Purpose. Platelet-derived growth factor-BB (PDGF-BB) is a well characterized wound healing protein known to be chemotactic and mitogenic for cells of mesenchymal origin, including osteoblasts and chondrocytes. Biocompatible scaffolds, combined with growth factors such as PDGF-BB, have potential to stimulate regeneration and repair of osseous and cartilaginous tissues. The purpose of this study was to determine the efficacy and safety of recombinant human PDGF-BB (rhPDGF-BB) combined with a collagen implant to augment healing of osteochondral defects. Method. A single osteochondral defect (8mm x 8mm) was created in the medial femoral condyle of 32 adult goats. Collagen implants(8.5mm x 8mm) hydrated with four doses of rhPDGF-BB (0g, 15g, 75g, 500g) were press-fit into the defect. Defects in four animals were left untreated. All goats were sacrificed 12 weeks postoperatively. Macroscopic evaluation and quantitative CT analyses were performed. Histologic sections were stained with Safranin O/Fast Green and assessed with a modified ODriscoll scoring scale for cartilage and bone repair. Significance was determined by One-Way ANOVA or nonparametric Kruskal-Wallis. Results. Macroscopic evaluation indicated significant improvement of the gross cartilage repair score for the rhPDGF-BB treatment groups compared to the 0g rhPDGF-BB control (500g;0g) and empty defect groups (500,75,15g; Empty). MicroCT analysis indicated a significant increase in trabecular number for the 500g group compared to 0g control, 75g, and Empty groups(p=0.004). Average bone volume reconstitution for the 500g group was increased (58.8%) compared to the 0g control. The total cartilage repair score was significantly improved (p=0.048) in the 500g treatment group (14.30.3) compared to the 0g control group (12.10.4). All rhPDGF-BB treatment groups exhibited increased Safranin-O staining of the matrix compared to the 0g control group, and a significantly decreased incidence(p=0.01) of subchondral cyst formation compared to the empty defect group. Conclusion. The results of this study indicate that rhPDGF-BB, combined with a collagen implant, is safe and improves repair of large osteochondral defects located in a high-load bearing region in a caprine model. Increases in gross scoring and histopathologic cartilage repair score for the rhPDGF-BB treatment groups, in addition to the presence of bony bridging, especially for the 500g rhPDGF-BB treatment group, indicate enhanced reconstitution of the subchondral bone and overlying repair tissue. The cartilage repair score was increased, on average, in the empty defect group relative to the 0g rhPDGF-BB group, however this score may be partially inflated due to collapse of the surrounding native tissue into the defect. Combined with a significant decrease in cyst formation in all rhPDGF-BB treatment groups, these results suggest that rhPDGF-BB, combined with a collagen implant, may have promise as a therapeutic agent for osteochondral defect repair

Osteochondral (OC) defects of the knee are associated with pain and significant limitation of activity. Studies have demonstrated the therapeutic efficacy of mesenchymal stem cell (MSC) therapies in treating osteochondral defects. There is increasing evidence that the efficacy of MSC therapies may be a result of the paracrine secretion, particularly exosomes. Here, we examine the effects of MSC exosomes in combination with Hyaluronic Acid (HA) as an injectable therapy on functional osteochondral regeneration in a rabbit osteochondral defect model. Exosomes were purified from human MSC conditioned medium by size fractionation. A circular osteochondral defect of 4.5 mm diameter and 2.5 mm depth was surgically created in the trochlear grooves of 16 rabbit knees. Thereafter, eight knees received three weekly injections of 200 µg of exosomes in one ml of 3% HA, and the remaining eight knees received three weekly injections of one ml of 3% HA only. The rabbits were sacrificed at six weeks. Analyses were performed by macroscopic and histological assessments, and functional competence was analysed via Young Modulus calculation at five different points (central, superior, inferior, medial and lateral) of the repaired osteochondral defect site. MSC exosomes displayed a modal size of 100 nm and expressed exosome markers (CD81, TSG101 and ALIX). When compared to HA alone, MSC exosomes in combination with HA showed significantly better repair histologically and biomechanically. The Young Modulus was higher in 4 out of the 5 points. In the central region, the Young Modulus of MSC exosome and HA combination therapy was significantly higher: 5.42 MPa [SD=1.19, 95% CI: 3.93–6.90] when compared to HA alone: 2.87 MPa [SD=2.10, 95% CI: 0.26–5.49], p < 0 .05. The overall mean peripheral region was also significantly higher in the MSC exosome and HA combination therapy group: 5.87 MPa [SD=1.19, 95% CI: 4.40–7.35] when compared to HA alone: 2.70 MPa [SD=1.62, 95% CI: 0.79–4.71], p < 0 .05. The inferior region showed a significantly higher Young Modulus in the combination therapy: 7.34 MPa [SD=2.14, 95% CI: 4.68–10] compared to HA alone: 2.92 MPa [SD=0.98, 95% CI: 0.21–5.63], p < 0.05. The superior region showed a significantly higher Young Modulus in the combination therapy: 7.31 MPa [SD=3.29, 95% CI: 3.22–11.39] compared to HA alone: 3.59 MPa [SD=2.55, 95% CI: 0.42–6.76], p < 0.05. The lateral region showed a significantly higher Young Modulus in the combination therapy: 8.05 MPa [SD=2.06, 95% CI: 5.49–10.61] compared to HA alone: 3.56 MPa [SD=2.01, 95% CI: 1.06–6.06], p < 0.05. The medial region showed a higher Young Modulus in the combination therapy: 6.68 MPa [SD=1.48, 95% CI: 4.85–8.51] compared to HA alone: 3.45 MPa [SD=3.01, 95% CI: −0.29–7.19], but was not statistically significant. No adverse tissue reaction was observed in all the immunocompetent animals treated with MSC exosomes. Three weekly injections of MSC exosomes in combination with HA therapy results in a more functional osteochondral regeneration as compared to HA alone

The parameters to be considered in the selection of a cartilage repair strategy are: the diameter of the chondral defect; the depth of the bone defect; the location of the defect (weight bearing); alignment. A chondral defect less than 3 cm in diameter can be managed by surface treatment such as microfracture, autologous chondrocyte transplantation, mosaicplasty, or periosteal grafting. An osteochondral defect less than 3 cm in diameter and less than 1 cm in depth can be managed by autologous chondrocyte transplantation, mosaicplasty or periosteal grafting. An osteochondral defect greater than 3 cm in diameter and 1 cm in depth is best managed by an osteochondral allograft. If there is an associated knee deformity, then an osteotomy should also be performed with all of the aforementioned procedures. In our series of osteochondral allografts for large post-traumatic knee defects realignment osteotomy is performed about 60% of the time in order to off load the transplant. To correct varus we realign the proximal tibia with an opening wedge osteotomy. To correct valgus, we realign the distal femur with a closing wedge osteotomy. Our results with osteochondral allografts for the large osteochondral defects of the knee have been excellent in 85% of patients at an average follow-up of 10 years. The Kaplan-Meier survivorship at 15 years is 72%. At an average follow-up of 22 years in 58 patients with distal femoral osteochondral allograft, 13 have been revised (22%). The 15-year survivorship was 84%. The results for the hip are early. To date we have performed this procedure on 16 patients. Surgical dislocation of the hip is carried out via a trochanteric osteotomy and the defect defined and trephined out. A press-fit fresh osteochondral allograft is inserted using the trephine technique. We have published our early results on a series of 8 patients with 5 good to excellent results, 1 fair result and 2 failures

An osteochondral defect greater than 3cm in diameter and 1cm in depth is best managed by an osteochondral allograft. If there is an associated knee deformity, then an osteotomy is performed. In our series of osteochondral allografts for large post-traumatic knee defects realignment osteotomy is performed about 60% of the time in order to off-load the transplant. To correct varus we realign the proximal tibia with an opening wedge osteotomy. To correct valgus, we realign the distal femur with a closing wedge osteotomy. Our results with osteochondral allografts for the large osteochondral defects of the knee both femur and tibia, have been excellent in 85% of patients at an average follow-up of 10 years. The Kaplan-Meier survivorship at 15 years is 72%. At an average follow-up of 22 years in 58 patients with distal femoral osteochondral allograft, 13 have been revised (22%). The 15-year survivorship was 84%. Retrieval studies of 24 fresh osteochondral grafts obtained at graft revision or conversion total knee replacement at an average of 12 years (5 – 25) revealed the following. In the areas where the graft was still intact, the cartilage was of normal thickness and architecture. Matrix staining was normal except in the superficial and upper mid zones. Chondrocytes were mostly viable but there was chondrocyte clusters and loss of chondrocyte polarity. Host bone had extended to the calcified cartilage but variable remnants of dead bone surrounded by live bone persisted. With a stable osseous base the hyaline cartilage portion of the graft can survive for up to 25 years

The zonal organization of articular cartilage is crucial in providing the tissue with mechanical properties to withstand compression and shearing force. Current treatments available for articular cartilage injury are not able to restore the hierarchically organized architecture of the tissue. Implantation of zonal chondrocyte as a multilayer tissue construct could overcome the limitation of current treatments. However, it is impeded by the lack of efficient zonal chondrocyte isolation protocol and dedifferentiation of chondrocytes during expansion on tissue culture plate (TCP). This study aims to develop a protocol to produce an adequate number of high-quality zonal chondrocytes for clinical application via size-based zonal chondrocyte separation using inertial spiral microchannel device and expansion under dynamic microcarrier culture. Full thickness (FT) chondrocytes isolated from porcine femoral condyle cartilage were subjected to two serial of size-based sorting into three subpopulations of different cell sizes, namely small (S1), medium (S2), and large (S3) chondrocytes. Zonal phenotype of the three subpopulations was characterised. To verify the benefit of stratified zonal chondrocyte implantation in the articular cartilage regeneration, a bilayer hydrogel construct composed of S1 chondrocytes overlaying a mixture of S2 and S3 (S2S3) chondrocytes was delivered to the rat osteochondral defect model. For chondrocyte expansion, two dynamic microcarrier cultures, sort-before-expansion and sort-after-expansion, which involved expansion after or before zonal cells sorting, were studied to identify the best sort-expansion strategy. Size-sorted zonal chondrocytes showed zone-specific characteristics in qRT-PCR with a high level of PRG4 expression in S1 and high level of aggrecan, Type II and IX collagen expression in S2 and S3. Cartilage reformation capability of sorted zonal chondrocytes in three-dimensional fibrin hydrogel showed a similar trend in qRT-PCR, histology, extracellular matrix protein quantification and mechanical compression test, indicating the zonal characteristics of S1, S2 and S3 as superficial (SZ), middle (MZ) and deep (DZ) zone chondrocytes, respectively. Implantation of bilayered zonal chondrocytes resulted in better cartilage tissue regeneration in a rat osteochondral defect model than FT control group, with predominantly Type II hyaline cartilage tissue and significantly lower Type I collagen. Dynamic microcarrier expansion of sorted zonal chondrocytes was able to retain the zonal cell size difference that correlate to zonal phenotype, while maintaining the rounded chondrocyte morphology and F-actin distribution similar to that in mature articular cartilage. With the better retention of zonal cell size and zonal phenotype relation on microcarrier, zonal cells separation was achievable in the sort-after-expansion strategy with cells expanded on microcarrier, in comparison to cells expanded on TCP. Inertial spiral microchannel device provides a label-free and high throughput method to separate zonal chondrocytes based on cell size. Stratified implantation of zonal chondrocytes has the potential to improve articular cartilage regeneration. Dynamic microcarrier culture allows for size-based zonal chondrocyte separation to be performed on expanded chondrocytes, thus overcoming the challenge of limited tissue availability from the patients. Our novel zonal chondrocyte isolation and expansion protocol provide a translatable strategy for stratified zonal chondrocyte implantation that could improve articular cartilage regeneration of critical size defects

INTRODUCTION. Osteochondral defects are still a challenge for the orthopaedic surgeon, since most of the current surgical techniques lead to fibrocartilage formation and poor subchondral regeneration, often associated to joint stiffness and/or pain. Thinking of the ideal osteochondral graft from both the surgical an commercial point of view, it should be an off-the-shelf product; this is the research direction and the explanation for the new biomaterials recently proposed to repair osteochondral defect inducing an “in situ” cartilage regeneration starting from the time of the implantation into the defect site. For the clinical pilot study we performed, a newly developed nanostructured biomimetic scaffold was used to treat chondral and osteochondral lesions of the knee; its safety and manageability, as much as the surgical procedure reproducibility and the clinical outcome, were evaluated in order to test its intrinsic potential without any cells colture aid. MATERIALS AND METHODS. A new osteochondral scaffold was obtained by enucleating equine collagen type 1 fibrils with hydroxyapatite nanoparticles in 3 different layers with 3 different gradient ratios at physiological conditions. 30 patients (9F, 21M, mean age 29,3yy) affected by either chondral or osteochondral lesions of the knee (8 medial femoral condyles, 5 lateral femoral condyles, 12 patellae, 8 femoral throcleas) underwent the scaffold implantation from January to July 2007. The sizes of the lesions were in between 2 and 6 squared cm. All patients and their clinical outcome were analyzed prospectively at 6, 12, 24 and 36 months using the Cartilage standard Evaluation Form as proposed by ICRS and an high resolution MRI. RESULTS. We observed a statistically significant scores improvement and function recovery comparing the pre-operative to the follow-up parameters evaluated. Moreover, we noticed a better improvement from 12 to 24mm follow up while the good results gained at 2yy were confirmed at 3yy follow up evaluation. The MOCART scoring scale was used to analyze the MRIs. In 80% of cases we obtained a complete filling of the cartilage defect and in some patients we even appreciated articular surface congruency. In this series we report 1 failure followed by a re-operation with different technique. CONCLUSIONS. This new minimally invasive one-step surgical approach to osteochondral defects seems to be an easy and effective procedure. The results obtained are very encouraging and this procedure show satisfactory outcomes even in big osteochondral defects

An osteochondral defect greater than 3cm in diameter and 1cm in depth is best managed by an osteochondral allograft. If there is an associated knee deformity, then an osteotomy was performed. In our series of osteochondral allografts for large post-traumatic knee defects, realignment osteotomy is performed about 60% of the time in order to off load the transplant. To correct varus we realign the proximal tibia with an opening wedge osteotomy. To correct valgus, we realign the distal femur with a closing wedge osteotomy. Our results with osteochondral allografts for the large osteochondral defects of the knee both femur and tibia, have been excellent in 85% of patients at an average follow-up of 10 years. The Kaplan-Meier survivorship at 15 years is 72%. At an average follow-up of 22 years in 58 patients with distal femoral osteochondral allograft, 13 have been revised (22%). The 15-year survivorship was 84%. Retrieval studies of 24 fresh osteochondral grafts obtained at graft revision or conversion to total knee replacement at an average of 12 years (5 – 25) revealed the following. In the areas where the graft was still intact, the cartilage was of normal thickness and architecture. Matrix staining was normal except in the superficial and upper mid-zones. Chondrocytes were mostly viable but there was chondrocyte clusters and loss of chondrocyte polarity. Host bone had extended to the calcified cartilage but variable remnants of dead bone surrounded by live bone persisted. With a stable osseous base the hyaline cartilage portion of the graft can survive for up to 25 years

A new surgical hybrid technique involving the combination of autologous bone plug(s) and autologous chondrocyte implantation (AOsP-ACI) was used and evaluated as a treatment option in 15 patients for repair of large osteochondral defects in knee (N=12) and hip joints (N=3). Autologous Osplugs were used to contour the articular surface and the autologous chondrocytes were injected underneath a biological membrane covering the plug. The average size of the osteochondral defects treated was 4.5cm. 2. The average depth of the bone defect was 26mm. The patients had a significant improvement in their clinical symptoms at 12 months with significant increase in the Lysholm Score and Harris Hip Score (p = 0.031). The repaired tissue was evaluated using Magnetic Resonance Imaging, Computerised Tomography, arthroscopy, histology and immunohistochemistry (for expression of type I and II collagen). Magnetic Resonance Imaging, Computerised Tomography and histology at 12 months revealed that the bone plug became well integrated with the host bone and repair cartilage. Arthroscopic examination at 12 months revealed good lateral integration of the AOsP-ACI with the surrounding cartilage. Immunohistochemistry revealed mixed fibro-hyaline cartilage. We conclude that the hybrid AOsP-ACI technique provides a promising surgical approach for the treatment of patients with large osteochondral defects. This study highlights the use of this procedure in two different weightbearing joints and demonstrates good early results which are encouraging. The long term results need to be evaluated

Large osteochondral defects of the glenohumeral joint are difficult to treat in young, active patients. When initial non-operative treatment with physical therapy, non-steroidal anti-inflammatory medications, corticosteroid injections, and viscosupplementation fails, surgery may become an option for some patients. Traditional shoulder arthroplasty and hemiarthroplasty provide excellent function and pain relief that can be long-lasting, but these treatments are still very likely to fail during a young patient's lifetime, and results have been unsatisfactory in many younger patients. Microfracture and autologous chondrocyte implantation (ACI) have been used in the shoulder, but their use has been limited to small defects. Other techniques that incorporate soft-tissue coverage of larger osteochondral defects have the benefit of preserving bone, but have not provided consistently good results. Advanced surgical techniques have been developed including all-arthroscopic osteochondral graft resurfacing of the humerus and glenoid for the treatment of osteoarthritis. This method of ‘biological resurfacing’ of the joint without using prosthetic implants may offer potential benefits to these young patients with shoulder arthritis including faster rehabilitation, pain relief, and easier revision surgery, if necessary. Early outcomes are encouraging in many cases, but inconsistent overall, with pain relief being the most reliable indicator of patient satisfaction

Chondral defects on the patella are a difficult problem in the young active patient and there is no consensus on how to treat these injuries. Fresh osteochondral allografts are a valid option for the treatment of full-thickness osteochondral defects and can be used to restore joint function and reduce pain. The primary purpose of this study was to investigate the clinical and subjective outcomes of a series of patients following fresh osteochondral allograft transplantation for isolated chondral defects of the patella. A series of 5 patients underwent surgery using an open approach for graft transplantation. A strict protocol for the allograft tissue was followed. Transplant recipients must be aged <60, have a full-thickness, isolated chondral lesion and have failed previous traditional treatments. The fresh allografts are hypothermically stored at 4°C in X-VIVO10 media for up to 30 days to maintain cartilage viability. Pre- and post-operative clinical measures including knee stability, range of motion, and quadriceps girth were completed. Post-operative plain radiographs were completed including weight-bearing AP, lateral and skyline views. Patient-centred outcome measures including the Knee Osteoarthritis Outcome Score (KOOS) and the Knee Society Score (KSS) were gathered a minimum of 1-year post-operative. Descriptive and demographic data were collected for all patients. A paired t-test was employed to determine the difference between the pre-operative and post-operative outcomes. All patients were female, with a mean age of 27.4 (SD 3.65). Knee ligament stability was similar pre- and post-operatively. Knee ROM assessment of flexion and extension demonstrated a less than 10° increase from pre to post-operative. Quadriceps girth measurements demonstrated a mean change of 0.5 cm from pre- to post-operative for the surgical limb. Post-operative radiographs demonstrated incorporation of the graft in 4/5 cases within 6-months of surgery. One patient developed fragmentation of the graft after 18-months, and one patient had a subsequent trochleoplasty for persistent pain. The mean KOOS domain scores demonstrated significant improvement (p<0.05) as follows: Symptoms pre-op = 28.57, post-op = 55; Pain pre-op 28.89, post-op = 57.22; ADLs pre-op = 48.92, post-op = 66.18; Sports/Recreation pre-op = 6, post-op = 32; and QoL pre-op = 12.5, post-op = 42.5. Mean pre-op surgical versus non-surgical limb KSS scores were 107.4 and 179 respectively. The mean post-op surgical versus non-surgical limb KSS scores were 166 and 200. Isolated chondral defects of the patella can cause substantial pain, reduced function, and can be challenging to address surgically. This series of 5 cases demonstrated improved function, KOOS and KSS for 4/5 patients. To our knowledge this is a novel biological procedural technique for this problem, which has shown promising results making it a viable treatment option for young active patients with osteochondral defects of the patella

Introduction. Osteochondral defects of the knee may occur following patella dislocation or following direct trauma or twisting injuries to the knee in adolescents. Often a diagnostic and therapeutic challenge, if these lesions are left, posttraumatic osteoarthritis may occur. This retrospective single centre study presents the short-term results following operative fixation of osteochondral fragments of the knee using Omnitech ® screws. Method. All skeletally immature patients presenting with an osteochondral fracture of their femur or patella confirmed on xray and MRI were identified. Arthroscopic evaluation of the osteochondral defect was performed followed by open reduction and internal fixation of the osteochondral fragment using Omnitech ® screws. A standard postoperative rehabilitation protocol was followed. Patients were evaluated at follow-up using a Knee Injury and Osteoarthritis Outcome Score (KOOS). Results. Eight patients were identified. The mean age at time of injury was 15 years (range 14–16) for two girls and 14.4 years (range 13–16) for six boys. The lateral femoral condyle was involved in six cases and patella in two cases. At mean follow up of 14 months (range 1–38) there was no revision for failure and no postoperative complications. The KOOS score (out of 100) at final follow up was subdivided as follows; Pain, 93 (range 81–100), other symptoms, 77 (range 36–100), function in daily living (ADL), 97 (range 84–100), function in sport and recreation, 84 (range 55–100) and knee related quality of life, 79 (range 44–100). Discussion. The short-term results of using Omnitech® screws are promising. Subchondral screw placement with adequate compression of the osteochondral fragment is achievable with Omnitech ® screws. Seven patients are back to their pre-injury sporting activity and one patient is currently undergoing postoperative rehabilitation, one month following surgery

Purpose. We report on minimum 2 year follow-up results of 71 patients randomised to autologous chondrocyte implantation (ACI) using porcine-derived collagen membrane as a cover (ACI-C) and matrix-induced autologous chondrocyte implantation (MACI) for the treatment of osteochondral defects of the knee. Introduction. ACI is used widely as a treatment for symptomatic chondral and osteochondral defects of the knee. Variations of the original periosteum-cover technique include the use of porcine-derived type I/type III collagen as a cover (ACI-C) and matrix-induced autologous chondrocyte implantation (MACI) using a collagen bilayer seeded with chondrocytes. Results. 71 patients with a mean age of 33 years (15-48) were randomised to undergo either an ACI-C or a MACI. 37 had ACI-C and 34 MACI. The mean size of the defect was 5.0cm2. Mean duration of symptoms was 104.4 months (9-456). Mean follow-up was 33.5 months (24-45). Functional assessment using the modified Cincinnati knee score, the Bentley functional rating score and the visual analogue score was carried out. Assessment using the modified Cincinnati knee score showed a good to excellent result in 57.1% of patients followed up at 2 years, and 65.2% at 3 years in the ACI-C group; and 63.6% of patients at 2 years, and 64% at 3 years in the MACI group. Arthroscopic assessments showed a good to excellent International Cartilage Repair Society score in 81.8% of ACI-C grafts and 50% of MACI grafts. Hyaline-like cartilage or hyaline-like cartilage with fibrocartilage was found in biopsies of 56.3% of the ACI-C grafts and 30% of the MACI grafts after 2 years. Conclusion. At this stage of the trial we conclude that the clinical, arthroscopic and histological outcomes are comparable for both ACI-C and MACI

Background. An osteochondral defect in the knees of young active patients represents a treatment challenge to the orthopaedic surgeon. Early studies with allogenic cartilage transplantation showed this tissue to be immunologically privileged, showed fresh grafts to maintain hyaline cartilage, and surviving chondrocytes several years after implantation. Methods. Between January 1978 and October 1995 we enrolled 63 patients in a prospective non-randomised study of fresh osteochondral allografts for post-traumatic distal femur defects in our institute. Five international patients who were lost to follow-up were excluded from this study. The indications for the procedure were: patients younger than 50 years of age having unipolar post-traumatic defects, or osteochondritis dissecans larger than three cm in diameter and one cm in depth. Results. Fifty-eight patients, ages 11-48 (mean 28) were followed for 15-32 years (mean 21.8 years). Thirteen of the 58 grafts have subsequently required further surgery, with three having graft removal and ten converted to total knee arthroplasty. Three patients died during the study due to unrelated causes and are included in the survivorship curve. Kaplan-Meier survivorship analysis showed: 91%, 84%, 69%, and 59% graft survival at 10, 15, 20, and 25 years, respectively. Patients with surviving grafts had good function, with a mean modified Hospital for Special Surgery score of an average 86 at 20 years or more following the allograft transplantation surgery. Late osteoarthritic degeneration as was seen on radiographs was associated with lower Hospital for Special Surgery scores representing patients with poorer clinical outcome. Conclusion. The authors confirm the value of fresh osteochondral allograft as a long term solution for articular defect in the knees of young patients. We recommend the use of fresh osteochondral allograft for treatment of large osteochondral defects in the distal femur of young and active patients

Adult articular cartilage mechanical functionality is dependent on the unique zonal organization of its tissue. Current mesenchymal stem cell (MSC)-based treatment has resulted in sub-optimal cartilage repair, with inferior quality of cartilage generated from MSCs in terms of the biochemical content, zonal architecture and mechanical strength when compared to normal cartilage. The phenotype of cartilage derived from MSCs has been reported to be influenced by the microenvironmental biophysical cues, such as the surface topography and substrate stiffness. In this study, the effect of nano-topographic surfaces to direct MSC chondrogenic differentiation to chondrocytes of different phenotypes was investigated, and the application of these pre-differentiated cells for cartilage repair was explored. Specific nano-topographic patterns on the polymeric substrate were generated by nano-thermal imprinting on the PCL, PGA and PLA surfaces respectively. Human bone marrow MSCs seeded on these surfaces were subjected to chondrogenic differentiation and the phenotypic outcome of the differentiated cells was analyzed by real time PCR, matrix quantification and immunohistological staining. The influence of substrate stiffness of the nano-topographic patterns on MSC chondrogenesis was further evaluated. The ability of these pre-differentiated MSCs on different nano-topographic surfaces to form zonal cartilage was verified in in vitro 3D hydrogel culture. These pre-differentiated cells were then implanted as bilayered hydrogel constructs composed of superficial zone-like chondro-progenitors overlaying the middle/deep zone-like chondro-progenitors, was compared to undifferentiated MSCs and non-specifically pre-differentiated MSCs in a osteochondral defect rabbit model. Nano-topographical patterns triggered MSC morphology and cytoskeletal structure changes, and cellular aggregation resulting in specific chondrogenic differentiation outcomes. MSC chondrogenesis on nano-pillar topography facilitated robust hyaline-like cartilage formation, while MSCs on nano-grill topography were induced to form fibro/superficial zone cartilage-like tissue. These phenotypic outcomes were further diversified and controlled by manipulation of the material stiffness. Hyaline cartilage with middle/deep zone cartilage characteristics was derived on softer nano-pillar surfaces, and superficial zone-like cartilage resulted on softer nano-grill surfaces. MSCs on stiffer nano-pillar and stiffer nano-grill resulted in mixed fibro/hyaline/hypertrophic cartilage and non-cartilage tissue, respectively. Further, the nano-topography pre-differentiated cells possessed phenotypic memory, forming phenotypically distinct cartilage in subsequent 3D hydrogel culture. Lastly, implantation of the bilayered hydrogel construct of superficial zone-like chondro-progenitors and middle/deep zone-like chondro-progenitors resulted in regeneration of phenotypically better cartilage tissue with higher mechanical function. Our results demonstrate the potential of nano-topographic cues, coupled with substrate stiffness, in guiding the differentiation of MSCs to chondrocytes of a specific phenotype. Implantation of these chondrocytes in a bilayered hydrogel construct yielded cartilage with more normal architecture and mechanical function. Our approach provides a potential translatable strategy for improved articular cartilage regeneration using MSCs

The results for autologous chondrocyte implantation (ACI) in the treatment of osteochondral defects in the knee are encouraging. At present, two techniques have been described to retain the chondrocyte suspension within the defect. The first involves using a periosteal flap harvested from the distal femur and the second involves using a type I/III collagen membrane. To the authors' knowledge there are no comparative studies of these two techniques in the current literature. A total of 68 patients with a mean age of 30.52 years (range 15 to 52 years) with symptomatic articular cartilage defects were randomised to have either ACI with a periosteal cover (33 patients) or ACI with a type I/III collagen cover (35 patients). The mean defect size was 4.54 cm. 2. (range 1 to 12 cm. 2. ). All patients were followed up at 24 months. A functional assessment using the Modified Cincinnati score showed that 74% of patients had a good or excellent result following the ACI with collagen cover compared with 67% after the ACI with periosteum cover at 2 years (p>0.05). Arthroscopy at 1 year also demonstrated similar results for both techniques. However, 36.4% of the periosteum covered grafts required shaving for hypertrophy compared with 1 patient for the collagen covered technique. This prospective, randomised study has shown no statistical difference between the clinical outcome of ACI with a periosteal cover versus ACI with a collagen cover at 2 years. A significant number of patients who had the ACI with periosteum technique required shaving of a hypertrophied graft within the first year of surgery. We conclude that there is no advantage in using periosteum as a cover for retaining the chondrocytes within an osteochondral defect; as a result we advocate the use of an alternative cover such as a porcine-derived, type I/III collagen membrane

Introduction. Young, high-demand patients with large post-traumatic tibial osteochondral defects are difficult to treat. Fresh osteochondral allografting is a joint-preserving treatment option that is well-established for such defects. Our objectives were to investigate the long-term graft survivorships, functional outcomes and associated complications for this technique. Methods. We prospectively recruited patients who had received fresh osteochondral allografts for post-traumatic tibial plateau defects over 3cm in diameter and 1cm in depth with a minimum of 5 years follow-up. The grafts were retrieved within 24 hours, stored in cefalozolin/bacitracin solution at 4°C, non-irradiated and used within 72 hours. Tissue matching was not performed but joints were matched for size and morphology. Realignment osteotomies were performed for malaligned limbs. The Modified Hospital for Knee Surgery Scoring System (MHKSS) was used for functional outcome measure. Kaplan-Meier survivorship analysis was performed with conversion to TKR as end point for graft failure. Results. Of 132 patients identified, 14 were lost to follow-up and 37 had less than 5 years follow-up, leaving 81 patients. There were 29 conversions to TKR at a mean of 12 (3-23) years post-operatively. The remaining 52 patients had a mean MHKSS score of 83 (49-100) with a mean follow-up of 11.7 (5-34) years. The Kaplan-Meier graft survivorships were 94% at 5 years (SE 2.7), 83% at 10 years (SE 4.6), 62% at 15 years (SE 7.4) and 45% at 20 years (SE 8.5). Associated complications included infection (1.2%) treated by 2-stage TKR, graft collapse (8.6%) treated by TKR, osteotomy and conservatively and knee pain relieved by hardware removal (7.4%). Conclusion. Fresh osteochondral allograft is a successful treatment option for large post-traumatic tibial osteochondral defects in young patients, with satisfactory long term survivorships and functional outcomes with acceptable complication rates

The current study aims to ascertain the outcome of ACI with simultaneous transplantation of an autologous bone plug for the restoration of osteoarticular defects in the femoral condyle of the knee (‘Osplug’ technique). Seventeen patients (mean age of 27±7 years), twelve with Osteochondritis dissecans (OD) and five with an osteochondral defect (OCD) was treated with unicortical autologous bone graft combined with ACI (‘Osplug’ technique). Functional outcome was assessed with Lysholm scores obtained for 5 years post-operatively. The repair site was evaluated with the Oswestry Arthroscopy Score (OAS), MOCART MRI score and ICRS II histology score. The mean defect size was 4.5±2.6 SD cm² and mean depth was 11.3±5 SD mm. A significant improvement of Lysholm score from 45 (IQR 24, range 16–79) to 77 (IQR 28, range 41–100) at 1 year (p-value 0.001) and 70 (IQR 35, range 33–91) at 5 years (p-value 0.009). The mean OAS of the repair site was 6.2 (range 0–9) at a mean of 1.3 years. The mean MOCART score was 61 ± 22SD (range 20–85) at 2.6 ± 1.8SD years. Histology demonstrated generally good integration of the repair cartilage with the underlying bone. Poor lateral integration of the bone graft on MRI and low OAS were significantly associated with a poor outcome and failure. The Osplug technique shows significant improvement of functional outcome for up to 5 years. This is the first report describing the association of bone graft integration with functional outcome after such a procedure

A retrospective review of 57 military patients undergoing ankle arthroscopy between 1999 and 2011 was performed. A case-note review of medical records was undertaken pertaining to military role, ankle injury sustained, mechanism, presenting symptoms and their duration. Arthroscopic findings were compared to findings on radiographs and MRI scans. At first presentation 23 patients had features of arthritis on radiographs. We found MRI was both highly sensitive (97.7%) and specific (93.4%) in detecting osteochondral defects (OCD). 16 of the patients had evidence of osteochondral injury. All OCDs picked up on MRI were confirmed at arthroscopy. Ankle injury may not be a benign injury in military personnel, with over half of these young patients having radiological features of osteoarthritis at presentation. We found MRI an effective tool for identifying occult injuries not seen on radiographs. Lateral ligament injury with associated gutter scarring can be successfully treated with arthroscopic debridement. This suggests pseudoinstability rather than a true mechanical instability as the main cause for patient's symptoms in this cohort

PURPOSE. Recently, in tissue engineering several methods using stem cells have been developed to repair chondral and osteochondral defects. Most of these methods rely on the use of scaffolds. Studies in the literature have demonstrated, first in animals and then in humans, that the use of mesenchymal stem cells withdrawn by several methods from adipose tissue allows to regenerate hyaline articular cartilage. In fact, it has been cleared that adipose-derived cells have multipotentiality equivalent to bone marrow-derived stem cells and that they can very easily and very quickly be isolated in large amounts enabling their immediate use in operating room for one-step cartilage repair techniques. The purpose of this study is to evaluate the therapeutic effect of adipose-derived stem cells on cartilage repair and present our experience in the treatment of knee cartilage defects by the novel AMIC REPAIR TECHNIQUE AUGMENTED by immersing the collagen scaffold with mesenchymal stem cells withdrawn from adipose tissue of the abdomen. MATERIALS AND METHODS. Fat tissue processing involves mechanical forces and does not mandatorily require any enzymatic or chemical treatment in order to obtain the regenerative cells from the lipoaspirate. In our study, mesenchymal adipose stem cells were obtained by non-enzymatic filtration or microfragmentation of lipoaspirates of the abdomen adipose tissue that enabled the separation of the stromal vascular fraction and were used in one-step reconstruction of knee cartilage defects by means of this new AUGMENTED AMIC TECHNIQUE. The focal defects underwent bone marrow stimulation microfractures, followed by coverage with collagen double layer resorbable membrane (Chondro-gide. TM. -Geistlich Pharma AG, Wolhusen, Switzerland) soaked in the cells obtained from fat in 18 patients, aged between 31 and 58 years, at the level of the left knee in 10 cases and in the right in eight, with follow-up ranging between 12 and 36 months. RESULTS: Surgical procedures have been completed without technical problems neither intraoperative or early postoperative complications. The evaluation scores (IKDC, KOOS and VAS) showed a significant improvement, more than 30%, at the initial 6 months follow-up and furtherly improved in the subsequent follow-ups. Also the control MRIs showed a progressive filling and maturation of the repair tissue of the defects. CONCLUSIONS. Since we are reporting a short and medium-term experience, it is not, of course, possible to provide conclusive assessment considerations on this technique, as the experience has to mature along with the progression of follow-ups. The simplicity together with the absence of intraoperative difficulties or immediate complications and the experience gained by other authors, first in animals and then in early clinical cases, makes it, however, possible to say that this can be considered one of the techniques to which resort for one-step treatment of cartilage defects in the knee because it improves patient's conditions and has the potential to regenerate hyaline-like cartilage. Future follow-up works will confirm the results

Cartilage repair strategies have been applied successfully to the knee, but only recently and with limited experience to the hip. The indications for these strategies have been well defined for the knee and are defined by the diameter and depth of the defects that are mainly post traumatic and degenerative. Viscosupplementation is an intra-articular therapy that theoretically restores the protective effects of hyaluronic acid. This therapy has been widely used for osteoarthritis of the knee with some early preliminary promising results for osteoarthritis of the hip. Microfracture can be performed arthroscopically or as part of an open procedure. This procedure is indicated for smaller lesions less than 3cm in diameter and 1cm in depth. Widely used in the knee, the results in the hip are limited but promising. The repair tissue is however fibrocartilage. Autologous chondrocyte transplantation can yield hyaline like repair cartilage with good mid- to long-term results in the knee. The indications are chondral defects greater than 3cm in diameter or osteochondral defects less than 1cm in depth. Its use in the hip has been limited with only a few published papers. The procedure requires two stages. The first stage which involves harvesting the cartilage can be done arthroscopically, and the second stage which involves transplantation of the cultured chondrocytes can be done arthroscopically or open. Larger lesions greater than 3cm in diameter and 1cm in depth, can be managed by osteochondral allografts. The published mid- to long-term results for the knee have been encouraging. The results for the hip are early. To date we have performed this procedure on 16 patients. Surgical dislocation of the hip is carried out via a trochanteric osteotomy and the defect defined and trephined out. A press-fit fresh osteochondral allograft is inserted using the trephine technique. We have published our early results on a series of 8 patients with 5 good to excellent results, 1 fair results and 2 failures