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

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

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

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

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

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

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.

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

Aim: To determine the intra operative biomechanical properties of a semitendinosus graft used in ACL reconstruction. Introduction: ACL reconstruction has become a commonly performed operation with 1,139 of these procedures being performed in South Australia in 1997 (SA Health Commission). The majority of the scientific literature is based on data obtained from elderly cadaveric material. Little is known about the biomechanical properties of the soft tissue grafts currently used prior to implantation. The correct preconditioning and intraoperative tensioning of the soft tissue grafts has also not been investigated. The initial graft biomechanical properties are important. Inadequate tension will lead to continuing instability whilst excessive tension may cause accelerated joint arthrosis. The tension in the graft may decrease by 30% if it has not been cyclically pretensioned. Methods: A machine has been designed that will allow the intraoperative biomechanical testing of soft tissue grafts immediately prior to their implantation into the patient during ACL reconstruction. Data will be available on creep, stress relaxation, and tensile testing. This device will also allow the accurate preconditioning of the graft, providing objective data that can then be compared to the subsequent clinical progress of the patient. All testing will be accomplished during the time it takes to prepare the tunnels for insertion of the graft, and as such will not prolong unnecessarily the operative time. Procedure: Once the graft has been prepared prior to fixation, it will be placed between two clamps. One is fixed to a load cell whilst the other is coupled to a linear actuator. The linear actuator will be driven by a computer controlled stepper motor under close-loop control. Custom software will cyclically load the autograft between two definable load points. A linear variable differential transformer (LVDT) will be used to monitor displacement of the autograft and load will be monitored with a load cell of capacity 125Kg. This set-up will be immersed in a saline water bath maintained at body temperature during testing. The load cell will be hermetically sealed, with clamps and water bath being autoclavable. With the facilities for draping, the test area will remain sterile. The auto graft clamps will be designed to allow fixation of various graft materials (eg semitendinosus, gracilis, bone-patella tendon-bone) and adjustable for graft lengths. The water bath will house a thermocouple, heating mat and controller to maintain the saline temperature to within 1°C. The testing system will be mounted on a stainless steel trolley for mobility in the operating room with an underlying shelf to house the associated electronics and a retractable side draw for storage of the laptop computer. The autograft will be preconditioned between two known loads for 20 cycles recording load and displacement simultaneously on a laptop computer. Once preconditioned, the autograft will then be used for the ACL reconstruction in the standard way. Summary: Objective data on preconditioning of ACL grafts, has never before been available intra-operatively. We outline the experimental set-up which has been designed and is undergoing testing prior to its use in a prospective study

Aims: Serial dilation of the walls of the bone tunnel has been advocated to provide more dense bone-tunnel walls and optimal conditions for rigid fixation in anterior cruciate ligament (ACL) reconstruction with soft tissue grafts. The aim of this study was to compare the initial fixation strength obtained using serial dilation versus conventional extraction drilling in ACL reconstruction. Methods: Initial strength of doubled anterior tibialis tendon grafts fixed with bioabsorbable interference screw was assessed in 21 pairs of human cadaver tibiae. Bone tunnels were created with either serial dilation or conventional extraction drilling (cannulated drill bits). The specimens were subjected to a cyclic-loading test (1500 loading cycles between 50 and 200 N at 0.5 Hz frequency). The specimens surviving the cyclic-loading test were loaded to failure at a rate of 1.0 m/min (single-cycle load-to-failure test). Results: During the cyclic-loading test, no significant stiffness or displacement differences were observed between the two bone-tunnel techniques. Three specimens failed in the serial-dilation group, while there were six failures in the extraction-drilling group. In the subsequent single-cycle load-to-failure test, the average yield load was 473 ± 110 N for the serial-dilation group and 480 ± 115 N for the extraction-drilling group (P=0.97). No significant difference between the two bone-tunnel techniques was found with regard to stiffness nor mode of failure. Conclusions: Serial dilation of the bone-tunnel walls does not increase the initial fixation strength of soft tissue grafts in ACL reconstruction

Current issues being debated in ACL reconstruction include injury prevention, graft choice, graft positioning, graft fixation, graft remodelling and rehabilitation. Tissue engineering, the alteration of biological mechanisms by application of novel proteins, enzymes and hormones, is rapidly changing the way we approach all aspects of surgery. Tissue engineering techniques in ACL/PCL reconstruction focus on new biosynthetic ACL material, fixation of soft tissue grafts to bony tunnels and graft remodelling. OP-1 is recombinant human Osteogenic Protein 1 (BMP-7). It is a member of the Transforming Growth Factor β (TGFβ) super family. OP-1 promotes the recruitment, attachment, proliferation and differentiation of pluripotential mesenchymal stem cells. It promotes both osteogenesis and chondrogenesis. The carrier is highly purified bovine bone type 1 collagen, which provides an osteoconductive matrix. We have completed a study assessing the use of OP-1 as a means of enhancing early biological fixation of soft tissue grafts within bone tunnels in a sheep ACL model. We have commenced a clinical trial using OP-1 in adult ACL reconstruction, believing that OP-1 will enhance early biological graft fixation, and hence, improve clinical results, speed up rehabilitation and prevent tunnel widening. Other studies have shown the beneficial effects of BMP-2 on an extraarticular bone tendon fixation model, the use of TGF-B to enhance graft remodelling and the application of gene therapy to deliver BMP’s for enhanced graft fixation. Several projects are underway looking at creating biosynthetic ACL grafts using tissue engineering techniques. As opposed to purely synthhetic grafts, bioACL grafts are made of a collagen scaffold, allowing for remodelling and revascularisation. ACL reconstructive surgery is constantly evolving. Tissue engineering may provide us with a means of minimising morbidity, accelerating rehabilitation and improving the clinical outcome following this common surgery

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

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

Composite tissue defects in absence of general contra-indications are now routinely dealt by composite free tissue transfers which now stand as routine procedures. When dealing with amputations of the thumb several reconstructive procedures are now available and should be tailored on individual basis. Microvascular surgical techniques are especially gratifying when the appropriate indications are followed: young age, absence of systemic diseases no alcohol or smoke abuse. A custom – made thumb can be reconstructed assembling in a single composite tissue graft different tissues harvested from various parts of the body. An outcome study as been performed on 72 patients where the wrap-around technique, the second and great toe transfer have been carried out. Overall assessment included, as a preliminary analysis, the of vassessement behaviour of each single transferred tissue: the nail complex, the pulp and the bone. Donor – site problems at the foot were assessed by gait analysis. Vascular complications were recorded in 5% of the patients, and 89% of the patients had excellent outcomes

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

Introduction and purpose: Cortical strut autografts provide primary stability to resolve fractures or pseudoarthrosis associated with major bone loss, or fractures close to joint prostheses. Materials and methods: We present 8 cases in which strut autografts were used: one pseudoarthrosis of the humerus, three periprosthetic fractures in TKR and four fractures associated with hip prosthesis surgery. We resolved the humeral pseudoarthrosis with struts and a PCL plate plus cancellous tissue graft. For the periprosthetic fractures of the knee and hip we used revision prostheses with extension stems plus struts, held in place with cerclage wires or compression bands, with or without plates. In all cases functional rehabilitation started early. The mean non-weight-bearing period for lower limbs was 10 weeks (8–12 months). Results: Primary stability made it possible to begin rehabilitation early in all cases. Total consolidation of the grafts in a mean time of 5 months (4–7 months), with complete recovery of bone stock. Excellent functional outcome with full return to daily activity as before surgery. Conclusions: The use of strut autografts associated with osteosynthesis and/or revision prosthesis implantation makes it possible to resolve cases that require a large amount of bone graft and provides sufficient primary stability for fast rehabilitation. The proper final consolidation of the grafts and complete recovery of bone stock provides stability with full guarantee of long-term success

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

The choice of treatment for open fractures is conditioned by the care of bone and soft tissue. Grade I open fractures can be treated as closed fractures, according to the centre’s protocol. In Grade II open fractures skin wounds must be left open, and the suture should be delayed for at least a week. Most authors perform fixation by means of intramedullary nails. In our opinion, external fixation is the best choice in these cases. The skin cannot be closed in Grade III open fractures, and the basic point of treatment is adequate surgical debridement. The fixation must be done by external fixation. To achieve the treatment in an emergency situation, the device to be used must be quick and simple like a monolateral device that can be changed into a more complex one, such as an Ilizarov. The Ilizarov technique uses distractional osteogenesis that can fill bone and soft tissue loss without further bone or soft tissue grafting. Following these general guidelines, each district has its own particular approach to treating open fractures. Internal fixation by DCP plates is always indicated for forearm fractures. For a humerus fracture, simple direct shortening and external fixation can fill bone loss. Patients with fractures of the femur usually have multiple injuries. The problem is to provide a quick fixation in order to allow for easier intensive care. External fixation is the most indicated technique