Introduction. Ostochondral lesion of the knee is a common cause of chronic knee pain. Arthroscopic treatment with subcondral microfracture is a widespread technique leading to noticeable improvement of knee function and pain. To improve the effectiveness of this treatment options, we thought to add intra (PRF) or post-operative (PRP) growth factors. Platelet rich plasma (PRP) is obtained by centrifugation of the blood to produce a plasma with high concentration of platelets and growth factors. This latter represents a promising method to manage degenerative cartilage lesion and can be used postoperatively to improve clinical results of patients treated arthroscopically. Platelet Rich Fibrin (PRF) has been presented as a second-generation platelet concentrate, and it is used intraoperatively to cover the microfracuteres’ holes. No literature was found about using of PRF intraoperative in association with arthroscopic microfracture technique. The aim of this study is to compare clinical outcomes of the treatment of knee osteochondral lesion using arthroscopic microfracture technique alone or in association with PRF Intraoperative application using “Vivostat” system or with PRP “ReGen Lab” postoperative injection. Patients & Methods. 90 patients with clinical and radiographic evidence of osteochondral lesion of the medial or lateral compartment of the knee were enrolled. All patients received arthroscopic debridement and Microfractures and were randomised into 3 groups: 30 patients received microfractures and intraoperative PRF “Vivostat” injection(Group A), 30 patients received microfracture and 3 intra-articular injections of 5.5 mL PRP “Regen”(Group B), 30 patients received microfracture only. IKDC, KOOS and VAS score were administered to all patients before starting the treatment, at 1, 6 and 12 months from the end of the management. Results. Patients who received microfracture and PRF intraoperative application provided the best outcomes, showing a significant higher clinical scores (P<0.001) compared to the other two groups. Patients underwent PRP postoperative administration reported significant higher score than those undergoing arthroscopic microfracture alone (P<0.005), but lesser than Intraoperative PRF group at 6 months and 1 year follow up. Discussion/Conclusion. Treatment of osteochondral lesions of the knee using microfracture technique significantly improved functional and pain scores from the pre- to postoperatively time in the overall cohort. Intraoperative application of PRF shows significantly better outcome than postoperative PRP injections. However, additional treatment with intra-articular PRP injection as an adjunct to microfracture technique may offer better clinical outcomes over microfracture technique alone

Abstract. Objectives. The ability to predict which patients will improve following routine surgeries aimed at preventing the progression of osteoarthritis is needed to aid patients being stratified to receive the most appropriate treatment. This study aimed to investigate the potential of a panel of biomarkers for predicting (prior to treatment) the clinical outcome following treatment with microfracture or osteotomy. Methods. Proteins known to relate to OA severity, with predictive value in autologous cell implantation treatment or that had been identified in proteomic analyses (aggrecanase-1/ ADAMTS-4, cartilage oligomeric matrix protein (COMP), hyaluronic acid (HA), Lymphatic Vessel Endothelial Hyaluronan Receptor-1, matrix metalloproteinases-1 and −3, soluble CD14, S100 calcium binding protein A13 and 14-3-3 protein theta) were assessed in the synovial fluid (SF) of 19 and 13 patients prior to microfracture or osteotomy, respectively, using commercial immunoassays. Levels of COMP and HA were measured in the plasma of these patients. To find predictors of postoperative function, multiple linear regression analyses were performed. Results. Linear regression analyses demonstrated that a lower concentration of HA in pre-operative SF was predictive of improved knee function (higher Lysholm score) following microfracture surgery. Further, lower pre-operative activity of ADAMTS-4 in SF was a significant, independent predictor of higher post-operative Lysholm score (improved joint function) following osteotomy surgery. Conclusion. This study is novel in identifying biomarkers with the potential to predict clinical outcome in patients treated with microfracture or osteotomy of the knee. Lower concentrations of HA and undetectable activity of ADAMTS-4 in the joint fluid of individuals with cartilage defects/early-OA may be used in algorithms to stratify patients to the most appropriate surgery. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Surgical microfracture is considered a first line treatment for talar osteochondral defects. Pain reduction, functional improvement and patient satisfaction are described to be 61–86% in both primary and secondary osteochondral defects. However, limited research is available whether improvement of the surgical technique is possible. We do know that the current rigid awls and drills limit the access to all locations in human joints and increase the risk of heat necrosis of bone. Application of a flexible water jet instrument to drill the microfracture holes can improve the reachability of the defect without inducing thermal damage. The aim of this study is to determine whether water jet drilling is a safe alternative compared to conventional microfracture awls by studying potential side effects and perioperative complications, as well as the quality of cartilage repair tissue in a caprine model. 6 mm diameter talar chondral defects were created bilaterally in 6 goats (12 samples). One defect in each goat was treated with microfracture holes created with conventional awls. The contralateral defect was treated with holes created with 5 second water jet bursts at a pressure of 50 MPa. The pressure was generated with a custom-made setup using an air compressor connected to a 300 litre accumulator that powered an air driven high-pressure pump (P160 Resato, Roden, The Netherlands, . www.resato.com. ). Postoperative complications were recorded. After 24 weeks, analyses were performed using the ICRS macroscopic score and the modified O'Driscoll histological score. Wilcoxon ranked sum tests were used to assess significant differences between the two instrument groups using each goat as its own control (p ≤ 0.05). One postoperative complication was signs of a prolonged wound healing with swelling and reluctance to weight bearing starting two days after surgery on the water jet side. Antibiotics were administered which resolved the symptoms. The median total ICRS score for the tali treated with water jets was 9,5 (range: 6–12) and 9 (range 2–11) for Observer 1 and 2 respectively; and for the tali treated conventionally this was 9,5 (range 5–11) and 9 range (2–10). The median total Modified O'Driscoll score for the tali treated with water jets was 15 (range: 7–17) and 13 (range: 3–20) for Observer 1 and 2 respectively; and for the tali treated conventionally was 13 (range: 11–21) and 15 (range: 9–20). No differences were found in complication rate or repair tissue quality between the two techniques. The results suggest that water jet drilling can be a safe alternative for conventional microfracture treatment. Future research and development will include the design of an arthroscopic prototype of the water jet drill. The focus will be on stability in nozzle positioning and minimized sterile saline consumption to further the decrease the risk of soft tissue damage

Abstract. Objectives. The aim of this work was to compare the different techniques and the different fluid permeability of the tissue following each technique through assessing the flow of radiopaque contrast agent using μCT image analysis and 3D modelling. Methods. Donated human tali specimens (n=12) were prepared through creating a 10mm diameter chondral defect in three different regions of each talus. Each region then underwent one of three surgical techniques: 1) Fine wire drilling, 2) Nanofracture or 3) Microfracture, equidistant sites in each defect to ensure even distribution. Each region then had an addition of 0.1 ml radiopaque contrast agent (Omnipaque™ 300), imaged using a clinical μCT scanner (SCANCO Medical AG, 73.6 μm resolution). Each μCT scan was segmented using Slicer 3D software (The Slicer Community, 2023 3D Slicer (5.2.2)). The segmentation package was used to segment the bone and contrast agent regions in each different surgical site of each sample. Each defect site was created into a cylinder and the ratio of segmented pixels of contrast agent against bone. Results. The μCT analysis indicated that across the 12 samples, eight nanofracture regions demonstrated flow of the contrast agent either to the depth of the fracture site or deeper. Some lateral flow was also observed in these sites. eight microfracture regions demonstrated that the flow of the contrast agent was localised to the fracture site and a preferential flow laterally. In only one sample, did a fine wire drilling region demonstrate any fluid flow. In this sample, contrast agent had permeated through the drilling site to the bottom and some sub-site permeation was observed. However, in all samples that showed no permeation of contrast agent through the fracture site, a layer of contrast agent on the chondral surface or minor permeation through to the sub-chondral surface. Segmentation of each sample site showed a significant increase (n=12, p<0.05) in fluid flow of the contrast agent in the nanofracture sites (11%) compared to microfracture (5%) and fine wire drilling (2%). Conclusions. Nanofracture showed significantly improved fluid permeability throughout the surrounding trabecular structure, when compared to microfracture and fine wire drilling. Microfracture appears to allow some fluid flow, but only confined to the immediate area around the fracture site, while fine wire drilling appears to allow a comparably small amount, if not no fluid flow through the surrounding trabecular tissue. This conclusion is reinforced by previous literature that concluded the damage to the structure of the trabecular tissue is reduced when using nanofracture, compared to the other two techniques. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

Background. Microfracture (MF) and Autologous Chondrocyte Implantation (ACI) are used to repair symptomatic condylar cartilage defects (grade II-IV Outerbridge). Superiority of ACI to MF is still debated. The aim of the study was to conduct a systematic literature review, compare superiority of ACI versus MF in a meta-analysis and investigate the correlation between patient age and outcome of both treatments. Methods. Extended literature search was conducted (papers from January 2001 to present), looking at patient characteristics, pre- and post-operative scores and cartilage repair assessment evaluation. Methodological quality was verified through modified Coleman score and assessment bias. A fixed-effect meta-analysis was conducted, comparing post-operative standardised mean differences between ACI and MF. Pearson correlation coefficient between post-operative score and age was calculated against ACI and MF. Results. of 490 studies systematically analysed, 8 met the inclusion criteria, accounting for 255 patients treated with ACI and 259 with MF. Overall mean postoperative scores were 81.38±8.31 for ACI and 74.9±7.0 for MF, with no significant difference (p=0.13). The average modified Coleman score of the studies was 82.6, with low bias among them. The meta-analysis displayed an overall effect estimate of 0.3 favouring ACI treatment versus MF (95%CI=0.12–0.48, P=0.001). Significant heterogeneity was although observed (I2>70%). Pearson correlation coefficient calculated between mean post-operative score and mean age, surprisingly failed to indicate clear correlation for ACI (r=0.11) and MF (r=0.18) respectively. Conclusions. Minor statistically significant superiority of ACI intervention versus MF in knee cartilage repair was found, together with high levels of heterogeneity, halting the possibility to make full recommendation of ACI versus MF. Level of Evidence. Ia (systematic review and meta-analysis)

Arthroscopic management of femoroacetabular impingement (FAI) has become the mainstay of treatment. However, chondral lesions are frequently encountered and have become a determinant of less favourable outcomes following arthroscopic intervention. The aim of this systematic review and meta-analysis was to assess the outcomes of hip arthroscopy (HA) in patients with FAI and concomitant chondral lesions classified as per Outerbridge. A systematic search was performed using the PRISMA guidelines on four databases including MEDLINE, EMBASE, Cochrane Library and Web of Science. Studies which included HA as the primary intervention for management of FAI and classified chondral lesions according to the Outerbridge classification were included. Patients treated with open procedures, for osteonecrosis, Legg-Calve-Perthes disease, and previous ipsilateral hip fractures were excluded. From a total of 863 articles, twenty-four were included for final analysis. Demographic data, PROMs, and radiological outcomes and rates of conversion to total hip arthroplasty (THA) were collected. Risk of bias was assessed using ROBINS-I. Improved post-operative PROMs included mHHS (mean difference:-2.42; 95%CI:-2.99 to −1.85; p<0.001), NAHS (mean difference:-1.73; 95%CI: −2.23 to −1.23; p<0.001), VAS (mean difference: 2.03; 95%CI: 0.93-3.13; p<0.001). Pooled rate of revision surgery was 10% (95%CI: 7%-14%). Most of this included conversion to THA, with a 7% pooled rate (95%CI: 4%-11%). Patients had worse PROMs if they underwent HA with labral debridement (p=0.015), had Outerbridge 3 and 4 lesions (p=0.012), concomitant lesions of the femoral head and acetabulum lesions (p=0.029). Reconstructive cartilage techniques were superior to microfracture (p=0.042). Even in concomitant lesions of the femoral head and acetabulum, employing either microfracture or cartilage repair/reconstruction provided a benefit in PROMs (p=0.027). Acceptable post-operative outcomes following HA with labral repair/reconstruction and cartilage repair in patients with FAI and concomitant moderate-to-severe chondral lesions, can be achieved. Patients suffering from Outerbridge 3 and 4 lesions, concomitant acetabular rim and femoral head chondral lesions that underwent HA with labral debridement, had worse PROMs. Reconstructive cartilage techniques were superior to microfracture. Even in concomitant acetabular and femoral head chondral lesions, employing either microfracture or cartilage repair/reconstruction was deemed to provide a benefit in PROMs

Rotator cuff repair has excellent clinical outcomes but continues to be a challenge when it comes to large and massive tears as well as revision procedures. Reported symptomatic retear rates are still too high to be acceptable. The purpose of the present study was to evaluate the effectiveness of a combination of augmentation techniques consisting of microfractures of the greater tuberosity, extracellular matrix (ECM) patch graft and subsequent platelet concentrate (PC) subacromial injections in revision rotator cuff repair. The study was designed as a retrospective comparative study on prospectively collected data from a consecutive cohort of patients. All patients who underwent arthroscopic revision rotator cuff repair for symptomatic failure of previous posterosuperior rotator cuff repair were considered eligible for the study. Symptomatic failure had been diagnosed according to clinical examination and confirmed by magnetic resonance imaging (MRI). Structural integrity had been assessed on MRI and classified according to Sugaya classification. Only patients affected by stage IV-V were considered eligible. Tear reparability was confirmed during arthroscopy. Only patients with a minimum 2 years follow-up were included. Patients were divided in two groups. In group 1 (control group) a standard arthroscopic revision and microfractures of the greater tuberosity were performed; in group 2 (experimental group), microfractures of the greater tuberosity and a ECM patch graft were used to enhance tendon repair, followed by postoperative PC injections. Minimum follow-up was 12 months. Primary outcome was the Constant-Murley score (CMS) normalized for age and gender. Subjective outcome was assessed with the Disabilities of the Arm, Shoulder and Hand (DASH) score in its short version (Quick-DASH). Tendon integrity was assessed with MRI at 6 months after surgery. Comparison between groups for all discrete variables at baseline and at follow-up was carried out with the Student's t-test for normally distributed data, otherwise Mann-Whitney U-test was used. Within-group differences (baseline vs follow-up) for discrete variables were analyzed by paired t-test, or by Wilcoxon signed-rank test in case of data with non-normal distribution. Differences for categorical variables were assessed by chi-squared test. Significance was considered for p values < 0.05. Forty patients were included in the study (20 patients for each group). The mean follow-up was 13 ± 1.6 months. No patients were lost at the follow up. Comparison between groups did not show significant differences for baseline characteristics. At follow-up, mean CMS was 80.7 ± 16.6 points in group 1 and 91.5 ± 11.5 points in group 2 (p= 0.022). Mean DASH score was 28.6 ± 21.6 points in group 1 and 20.1 ± 17.4 points in group 2 (p= 0.178). Post-operative MRI showed 6 healed shoulders in Group 1 and 16 healed shoulders in Group 2 (p<0.004). No postoperative complications were reported in both groups. The combination of microfractures of the greater tuberosity, ECM patch graft, and subsequent PC subacromial injections is an effective strategy in improving tendon healing rate

For chondral damage in younger patients, surgical best practice is microfracture, which involves drilling into the bone to liberate the bone marrow. This leads to a mechanically inferior fibrocartilage formed over the defect as opposed to the desired hyaline cartilage that properly withstands joint loading. While some devices have been developed to aid microfracture and enable its use in larger defects, fibrocartilage is still produced and there is no clear clinical improvement over microfracture alone in the long term. Our goal is to develop 3D printed devices, which surgeons can implant with a minimally invasive technique. The scaffolds should match the functional properties of cartilage and expose endogenous marrow cells to suitable mechanobiological stimuli in-situ, in order to promote healing of articular cartilage lesions before they progress to osteoarthritis, and rapidly restore joint health and mobility. Importantly, scaffolds should direct a physiological host reaction, instead of a foreign body reaction, associated with chronic inflammation and fibrous capsule formation, negatively influencing the regenerative outcome. Our novel silica/polytetrahydrofuran/polycaprolactone hybrids were prepared by sol-gel synthesis and scaffolds were 3D printed by direct ink writing. 3D printed hybrid scaffolds with pore channels of ~250 µm mimic the compressive behaviour of cartilage. Our results show that these scaffolds support human bone marrow stem/stromal cell (hMSC) differentiation towards chondrogenesis in vitro under hypoxic conditions to produce markers integral to articular cartilage-like matrix evaluated by immunostaining and gene expression analysis. Macroscopic and microscopic evaluation of subcutaneously implanted scaffolds in mice showed that scaffolds caused a minimal resolving inflammatory response. Our findings show that 3D printed hybrid scaffolds have the potential to support cartilage regeneration. Acknowledgements: Authors acknowledge funding provided by EPSRC grant EP/N025059/1

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

Thermal osteonecrosis is a side effect when used Kirschner (K) wires and drills in orthopaedic surgeries. This osteonecrosis may endanger the fixation. Orthopaedic surgeons sometimes have to use unsharpened K-wires in emergent surgery. The thermal effect of used and unsharpened K wire is ambiguous to the bone. This experimental study aims to assess the thermal osteonecrosis while drilling bone with three different types of K-wires especially a previously used unsharpened wire and its thermographic measurements correlation. Two different speeds of rotation were chosen to investigate the effect of speed on thermal necrosis to the bone. A total of 16 New Zealand white rabbits weighing a mean of 2.90 kg (2.70 – 3.30 kg) were used. All rabbits were operated under general anaesthesia in a sterile operating room. Firstly, 4 cm longitudinal lateral approach was used to the right femur and then the femur was drilled with 1.0 mm trochar tip, spade tip and previously used unsharpened K-wires and 1.0 mm drill bit at 1450 rpm speed. Left femur was drilled with same three type K-wires and drill bit at 330 rpm speed. One cm distance was left among four penetrations on the femur. The thermal changes were recorded by Flir® E6 Thermal Camera from 50 cm distance and 30-degree angle. Thermographic measurements saved for every drilling process and recorded for the highest temperature (°C) during the drilling. All subjects were sacrificed post-operatively on the eighth day and specimens were prepared for the histological examination. The results of osteonecrosis assessment score and thermographic correlation were evaluated statistically. Histological specimens were evaluated by the scoring of osteonecrosis, osteoblastic activity, haemorrhage, microfracture and inflammation. Results were graded semi-quantitatively as none, moderate or severe for osteonecrosis, haemorrhage and inflammation. The microfracture and osteoblastic activity were evaluated as present or absent. There was no meaningful correlation between osteonecrosis and the drilling speed (p=0.108). There was less microfracture zone which was drilled with trochar tip K-wires at 1450 rpm speed (p=0.017). And the drilling temperature of trochar tip K-wires was higher than the others(p=0.001). Despite this evaluation, osteonecrosis zone of spade and unsharpened tip K-wires were more than trochar tip K-wires (p=0.039). The drill bit at 330 rpm caused the least osteonecrosis and haemorrhage and respectfully the lowest drilling temperature (p=0,001). The osteoblastic activity shows no difference between the groups. (p=0,122; 0,636;0.289). On the contrary to the literature, our experiment showed that there is no meaningful correlation between osteonecrosis score and temperature produced by drilling. The histological assessment showed the osteonecrosis during short drilling time but, not clarify the relation with drilling temperature. Eventually, the osteonecrosis showed a positive correlation with drilling time independently of drilling temperature at 330 rpm. (p=0,042) These results show that we need more studies to understand about osteonecrosis and its relationship with drilling heat temperature. Trochar tip K-wires creates higher drilling temperature but less osteonecrosis than a spade and unsharpened cut tip K-wires. Using unsharpened tip K-wire causes more osteonecrosis. Previously used and, unsharpened K-wires should be discarded

Lesions in the joint surface are commonly treated with osteoarticular autograft transfer system (OATS), autologous cell implantation (ACI/MACI), or microfracture. Tissue formed buy the latter commonly results in mechanically inferior fibrocartilage that fails to integrate with the surrounding native cartilage, rather than durable hyaline cartilage. Fractional laser treatment to make sub-millimeter (<500 µm) channels has been employed for tissue regeneration in the skin to facilitate rejuvenation without typical scarring. Additionally, we have pioneered a means to generate articular cartilage matrix from chondrocytes—dynamic Self-Regenerating Cartilage (dSRC). Combining these two approaches by performing fractional laser treatment of the joint cartilage and treating with dSRC is a new paradigm for joint surface restoration. This approach was refined in a series of in vitro experiments and tested in swine knee defects during a 6-month study in 12 swine. dSRC are generated by placing 10. 7. swine knee chondrocytes into sealed 15-mL polypropylene tubes and cultured on a rocker at 40 cycles per minute for 14 days at 37°C. The chondrocytes aggregate and generate new extracellular matrix to form a pellet of dSRC. Channels of approximately 300-500 µm diameter were created by infrared laser ablation in swine cartilage (in vitro) and swine knees (in vivo). The diameter and depth of the ablated channel in the cartilage was controlled by the light delivery parameters (power, spot size, pulse duration) from a fractional 2.94 µm Erbium laser. The specimens were evaluated with histology (H&E, safranin O, toluidine blue) and polarized-sensitive optical coherence tomography for collagen orientation. We can consistently create laser-ablated channels in the swine knee and successfully implant new cartilage from dSRC to generate typical hyaline cartilage in terms of morphology and biochemical properties. The neocartilage integrates with host cartilage in vivo. These findings demonstrate our novel combinatorial approach for articular cartilage rejuvenation

Articular cartilage injury has a high prevalence in elite and recreational athletes. Articular cartilage repair remains a challenge due to cost effectiveness and clinical effectiveness issues. There are now several effective technologies and it is possible to return to competitive sports following many of the procedures available. The durability of repair tissue is variable and there remains extensive growth in the Scientific world. Evolving cartilage restoration technologies focus on increasing cartilage quality and quantity, while optimising surgery and rehabilitation. In UK ACI has undergone extensive cost effectiveness analysis and the in-depth review has shown that ACI is cost effective compared to microfracture. ACI is indicated for lesions >2cm sq but NICE has considered that it is not indicated for problems after microfracture. This presentation details the various options available to surgeons and examines the cost effectiveness

Symptomatic articular cartilage defects are one of the most common knee injuries, arising from acute trauma, overuse, ligamentous instability, malalignment, meniscectomy, osteochondritis dissecans. Surgical treatment options include bone marrow–stimulating techniques such as abrasion arthroplasty and microfracture, osteochondral mosaicplasty, corrective osteotomy, cartilage resurfacing techniques and tissue engineering techniques using combinations of autologous cells (chondrocytes and mesenchymal stem cells), bioscaffolds, and growth factors. Matrix induced autologous chondrocyte implantation (MACI) is considered the most surgically simple form of autologous chondrocyte implantation. Our group has involved in the development of MACI since 2000 and has led to the FDA approval of MACI as the first tissue engineering product for cartilage repair in 2016. In this article, we have documented the characterisation of autologous chondrocytes, the surgical procedure of MACI and the long term clinical assessment (15 years) of patients with treatment of MACI. We have also reported the retrospective survey in patients with MACI in Australia. Our results suggest that MACI has gained good to excellent long term clinical outcome and probably can delay total knee replacement. However, restoration of hyaline-like cartilage by MACI may be interrupted by the osteoarthritic condition of the joint in patients with progressed osteoarthritis. In addition, because articular cartilage and subchondral bone are considered a single functional unit that is essential for joint function, many cartilage repair technologies including MACI and microfractures have failed short to address the functional barrier structure of osteochondral unit. Further studies are required to develop tissue engineering osteochondral construct that is able to fulfil the function of articular cartilage-subchondral bone units

Abstract. Background. Recurrent patellar dislocation in combination with cartilage injures are difficult injuries to treat with confounding pathways of treatment. The aim of this study is to compare the clinical and functional outcomes of patients operated for patellofemoral instability with and without cartilage defects. Methods. 82 patients (mean age-28.8 years) with recurrent patellar dislocations, who underwent soft-tissue or bony procedures, were divided into 2 matched groups (age, sex, follow-up and type of procedure) of 41 each based on the presence or absence of cartilage defects in patella. Chondroplasty, microfracture, osteochondral fixation or AMIC-type procedures were done depending on the nature of cartilage injury. Lysholm, Kujala, Tegner and Subjective Knee scores of both groups were compared and analysed. Complications and return to theatre were noted. Results. With a mean follow-up of 8 years (2 years-12.3 years), there was a significant improvement observed in all the mean post-operative Patient Reported Outcome Measures (p<0.05) of both the groups, as compared to the pre-operative scores. Comparing the 2 groups, post-operative Lysholm, Kujala and Subjective knee scores were significantly higher in patients operated without cartilage defects (p<0.05). 3 patients operated for PFJ instability with cartilage defects had to undergo patellofemoral replacement in the long term. Odds ratio for developing complications is 2.6 for patients operated with cartilage defects. Conclusion. Although there is a significant improvement in the long term outcome scores of patients operated for recurrent patellar dislocation with cartilage defects, the results are significantly inferior as compared to those without cartilage defects, along with a higher risk of developing complications and returning to theatre. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Background. Recurrent patellar dislocation in combination with cartilage injures are difficult injuries to treat with confounding pathways of treatment. The aim of this study is to compare the clinical and functional outcomes of patients operated for patellofemoral instability with and without cartilage defects. Methods. 82 patients (mean age-28.8 years) with recurrent patellar dislocations, who underwent soft-tissue or bony procedures, were divided into 2 matched groups (age, sex, follow-up and type of procedure) of 41 each based on the presence or absence of cartilage defects in patella. Chondroplasty, microfracture, osteochondral fixation or Autologous Matrix-Induced Chondrogenesis(AMIC)-type procedures were done depending on the nature of cartilage injury. Lysholm, Kujala, Tegner and Subjective Knee scores of both groups were compared and analysed. Complications and return to theatre were noted. Results. With a mean follow-up of 8 years (2 years-12.3 years), there was a significant improvement observed in all the mean post-operative Patient Reported Outcome Measures (p<0.05) of both the groups, as compared to the pre-operative scores. Comparing the 2 groups, post-operative Lysholm, Kujala and Subjective knee scores were significantly higher in patients operated without cartilage defects (p<0.05). 3 patients operated for patellofemoral instability with cartilage defects had to undergo patellofemoral replacement in the long term. Odds ratio for developing complications is 2.6 for patients operated with cartilage defects. Conclusion. Although there is a significant improvement in the long term outcome scores of patients operated for recurrent patellar dislocation with cartilage defects, the results are significantly inferior as compared to those without cartilage defects, along with a higher risk of developing complications and returning to theatre

Abstract. Introduction. Ankle arthritis is estimated to affect approximately 72 million people worldwide. Treatment options include fusion and total ankle replacement (TAR). Clinical performance of TAR is not as successful as other joint replacement and failure is poorly understood. Finite element analysis offers a method to assess the strain in bone implanted with a TAR. Higher strain has been associated with microfracture and alters the bone-implant interface. The aim of this study was to explore the influence of implant fixation on strain within the tibia when implanted with a TAR through subject-specific models. Methods. Five cadaveric ankles were scanned using a Scanco Xtreme CT. The Tibia and Talus were segmented from each scan and virtually implanted with a Zenith TAR (Corin, UK) according to published surgical technique. Patient specific models were created and run at five different positions of the gait cycle corresponding to peak load and flexion values identified from literature. Bone material properties were derived from CT greyscale values and all parts were meshed with linear tetrahedral elements. The implant-bone interface was adjusted to fully-fixed or frictionless contact, representing different levels of fixation post-surgery. Strain distributions around the tibial bone fixation were measured. Results. Initial results showed clear differences in strain distributions both between different ankle specimens and fixation levels, with highest strain occurring within the bone at the tip of the tibial stem. Frictionless contact gave higher strain outputs than fully-fixed for all specimens with a range 0.12–0.3% and 0.07%–0.13% respectively. Conclusions. In all specimens, strain was higher in the frictionless contact, which may be considered representative of no bony ingrowth, highlighting fixation may be a critical factor in TAR failure. Differences observed between specimens highlights that TAR may not be a suitable intervention for all patients, due to variation in bone quality and anatomy. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

The goal of surgery for osteochondral lesions is to regenerate the damaged cartilage with ideally hyaline cartilage. The current gold standard treatment is bone marrow stimulation (BMS) by microfracture. In reality however BMS typically results in the generation of fibrocartilage. Orthobiologics including bone marrow aspirate, platelet rich plasma and hyaluronic acid products have been shown to promote cartilage healing and potentially increase the formation of hyaline cartilage in treated lesions. However the role of these products, the timing of their administration and frequency of application are still not clearly defined and their routine use is still not recommended. These issues and future directions for research and future clinical application will be discussed

Aim of the study was to evaluate if abrasion-arthroplasty (AAP) and abrasion-chondroplasty (ACP) leads to a release of mesenchymal stem cell (MSC) like cells from the bone marrow to the joint cavity where they probably differentiate into a chondrogenic phenotype. Introduction. Cartilage demage is a sever problem in our aging society. About 5 million people only in Germany are affected. Osteoathritis is a degeneration of cartilage caused by aging or traumata 50 % of the people over 40 have signs of osteoarthritis. But the ability of self-regeneration of cartilage is strongly limited. There are different approaches to therapy osteoathritic lesions. Arthroscopic treatment of OA includes bone marrow stimulation technique such as abrasion arthroplasty (AAP) and microfracturing (MF). Beside the support of chondrocyte progenitor cells the environment is also important for the commitment to chondrocytes. Therefore insulin-like growth factor-1 (IGF-1) and transforming growth factor beta-1 (TGF-β1) are important factors during the regeneration process. In the present study we characterised the heamarthrosis and the released cells after AAP and its ability to differentiate into the chondrocyte lineage. Material and Methods. Postoperative haemarthrosis was taken 5, 22 or 44 hours after surgery. 7.5 mg Dexamethasone (Corticosteroid) was administered into the knee joint to prevent postoperative inflammation. Mononuclear cells were isolated from haemarthrosis from the drainage bottle by ficoll density gradient centrifugation. The isolated cells were characterised using fluorescence-activated cell-sorting (FACS) analysis for characteristic markers of MSC such as CD 44, 73, 90, 105. After expanding cells were cultured in a pellet culture. After 3 weeks, histochemistry and immunohistochemistry against Sox9, collagen II and proteoglycan were performed. The release of IGF1, BMP4 and BMP7 was analysed in haemarthrosis serum by ELISA and Luminex technology. Results. The isolated cells after AAP are positive for the mesenchymal stem cell marker CD105, CD90, CD73, CD 44 and negative for the marker of hematopoetic stem cells CD 34. Isolated cells after ACP couldn't be expanded for further characterizations. The staining of the 3D-culture revealed a positive signal for the chondrogen transcription factor Sox9 and the expression of extracellular markerproteins like collagen type II and proteoglycan. Both surgery techniques, AAP and ACP provides a chondrogenic environment. We were able to detect IGF-1, TGFß, BMP4 and BMP7 in the haemarthrosis. Discussion. The benefit of abrasion arthroplasty surgery and microfracturing is controversial discussed because they do not consistently result in hyaline cartilage. But the opening of the bone marrow allows the release of monocytic cells which have the potential to differentiate into a chondrogenic phenotype. In 3D-culture these cells express Sox9 and a collagen proteoglycan rich matrix. The haemarthrosis provides also a cartilage-stimulating environment. We could detect IGF1, TGFβ, BMP4 and 7 which could enhance the commitment concerning differentiation of MSCs to a chondrogenic lineage concerning the production of cartilage specific extracellular matrix. Taken together our study provides the evidence for a therapeutic benefit of opening bone marrow in order to generate neocartilage after AAP

Osteoarthritis (OA) affects millions of people and is the fastest growing cause of disability worldwide. In order to address this burden, early intervention strategies have been proposed. Therapies that utilise bone marrow stromal cells (BM-MSCs) to induce cartilage repair, either as a cell therapy or by endogenous release by drilling or microfracture, have proved promising. However, limitations include fibrotic features of the regenerated cartilage that may affect mechanical properties and therefore the longevity of such a repair. In order to improve this regenerative technique, further research is required to understand the key players in the repair mechanism. An interaction, which may be important, is that between BM-MSCs and the resident chondrocytes. The aim of this study is to understand the interplay between BM-MSC and resident chondrocytesisolated from different zonal locations within the human knee. We compared chondrocytes from three different cartilage areas: chondrocytes from 1) the superficial zone (SZ) and 2) the middle-deep (MDZ) zone of non-weight bearing femoral condyles, and from 3) the osteoarthritic zone (OAZ) of patients undergoing knee replacement. First, we evaluated the influence of different chondrocytes on BM-MSCs monolayer in a transwell co-culture, assessing transcript levels of early chondrogenic markers including Sox9 and Col1. Secondly, in a 3D co-culture system, we evaluated how cartilage chips from the three different zones affect the chondrogenic differentiation of BM-MSC pellets. Results indicated that cells from the SZ induce chondrogenic differentiation of BM-MSCs when co-cultured. In contrast, MDZ and OAZ have a negative effect, compared to control conditions. Our findings suggest that chondrocytes from the SZ, a zone which has been reported to reduce with age and may be lost in advanced OA, is important to direct BM-MSCs differentiation towards the chondrogenic fate. This may be relevant to cartilage repair strategies

Osteoarthritis is characterised by the loss and damage of cartilage in synovial joints. Whilst joint replacement is the gold standard for end stage disease, repair or regenerative strategies aim to slow disease progression, maintain joint function and defer the need for joint replacement. One approach seeks to target endogenous repair after drilling or microfracture (a type of trauma induced repair) in the area of cartilage loss – connecting the defect to the underlying bone marrow niche. The rationale of this approach is that cells delivered to the defect site, from the bone marrow, will bring about cartilage repair. Bone marrow contains multipotent cells, including stem and stromal populations, of both the haematopoietic and skeletal systems. Bone marrow mesenchymal stromal cells (BMSCs) are characterised by tri-lineage differentiation (bone, cartilage and adipose tissue) and contribute to the formation of the bone marrow niche, which maintains haematopoietic stem cell quiescence. This quiescence ensures life-long haematopoiesis and the supply of mature blood cells to the haematopoietic system. In this study we investigate the interactions between haematopoietic and BMSCs (in both human and mouse cultures) specifically to understand the consequences on BMSCs during tissue repair. A murine MSC cell-line model was co-cultured with enriched fractions of primary murine haematopoietic progenitor cells isolated based on c-Kit, Sca-1, and lineage markers. Similarly, human bone marrow derived MSCs were co-cultured with primary bone marrow haematopoietic fractions isolated based on CD34, CD38 and lineage markers. Using confocal microscopy, we demonstrated that the two cell populations directly interact through cell-cell contact with haematopoietic cells located above and below the MSC monolayer. Cultures were then pushed to differentiate down the osteogenic lineage. Results indicate that MSCs co-cultured with haematopoietic cells exhibited significant inhibition of osteogenesis when analysed by functional assay of matrix mineralisation and gene expression analysis for transcripts including Runx2, Osterix and type I collagen. These data support the hypothesis that hematopoietic progenitor cells influence both the local homeostasis of the bone marrow as well as the repair potential of stromal cells. Such interactions could be important for the resolution of injury after trauma induced repair. Furthermore, manipulation of these interactions, such as the administration of haematopoietic cell stimulating agents, could be used to improve treatment outcomes