Articular cartilage is often damaged, and its treatment is usually performed by surgical operation. Today, tissue engineering offers an alternative treatment option for injuries or diseases with increasing importance. Infrapatellar fat pad (IPFP) is a densely vascularized and innervated extra synovial tissue that fills the anterior knee compartment. Adipose-derived stem cells from infrapatellar fat pad (IPFP-ASCs) have multipotency means that they can differentiate into connective tissue cells and have age-independent differentiation capacity as compared to other stem cells. In this study, the osteochondral tissue construct was designed with different inner pattern due to original osteochondral tissue structure and fabrication of it was carried out by 3D printing. For this purpose, alginate (3% w/v) and carboxymethylcellulose (CMC) (9%w /v) were used as bioink. Also, IPFP-ASCs were isolated with enzymatic degradation. Osteogenic and chondrogenic differentiation of IPFP-ASCs were investigated with Alizarin Red and Alcian Blue staining, respectively. IPFP-ASCs-laden osteochondral graft differentiation will be induced by controlled release of growth factor BMP-2 and TGF-β. Before this step, nanocapsules formation with double emission technique with model protein BSA was carried out with different concentration of PCL (5%,10% and 20%). The morphology and structure of the nanocapsules were determined with scanning electron microscopy (SEM). Also, we successfully designed and printed alginate and CMC based scaffold with 20 layers. Chondrogenic and osteogenic differentiation of IPFP-ASCs with suitable culture conditions was obtained. The isolation of IPFP-ASCs, formation of the nanocapsules, and 3D printing of osteochondral graft were carried out successfully

Autologous osteochondral transplantation (AOT) is an effective treatment for large Osteochondral Lesions of the Talus (OLT), however little is reported on an athletic population, who are likely to place higher demands on the reconstruction. The aim is to report the outcomes of large OLT (>150mm. 2. ) within an athletic population. The study population was limited to professional or amateur athletes (Tegner score >6) with an OLT of size 150mm. 2. or greater. The surgical intervention was AOT with a donor site from the lateral femoral condyle. Clinical outcomes at a minimum of 24 months included Return to Sport, VAS and FAOS Scores. In addition, graft incorporation was evaluated by MRI using MOCART scores at 12 months post-surgery. 38 athletes including 11 professional athletes were assessed. Mean follow-up was 46 months. Mean lesion size was 249mm. 2. 33 patients returned to sport at their previous level and one did not return to sport (mean return to play 8.2 months). Visual analogue scores improved from 4.53 pre-operatively to 0.63 post-operatively (p=0.002). FAOS Scores improved significantly in all domains (p< 0.001). Two patients developed knee donor site pain, and both had three osteochondral plugs harvested. Univariant analysis demonstrated no association between pre-operative patient or lesion characteristics and ability to return to sport. However, there was a strong correlation between MOCART scores and ability to return to sport (AUC=0.89). Our study suggests that AOT is a viable option in the management of large osteochondral talar defects in an athletic population, with favourable return to sport levels, patient satisfaction, and FAOS/VAS scores. The ability to return to sport is predicated upon good graft incorporation and further research is required to optimise this technique. Our data also suggests that patients should be aware of the increased risk of developing knee donor site pain when three osteochondral plugs are harvested

Introduction. The purpose of this study was to examine trends in patient characteristics and clinical outcomes that occur with age as a statistical variable when performing autologous osteochondral transplantation (AOT) for the treatment of osteochondral lesions of the talus (OLT). Methods. A retrospective cohort study for AOT procedures on 78 patients from 2006 to 2019. was conducted Clinical outcomes were evaluated via FAOS scores. A multivariable linear regression was used to assess the independent factors predictive of the first post-operative FAOS after AOT. The independent variables included pre-operative FAOS, age, defect size, shoulder lesion, cystic lesion, prior traumatic injury, and history of microfracture surgery. A p-value <.05 was considered significant and 95% confidence limits (95% CL) for regression coefficient estimates (est.) were calculated. Results. 78 patients were included with a mean age of 35.5 ± 13.6years at a mean follow-up was 54.4 ± 18.9 months. The mean pre-operative FAOS was 54.3 ± 19.4 and the mean post-operative FAOS was 83.4 ± 13.6. The mean defect size was 109.3±62.4 mm2. The multivariable linear regression showed that the pre-operative FAOS was associated with a higher post-operative FAOS (est., 95% CL: 0.16, 0.012 – 0.307; p=0.034). Defect size (est., 95% CL: −0.05, −0.097 – −0.003; p=0.0358), having a shoulder lesion (est., 95% CL: −9.068, −15.448 – −2.688; p=0.006), or having a prior microfracture surgery (est., 95% CL: −7.07, −13.118 – −1.021; p=0.0226) were associated with a lower post-operative FAOS. Conclusion. Patient age was not an independent risk factor for inferior clinical outcomes after AOT for OLT. Additionally, cystic lesions, or lesions with a traumatic aetiology were not significantly associated with post-operative FAOS. Having a shoulder lesion had the largest marginal effect on post-operative FAOS. These findings provide important information for providers when counseling and selecting patients for AOT procedure for treatment of OLT

Autologous osteochondral grafting has demonstrated positive outcomes for treating articular cartilage defects by replacing the damaged region with a cylindrical graft consisting of bone with a layer of cartilage, taken from a non-loadbearing region of the knee. Despite positive clinical use, factors that cause graft subsidence or poor integration are relatively unknown. The aim of this study was to develop finite element (FE) models of osteochondral grafts within a tibiofemoral joint and to investigate parameters affecting osteochondral graft stability. Initial experimental tests on cadaveric femurs were performed to calibrate the bone properties and graft-bone frictional forces for use in corresponding FE models, generated from µCT scan data. The effects of cartilage defects and osteochondral graft repair were measured by examining contact pressure changes using in vitro tests on a single cadaveric human tibiofemoral joint. Six defects were created in the femoral condyles which were subsequently treated with osteochondral autografts or metal pins. Matching µCT scan-based FE models were created, and the contact patches were compared. Sensitivity to graft bone properties was investigated. The bone material properties and graft-bone frictional forces were successfully calibrated from the initial tests with good resulting levels of agreement (CCC=0.87). The tibiofemoral joint experiment provided a range of cases to model. These cases were well captured experimentally and represented accurately in the FE models. Graft properties relative to host bone had large effects on immediate graft stability despite limited changes to resultant cartilage contact pressure. Model confidence was built through extensive validation and sensitivity testing, and demonstrated that specimen-specific properties were required to accurately represent graft behaviour. The results indicate that graft bone properties affect the immediate stability, which is important for the selection of allografts and design of future synthetic grafts. Acknowledgements. Supported by the EPSRC-EP/P001076

INTRODUCTION. Osteochondral lesions of the knee are relatively common both in young and senior population. The very disabling clinical symptoms, in association to the scarce regenerative capacity of the articular cartilage and the increased risk of developing a secondary osteoarthritis make an effective treatment mandatory. MATERIALS AND METHODS. From December 2008 to January 2013, 34 patients (35 knees), 24 males and 10 females (mean age 36.2 years range 14–66) underwent implant of Maioregen® (Finceramica Faenza S.P.A, Italy) biomimetic osteochondral scaffold. In 17 cases the osteochondral lesion was cause by an osteochondritis dissecans (acute or sequela), in 13 cases by a spontaneous osteonecrosis and in 4 cases the etiology was traumatic. Patients were evaluated with subjective IKDC and Tegner Lysholm scores, VAS and Tegner Activity Scale before surgery and at regular follow up (mean follow up 38.4 months, range 13 months max 63 months). RESULTS. Both Lysholm and IKDC Subjective scores significantly increased from 57.5 and 48.2 before surgery to 89.7 and 76.3 at 1 year follow up. Mean VAS scale score decreased from 6.3 to 2 at 1 year follow up. At 3 years follow up 20 evaluated patients showed an increment on both scales (Lysholm 92.38, IKDC 84.7). Only 4 patients were evaluated at 5 years follow up with mean subjective IKDC 92.5, Lysholm 98.75 and VAS 1. DISCUSSION. Maioregen ® biomimetic osteochondral scaffold showed very good results as surgical treatment option in treating ICRS grade 3–4 osteochondral lesions whatever the etiology. In particular, the implant showed good results also in treatment of osteonecrosis and could provide an alternative to unicompartimental arthroplasty in young and active patients

Purpose. Osteochondral lesions of the knee are relatively common both in young and senior population. The very disabling clinical symptoms, in association to the scarce regenerative capacity of the articular cartilage and the increased risk of developing a secondary osteoarthritis make an effective treatment mandatory. Methods and Materials. From December 2008 to January 2013, 34 patients (35 knees), 24 males and 10 females (mean age 36.2 years range 14–66) underwent implant of Maioregen® (Finceramica Faenza S.P.A, Italy) biomimetic tri-layer osteochondral scaffold. In 17 cases the osteochondral lesion was cause by an osteochondritis dissecans (acute or sequela), in 13 cases by a spontaneous osteonecrosis and in 4 cases the etiology was traumatic. Patients were evaluated with subjective IKDC and Tegner Lysholm scores, VAS and Tegner Activity Scale before surgery and at regular follow up (mean follow up 38.4 months, range 13 months max 63 months). Results. Both Lysholm and IKDC Subjective scores significantly increased from 57.5 and 48.2 before surgery to 89.7 and 76.3 at 1 year follow up. Mean VAS scale score decreased from 6.3 to 2 at 1 year follow up. At 3 years follow up 20 evaluated patients showed an increment on both scales (Lysholm 92.38, IKDC 84.7). Only 4 patients were evaluated at 5 years follow up with mean subjective IKDC 92.5, Lysholm 98.75 and VAS 1. Conclusion. Maioregen® biomimetic osteochondral scaffold showed very good results as surgical treatment option in treating ICRS grade 3–4 osteochondral lesions whatever the etiology. In particular, the implant showed good results also in treatment of osteonecrosis and could provide an alternative to unicompartimental arthroplasty in young and active patients

Introduction and Objectives: Osteochondral lesions of the talus are difficult to treat due to difficult access, vascularisation, and because the head of the talus is a region with significant mechanical load. Among the therapeutic options for osteochondral lesions of the head of the talus, we present a treatment alternative using mosaicplasty with an autologous osteochondral graft taken from the knee. Materials and Methods: We have treated 8 patients affected with osteochondral lesions of the head of the talus (7 medial and 1 lateral) of greater than 7mm diameter, younger than 45 years of age, and with no instability of the ligament. The talus was approached in all cases by means of osteotomy of the malleolus. Osteocartilaginous cores were collected from the ipsilateral lateral condyle of the ipsilateral knee with minimal arthrotomy. Rehabilitation began between days 3 and 5 with no weight bearing before the 6th week. Results were measured by means of CTscan, MRI, and pathology, and clinically using the Maryland scale. Results: All patients presented with evidence of osteointegration of the osteochondral graft. All were classified as excellent or good on the Maryland scale. Functional results were good with flexion and extension movements of the ankle practically symmetrical with the healthy limb. There were no complications in the donor site or infections. None of the patients has required repeat treatment except in the cases in which material for osteosynthesis was removed from the malleolus. Discussion and Conclusions: We believe that in view of the results of mosaicplasty with an autologous osteochondral graft taken from the knee, this provides a new therapeutic approach to treatment of grade III and IV osteochondral lesions of the talus. The most significant advantages of this technique include the repair of articular cartilage with type II collagen and an earlier discharge time due to osseous integration. The most important disadvantages were potential morbidity associated with the donor site and the technical difficulty in achieving convexity

Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis, which occurs secondary to traumatic joint injury which is known to cause pathological changes to the osteochondral unit. Articular cartilage degradation is a primary hallmark of OA, and is normally associated with end-stage disease. However, subchondral bone marrow lesions are associated with joint injury, and may represent localized bone microdamage. Changes in the osteochondral unit have been traditionally studied using explant models, of which the femoral-head model is the most common. However, the bone damage caused during harvest can confound studies of microdamage. Thus, we used a novel patellar explant model to study osteochondral tissue dynamics and mechanistic changes in bone-cartilage crosstalk. Firstly, we characterized explants by comparing patella with femoral head models. Then, the patellar explants (n=269) were subjected to either mechanical or inflammatory stimulus. For mechanical stimulus 10% strain was applied at 0.5 and 1 Hz for 10 cycles. We also studied the responses of osteochondral tissues to 10ng/ml of TNF-α or IL-1β for 24hrs. In general the findings showed that patellar explant viability compared extremely well to the femoral head explant. Following IL-1β or TNF-α treatment, MMP13, significantly increased three days post exposure, furthermore we observed a decrease in sulfate glycoaminoglycan (sGAG) content. Bone morphometric analysis showed no significant changes. Contrastingly, mechanical stimulation resulted in a significant decrease sGAG particularly at 0.5Hz, where an increase in MMP13 release 24hrs post stimulation and an upregulation of bone and cartilage matrix degradation markers was observed. Furthermore, mechanical stimulus caused increases in TNF-α, MMP-8, VEGF expression. In summary, this study demonstrates that our novel patella explant model is an excellent system for studying bone-cartilage crosstalk, which responds well to both mechanical and inflammatory stimulus and is thus of great utility in the study of PTOA

Introduction Twelve patients with an osteochondral lesion of the talus were treated with excision of the lesions and local osteochondral autogenous grafting. Methods The lesion was accessed through a replaceable bone block removed from the anterior tibial plafond. The graft was harvested from the medial or lateral talar articular facet on the same side of the lesion. The average age of the patients was 41 years and duration of symptoms was 90 months (average). There were six males and six females with the right talus involved in eight and the left in four patients. Graft sizes ranged from four to eight millimetres in diameter. Results There was a significant improvement in the AOFAS score from 64.4 (average) pre-operatively to 90.8 (average post-operatively (p< 0.0001) at follow-up of 25.3 months (average). The AOFAS score was slightly higher in patients under 40 years of age and in those without pre-existing joint arthritis. All patients were very satisfied with the procedure. Arthroscopy performed in two patients at six and 12 months following surgery showed good graft incorporation. No complications occurred at the donor site or the site of the bone block removal on the distal tibia. Conclusions The results showed that stage III and stage IV talar osteochondral lesions can be accessed successfully excising a tibial bone block and using local autogenous osteochondral graft harvested from the ipsilateral talar articular facet. In relation to the conduct of this study, one or more of the authors has received, or is likely to receive direct material benefits

Abstract. Background. Osteochondral allograft (OCA) transplantation is a clinically and cost-effective option for symptomatic cartilage defects. In 2017 we initiated a program for OCA transplantation for complex chondral and osteochondral defects as a UK tertiary referral centre. Aim. To characterise the complications, re-operation rate, graft survivorship and clinical outcomes of knee OCA transplantation. Methodology. Analysis of a prospectively maintained database of patients treated with primary OCA transplantation from 2017 to 2021 with a minimum of one-year follow-up. Patient reported outcome measures (PROMs), complications, re-operations and failures were evaluated. Results. 37 patients with 37 knee OCA procedures were included (mean age 31.6 years [16–49 years]). Mean BMI 26.6 kg/m2 (19.1–35.9 kg/m2). The mean chondral defect size was 3cm2 (1.2–7.3 cm2). Mean duration of follow-up was 3.1 years (1–5.3 years). 16 patients underwent meniscal allograft transplantation (MAT), 6 underwent osteotomy and 4 underwent ligament reconstruction as concurrent procedures. Significant improvements in mean PROMs were noted at 12 months. 16 patients had reoperations of which 5 had more than one surgery. Of these patients 6 were related to OCA (mainly debridement and revision OCA in one patient), and the remainder were related to additional procedures including removal of plate in 2 patients. The overall failure rate was 1 in 37 patients (3%). Conclusions. Early experience of OCA as a treatment option for complex chondral and osteochondral lesions in the knee shows satisfactory results. The reoperation rate is high but at mean follow-up of 3.1 years the survival rate was 97%

Osteochondral glenoid loss is associated with recurrent shoulder instability. The critical threshold for surgical stabilization is multidimensional and conclusively unknown. The aim of this work was to provide a well- measurable surrogate parameter of an unstable shoulder joint for the frequent anterior-inferior dislocation direction. The shoulder stability ratio (SSR) of 10 paired human cadaveric glenoids was determined in anterior-inferior dislocation direction. Osteochondral defects were simulated by gradually removing osteochondral structures in 5%-stages up to 20% of the intact diameter. The glenoid morphological parameters glenoid depth, concavity gradient, and defect radius were measured at each stage by means of optical motion tracking. Based on these parameters, the osteochondral stability ratio (OSSR) was calculated. Correlation analyses between SSR and all morphological parameters, as well as OSSR were performed. The loss of SSR, concavity gradient, depth and OSSR with increasing defect size was significant (all p<0.001). The loss of SSR strongly correlated with the losses of concavity gradient (PCC = 0.918), of depth (PCC = 0.899), and of OSSR (PCC = 0.949). In contrast, the percentage loss based on intact diameter (defect size) correlated weaker with SSR (PCC=0.687). Small osteochondral defects (≤10%) led to significantly higher SSR decrease in small glenoids (diameter <25mm) compared to large (≥ 25mm) ones (p ≤ 0.009). From a biomechanical perspective, the losses of concavity gradient, glenoid depth and OSSR correlate strong with the loss of SSR. Therefore, especially the loss of glenoidal depth may be considered as a valid and reliable alternative parameter to describe shoulder instability. Furthermore, smaller glenoids are more vulnerable to become unstable in case of small osteochondral loosening. On the other hand, the standardly used percentage defect size based on intact diameter correlates weaker with the magnitude of instability and may therefore not be a valid parameter for judgement of shoulder instability

Osteochondral autologous transplantation (OATS) is a new technique for the treatment of osteochondral defects. In a prospective randomised study, between November 1996 and June 2000 we used the OATS technique to treat 136 patients (90 male, 46 female) with a mean osteochondral defect of 3.3 cm2. The defect was in the medial femoral condyle in 54 cases, the lateral femoral condyle in nine, the patella in 15, the trochlea in six, the tibial plateau in one, the talus in 29, the tibial plafond in two, the capitellum in four. There were 16 other locations. The procedure was performed either open or arthroscopically. A mean of 2.2 cylinders was transplanted. At the same time, we treated malalignment by high tibial osteotomy (HTO) in 20 patients, and instability by anterior (ACL) or posterior cruciate ligament (PCL) reconstruction in 16. Five patients required reconstruction of both ACL and PCL. The Lysholm score in the lower limbs increased from a preoperative mean of 58.3 (20 to 77) to a mean of 90.2 (70 to 100). Treatment by OATS alone increased the score from 62.9 to 91.6. The combination of OATS and HTO increased the score from 65.2 to 91.6. With additional ACL/PCL reconstruction, the score increased from 49.9 to 82.6. The combination of OATS, HTO and ACL/PCL reconstruction increased the Lysholm score from 55.5 to 85.5. Control postoperative MRI with IV contrast (Gd-DTPA) showed incorporation of all but one cylinder. Complications included one case of arthrofibrosis and sinking of one cylinder. One patient developed regional pain syndrome and three had pain at the malleolar osteotomy site, resolved by screw removal. For four weeks after the operation, 10% of patients complained of pain at the donor side in the lateral femoral condyle. There were no complications related to OATS performed in the upper limbs, and control MRI three months postoperatively showed incorporation of all cylinders. The results are encouraging, and give rise to the hope that this cost-effective and safe new treatment for limited osteochondral defects may delay or even prevent the onset of osteoarthritis

Twelve patients with an osteochondral lesion of the talus were treated with local osteochondral autogenous grafting. The graft was harvested locally from the medial or lateral talar articular facet. The procedure was combined with an osteotomy of the anterior tibial plafond modifying the technique of Flick and Gould. The average age of the patients was 41 years (range 19 to 68) with an average duration of symptoms of 90 months (range 3 – 240 months). There were six males and six females with the right talus involved in eight and the left in four patients. Results showed an improvement in the AOFAS score from an average of 69 pre-operatively to 90.2 post-operatively, at an average follow up of 15 months (range 6 to 31 months). The results tended to improve with time and was higher for patients under 40 years of age and in those without pre-existing joint arthritis. All patients were very satisfied with the procedure. Arthroscopy performed in two patients at six and 12 months following surgery showed good graft incorporation. No complications were seen from the donor site or from the osteotomy site on the distal tibia. Our results show that stage III and IV talar lesions can be treated successfully using local autogenous osteochondral graft from the medial or lateral talar articular facet

As arthroplasty demand grows worldwide, the need for a novel cost-effective treatment option for articular cartilage (AC) defects tailored to individual patients has never been greater. 3D bioprinting can deposit patient cells and other biomaterials in user-defined patterns to build tissue constructs from the “bottom-up,” potentially offering a new treatment for AC defects. The aim of this research was to create bioinks that can be injected or 3D bioprinted to aid osteochondral defect repair using human cells. Novel composite bioinks were created by mixing different ratios of methacrylated alginate (AlgMA) with methacrylated gelatin (GelMA). Chondrocytes or mesenchymal stem cells (MSCs) were then encapsulated in the bioinks and 3D bioprinted using a custom-built extrusion bioprinter. UV and double-ionic (BaCl2 and CaCl2) crosslinking was deployed following bioprinting to strengthen bioink stability in culture. Chondrocyte and MSC spheroids were also produced via 3D culture and then bioprinted to accelerate cell growth and development of ECM in bioprinted constructs. Excellent viability of chondrocytes and MSCs was seen following bioprinting (>95%) and maintained in culture over 28 days, with accelerated cell growth seen with inclusion of MSC or chondrocyte spheroids in bioinks (p<0.05). Bioprinted 10mm diameter constructs maintained shape in culture over 28 days, whilst construct degradation rates and mechanical properties were improved with addition of AlgMA (p<0.05). Composite bioinks were also injected into in vitro osteochondral defects (OCDs) and crosslinked in situ, with maintained cell viability and repair of osteochondral defects seen over a 14-day period. In conclusion we developed novel composite AlgMA/GelMA bioinks that can be triple-crosslinked, facilitating dense chondrocyte and MSC growth in constructs following 3D bioprinting. The bioink can be injected or 3D bioprinted to successfully repair in vitro OCDs, offering hope for a new approach to treating AC defects

As arthroplasty demand grows worldwide, the need for a novel cost-effective treatment option for articular cartilage (AC) defects tailored to individual patients has never been greater. 3D bioprinting can deposit patient cells and other biomaterials in user-defined patterns to build tissue constructs from the “bottom-up,” potentially offering a new treatment for AC defects. The aim of this research was to create bioinks that can be injected or 3D bioprinted to aid osteochondral defect repair using human cells. Novel composite bioinks were created by mixing different ratios of methacrylated alginate (AlgMA) with methacrylated gelatin (GelMA). Chondrocytes or mesenchymal stem cells (MSCs) were then encapsulated in the bioinks and 3D bioprinted using a custom-built extrusion bioprinter. UV and double-ionic (BaCl2 and CaCl2) crosslinking was deployed following bioprinting to strengthen bioink stability in culture. Chondrocyte and MSC spheroids were also bioprinted to accelerate cell growth and development of ECM in bioprinted constructs. Excellent viability of chondrocytes and MSCs was seen following bioprinting (>95%) and maintained in culture over 28 days, with accelerated cell growth seen with inclusion of MSC or chondrocyte spheroids in bioinks (p<0.05). Bioprinted 10mm diameter constructs maintained shape in culture over 28 days, whilst construct degradation rates and mechanical properties were improved with addition of AlgMA (p<0.05). Composite bioinks were also injected into in vitro osteochondral defects (OCDs) and crosslinked in situ, with maintained cell viability and repair of osteochondral defects seen over a 14-day period. In conclusion we developed novel composite AlgMA/GelMA bioinks that can be triple-crosslinked, facilitating dense chondrocyte and MSC growth in constructs following 3D bioprinting. The bioink can be injected or 3D bioprinted to successfully repair in vitro OCDs, offering hope for a new approach to treating AC defects

Osteochondral autologous transplantation (OATS) is a new technique for the treatment of osteochondral defects. In a prospective study between April 1996 und May 2001 we used the OATS technique to treat 201 patients (125 male, 76 female) with a mean osteochondral defect of 3,3 cm. 2. The defect was in the medial femoral condyle in 96 cases, the lateral femoral condyle in 16, the patella in 22, the trochlea in seven, the tibial plateau in one, the talus in 48, the tibial plafond in two and capitellum in four. There were 17 other locations. The procedure was performed either open or arthroscopically. A mean of 2,2 cylinders was transplanted. The Lysholm score in the lower limbs increased from a preoperative mean of 58,3 (20 to77) to a mean of 90,2 (70 to 100). Treatment by OATS alone increased the score from 65,2 to 91,6. With additional ACL/PCL reconstruction, the score increased from 49,9 to 82,6. The combination of OATS, HTO, ACL/PCL reconstruction increased the Lysholm score from 55,5 to 85,5. Ten per cent of patients complained of pain at the donor site in the lateral femoral condyle. There were no complications related to OATS performed in the upper limbs, and control MRI three months postoperatively showed incorporation of all cylinders. The results are encouraging, and give rise, to the hope that this cost-effective and safe treatment for limited osteochondral defects may delay or even prevent the onset of osteoarthritis

The fixation of articular fractures, with many small osteochondral fragments, is a challenging unmet need where a bone adhesive would be a useful adjunct to standard treatments. Whilst there are no such adhesives in current clinical use, preclinical animal models have demonstrated good healing of bone in unloaded models using an adhesive based on phosphoserine modified calcium phosphate cement (PM-CPC). An ex-vivo human bone core model has shown that this adhesive bonds freshly harvested human bone. To confirm this adhesive is capable of supporting loaded osteochondral fragments a porcine model has been developed initially ex-vivo on the path to an in-vivo study. In this model bone cores, harvested from the medial knee condyle, are glued in place with the adhesive. In-vivo adjacent pairs of bone cores would be replaced with adhesive and a control with conventional pin fixation respectively. As osteochondral bone fragments have both bone and cartilage components, this suggested a dual adhesive strategy in which components designed for each tissue type are used. This concept has been explored in an ex-vivo porcine pilot study presented herewith. At the subchondral bone level, the PM-CPC was used. At the cartilage level, a second adhesive, a methacrylated phosphoserine containing hyaluronic acid (MePHa) hydrogel designed specifically for soft tissues was applied. This is a challenging model as both adhesives have to be used simultaneously in a wet field. The pilot showed that once the subchondral component is glued in place, the PM-CPC adhesive intruding into the cartilage gap can be removed before applying the cartilage adhesive. This enabled the MePHa adhesive to be injected between the cut cartilage edges and subsequently light-cured. This two-stage gluing method is demanding and an in-vivo pilot is necessary to perfect and prove the operative technique. Acknowledgements: The human bone core project was partially financed by Innovation Fund of Västra Götaland Region, Sweden. The MePHa hydrogel work was supported by a Swiss National Fund grant # CR23I3_159301

Introduction and Objective. Several in vitro studies have shed light on the osteogenic and chondrogenic potential of graphene and its derivatives. Now it is possible to combine the different biomaterial properties of graphene and 3D printing scaffolds produced by tissue engineering for cartilage repair. Owing to the limited repair capacity of articular cartilage and bone, it is essential to develop tissue-engineered scaffolds for patients suffering from joint disease and trauma. However, chondral lesions cannot be considered independently of the underlying bone tissue. Both the microcirculation and the mechanical support provided with bone tissue must be repaired. One of the distinctive features that distinguish graphene from other nanomaterials is that it can have an inductive effect on both bone and cartilage tissue. In this study, the effect of different concentrations of graphene on the in vivo performance of single-layer poly-ε-caprolactone based-scaffolds is examined. Our hypothesis is that graphene nanoplatelet- containing, robocast PCL scaffolds can be an effective treatment option for large osteochondral defect treatment. For this purpose, different proportions of graphene- containing (1%,3%,5%,10 wt%) PCL scaffolds were studied in a 5mm diameter osteochondral defect model created in the rabbit knee. Materials and Methods. In the study graphene-containing (1, 3, 5, 10 wt%), porous and oriented poly-ε-caprolactone-based scaffolds were prepared by robocasting method to use in the regeneration of large osteochondral defects. Methods: The scaffolds were implanted into the full-thickness osteochondral defect in a rabbit model to evaluate the regeneration of defect in vivo. For this purpose, twenty female New Zealand white rabbits were used and they were euthanized at 4 and 8 weeks of implantation. The reparative osteochondral tissues were harvested from rabbit distal femurs and then processed for gross appearance assessment, radiographic imaging, histopathological and immunohistochemical examinations. Results. Results revealed that, graphene- containing graft materials caused significant amelioration at the defect areas. Graphene-containing graft materials improved the fibrous, chondroid and osseous tissue regeneration compared to the control group. The expressions of bone morphogenetic protein-2 (BMP-2), collagen-1 (col-1), vascular endothelial growth factor (VEGF) and alkaline phosphatase (ALP) expressions were more prominent in graphene- containing PCL implanted groups. Results also revealed that the ameliorative effect of graphene increased by the elevation in concentration. The most prominent healing was observed in 10 wt% graphene-containing PCL based composite scaffold implanted group. Conclusions. This study demonstrated that graphene- containing, robocast PCL scaffolds has efficacy in the treatment of large osteochondral defect. Subchondral new bone formation and chondrogenesis were observed based on immunohistochemical examinations. 3D printed PCL platforms have great potential for the investigation of the osteochondral regeneration mechanism. The efficacy of graphene-containing PCL scaffolds on osteogenesis, vascularization, and mineralization was shown at different graphene concentrations at 4th and 8th weeks. Immunohistochemical studies showed statistical significance in the 5wt% and 10 wt% graphene-containing groups compared to the 1wt% and 3 wt% graphene-containing groups at the end of the eighth week

Joint surface restoration of deep osteochondral defects represents a significant unmet clinical need. Moreover, untreated lesions lead to a high rate of osteoarthritis. The current strategies to repair deep osteochondral defects such as osteochondral grafting or sandwich strategies combining bone autografts with ACI/MACI fail to generate long-lasting osteochondral interfaces. Herein, we investigated the capacity of juvenile Osteochondral Grafts (OCGs) to repair osteochondral defects in skeletally mature animals. With this regenerative model in view, we set up a new biological, bilayered, and scaffold-free Tissue Engineered (TE) construct for the repair of the osteochondral unit of the knee. Skeletally immature (5 weeks old) and mature (11 weeks old) Lewis rats were used. Cylindrical OCGs were excised from the intercondylar groove of the knee of skeletally immature rats and transplanted into osteochondral defects created in skeletally mature rats. To create bilayered TE constructs, micromasses of human periosteum-derived progenitor cells (hPDCs) and human articular chondrocytes (hACs) were produced in vitro using chemically defined medium formulations. These constructs were subsequently implanted orthotopically in vivo in nude rats. At 4 and 16 weeks after surgery, the knees were collected and processed for subsequent 3D imaging analysis and histological evaluation. Micro-computed tomography (µCT), H&E and Safranin O staining were used to evaluate the degree of tissue repair. Our results showed that the osteochondral unit of the knee in 5 weeks old rats exhibit an immature phenotype, displaying active subchondral bone formation through endochondral ossification, the absence of a tidemark, and articular chondrocytes oriented parallel to the articular surface. When transplanted into skeletally mature animals, the immature OCGs resumed their maturation process, i.e., formed new subchondral bone, partially established the tidemark, and maintained their Safranin O-positive hyaline cartilage at 16 weeks after transplantation. The bilayered TE constructs (hPDCs + hACs) could partially recapitulate the cascade of events as seen with the immature OCGs, i.e., the regeneration of the subchondral bone and the formation of the typical joint surface architecture, ranging from non-mineralized hyaline cartilage in the superficial layers to a progressively mineralized matrix at the interface with a new subchondral bone plate. Cell-based TE constructs displaying a hierarchically organized structure comprising of different tissue forming units seem an attractive new strategy to treat osteochondral defects of the knee

The clinical success of osteochondral autografts is heavily reliant on their mechanical stability, as grafts which protrude above or subside below the native cartilage can have a negative effect on the tribological properties of the joint [1]. Furthermore, high insertion forces have previously been shown to reduce chondrocyte viability [2]. Commercial grafting kits may include a dilation tool to increase the diameter of the recipient site prior to insertion. The aim of this study was to evaluate the influence of dilation on the primary stability of autografts. Six human cadaveric femurs were studied. For each femur, four 8.5 × 8mm autografts were harvested from the trochlear groove and implanted into the femoral condyles using a Smith & Nephew Osteochondral grafting kit. Two grafts were implanted into dilated recipient sites (n=12) and two were implanted with no dilation (n=12). Insertion force was measured by partially inserting the graft and applying a load at a rate of 1 mm/min, until the graft was flush with the surrounding cartilage. Push-in force was measured by applying the same load, until the graft had subsided 4mm below congruency. Significance was taken as (p<0.05). Average maximum insertion force of dilated grafts was significantly lower (p<0.001) than their non-dilated equivalent [28.2N & 176.7N respectively]. There was no significant difference between average maximum push-in force between the dilated and non-dilated groups [1062.8N & 1204.2N respectively]. This study demonstrated that significantly less force is required to insert dilated autografts, potentially minimising loss of chondrocyte viability. However, once inserted, the force required to displace the grafts below congruency remained similar, indicating a similar degree of graft stability between both groups