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Objective: To systematically review the literature and analyze clinical outcomes and return-to-sport after surgical management of cartilage injuries in football players., Design: A systematic literature review was performed in August 2023 on PubMed, WebOfScience, and Cochrane Library to collect studies on surgical strategies for cartilage lesions in football players. Methodological quality and risk of bias were assessed with the modified Coleman Methodology score and RoB2 and RoBANS2 tools., Results: Fifteen studies on 409 football players (86% men, 14% women) were included: nine prospective and two retrospective case series, one randomized controlled trial, one prospective comparative study, one case report, and one survey. Bone marrow stimulation (BMS) techniques were the most documented. The lesion size influenced the treatment choice: debridement was used for small lesions (1.1 cm 2 ), BMS, osteochondral autograft transplantation (OAT), matrix-assisted autologous chondrocytes transplantation (MACT), and scaffold-augmented BMS for small/mid-size lesions (2.2-3.0 cm 2 ), and autologous chondrocytes implantation (ACI) for larger lesions (5.8 cm 2 ). The surgical options yielded different results in terms of clinical outcome and return-to-sport, with fastest recovery for debridement and scaffold-augmented BMS. The current evidence is limited with large methodological quality variation (modified Coleman Methodology score 43.5/100) and a high risk of bias., Conclusions: Decision-making in cartilage injuries seems to privilege early return-to-sport, making debridement and microfractures the most used techniques. The lesion size influences the treatment choice. However, the current evidence is limited. Further studies are needed to confirm these findings and establish a case-based approach to treat cartilage injuries in football players based on the specific patient and lesion characteristics and the treatments' potential in terms of both return-to-sport and long-term results., Level of Evidence: Systematic review, level IV., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Biological agents like growth factors (ie, platelet rich plasma) and mesenchymal stem cells are rising in popularity among orthopedics. Orthobiologics therapy aims to fill the gap between conventional conservative therapies like hyaluronic acid and surgery, especially for cartilage disease. Ankle cartilage defects are very symptomatic and could lead to a severe decrease of quality of life in patients, because of pain, swelling, and inability to walk without pain. In this scenario, this paper aims to systematically review the current literature available about biological therapies for ankle cartilage., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: New scaffold-based cartilage regeneration techniques have been developed to improve the results of microfractures also in complex locations like the patello-femoral joint. The aim of this study was to analyse the results obtained in patellar lesions treated with a bioscaffold,  a mixture composed by a chitosan solution, a buffer, and the patient's whole blood  which forms a stable clot into the lesion., Methods: Fifteen patients with ICRS grade 3-4 cartilage lesions of the patellar surface were treated with a chitosan bioscaffold. Fourteen patients were clinically and radiologically evaluated prospectively for a minimum follow-up of 2 years with IKDC, KOOS, Tegner score, and MRI. The mean age of patients at the time of surgery was 31.8 ± 11.9 and nine patients presented degenerative aetiology, four patients with previous trauma, and 1 patient with osteochondritis dissecans.  RESULTS: The IKDC subjective score improved from 46.2 ± 19.3 preoperatively to 69.5 ± 20.3 (p < 0.05) and 74.1 ± 23.2 (p < 0.05) at 12 and 24 months, respectively. Also KOOS Pain, KOOS Sport/Rec and KOOS QOL showed a significant improvement from baseline to 12 months and to the final follow-up. MRI evaluation showed a complete filling of the cartilage defect at the final follow-up in 70% of the lesions, obtaining a total MOCART 2.0 score of 71.5 ± 13.6 at 24 months after surgery., Conclusion: Chondral patellar lesions represent a complex pathology, with lower results compared to other sites. This bioscaffold represents a safe surgical treatment providing a significant clinical improvement at 24 months in the treatment of patellar cartilage lesions., Level of Evidence: IV., (© 2022. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

The degeneration of osteochondral tissue represents one of the major causes of disability in modern society and it is expected to fuel the demand for new solutions to repair and regenerate the damaged articular joints. In particular, osteoarthritis (OA) is the most common complication in articular diseases and a leading cause of chronic disability affecting a steady increasing number of people. The regeneration of osteochondral (OC) defects is one of the most challenging tasks in orthopedics since this anatomical region is composed of different tissues, characterized by antithetic features and functionalities, in tight connection to work together as a joint. The altered structural and mechanical joint environment impairs the natural tissue metabolism, thus making OC regeneration even more challenging. In this scenario, marine-derived ingredients elicit ever-increased interest for biomedical applications as a result of their outstanding mechanical and multiple biologic properties. The review highlights the possibility to exploit such unique features using a combination of bio-inspired synthesis process and 3D manufacturing technologies, relevant to generate compositionally and structurally graded hybrid constructs reproducing the smart architecture and biomechanical functions of natural OC regions.

Background: Lesions of the articular cartilage, with or without involvement of the subchondral bone, are a common cause of pain and dysfunction in the knee. Although several treatment options have been developed, the majority of previous clinical trials examined patients with isolated or focal midsized defects, which rarely represent the condition found in the general population. Rather, cartilage lesions are often associated with the presence of mild to moderate osteoarthritic changes., Purpose: The present multicenter randomized controlled trial compared the clinical and radiographic outcomes of an aragonite-based osteochondral implant with a control group (arthroscopic debridement/microfractures) in patients affected by joint surface lesions of the knee, including those with concurrent mild to moderate osteoarthritis., Study Design: Randomized controlled trial; Level of evidence, 1., Methods: A total of 251 patients were enrolled in 26 medical centers according to the following criteria: age 21 to 75 years, up to 3 cartilage defects of International Cartilage Regeneration & Joint Preservation Society grade 3a or above located on the femoral condyles and/or trochlea, total treatable area from 1 to 7 cm 2 , bony defect depth ≤8 mm, and knee osteoarthritis grade 0 to 3 according to Kellgren-Lawrence score. Patients were randomized to the aragonite-based implant or debridement/microfracture control arm in a 2:1 ratio. Evaluation was performed at 6, 12, 18, and 24 months based on overall Knee injury and Osteoarthritis Outcome Score (KOOS) as the primary endpoint, and the KOOS subscales (Pain, Quality of Life, Activities of Daily Living), percentage of responders, and International Knee Documentation Committee (IKDC) subjective score as the secondary endpoints. Patients also underwent magnetic resonance imaging evaluation at 12 and 24 months to assess defect fill grade. Failures (ie, need for any secondary treatment) and adverse events were also recorded., Results: The implant group showed a statistically superior outcome in the primary endpoint and all secondary endpoints at each follow-up. The magnitude of improvement in the implant group was twice as large as that in the control group in terms of mean KOOS improvement at 2 years. Responder rate (defined as at least a 30-point improvement in overall KOOS) was 77.8% in the implant group as opposed to 33.6% in the control ( P < .0001). Statistically superior results were seen in the IKDC score as well. At 24 months, 88.5% of the implanted group had at least 75% defect fill on magnetic resonance imaging as compared with 30.9% of controls ( P < .0001). The failure rate was 7.2% for the implant group versus 21.4% for control., Conclusion: This aragonite-based scaffold was safe and effective in the treatment of chondral and osteochondral lesions in the knee, including patients with mild to moderate osteoarthritis, and provided superior outcomes as compared with the control group., Registration: NCT03299959 (ClinicalTrials.gov identifier).

Aims: For patients with cartilage defects of the knee, a new biocompatible and in situ cross-linkable albumin-hyaluronan-based hydrogel has been developed for matrix-associated autologous chondrocyte implantation (M-ACI) - NOVOCART Inject plus (Ninject; TETEC AG, Reutlingen, Germany). We aimed to estimate the potential cost-effectiveness of NInject, that is not available on the market, yet compared to spheroids of human autologous matrix-associated chondrocytes (Spherox; CO.DON GmbH, Leipzig, Germany) and microfracture., Materials and Methods: An early Markov model was developed to estimate the cost-effectiveness in the United Kingdom (UK) from the payer perspective. Transition probabilities, response rates, utility values and costs were derived from literature. Since NInject has not yet been launched and no prices are available, its costs were assumed equal to those of Spherox. Cycle length was set at one year and the time horizon chosen was notional patients' remaining lifetime. Model robustness was evaluated with deterministic and probabilistic sensitivity analyses (DSA; PSA) and value of information analysis (VOIA). The Markov model was built using TreeAge Pro Healthcare., Results: NInject was cost-effective compared to microfracture (ICER: ₤5,147) while Spherox was extendedly dominated. In sensitivity analyses, the ICER exceeded conventional WTP threshold of ₤20,000 only when the utility value after successful first treatment with NInject was decreased by 20% (ICER: ₤69,620). PSA corroborated the cost-effectiveness findings of NInject, compared to both alternatives, with probabilities of 60% of NInject undercutting the aforementioned WTP threshold and being the most cost-effective alternative. The VOIA revealed that obtaining additional evidence on the new technology will likely not be cost-effective for the UK National Health Service., Limitations and Conclusion: This early Markov model showed that NInject is cost-effective for the treatment of articular cartilage defects in the knee, compared to Spherox and microfracture. However, as the final price of NInject has yet to be determined, the cost-effectiveness analysis performed in this study is provisional, assuming equal prices for NInject and Spherox.

Osteoarthritis (OA) is a common degenerative joint disease treated mostly symptomatically before approaching its definitive treatment, joint arthroplasty. The rapidly growing prevalence of OA highlights the urgent need for a more efficient treatment strategy and boosts research into the mechanisms of OA incidence and progression. As a multifactorial disease, many aspects have been investigated as contributors to OA onset and progression. Differences in gender appear to play a role in the natural history of the disease, since female sex is known to increase the susceptibility to its development. The aim of the present review is to investigate the cues associated with gender by analyzing various hormonal, anatomical, molecular, and biomechanical parameters, as well as their differences between sexes. Our findings reveal the possible implications of gender in OA onset and progression and provide evidence for gaps in the current state of art, thus suggesting future research directions.

Purpose: The aim of this study was to compare three procedures to exploit adipose-derived cells for the treatment of osteoarthritis (OA) in a preclinical model, to understand their therapeutic potential and identify the most suitable approach for the clinical application., Methods: Biological samples from adipose tissue, processed by mechanical micro-fragmentation (MF), enzymatic digestion (SVF) or cell expansion (ADSCs), were first characterized in vitro and then used in vivo in a surgically induced OA rabbit model: Group 1-control group (untreated 12 knees/saline 12 knees), Group 2-MF (24 knees), Group 3-SVF (24 knees), Group 4-ADSCs (24 knees). Macroscopic, histological, histomorphometric, immunohistochemical and blood and synovial fluid analyses were evaluated at 2 and 4 months from the treatments., Results: Samples obtained by the three procedures yielded 85-95% of viable cells. In vivo assessments showed no significant side effects or inflammatory responses after the injection. The macroscopic Hanashi score did not show significant differences among treated groups and controls. The histopathological evaluation of synovial tissues showed lower signs of synovitis for MF, although the semiquantitative analysis (Krenn score) did not reach statistical significance. Instead, MF showed the best results both in terms of qualitative and semi-quantitative evaluations of articular cartilage, with a more uniform staining, a smoother surface and a significantly better Laverty score (p = 0.004)., Conclusion: MF, SVF, and expanded ADSCs did not elicit significant local or systemic adverse reactions in this preclinical OA model. Among the different methods used to exploit the adipose tissue potential, MF showed the most promising findings in particular in terms of protection of the articular surface from the joint degenerative OA processes., Level of Evidence: Preclinical animal study., (© 2021. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Objective: To develop patient-focused consensus guidelines on the indications for the use of scaffolds to address chondral and osteochondral femoral condyle lesions., Design: The RAND/UCLA Appropriateness Method (RAM) was used to develop patient-specific recommendations by combining the best available scientific evidence with the collective judgement of a panel of experts guided by a core panel and multidisciplinary discussers. A list of specific clinical scenarios was produced regarding adult patients with symptomatic lesions without instability, malalignment, or meniscal deficiency. Each scenario underwent discussion and a 2-round vote on a 9-point Likert-type scale (range 1-3 "inappropriate," 4-6 "uncertain," 7-9 "appropriate"). Scores were pooled to generate expert recommendations., Results: Scaffold (chondral vs. osteochondral), patient characteristics (age and sport activity level), and lesion characteristics (etiology, size, and the presence of osteoarthritis [OA]) were considered to define 144 scenarios. The use of scaffold-based procedures was considered appropriate in all cases of chondral or osteochondral lesions when joints are not affected by OA, while OA joints presented more controversial results. The analysis of the evaluated factors showed a different weight in influencing treatment appropriateness: the presence of OA influenced 58.3% of the indications, while etiology, size, and age were discriminating factors in 54.2%, 29.2%, and 16.7% of recommendations, respectively., Conclusions: The consensus identified indications still requiring investigation, but also the convergence of the experts in several scenarios defined appropriate or inappropriate, which could support decision making in the daily clinical practice, guiding the use of scaffold-based procedures for the treatment of chondral and osteochondral knee defects.

Background: Cell-free devices have been introduced to restore osteochondral defects, avoiding the limitations of cell-based procedures. Among these, an osteochondral scaffold made of type I collagen and hydroxyapatite has been investigated with promising results up to medium-term follow-up. However, the clinical and imaging results over time still need to be documented., Purpose: To evaluate the clinical outcome and tissue maturation at long-term follow-up after the implantation of the osteochondral scaffold., Study Design: Case series; Level of evidence, 4., Methods: A total of 24 patients (7 women, 17 men; age, 36 ± 9.5 years) underwent surgical implantation of the osteochondral scaffold and were prospectively evaluated before surgery, at 2-, 5-, and 10-year follow-up. The mean defect size was 2.9 ± 1.4 cm 2 . Patients were evaluated using the International Knee Documentation Committee (IKDC) subjective and objective scores, and the activity level was documented with the Tegner score. Magnetic resonance imaging (MRI) evaluation involved the use of the magnetic resonance observation of cartilage repair tissue score combined with 5 more variables focused on the bone layer., Results: A statistically significant improvement of all clinical scores was documented from the baseline to the final evaluation. The IKDC subjective score improved from the preoperative level to 2 years (41 ± 13.2 and 77.1 ± 14.6, respectively) ( P < .0005), with stable results up to 10 years (77.4 ± 19.4). The IKDC objective score changed from 52% of normal and nearly normal knees before the treatment to 84% at 10 years ( P < .0005). Tegner sports activity at the final evaluation (3.8 ± 1.7) was higher compared with the preoperative level (1.6 ± 1.1; P < .05), but it remained significantly lower compared with the preinjury level (5.5 ± 2.6; P < .05). Treatment failed in 1 patient. Persisting graft alterations were observed on MRI scans, although without correlating with the clinical outcome., Conclusion: The regenerative potential of this scaffold is limited, as demonstrated by the signal alterations persisting over time on MRI scans. On the other hand, the clinical improvement was significant and stable over time both in terms of subjective and objective outcomes, including activity level, with overall good results.

To present initial results of a novel, bi-phasic, porous, biodegrade, and cell-free aragonite-based scaffold for treating complex osteochondral lesions of the talus (OLT). Four subjects (2 males and 2 females; 34-61 years old) were operated on their ankles due to chronic and deep OLT-Hepple grades 4 or 5 (1.8-2.2 cm 2 ). Three subjects had OLT on the medial central trochlea, and 1 had a combined medial and lateral lesions. OLT were exposed through medial malleolus osteotomy, with an additional lateral arthrotomy in the combined lesions. Bi-phasic porous osteochondral scaffolds (single implant or 2 implants) were implanted in a press-fit manner using a designated surgical toolset. Treatment outcome was followed clinically (Foot and Ankle Outcome Score, EQ-5D 3L, Tegner activity scale) and by medical imaging (radiographs, magnetic resonance imaging) from 18 to 32 months. All Foot and Ankle Outcome Score values increased from preoperative to final follow-up values (Symptoms 62 to 71, Pain 53 to 84, ADL 60 to 89, Sport 19 to 65, and QoL 18 to 47). EQ-5D 3L increased from 0.59 to 0.76, and Tegner activity values increased from 1.5 to 3. Kellgren-Lawrence ankle radiographic scores remained stable (2 to 2). Postoperative MR evaluation demonstrated cartilage defect fill of 75% to 100% respect to the native cartilage in 3 subjects (4 OLTs), while 1 lesion was filled 25% to 50%. No graft related serious adverse events or graft failures were reported. The use of a bi-phasic osteochondral biodegradable aragonite-based scaffold in the treatment of complex OLT during the reported period presented positive and promising clinical and radiologic outcome, without serious adverse events or graft failures., (Copyright © 2020 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Osteoarthritis (OA) is considered a contraindication to most cartilage repair techniques. Several regenerative approaches have been attempted with the aim of delaying or preventing joint replacement, with controversial results. Currently, there is a paucity of data on the use of single-step techniques, such as cell-free biomimetic scaffolds, for the treatment of joint surface lesions (JSLs) in OA knees., Purpose: To present the 2-year follow-up clinical and radiological outcomes after implantation of a novel, cell-free aragonite-based scaffold for the treatment of JSLs in patients with mild to moderate knee OA in a multicenter prospective study., Study Design: Case series; Level of evidence, 4., Methods: A total of 86 patients, 60 male and 26 female, with a mean age of 37.4 ± 10.0 years, mild to moderate knee OA, and a mean defect size of 3.0 ± 1.7 cm 2 , were recruited at 8 medical centers according to the following criteria: radiographic mild to moderate knee OA (Kellgren-Lawrence grade 2 or 3); up to 3 treatable chondral/osteochondral defects (International Cartilage Repair Society grades 3 and 4) on the femoral condyles or trochlea; a total defect size ≤7 cm 2 ; and no concurrent knee instability, severe axial malalignment, or systemic arthropathy. All patients were evaluated at baseline and at 6, 12, 18, and 24 months after implantation using the Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) subjective score. Additionally, magnetic resonance imaging (MRI) was performed to assess the amount of cartilage defect filling at the repaired site., Results: Significant improvement on all KOOS subscales was recorded from baseline (Pain: 49.6 ± 13.1; Activities of Daily Living [ADL]: 56.1 ± 18.4; Sport: 22.8 ± 18.8; Quality of Life [QoL]: 23.5 ± 16.5; Symptoms: 55.4 ± 19.9) to the 24 months' follow-up (Pain: 79.5 ± 21.1 [ P < .001]; ADL: 84.1 ± 21.4 [ P < .001]; Sport: 60.8 ± 31.9 [ P < .001]; QoL: 54.9 ± 30.4 [ P < .001]; Symptoms: 77.7 ± 21.2 [ P < .001]). The IKDC subjective score showed a similar trend and improved from 37.8 ± 14.7 at baseline to 65.8 ± 23.5 at 24 months ( P < .001). MRI showed a significant increase in defect filling over time: up to 78.7% ± 25.3% of surface coverage after 24 months. Treatment failure requiring revision surgery occurred in 8 patients (9.3%)., Conclusion: The use of an aragonite-based osteochondral scaffold in patients with JSLs and mild to moderate knee OA provided significant clinical improvement at the 24-month follow-up, as reported by the patients. These findings were associated with good cartilage defect filling, as observed on MRI.

Purpose: Aiming to prevent cartilage damage during early osteoarthritis (OA), the therapeutic challenge is to restore and maintain the physiological and functional properties of such a tissue with minimally invasive therapeutic strategies., Methods: Accordingly, an in vivo model of early OA in sheep was here treated through three different cell therapies (culture expanded ADSCs, SVF, and culture expanded AECs) thus to preserve the joint surface from the progression of the pathology. Three months after the treatment injections, their performance was assessed through mechanical automated mapping (Young's modulus and cartilage thickness), gross evaluation of articular surfaces, and biochemical analysis of the synovial fluid., Results: No severe degeneration was observed after three months from OA induction. Cartilage mechanical properties were crucial to identify early degeneration. All the treatments improved the macroscopic cartilage surface aspect and reduced pro-inflammatory cytokines in the synovial fluid. Among the three treatments, SVF highlighted the best performance while ADSCs the worst., Conclusion: Despite that the evaluated experimental time is an early follow-up and, thus, longer trial is mandatory to properly assess treatments effectiveness, the proposed multidisciplinary approach allowed to obtain preliminary, but also crucial, results concerning the reduction in OA signs on cartilage properties, in osteophyte development and in all the inflammatory markers.

Purpose: To investigate the safety and regenerative potential of a hemicondylar aragonite-based scaffold in the reconstruction of large osteochondral lesions occupying an extensive portion of the medial femoral condyle in a goat model., Methods: Eight Saanen goats were treated by the implantation of an aragonite-based scaffold (size: 19 × 8 × 8 mm) on a previously prepared hemicondylar osteochondral defect located in the right medial femoral condyle of the knee. Goats were euthanized after 12 months and the specimens underwent X-ray imaging, macroscopic, micro-computed tomography, histology, and immunohistochemistry evaluations to assess subchondral bone and cartilage regeneration., Results: In all 8 goats, no adverse event or persistent inflammation was observed. The evaluations performed showed integration of the scaffold, which almost completely resorbed at 12 months. In all animals, no signs of osteoarthritis progression were seen. Concurrent regeneration of the osteochondral unit was observed, with trabecular bone tissue replacing the implant and restoring the subchondral layer, and the formation of an overlying hyaline cartilage surface, well integrated within the surrounding native tissue, also was observed., Conclusions: The use of the hemicondylar biphasic aragonite-based implant in the treatment of osteochondral defects in the goat model proved to be technically feasible and safe. The scaffold degraded and was replaced by regenerated tissue within the 12-month study period, restoring the osteochondral unit both at the level of the cartilaginous layer and the subchondral bone., Clinical Relevance: The present animal study describes a scaffold-based procedure for the treatment of large condylar defects, which often require massive allograft or unicompartmental replacement. The aragonite-based implant promoted a regeneration of both cartilage and subchondral bone, and its use as a "biologic" unicondylar prosthesis might be feasible also in the clinical setting., (Copyright © 2020 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Purpose: Osteochondral implants are currently adopted for the treatment of symptomatic full-thickness chondral and osteochondral defects. Agili-C™ is a cell-free aragonite-based scaffold which aims to reproduce the original structure and function of the articular joint while directing the growth and regeneration of both cartilage and its underlying subchondral bone. The goal of the present study was to investigate the ex vivo mechanisms of action (MOA) of the Agili-C™ implant in the repair of full-thickness cartilage defects. In particular, we tested whether Agili-C™ implant has the potential to stimulate cartilage ingrowth through chondrocytes migration into the 3D interconnected porous structure of the scaffold, along with maintaining their viability and phenotype and the deposition of hyaline cartilage matrix., Methods: Articular cartilage samples were collected through the Gift of Hope Organ and Tissue Donor Network (Itasca, IL) within 24 h from death. For this study, cartilage from a total of 14 donors was used. To model a chondral defect, donut-shaped cartilage explants were prepared from each tissue specimen. The chondral phase of the Agili-C™ implant was placed inside the tissue in full contact and press fit manner. Cartilage explants with the Agili-C™ implant inside were cultured for 60 days. As a control, the same donut-shaped cartilage explants were cultured without Agili-C™, under the same culture conditions., Results: Using fresh human cadaveric articular cartilage tissue in a 60-day culture, it was demonstrated that chondrocytes were able to migrate into the Agili-C™ scaffold and contribute to the deposition of the extracellular matrix (ECM) rich in collagen type II and aggrecan, and lacking collagen type I. Additionally, we were able to show the formation of a layer populated by progenitor-like cells on the articular surface of the implant., Conclusions: The analysis of samples taken from knee and ankle joints of human donors with a wide age range and both genders supports the potential of Agili-C™ scaffold to stimulate cartilage regeneration and repair. Based on these results, the present scaffold can be used in the clinical practice as a one-step procedure to treat full-thickness chondral defects.

Purpose: To identify the most appropriate implantation strategy for a novel chondral scaffold in a model simulating the early post-operative phase, in order to optimize the implant procedure and reduce the risk of early failure., Methods: Eight human cadaveric limbs were strapped to a continuous passive motion device and exposed to extension-flexion cycles (0°-90°). Chondral lesions (1.8 cm diameter) were prepared on condyles, patella and trochlea for the implant of a bi-layer collagen-hydroxyapatite scaffold. The first set-up compared four fixation techniques: press-fit (PF) vs. fibrin glue (FG) vs. pins vs. sutures; the second compared circular and square implants; the third investigated stability in a weight-bearing simulation. The scaffolds were evaluated using semi-quantitative Drobnic and modified Bekkers scores., Results: FG presented higher total Drobnic and Bekkers scores compared to PF (both p = 0.002), pins (p = 0.013 and 0.001) and sutures (p = 0.001 and < 0.0005). Pins offered better total Drobnic and Bekkers scores than PF in the anterior femoral condyles (p = 0.007 and 0.065), similar to FG. The comparison of round and square implants applied by FG showed worst results for square lesions (Drobnic score p = 0.049, Bekkers score p = 0.037). Finally, load caused worst overall results (Drobnic p = 0.018)., Conclusions: FG improves the fixation of this collagen-HA scaffold regardless of lesion location, improving implant stability while preserving its integrity. Pins represent a suitable option only for lesions of the anterior condyles. Square scaffolds present weak corners, therefore, round implants should be preferred. Finally, partial weight-bearing simulation significantly affected the scaffold. These findings may be useful to improve surgical technique and post-operative management of patients, to optimize the outcome of chondral scaffold implantation.

Current therapeutic strategies for osteochondral restoration showed a limited regenerative potential. In fact, to promote the growth of articular cartilage and subchondral bone is a real challenge, due to the different functional and anatomical properties. To this purpose, alginate is a promising biomaterial for a scaffold-based approach, claiming optimal biocompatibility and good chondrogenic potential. A previously developed mineralized alginate scaffold was investigated in terms of the ability to support osteochondral regeneration both in a large and medium size animal model. The results were evaluated macroscopically and by microtomography, histology, histomorphometry, and immunohistochemical analysis. No evidence of adverse or inflammatory reactions was observed in both models, but limited subchondral bone formation was present, together with a slow scaffold resorption time.The implantation of this biphasic alginate scaffold provided partial osteochondral regeneration in the animal model. Further studies are needed to evaluate possible improvement in terms of osteochondral tissue regeneration for this biomaterial.

The evaluation of key factors modulating cell homing following injection can provide new insights in the comprehension of unsolved biological questions about the use of cell therapies for osteoarthritis (OA). The main purpose of this in vivo study was to investigate the biodistribution of an intra-articular injection of mesenchymal stromal cells (MSCs) and bone marrow concentrate (BMC) in a rabbit OA model and whether the additional use of sodium hyaluronate (HA) could modulate their migration and delay joint degeneration. OA was surgically induced in adult male New Zealand rabbits. A group of animals was used to test the biodistribution of labeled cells alone or with HA at 7 and 14 days to investigate cell migration. The efficacy of treatments was evaluated in other experimental groups at 2 months. Histology and immunohistochemistry for markers identifying anabolic and catabolic processes in the cartilage and meniscus, or macrophage subset population in the synovial membrane, were performed. Kruskal-Wallis test, followed by post hoc Dunn's test, and Spearman's rank-order correlation method were used. MSCs and BMC preferentially migrate toward tissue areas showing OA features in the meniscus and cartilage and in detail near inflammatory zones in the synovial membrane. The combination with HA contributed to boost cell migration toward articular cartilage. In general, both labeled cells combined with HA were found near cell cluster and fissures in the cartilage and meniscus, respectively, and close to areas of synovial membrane showing mainly anti-inflammatory macrophages. A promotion of joint repair was observed at different levels for all treatments, although BMC-HA treatment resulted as the best strategy to support joint repair. This last, displayed a good protein expression of type II collagen in the cartilage, as well as the presence of anti-inflammatory macrophages in the synovial membrane at 2 months from the treatment. Studies tracking cell biodistribution indicate that priming progenitor cells with HA modulated cell homing favoring not only attachment but also their integration within articular cartilage.

Purpose: To document the available evidence on the influence of cartilage lesions on the results of anterior cruciate ligament (ACL) surgery and their management to optimize the final outcome., Methods: A systematic review was performed on the PubMed database on articles dealing with cartilage lesions detected at the time of ACL reconstruction, by looking both for their influence on the clinical outcome and the results of their treatment. Reports on clinical, radiological, or second-look outcomes at any follow-up were included. Exclusion criteria were preclinical studies, reviews, or studies not reporting clinical, radiological, or second-look outcome after primary ACL reconstruction., Results: Thirty-seven studies were included for the final analysis. Twenty-seven focused on the influence of cartilage lesions on clinical outcome after ACL reconstruction in 47,837 patients. In total, 21/27 articles showed a correlation with a poorer outcome in terms of subjective, objective, and radiographic findings. Lesion location and depth influenced final results. Only 9.0 % of these defects were treated in the analysed studies, and only 10 manuscripts of overall low level evaluated the results of combined cartilage-ACL treatments., Conclusion: The majority of the literature supports the clinical relevance of cartilage lesions which are correlated with a poorer outcome after ACL reconstruction. Nonetheless, a large amount of chondral defects are actually not addressed, also considering the poor evidence for the benefits provided by cartilage treatments. In fact, only a few studies specifically focused on how to manage cartilage lesions found during ACL reconstruction and there is a lack of indications for the most appropriate treatment approach., Level of Evidence: IV.

Background: Age is commonly accepted as a negative prognostic factor in cartilage surgery, and cutoff values of 30 to 40 years have been previously suggested as treatment indication. However, the lower outcome scores documented in older patients do not take in consideration the decreasing requirements of an aging joint., Purpose: To analyze the real effect of age in terms of recovery with respect to the functional level expected for different age categories of patients treated for cartilage lesions., Study Design: Cohort study; Level of evidence, 3., Methods: Patients with International Cartilage Repair Society (ICRS) grade 3-4 defects, involving femoral condyles or trochlea without osteoarthritis, were treated with arthroscopic matrix-assisted autologous chondrocyte transplantation; 157 patients were evaluated with IKDC subjective and Tegner scores before surgery and then after 2 and 10 years. Results were first evaluated by dividing patients into 2 age groups according to the generally approved cutoff value of 40 years. The analysis was then repeated after the scores of each patient were standardized according to the score achievable per the normative data in healthy patients for the corresponding sex and age category., Results: A significant improvement in all scores was observed. IKDC subjective score improved from 38.9 ± 14.5 to 74.7 ± 21.8 at 10 years. When a cutoff value of 40 years was used, older patients reached a significantly worse IKDC subjective value at 10 years (65.8 ± 24.3 vs 77.2 ± 20.4, P = .007). However, different findings were obtained after the scores were standardized. Although optimal results were still found in younger patients (<30 years), patients older than 40 years also appeared to benefit from the treatment, and no significant differences were noted compared with the younger population., Conclusion: The benefit of cartilage treatments in patients with increasing age but without any sign of osteoarthritis was higher than previously reported in literature. In fact, when the decreasing functional level expected by an aging population was considered, standardized results showed an overall benefit after cartilage treatment in patients older than 40 years that was not significantly different from the outcome achieved in younger patients. Thus, age is not a strict contraindication as previously suggested, and future studies should consider standardization of data to prove the real age limit of cartilage treatments.

Background: The treatment of symptomatic cartilage defects of the patella is particularly challenging, and no gold standard is currently available., Purpose: To evaluate the clinical results of a biphasic cell-free collagen-hydroxyapatite scaffold and to evaluate osteochondral tissue regeneration with magnetic resonance imaging (MRI)., Study Design: Case series; Level of evidence, 4., Methods: Thirty-four patients (18 men and 16 women; mean ± SD: age, 30.0 ± 10 years) were treated by scaffold implantation for knee chondral or osteochondral lesions of the patella (area, 2.1 ± 1 cm 2 ). The clinical evaluation was performed prospectively at 12 and 24 months via the IKDC (International Knee Documentation Committee; objective and subjective) and Tegner scores. MRI evaluation was performed at both follow-ups in 18 lesions through the MOCART score (magnetic resonance observation of cartilage repair tissue) and specific subchondral bone parameters., Results: A statistically significant improvement in all the scores was observed at 12- and 24-month follow-up as compared with the basal evaluation. The IKDC subjective score improved from 39.5 ± 14.5 to 61.9 ± 14.5 at 12 months ( P > .0005) with a further increase to 67.6 ± 17.4 at 24 months of follow-up (12-24 months, P = .020). The MRI evaluation showed a stable value of the MOCART score between 12 and 24 months, with a complete filling of the cartilage in 87.0% of the lesions, complete integration of the graft in 95.7%, and intact repair tissue surface in 69.6% at final follow-up. The presence of osteophytes or more extensive bony overgrowth was documented in 47.8% of the patients of this series, but no correlation was found between MRI findings and clinical outcome., Conclusion: The implantation of a cell-free collagen-hydroxyapatite osteochondral scaffold provided a clinical improvement at short-term follow-up for the treatment of patellar cartilage defects. Women had lower outcomes, and the need for realignment procedures led to a slower recovery. MRI evaluation showed some abnormal findings with the presence of bone overgrowth, but no correlation has been found with the clinical outcome.

Long-term results of autologous chondrocyte implantation and matrix-assisted autologous chondrocyte transplantation in the knee are satisfying, but not enough attention has been paid to the evaluation of failures. Thus, a systematic review of the literature was performed, underlining a failure rate in the 58 included articles of 14.9% among 4294 patients, most of them occurring in the first 5 years after surgery, and with no difference between autologous chondrocyte implantation and matrix-assisted autologous chondrocyte transplantation. Failures are very heterogenously defined in the current literature. A widely accepted definition is needed, and a comprehensive definition taking into consideration the patient's perception of the outcome, not just the surgeon's or researcher's point of view, would be advisable. Finally, there is no agreement on the most appropriate treatment of failures, and further studies are needed to give better indications to properly manage patients failed after cartilage procedures., Level of Evidence: Level IV.

The surgical treatment of knee articular focal lesions may offer heterogeneous clinical results. Osteochondritis dissecans (OCD) lesions showed to heal better than degenerative lesions (DL) but the underlying biological reasons are unknown. We evaluated the basal histological and immunohistochemical characteristics of these lesions analyzing a series of osteochondral fragments from young patients with similar age but presenting different etiology. Osteochondral tissue samples were stained with Safranin O and graded using a histological score. Markers of mesenchymal progenitor cells (CD146), osteoclasts (tartrate-resistant acid phosphatase, TRAP), and vessels (CD34) were evaluated. Histological score showed a higher degeneration of both cartilage and bone compartments in OCD compared to DL fragments. Only CD146-positive cells were found at the same percentage in cartilage compartment of both DL and OCD patients. By contrast, in the bone compartment a significantly higher percentage of CD146, TRAP, and CD34 markers was found in OCD compared to DL patients. These data showed distinct histological characteristics of osteochondral focal lesions located in the same anatomical region but having a different etiology. The higher percentages of these markers in OCD than in DL, mainly associated with a high bone turnover, could help to explain the higher clinical healing potential of OCD patients.

Introduction: Chondral and osteochondral lesions represent a debilitating disease. Untreated lesions remain a risk factor for more extensive joint damage. The objective of this clinical study is to evaluate safety and early results of an aragonite-based scaffold used for osteochondral unit repair, by analysing both clinical outcome and MRI results, as well as the benefits of the procedure optimization through novel tapered shaped implants., Methods: A crystalline aragonite bi-phasic scaffold was implanted in patients affected by focal chondral-osteochondral knee lesions of the condyle and trochlea. Twenty-one patients (17 men, 4 women with a mean age of 31.0 ± 8.6 years) without severe OA received tapered shaped implants for the treatment of 2.5 ±1.7 cm 2 sized defects. The control group consisted of 76 patients selected according to the same criteria from a database of patients who previously underwent implantation of cylindrical-shaped implants. The clinical outcome of all patients was evaluated with the IKDC subjective score, the Lysholm score, and all 5 KOOS subscales administered preoperatively and at 6 and 12 months after surgery, while MRI evaluation was performed at the 12 month follow-up., Results: A statistically significant improvement in all clinical scores was documented both in the tapered implants and the cylindrical group. No difference could be detected in the comparison between the improvement obtained with the two implant types, neither in the clinical nor in imaging evaluations. A difference could be detected instead in terms of revision rate, which was lower in the tapered implant group with no implant removal - 0% vs 8/76-10.5% failures in the cylindrical implants., Conclusions: This study highlighted both safety and potential of a novel aragonite-based scaffold for the treatment of chondral and osteochondral lesions in humans. A tapered shape relative to the cylindrical shaped implant design, improved the scaffold's safety profile. Tapered scaffolds maintain the clinical improvement observed in cylindrical implants while reducing the postoperative risk of revision surgery. This aragonite-based implant was associated with a significant clinical improvement at the 12 month follow-up. Moreover, MRI findings revealed graft integration with good bone and cartilage formation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The diagnosis and the prompt treatment of early osteoarthritis (OA) represent vital steps for delaying the onset and progression of fully blown OA, which is the most common form of arthritis, involving more than 10 % of the world's population older than 60 years of age. Nonsurgical treatments such as physiotherapy, anti-inflammatory medications, and other disease-modifying drugs all have modest and short-lasting effect. In this context, the biological approaches have recently gained more and more attention. Growth factors, blood derivatives, such as platelet concentrates, and mesenchymal adult stem cells, either expanded or freshly isolated, are advocated amongst the most promising tool for the treatment of OA, especially in the early phases. Primarily targeted towards focal cartilage defects, these biological agents have indeed recently showed promising results to relieve pain and reduce inflammation in patients with more advanced OA as well, with the final aim to halt the progression of the disease and the need for joint replacement. However, despite of a number of satisfactory in vitro and pre-clinical studies, the evidences are still limited to support their clinical efficacy in OA setting.

There is an increasing awareness on the importance in identifying early phases of the degenerative processes in knee osteoarthritis (OA), the crucial period of the disease when there might still be the possibility to initiate treatments preventing its progression. Early OA may show a diffuse and ill-defined involvement, but also originate in the cartilage surrounding a focal lesion, thus necessitating a separate assessment of these two entities. Early OA can be considered to include a maximal involvement of 50 % of the cartilage thickness based on the macroscopic ICRS classification, reflecting an OARSI grade 4. The purpose of this paper was to provide an updated review of the current status of the diagnosis and definition of early knee OA, including the clinical, radiographical, histological, MRI, and arthroscopic definitions and biomarkers. Based on current evidence, practical classification criteria are presented. As new insights and technologies become available, they will further evolve to better define and treat early knee OA.

In recent years treatment of early osteoarthritis came more and more into focus of orthopaedic research. In particular regenerative therapy options seem to have a high potential to fill the existing treatment gap for patients with early osteoarthritic changes. This article focuses on basic science, recent developments and available clinical data in the important field of operative regeneration procedures for treatment of chondral and osteochondral defects in early degenerative joints. It highlights current knowledge and perspectives of treatment options like microfracture, autologous or allogenous osteochondral transplantations and autologous chondrocyte transplantation. Further the role of biomaterials in a degenerative joint environment is illuminated. First clinical data of regenerative therapy in early osteoarthritis are encouraging to intensify research efforts in this important field. Future treatment perspectives for patients who suffer from early degenerative cartilage changes are discussed.

Mesenchymal stem cells (MSCs) have emerged as a promising option to treat articular defects and early osteoarthritis (OA) stages. However, both their potential and limitations for a clinical use remain controversial. Thus, the aim of this systematic review was to examine MSCs treatment strategies in clinical settings, in order to summarize the current evidence of their efficacy for the treatment of cartilage lesions and OA.Among the 60 selected studies, 7 were randomized, 13 comparative, 31 case series, and 9 case reports; 26 studies reported the results after injective administration, whereas 33 used surgical implantation. One study compared the two different modalities. With regard to the cell source, 20 studies concerned BMSCs, 17 ADSCs, 16 BMC, 5 PBSCs, 1 SDSCs, and 1 compared BMC versus PBSCs. Overall, despite the increasing literature on this topic, the evidence is still limited, in particular for high-level studies. On the other hand, the available studies allow to draw some indications. First, no major adverse events related to the treatment or to the cell harvest have been reported. Second, a clinical benefit of using MSCs therapies has been reported in most of the studies, regardless of cell source, indication, or administration method. This effectiveness has been reflected by clinical improvements and also positive MRI and macroscopic findings, whereas histologic features gave more controversial results among different studies. Third, young age, lower BMI, smaller lesion size for focal lesions, and earlier stages of OA joints have been shown to correlate with better outcomes, even though the available data strength does not allow to define clear cutoff values. Finally, definite trends can be observed with regard to the delivery method: currently cultured cells are mostly being administered by i.a. injection, while one-step surgical implantation is preferred for cell concentrates. In conclusion, while promising results have been shown, the potential of these treatments should be confirmed by reliable clinical data through double-blind, controlled, prospective and multicenter studies with longer follow-up, and specific studies should be designed to identify the best cell sources, manipulation, and delivery techniques, as well as pathology and disease phase indications.

Purpose: "Early Osteoarthritis (EOA)" has been defined combining clinical, imaging and surgical parameters, with the aim to identify patients in early degenerative phases, who might benefit from the use of available regenerative procedures. Aim of this first clinical trial is to prospectively evaluate the results obtained in a group of patients meeting the inclusion criteria of "EOA" as proposed by the ESSKA Cartilage Committee, and surgically treated with the implantation of a multi-phasic osteochondral scaffold., Methods: 23 patients were prospectively evaluated at 12 and 24 months of follow-up. Etiology of the chondral or osteochondral defect was rated as microtraumatic or degenerative in 18 cases, and traumatic in 5 cases. Patients included were complaining of clinical symptoms like knee pain and affected by chondral and osteochondral lesions located at the femoral condyles or trochlea and MRI findings demonstrating articular cartilage degeneration and/or meniscal degeneration and/or subchondral bone marrow lesions., Results: All patients increased significantly in any clinical score adopted. The IKDC subjective score increased from 42.8 ± 13.8 at basal evaluation to 74.3 ± 17.4 at 12 months' (p < 0.0005), being stable (74.9 ± 20.4) up to the final follow-up of 24 months. Tegner score showed a statistically significant improvement in sports activity from 3.3 ± 2.7 pre-operative to 4.6 ± 2.2 at 12 months (p < 0.005), with a slight improvement to the final evaluation (4.7 ± 2.1; n.s.). However, the activity level was significantly lower than the pre-injury one (6.1 ± 2.6; p = 0.004). A significant difference was shown between patients younger versus older than 40 years, with younger patients had better clinical improvement (76.0 ± 18.6 vs 45.1 ± 38.8 respectively, p = 0.037)., Conclusions: The implantation of a multi-phasic osteochondral scaffold represents a good option after failure of conservative management for Early OA patients, where younger age represent an important factor for a better outcome. Longer follow-up is needed to evaluate the benefit over time., Level of Evidence: IV, case series., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: While midterm results of matrix-assisted autologous chondrocyte transplantation (MACT) are now available, less attention has been paid to the evaluation of failures of this surgical approach. Aim of this study was to analyse how "failures" are generally defined in cartilage surgery, in order to understand how the survival rate may change according to different definitions of failure., Methods: A systematic review on MACT in the knee was conducted to report failure rates as well as different failure definitions in the available literature. Afterwards, we analysed the survival curve at 8.5-year follow-up of a survey of 193 patients treated with MACT. Using different definitions to identify failures, we compared how the survival rate changed according to the different definitions of failure., Results: The systematic review on 93 papers showed that the average failure rate reported on 3,289 patients was 5.2 % at a mean 34 months of follow-up. However, 41 studies (44.1 %) did not even consider this aspect, and failures were variously defined, thus generating confusing data that make a meta-analysis or a study comparison meaningless. The failure analysis of the MACT survey showed that the survival curve changed significantly depending on the definition applied; in fact, the failure rate ranged from 3.6 to 33.7 %. According to a critical literature and survey analysis, we proposed a combined surgical- and improvement-based definition which led to a failure rate of 25.9 % at midterm/long-term follow-up., Conclusion: Nowadays, failure definitions of cartilage treatments differ in scientific articles, thus generating confusion and heterogeneous data even when applied to the same cohort of patients. While the literature analysis shows a low number of failures, this study demonstrated that if properly addressed with a comprehensive definition, the real failure rate of cartilage surgical procedures in the knee is higher than previously reported. Recognizing failures would give a better understanding and a more realistic prognosis to patients and physicians seeking treatment for cartilage lesions., Level of Evidence: IV.

Purpose: Regenerative scaffold-based procedures are emerging as a potential therapeutic option for the treatment of chondral and osteochondral lesions. In general, we can summarize most of the recent developments to reach clinical application into 2 major trends: the use of different cell sources or the application of biomaterials as a cell-free approach. The aim of this systematic review was to analyze both preclinical and clinical studies on these new trends to understand how the available evidence supports the use of cell sources or justifies the cell-free approach for the scaffold-based treatment of cartilage lesions., Methods: The research was performed using the PubMed database by looking at studies published in the English language referring to chondral or osteochondral defect repair with scaffold-based procedures until the end of 2013. The following strings were used: ("cartilage"[MeSH] AND "tissue scaffolds"[MeSH])., Results: The search showed an increasing number of published articles each year for both scaffold-based approaches, identifying a total of 305 articles. Among clinical trials, 116 used cell-based scaffold treatments and 11 used scaffolds alone. In the preclinical setting, a scaffold/cell combination was the most used treatment approach (133 v 45 articles), with mesenchymal stem cells (MSCs) being the favorite cell type. Bone marrow was the most used cell source, but other sources are gaining interest. Among articles comparing scaffolds with or without cells, the majority reported superior results for cells (71 of 89 articles). In the clinical setting, most of the articles analyzed chondrocyte-based scaffolds, with only 7 studies using MSCs; all cells were from bone marrow. Despite the lower number of articles, cell-free scaffolds are gaining popularity, with a recent increase in published studies showing promising results., Conclusions: This systematic review underlined the difficulties in understanding the real need for cells to increase the scaffold-based cartilage healing potential because of the heterogeneity of products used as well as the design of the published studies. Scaffold and cell combinations were the most investigated option in the preclinical setting, showing generally superior results, but in the clinical setting, both strategies remain used. In particular, although chondrocytes are the most commonly used cell type, research showed increasing interest in the potential of MSCs for cartilage regeneration. However, the difficulties in managing cell cultures, together with the development of a new generation of materials able to exploit the intrinsic tissue regeneration ability, justifies the clinical use of cell-free scaffolds, with increasing literature and promising preliminary results., Level of Evidence: Level IV, systematic review of Level I to IV studies., (Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: This study aims to document the long-term results in a group of patients treated with arthroscopic mosaicplasty for knee cartilage lesions, both in terms of clinical outcome and joint degeneration progression, evaluated by radiographs., Methods: 26 patients (19 men and 7 women, mean age 29 years, mean BMI 23) treated arthroscopically with mosaicplasty for cartilage defects of the femoral condyles (mean/median/mode size 1.9 standard deviation, SD 0.6 cm(2)) were prospectively evaluated at 12 years follow-up. The clinical outcome was analyzed with IKDC and Tegner scores. Range of motion, transpatellar and suprapatellar circumferences were also measured. Radiographs with weight-bearing antero-posterior and Rosenberg projections were used for radiological evaluation in 18 patients, applying both Kellgren-Lawrence score and a direct joint line measurement to assess osteoarthritis., Results: A significant improvement in all clinical scores was obtained from the basal evaluation to the 12-year follow-up (IKDC subjective score from 36.8 standard deviation, SD 13.0 to 77.3 standard deviation, SD 20.6, P<0.0005; Tegner score from 2.9 standard deviation, SD 1.3 to 5.2 standard deviation, SD 2.5, P<0.0005), and better results in patients with a higher pre-injury activity level and those requiring fewer plugs. The radiographic evaluation showed significantly poorer Kellgren-Lawrence scores and a reduction of the joint line in the treated compartments. Knees with 3-4 plugs presented a significantly higher joint degeneration level with respect to those implanted with 1-2 plugs., Conclusions: Mosaicplasty is an effective surgical option for small lesions of the femoral condyles. Although joint degeneration progression was present at 12 years, this did not affect significantly the clinical outcome which was satisfactory at long-term follow-up., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Osteochondral defects are often symptomatic and lead to deranged joint function. The spontaneous healing capacity of osteochondral defects is limited. In this case study, use of an acellular scaffold capable of induction of mesenchymal stem-cell migration is described. This scaffold was used on an Outerbridge grade IV medical condylar defect measuring ~2 cm2. At 24 mo follow-up, the articular surface appeared restored by MRI, and the patient returned to sports.

Purpose: The objective of this study was to examine whether different mechanical modifications and/or impregnation of hyaluronic acid (HA) might enhance aragonite-based scaffold properties for the regeneration of cartilage and bone in an animal model., Methods: Bi-phasic osteochondral scaffolds were prepared using coralline aragonite with different modifications, including 1- to 2-mm-deep drilled channels in the cartilage phase (Group 1, n = 7) or in the bone phase (Group 2, n = 8), and compared with unmodified coral cylinders (Group 3, n = 8) as well as empty control defects (Group 4, n = 4). In each group, four of the implants were impregnated with HA to the cartilage phase. Osteochondral defects (6 mm diameter, 8 mm depth) were made in medial and lateral femoral condyles of 14 goats, and the scaffolds were implanted according to a randomization chart. After 6 months, cartilage and bone regeneration were evaluated macroscopically and histologically by an external laboratory., Results: Group 1 implants were replaced by newly formed hyaline cartilage and subchondral bone (combined histological evaluation according to the ICRS II-2010 and O'Driscoll et al. 34 ± 4 n = 7). In this group, the cartilaginous repair tissue showed a smooth contour and was well integrated into the adjacent native cartilage, with morphological evidence of hyaline cartilage as confirmed by the marked presence of proteoglycans, a marked grade of collagen type II and the absence of collagen type I. The average scores in other groups were significantly lower (Group 2 (n = 8) 28.8 ± 11, Group 3 (n = 8) 23 ± 9 and Group 4 (empty control, n = 4) 19.7 ± 15)., Conclusions: The implants with the mechanical modification and HA impregnation in the cartilage phase outperformed all other types of implant. Although native coral is an excellent material for bone repair, as a stand-alone material implant, it does not regenerate hyaline cartilage. Mechanical modification with drilled channels and impregnation of HA within the coral pores enhanced the scaffold's cartilage regenerative potential. The modified implant shows young hyaline cartilage regeneration. This implant might be useful for the treatment of both chondral and osteochondral defects in humans.

Objective: To evaluate stability and integrity of bi-layer and three-layer collagen-hydroxyapatite (C-HA) osteochondral scaffolds in a human cadaveric knee exposed to continuous passive motion (CPM) with and without loading and the role of added fibrin glue to improve the press-fit fixation of C-HA scaffolds., Design: Osteochondral lesions (2.0 × 1.5 cm) were chiseled out on both condyles and trochlea in eight human cadaveric knees. A total of 24 bi-layer (5 mm, four in each condyle) or three-layer C-HA scaffolds (8 mm, eight in the trochlea, four in each condyle) were first press-fit implanted and underwent testing with CPM, 90 cycles, 0°-90°. The second set of 24 scaffolds was implanted in cleaned lesions with the addition of fibrin glue. Two knees with fibrin glue fixation were additionally exposed to 15 kg loading, with 30 cycles of CPM, 0°-30°. Then, the knees were reopened and the scaffolds were evaluated using semi-quantitative Drobnic and modified Bekkers scores., Results: All but two scaffolds remained in the lesions site throughout CPM. Two implants failed: both were bi-layer osteochondral scaffolds, press-fit implanted at the lateral femoral condyle (LFC). A statistically significant difference was obtained between press-fit and fibrin glue implants with both Drobnic (2.9 ± 0.7 vs 4.3 ± 0.1, P < 0.0005) and Bekkers (3.3 ± 1.0 vs 5.0 ± 0.1, P < 0.0005) scores. Additional knee loading did not affect fibrin glue scaffold fixation or integrity., Conclusion: This cadaveric study showed fibrin glue notably improved bi-layer or three-layer C-HA scaffold press-fit fixation regardless of lesion location. It is therefore recommended that fibrin glue be used during surgery to improve early post-operative C-HA scaffold stability and integrity., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Matrix-assisted autologous chondrocyte transplantation (MACT) has been shown to offer good outcomes at midterm follow-up, but results are heterogeneous among different patients and lesion types. Being part of the same joint, both patellar and trochlear cartilage lesions are commonly considered to be affected by the same treatment issues, and therefore, it is common practice to report results obtained treating these lesions together., Purpose: To determine, in a large cohort of patients prospectively followed at midterm follow-up for patellofemoral chondral defects, if patellar and trochlear defects actually represent different clinical conditions with different healing potentials after cartilage treatment., Study Design: Cohort study; Level of evidence, 2., Methods: A total of 49 consecutive patients with full-thickness patellofemoral chondral lesions of the knee were treated with MACT at the authors' institute and followed prospectively for a minimum follow-up of 5 years. Among these 49 patients, 28 were affected by patellar lesions, 17 were affected by trochlear lesions, and 4 had both patellar and trochlear defects. The clinical outcome was analyzed with International Knee Documentation Committee (IKDC) subjective, EuroQol visual analogue scale (EQ-VAS), Kujala, and Tegner scores., Results: A statistically significant improvement in all scores was observed after treatment. Patellar lesions required more realignment procedures and were more common in women. The comparative analysis showed better results for trochlear lesions compared with patellar lesions at all follow-ups, with mean IKDC scores at 5-year follow-up of 89.6 ± 12.7 and 69.7 ± 17.6, respectively (P < .0005). Better results were also shown for the mean Kujala score (92.4 ± 14.7 vs 81.5 ± 12.7, respectively; P = .012) and mean EQ-VAS score (90.0 ± 10.8 vs 81.9 ± 11.7, respectively; P = .027). Finally, the sport activity level evaluated with the Tegner score confirmed the same trend; even though neither patellar nor trochlear lesion groups reached the preinjury level, both improved after treatment, with a significantly higher improvement in the trochlear lesion group (5.9 ± 1.8 vs 3.9 ± 1.7, respectively; P < .0005)., Conclusion: Patient characteristics differ between patellar and trochlear cartilage defects, and moreover, the results obtained are significantly different, with a markedly good outcome in cases with trochlear lesions and less satisfactory results for patients affected by cartilage lesions of the patella. Thus, patellar and trochlear defects should be considered separately when evaluating the outcome of cartilage treatments in this anatomic region.

Background: Several cartilage lesions involve the subchondral bone, and there is a need for biphasic scaffolds to treat the entire osteochondral unit to reproduce the different biological and functional requirements and guide the growth of the 2 tissues., Purpose: To evaluate the results of a cell-free collagen-hydroxyapatite osteochondral scaffold at midterm, and to use magnetic resonance imaging (MRI) analysis to document the imaging evolution of the tissue regeneration process through 5 years of follow-up., Study Design: Case series; Level of evidence, 4., Methods: Twenty-seven patients (9 women, 18 men; mean age, 34.9 ± 10.2 years) treated for knee chondral or osteochondral lesions (size, 1.5-6 cm(2)) were followed for 2 and 5 years and were clinically evaluated using the International Knee Documentation Committee (IKDC) and Tegner scores. An MRI evaluation was performed at both follow-ups in 23 lesions, and the magnetic resonance observation of cartilage repair tissue (MOCART) score and specific subchondral bone parameters (bone regeneration, bone signal quality, osteophytes or upcoming bone front, sclerotic areas, and edema) were analyzed., Results: A statistically significant improvement in all clinical scores was observed from the initial evaluation to the 2- and 5-year follow-ups, and the results were stable over time. The mean IKDC subjective score improved from 40.0 ± 15.0 to 76.5 ± 14.5 (2-year follow-up) and 77.1 ± 18.0 (5-year follow-up) and the mean Tegner score from 1.6 ± 1.1 to 4.0 ± 1.8 (2-year follow-up) and 4.1 ± 1.9 (5-year follow-up). The MRI evaluation showed a significant improvement in both the MOCART score and subchondral bone status from 2 to 5 years. At 5 years, complete filling of the cartilage was shown in 78.3% of the lesions, complete integration of the graft was detected in 69.6% of cases, the repair tissue surface was intact in 60.9%, and the structure of the repair tissue was homogeneous in 60.9% of the cases. No correlation was found between MRI findings and clinical outcome., Conclusion: This osteochondral scaffold was used for the treatment of chondral and osteochondral knee defects with a single-step procedure. The study results highlighted the safety and potential of this procedure, which offered a good clinical outcome with stable results at midterm follow-up. Although the MRI findings improved over time, some abnormalities persisted, but no correlation was found between the imaging and clinical results.

Background: The primary aim of the present study is to evaluate the results obtained in challenging knee lesions with the implant of an osteochondral scaffold and concomitant treatment of all comorbidities. The secondary aim is to compare the results obtained with those found when a chondral scaffold was applied., Materials and Methods: Patients affected by complex lesions of the knee articular surface were included. "Complex cases" were defined according to the following criteria: previous clinical history of intra-articular fracture, lesion located at the tibial plateau, concurrent knee axial realignment procedure, concurrent meniscal scaffold or allograft implantation, and multiple articular surface lesions treated. Thirty-three patients were treated with the implantation of an osteochondral scaffold. The results of a homogeneous group of 23 patients previously treated and prospectively evaluated after implantation of a chondral scaffold were analyzed and compared., Results: IKDC subjective score improved significantly from pre-operative (40.4±14.1) to 12months' follow-up (69.6±17.0; p<0.0005) with a further improvement at the final evaluation at 24months (75.5±15.0; p=0.038). The same positive trend was confirmed by the VAS and Tegner scores. At final follow-up the group treated with the osteochondral scaffold presented a better subjective IKDC score with respect to the group treated with the chondral scaffold (p=0.034)., Conclusions: A regenerative procedure to address the entire osteochondral unit, together with the treatment of all comorbidities, might offer good results also in complex cases otherwise doomed to non-biological resurfacing., Level of Evidence Iii: Comparative study., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Sexual dimorphism in humans has already been documented at different levels, and preliminary findings also suggest the importance of patient sex on clinical outcome in the treatment of cartilage lesions., Purpose: To document and analyze the influence of sex on clinical outcome in a large cohort of patients treated with a cartilage regenerative procedure for knee chondral lesions and prospectively followed at midterm follow-up., Study Design: Cohort study; Level of evidence, 3., Methods: A total of 250 knees were treated with matrix-assisted autologous chondrocyte transplantation (MACT) and prospectively evaluated with International Knee Documentation Committee (IKDC), EuroQol visual analog scale (EQ-VAS), and Tegner scores at 1-, 2-, and minimum 5-year follow-ups to compare results obtained in men and women. The lesions were focal International Cartilage Repair Society grade III-IV chondral knee defects involving femoral condyles, trochleae, and patellae. Two homogeneous groups of 56 male patients and 56 female patients were then selected by a blinded statistician for a matched-pair analysis., Results: A statistically significant improvement in all the scores in both men and women was observed in the general population. The IKDC subjective score showed better results for men at all follow-up times: at 5 years, the mean IKDC subjective score was 79.5 ± 18.6 versus 64.3 ± 20.2 for men and women, respectively (P < .0005), and the same trend was confirmed with the EQ-VAS and Tegner scores. The matched-pair analysis confirmed the difference of final results achieved (74.1 ± 19.8 vs 63.7 ± 20.2, respectively; P = .006). However, men and women started with different preoperative levels, and the analysis of the improvement obtained was not significantly different. Finally, when scores were standardized for each patient, according to the mean score typical for the corresponding age and sex category in a healthy population, a sex-related difference was not confirmed at any of the follow-ups. Etiological factors, lesion site, and preinjury activity level differed in women and men of the general population and were the confounding factors responsible for the different outcome not confirmed by the analysis of homogeneous cohorts of patients., Conclusion: Women have a different knee chondral lesion pattern and more often have unfavorable conditions related to the cause of injury, site, and activity level, and they also have lower raw, not standardized, scores. However, a matched-pair analysis with data standardized for the specific patient categories showed that, on equal terms, women have the same possibilities for successful outcome as men after surgical treatment for knee cartilage regeneration.

Purpose: The aim of this systematic review is to examine the available clinical evidence in the literature to support mesenchymal stem cell (MSC) treatment strategies in orthopaedics for cartilage defect regeneration., Methods: The research was performed on the PubMed database considering the English literature from 2002 and using the following key words: cartilage, cartilage repair, mesenchymal stem cells, MSCs, bone marrow concentrate (BMC), bone marrow-derived mesenchymal stem cells, bone marrow stromal cells, adipose-derived mesenchymal stem cells, and synovial-derived mesenchymal stem cells., Results: The systematic research showed an increasing number of published studies on this topic over time and identified 72 preclinical papers and 18 clinical trials. Among the 18 clinical trials identified focusing on cartilage regeneration, none were randomized, five were comparative, six were case series, and seven were case reports; two concerned the use of adipose-derived MSCs, five the use of BMC, and 11 the use of bone marrow-derived MSCs, with preliminary interesting findings ranging from focal chondral defects to articular osteoarthritis degeneration., Conclusions: Despite the growing interest in this biological approach for cartilage regeneration, knowledge on this topic is still preliminary, as shown by the prevalence of preclinical studies and the presence of low-quality clinical studies. Many aspects have to be optimized, and randomized controlled trials are needed to support the potential of this biological treatment for cartilage repair and to evaluate advantages and disadvantages with respect to the available treatments., Level of Evidence: IV.

Background: Young patients with osteoarthritic knees are a challenging population because of a combination of high functional demands and limited indication for joint replacement., Purpose: To analyze the potential of the cartilage regenerative approach by documenting the results and failures of matrix-assisted autologous chondrocyte transplantation (MACT) at midterm follow-up., Study Design: Case series; Level of evidence, 4., Methods: Forty-four patients affected by cartilage lesions in osteoarthritic knees underwent MACT as a salvage procedure. The mean age at surgery was 42 years (range, 20-58 years), and the average defect size was 4 cm(2) (range, 1.5-9 cm(2)). Patients were prospectively evaluated with the subjective International Knee Documentation Committee (IKDC), EuroQol visual analog scale (EQ-VAS), and Tegner scores preoperatively; at 1, 2, and 5 years; and at a final assessment at 9 years' mean follow-up. Adverse events and failures were also reported., Results: A statistically significant improvement was observed in all scores from the initial evaluation to the final follow-up. The mean ± standard deviation IKDC subjective score improved from 38.0 ± 15.8 to 67.0 ± 18.3 at 2 years (P < .0005), with a subsequent decrease to 57.8 ± 20.6 at the final follow-up (P = .012). The same trend was confirmed by the EQ-VAS score. The activity level revealed by the Tegner score improved at all follow-ups but without achieving the preinjury level. The analysis of the influencing factors showed the importance of the meniscus condition, revealing a significantly inferior outcome in knees with previous or combined partial meniscectomy procedures. During the study period, 12 patients had failed results, producing a cumulative failure rate of 27.3%. At the last evaluation, half of the patients considered their condition not better than before the treatment, and 39% would not repeat the treatment considering the results obtained., Conclusion: Despite a statistically significant improvement, the clinical outcome was poor. A higher improvement could be obtained in patients who had not undergone previous or combined meniscectomies, but this was limited over time. The failure rate was also high, regardless of the degree of osteoarthritis. Tissue-engineered cartilage implantation is questionable for this indication, and the limits of this scaffold-based procedure have to be considered if it is used as a salvage procedure for young patients affected by knee osteoarthritis.

Purpose: The aim of this systematic review was to address the treatment of chondral and osteochondral knee lesions through the use of scaffolds, by showing surgical options and results of this scaffold-based repair approach for the healing of the articular surface., Methods: All studies published in English addressing cartilage scaffold-based treatment were identified, including those that fulfilled the following criteria: (1) Levels I to IV evidence addressing the outlined areas of interest, (2) measures of functional or clinical outcome, (3) knee cartilage lesions, and (4) minimum of 2 years of follow-up., Results: The analysis showed a progressively increasing number of articles per year from 1995 to February 2012. The number of selected articles was 51, with 40 focusing on 2-step procedures and 11 focusing on 1-step procedures. The evaluation of evidence level showed 3 randomized studies, 10 comparative studies, 33 case series, and 5 case reports., Conclusions: Regenerative scaffold-based procedures are emerging as a therapeutic option for the treatment of chondral lesions, but well-designed studies are lacking. Systematic long-term evaluation of these techniques and randomized studies are necessary to confirm the potential of this treatment approach, especially compared with the available traditional treatments. Different 1-step scaffold-based strategies are emerging to simplify the procedure and reduce costs., Level of Evidence: Level IV, systematic review of Level I to IV studies., (Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Cartilage injuries have a high incidence and a high impact on society. In an attempt to fulfill patients' expectations and successfully treat this pathology, various techniques have been developed over the years. Treatments proposed for cartilage lesions are described with their rationale and indications, ranging from conservative measures to surgical approaches, reparative or regenerative. Among the numerous and heterogeneous procedures proposed over time to treat cartilage defects none has clearly proven to lead to a hyaline articular surface nor to offer better clinical results. Regenerative procedures have been introduced as ambitious techniques that aim to overcome the limitations of the more traditional reparative approaches and restore the articular surface with a hyaline-like tissue; improvement in tissue engineering with new scaffolds as well as new regenerative options involving growth factors or MSCs are currently being investigated as promising solutions to further improve the treatment of cartilage lesions. However, the current literature findings are not conclusive. Randomized controlled trials are necessary to evaluate new regenerative approaches, to show clearly advantages and disadvantages with respect to the more traditional procedures, besides their potential, limits, and indications to improve the treatment of patients affected by chondral and osteochondral lesions. Since clear and commonly accepted treatment algorithms are not available in the literature, the massively increasing number of controversial results may be confusing for the orthopaedic surgeon who has to choose the proper management of patients with cartilage lesions. Thus, the results obtained through the study of the authors' 20 years' experience in cartilage treatment were analyzed to give some indications on the potential and limits of different treatment approaches available in clinical practice., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: Degenerative cartilage lesions present a negative joint environment, which may have a negative effect on the process of cartilage regeneration. The aim of this study is to analyze the clinical outcome obtained with the treatment for isolated degenerative knee cartilage lesions by second-generation arthroscopic autologous chondrocyte implantation (ACI)., Methods: Fifty-eight consecutive patients affected by focal degenerative chondral lesions of the femoral condyles and trochlea were treated by second-generation arthroscopic ACI. The mean age at surgery was 34.7 ± 9.1 years and the average defect size was 2.3 ± 0.9 cm(2). The patients were prospectively evaluated with IKDC, EQ-VAS, and Tegner scores preoperatively, at 2 and 6 years., Results: A statistically significant improvement was observed in all scores from the basal evaluation to the final follow-up. The IKDC subjective score improved from 39.3 ± 13.6 to 68.8 ± 22.7 and 68.5 ± 23.9 at the 2- and 6-year follow-ups, respectively, with a significant improvement (P < 0.0005) and stable results over time; the same trend was confirmed by the EQ-VAS and Tegner scores. The worst results were found in patients with a low physical activity level, women, and those having undergone previous surgery, whereas the symptom duration before surgery did not influence the final outcome. The failure rate was 18.5%., Conclusions: Despite a significant improvement, the results were lower with respect to the outcome reported in different study populations, and the number of failures was markedly higher, too. Tissue-engineered cartilage implantation is a promising approach for the treatment of degenerative chondral lesions, but graft properties, besides mechanical and biochemical joint environment, have to be improved., Level of Evidence: Case series, Level IV.

Purpose: Osteochondral defects (i.e., defects which affect both the articular cartilage and underlying subchondral bone) are often associated with mechanical instability of the joint and therefore with the risk of inducing osteoarthritic degenerative changes. This review addresses the current surgical treatments and most promising tissue engineering approaches for articular cartilage and subchondral bone regeneration., Methods: The capability to repair osteochondral or bone defects remains a challenging goal for surgeons and researchers. So far, most clinical approaches have been shown to have limited capacity to treat severe lesions. Current surgical repair strategies vary according to the nature and size of the lesion and the preference of the operating surgeon. Tissue engineering has emerged as a promising alternative strategy that essentially develops viable substitutes capable of repairing or regenerating the functions of damaged tissue., Results: An overview of novel and most promising osteochondroconductive scaffolds, osteochondroinductive signals, osteochondrogenic precursor cells, and scaffold fixation approaches are presented addressing advantages, drawbacks, and future prospectives for osteochondral regenerative medicine., Conclusion: Tissue engineering has emerged as an excellent approach for the repair and regeneration of damaged tissue, with the potential to circumvent all the limitations of autologous and allogeneic tissue repair., Level of Evidence: Systematic review, Level III.

Regenerative procedures aim to recreate a hyaline-like tissue, thus restoring a biologically and biomechanically valid articular surface with durable clinical results. Autologous chondrocyte implantation (ACI) has been developed two decades ago, and both the production of a hyaline-like articular surface and a satisfactory clinical outcome have been documented at medium-long follow-up. Bioengineering technology further improved this regenerative treatment approach to include matrix-assisted ACI (MACI) techniques. These procedures have been introduced in the clinical practice one decade ago, showing similar results while at the same time overcoming most of the concerns related to the first-generation ACI. The use of scaffolds to create a cartilage-like tissue in a three-dimensional culture system allows for the optimization of the procedure from both the biological and surgical point of view. However, despite thousands of treated patients and many published studies suggesting good clinical results and durability of these procedures, the properties of healthy, normal articular cartilage are still unmatched by any available substitute. Both indications and results of these substitutes are still controversial. The role of many variables that may influence the final outcome still need to be clarified to further improve the potential benefits of these biological regenerative procedures.

Young patients with early osteoarthritis (OA) represent a challenging population due to a combination of high functional demands and limited treatment options. Conservative measures such as injection and physical therapy can provide short-term pain relief but are only palliative in nature. Joint replacement, a successful procedure in the older population, is controversial in younger patients, who are less satisfied and experience higher failure rates. Therefore, while traditionally not indicated for the treatment of OA, cartilage repair has become a focus of increased interest due to its potential to provide pain relief and alter the progression of degenerative disease, with the hope of delaying or obviating the need for joint replacement. This review of cartilage repair techniques will discuss currently available procedures, specifically pertaining to experiences in the setting of early OA. Level of evidence IV.

Purpose: Platelet-rich plasma (PRP) therapy is a simple, low-cost and minimally invasive method that provides a natural concentrate of autologous blood growth factors (GFs) that can be used to enhance tissue regeneration. In a previous analysis of a 12-month follow-up study, promising results were obtained when treating patients affected by knee degeneration with PRP intra-articular injections. The main purpose of this study was to investigate the persistence of the beneficial effects observed., Methods: Of the 91 patients evaluated in the previous 12-month follow-up study, 90 were available for the 2-year follow-up (24 patients presented a bilateral lesion, in a total of 114 knees treated). All of the patients presented a chronic knee degenerative condition and were treated with three intra-articular PRP injections. IKDC and EQ-VAS scores were used for clinical evaluation. Complications, adverse events and patient satisfaction were also recorded., Results: All of the evaluated parameters worsened at the 24-month follow-up: these parameters were at significantly lower levels with respect to the 12-month evaluation (the IKDC objective evaluation fell from 67 to 59% of normal and nearly normal knees; the IKDC subjective score fell from 60 to 51), even if they remained higher than the basal level. Further analysis showed better results in younger patients (P = 0.0001) and lower degrees of cartilage degeneration (P < 0.0005). The median duration of the clinical improvement was 9 months., Conclusions: These findings indicate that treatment with PRP injections can reduce pain and improve knee function and quality of life with short-term efficacy. Further studies are needed to confirm these results and understand the mechanism of action, and to find other application modalities, with different platelet and GF concentrations and injection timing, which provide better and more durable results.

We evaluated long-term magnetic resonance imaging (MRI) features of Knee Osteochondral Autologous Transplantation (OAT)-Mosaicplasty and correlated MRI findings and clinical outcome. Twenty-four patients (mean age 29.9±8.7, 70.8% male) undergoing arthroscopic OAT between 1997 and 2000 were prospectively enrolled. The International Cartilage Repair Society (ICRS)/International Knee Documentation Committee (IKDC) scores and Tegner scores were employed for clinical evaluation. The magnetic resonance observation of cartilage repair tissue (MOCART) was utilized for description and assessment of the repair tissue. Median follow up was 113 months (interquartile range [IQR] 106-122). MRI showed good survival of grafted cartilage in 62.5% of patients. The integration of the graft was complete in 75% of cases, while the repaired tissue was intact in 62.5% and had an homogeneous structure in 70.8%. The MOCART score significantly correlated with objective and subjective scores (p=0.003 and p=0.002). Contrastingly, overall MOCART showed no correlation with the Tegner score. MRI revealed to be a powerful tool for non-invasive long-term assessment of OAT., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Osteochondral articular defects are a key concern in orthopaedic surgery. Current surgical techniques to repair osteochondral defects lead to poor subchondral bone regeneration and fibrocartilage formation, which is often associated with joint pain and stiffness. The objective of this pilot clinical study is to evaluate the performance and the intrinsic stability of a newly developed biomimetic osteochondral scaffold and to test the safety and the feasibility of the surgical procedure., Methods: A gradient composite osteochondral scaffold based on type I collagen-hydroxyapatite was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles. Thirteen patients (15 defect sites) were treated with scaffold implantation from January 2007 to July 2007: four at the medial femoral condyle, two at the lateral femoral condyles, five at the patellas and four at the trochleas. The mean size of the defects was 2.8 cm(2) (range: 1.5-5.9 cm(2)). All patients were followed up prospectively. High-resolution magnetic resonance imaging (MRI) was used to determine "the early postoperative adherence rate" at 4-5 weeks and 25-26 weeks after scaffold implantation. Moreover, the magnetic resonance observation of cartilage repair tissue (MOCART) score was performed on every MRI. Two second-looks were performed at 6 months; cartilage repair was assessed using the International Cartilage Repair Society (ICRS) visual scoring system and histological and immunohistochemical analysis of the two biopsies was carried out., Results: A completely attached graft and repair tissue were found in 13 of 15 lesions (86.7%). A partial detachment was observed in two patients (13.3%). No detached grafts were found. Complete filling of the cartilage defect and congruency of the articular surface were seen in 10 lesions (66.7%) with MRI evaluation at 6 months. The complete integration of the grafted cartilage was detected in eight lesions (53.3%). Subchondral bone changes (oedema or sclerosis) were found in eight defects (53.3%). Statistical analysis showed a significant improvement in the International Knee Documentation Committee (IKDC) subjective and objective scores from preoperative to 6 months' follow-up (p<0.0005). Visual scoring of the repaired tissue at second-look revealed a normal repair score in one case and a near-normal repair score in the other case. Histological analysis showed the formation of subchondral bone without the presence of biomaterial. The cartilage repair tissue appeared to be engaged in an ongoing maturation process., Conclusions: The technique is safe and MRI evaluation at short-term follow-up has demonstrated good stability of the scaffold without any other fixation device. The preliminary clinical results at short-term follow-up are encouraging. A clinical and MRI study with longer follow-up and randomised studies will be done to confirm the high potential of this novel osteochondral scaffold., (2009 Elsevier Ltd. All rights reserved.)