shift. At 2 years after surgery, all patients had returned to strenuous activities and normal or nearly normal overall IKDC score was documented in 94% of patients. There were no cases of limb malalignment or growth arrest. We present a large series of anatomic transphyseal ACL reconstruction in tanner stage 1 and 2 patients with open growth plates at a minimum of 2 years following surgery. Excellent clinical outcomes were obtained with high levels of return to desired activities. Importantly, no growth disturbances were seen in this series of patients

The key factors in Tissue Engineering are multipotent stem cells, growth factors (necessary to manipulate cell destiny) and scaffolds (3D constructs which support the growing tissue). Mesenchymal stem cells are the most important part of this equation, and it is procurement and manipulation of these that lies at the heart of tissue engineering. Luckily, mensenchymal stem cells can be obtained from many tissues, including synovium, bone marrow and periosteum. The use of bioreactors to optimise culture conditions and improve cell viability provides an opportunity to control stem cell destiny. Various Tissue Engineering strategies exist: manipulating cells in situ with osteogenic growth factors, such as BMP; implanting whole tissue grafts; and the use of Gene therapy. The tissues that concern orthopaedic surgeons are very diverse and no single tissue engineered construct will be able to fulfil all our clinical needs. Tissue engineering of articular cartilage is very difficult technically, but once accomplished will revolutionalise practice. The challenge lies in being able to produce cartilage as similar to native hyaline cartilage as possible. Although promising, ACI, using culture expanded cells, is able at best to produce hyaline-like cartilage but not the real thing. Multipotent mesenchymal stem cells are being used in this field. Even simply injecting these intraarticularly has been shown to retard the progression of OA in animal models. When attempting to regenerate meniscal cartilage, the mechanical properties of the scaffold become crucial, as the biomechanics of the knee are highly hostile. Ligaments and tendons, though the least complex tissues architecturally, have very high tensile properties which will be hard to replicate. The challenging aspects of Orthopaedic Tissue Engineering are manifold, yet the field itself is growing in leaps and bounds. Despite some initial setbacks, the new developments in this discipline are very encouraging

Introduction: Chronic ruptures of the distal biceps tendon are relatively infrequent and are complicated by the retraction of the tendon and extensive scar formation, which preclude satisfactory repair. Bibliographical data presents different surgical procedures for the reconstruction of chronic ruptures using allograft soft-tissue constructs with varying results. The purpose of this study was to describe the surgical technique for reconstruction of the tendon with local soft tissue as graft and to report our experience with this procedure. Methods: 17 patients with an average age of 54 years underwent surgical reconstruction of a chronic disruption of the distal biceps tendon. The mean interval between tendon rupture and reconstruction was 14 months. In all patients a flap from lacertus fibrosus was used in continuation with the remnants of the tendon. A based distally strip of the biceps was reversed and entubulated in the lacertous fibrosus flap and the whole construct was then advanced to the bicipital tuberosity. The biceps was released and mobilized as necessary. In addition, 3 patients underwent a fractional lengthening of the muscle. All procedures were performed through a single anterior approach. Anchors and anchor sutures were used to stabilize the tendon to the tuberosity. Results: After an average duration of follow-up of 3.5 years, all patients had an excellent subjective result and they had all returned to their previous occupation. Furthermore, the strength of flexion and supination was comparable with that on the contralateral side in 13 patients. According to the Mayo Elbow performance score, the results were excellent in 9 patients, good in 4 and fair in 4. Complications that were encountered included a superficial infection which resolved with oral antibiotics, a transient median nerve palsy and a case of puncture wound of the brachial artery. Conclusions: The aforementioned technique yields satisfactory postoperative results for this challenging problem with almost equal development of force and functionality on both sides and with a minimal possibility of re-rupture

Anterior Cruciate Ligament (ACL) reconstruction is a well established procedure for restoration of stability following ACL rupture. Several methods exist for fixation of soft tissue grafts on the tibia, without general agreement about the optimal method. This study compared two different methods of tibial fixation using hamstring grafts in ACL reconstruction. 113 consecutive patients were randomized into two groups at the time of surgery. In group one, fixation was with a metal interference screw (RCI) and staples and in group two, with a polyethylene screw and sheath (Intrafix). Evaluation of outcomes was conducted using KT-1000 arthrometer, Lysholm, IKDC subjective and Mohtadi scores. 7 reinjuries occurred within the time frame of the study, mostly related to sporting injuries, with 5 in group 2. 81% of remaining participants were successfully followed at 2 years post surgery. No significant difference in mean KT-1000 side-to-side measurements was found between groups at an average follow-up of 30 months (1.5 ± 1.9mm and 1.8 ± 1.9mm, respectively; p > 0.05). The mean Lysholm score for group one was 65.2 ± 15.5 preoperatively and 90.8 ± 9.5 postoperatively; for group two these scores were 62.0 ± 20.7 preoperatively and 88.8 ± 14.3 postoperatively. This improvement in scores after surgery was similar for both groups and was not significantly different between groups (p > 0.05). Both the IKDC subjective and Mohtadi scores showed significant (p < 0.05) improvements postoperatively compared with pre-operatively but no significant difference between fixation groups. There were no significant differences between the two groups for any outcome value, with both methods of graft fixation producing good results. The newer Intra-fix device had a higher reinjury rate but this was not significantly different from the screw and staple fixation, and on all other outcome measures the Intrafix device was equivalent to an interference screw and staples for tibial-sided graft fixation in ACL reconstruction

A seventy-one-years old, female, has been treated by hemodialysis from 1977 due to renal failure. In April 19, 1985, she had Charnley Low Friction Arthroplasty for right hip joint. She often felt mild pain on the joint from 2000. Radiograph showed central migration of the socket and huge cystic bone defect of the acetabulum surrounded by thin cortical bone like an egg-shell form. Tear drop (acetabular floor) was diminished due to massive bone destruction or severe osteolysis. CT showed that the diameter of the cavity was approximately 10 cm. In March 1, 2002, the socket was upside down and moving freely in the cavity. The patient could not weight-bear on right lower extremity but walk without two crutches. Hemiarthroplasty for her left hip joint (contra-lateral side) was done in June 26, 2006, due to femoral neck fracture. Because of continuous right hip joint pain and walking disturbance, she underwent revision surgery in May 20, 2008. At the surgery, the cavity was empty except for the socket and fibrous tissue. Impaction grafting by using morselized allograft including porous and solid hydroxyapatite granules (100 g and 40 g each) was done after the socket and the tissue were extracted. A custom made all polyethylene socket (73 × 68 mm in diameter) was fixed by polymethylmetacrylate bone cement. Postoperative course was uneventful. She can walk with one crutch and ride on/off a vehicles without help four months postoperatively. It is often difficult to reconstruct acetabulum with large bone defect in revision total hip arthroplasty. Especially, almost of support rings with hook cannot be applied in the case that the tear drop is destructive or absorbed. Impaction bone grafting is commonly used for reconstruction of bone defect in revision surgery. However, the extremely thick graft for large bone defect is at risk of collapsing lead to implant migration. The socket used in the case was custom made jumbo type to reduce the thickness of impaction grafting. It seems to be one of resolution to use the custom made jumbo socket for the case with large defect of acetabulum in revision total hip Arthroplasty

Purpose: B2A2-K-NS (B2A) is a synthetic receptor-targeted peptide that appears to amplify the biological response to rhBMP-2. In ectopic sites in vivo, B2A augments bony mineralization when combined with demineralized bone matrix. The purpose of this study was to determine if the synthetic peptide B2A2-K-NS coated on osteoconductive granules (B2A/G) enhances autograft fusion in a rabbit bilateral posterolateral spine fusion model. Method: Sixty skeletally mature New Zealand White Rabbits weighing 4.5–5.5 kg were entered into the study (IACUC #0511251). A single-level, bilateral posterolateral intertransverse process fusion was performed at L4-L5 with autogenous bone or an osteoconductive granule containing several coating concentrations of B2A. Animals were euthanized at 6 weeks post surgery. Results: Gross examination of the surrounding soft tissues and grafted area showed no adverse reactions to the osteoconductive granules with or without B2A. Radiographic fusion rates were similar to palpation fusion rates across all groups. When assessed by palpation, animals treated with 300 μg B2A/G had 80% fusion while those treated with 100 μg B2A/G (89%) and 50 μg B2A/G had 78% fusion. Animals receiving 0 μg B2A/G (granules only) had a fusion rate of 33% and autograft only animals had a fusion rate of 63%. Conclusion: In this model the B2A/G composition appeared to function as a graft enhancer and be more efficacious than autograft alone in this model. B2A peptide has a unique mechanism of action in that although it interacts with receptors for BMP-2, the action is mediated only in the presence of BMP-2 or an osteoinductive event. In this model, the decorticated TP and/or autogenous bone may have provided the necessary signals for B2A. These results suggest that B2A/G should be further investigated to determine mechanistic effects and clinical applications

We hypothesised that meniscal tears treated with mesenchymal stem cells (MSCs) together with a conventional suturing technique would show improved healing compared with those treated by a conventional suturing technique alone. In a controlled laboratory study 28 adult pigs (56 knees) underwent meniscal procedures after the creation of a radial incision to represent a tear. Group 1 (n = 9) had a radial meniscal tear which was left untreated. In group 2 (n = 19) the incision was repaired with sutures and fibrin glue and in group 3, the experimental group (n = 28), treatment was by MSCs, suturing and fibrin glue.

At eight weeks, macroscopic examination of group 1 showed no healing in any specimens. In group 2 no healing was found in 12 specimens and incomplete healing in seven. The experimental group 3 had 21 specimens with complete healing, five with incomplete healing and two with no healing. Between the experimental group and each of the control groups this difference was significant (p < 0.001).

The histological and macroscopic findings showed that the repair of meniscal tears in the avascular zone was significantly improved with MSCs, but that the mechanical properties of the healed menisci remained reduced.

Introduction: It is well known that the fate of biomaterials is determined by the distribution of proteins attached to the surface from the initial contact with blood or serum. This profile determines wether a material is inert, creates a foreign body response or is bioactive. Bioinert materials, such as polyethylene completely denature surface proteins, whilst materials inducing inflammatory responses are predisposed to complement protein attachment. Bioactive materials such autologous tissue grafts adsorb, but do not denature serum proteins such as fibronectin and Von Willebrand’s factor. This does not interfere with the healing cascade. This aim of this study is to prepare a synthetic bone graft substitute that activates the body’s autologous healing cascade by activating platelets, without activating a complement response through the controlled adsorption of serum proteins. Methods: Polymers composed of varied concentration of acrylic acid (AA) and comonomers (methyl, ethyl and butyl methacrylates (MMA, EMA, BMA)) were prepared in glass vials by free radical polymerisation. Fresh blood was collected from a healthy donor and pipetted immediately into each chamber. Glass was used as a control. The chambers were incubated at 37o C for 2 hours. The surface morphology was examined using Scanning Electron Microscopy (SEM). Concentration of complement protein C5a and prothrombin fragments 1 and 2 were determined using commercial ELISA kits. Foreign body reaction (FBR) initiated by the biomaterial was estimated by counting leukocytes on clot sections using immunofluorescence. Results: Extent of coagulation was correlated with plasma concentrations of Prothrombin fragments 1 and 2. These measurements show blood incubated with various polymers composed of different comonomers all promoted the formation of blood clots. It was found that the leukocyte population towards the interface of clot and polymer (AA:MMA) decreased with increasing surface acid concentration (65%AA:MMA 30 leukocytes/0.25mm2, glass 70 leukocytes/0.25mm2 (p< 0.05)). FBR is induced by the activation of complement system. The percentage of C5a concentration detected in blood incubated with various polymers composed of different comonomers relative to normal serum level of C5a (35ng/mL). No significant elevations of C5a were measured from polymer 65% AA:MMA and 65% AA:EMA. Glass induced vigorous complement response as expected. The synergistic combination of surface acid concentration and comonomers had a significant effect on extent of FBR. Increased acid concentration resulted in decreased C5a level with MMA and ET but increased level with BMA. Discussion: The functional groups exposed on the surface of a material influence whether leukocyte or platelet activation is responsible for the subsequent physiological response. By modifying the combinations of surface acid concentrations and comonomers, we show that a biomaterial with an appropriate surface chemistry promotes the platelet plug formation and coagulation but down regulated foreign body reaction. This study shows that that a biomaterial with the appropriate surface chemistry to evoke the same coagulation response as damaged tissue, mediated through platelet activation and intrinsic and extrinsic coagulation, initiates the initial pathways of the bone healing cascade. This material is a realistic candidate for biomaterial induced bone regeneration

Aims: Free vascularized fibular graft for osteonecrosis of the femoral head is a well established procedure based on the assumption that the graft will provide mechanical support, blood supply to the osteonecrotic head and to introduce mesenchymal stem cells into the affected area of the femoral head. Methods: We reviewed 25 cases to delineate the pathological features of femoral heads with AVN treated by vascularised fibular grafts which were retrieved at revision surgery when the construct was deemed clinically to have failed. Results: Review of the patients’ records disclosed that 60.8% were on steroid therapy when the AVN was diagnosed. The recorded time from first symptoms of failure to conversion to total hip arthroplasty was an average of 55 months. The length of the graft was divided into three zones : zone 3 the femoral neck; zone 2 the lower femoral head or “metaphysis”; zone 1 the more apical or epiphyseal component of the femoral head. The intention was to follow the vascularization of the pedicle and the changes in the three diverse areas of the specimen. The graft showed incorporation with the host bone. In the pedicle there was preservation of vascular patency and tissue viability. Conclusion: However, this healing process involved a slow reparative resorptive activity which undermined the joint surface. This could suggest that non-resorbable materials in place of tissue grafts can be expected to avoid the negative effect of creeping substitution as an undermining force in the repair and revascularisation of the necrotic area in the head

We attempted to repair full-thickness defects in the articular cartilage of the trochlear groove of the femur in 30 rabbit knee joints using allogenic cultured chondrocytes embedded in a collagen gel. The repaired tissues were examined at 2, 4, 8, 12 and 24 weeks after operation using histological and histochemical methods. The articular defect filling index measurement was derived from safranin-O stained sections. Apoptotic cellular fractions were derived from analysis of apoptosis in situ using TUNEL staining, and was confirmed using caspase-3 staining along with quantification of the total cellularity. The mean articular defect filling index decreased with time. After 24 weeks it was 0.7 (sd 0.10), which was significantly lower than the measurements obtained earlier (p < 0.01). The highest mean percentage of apoptotic cells were observed at 12 weeks, although the total cellularity decreased with time. Because apoptotic cell death may play a role in delamination after chondrocyte transplantation, anti-apoptotic gene therapy may protect transplanted chondrocytes from apoptosis.