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Purpose: To compare short‐term patient‐reported outcomes (PRO) of two contemporary matrix‐associated autologous chondrocyte implantation (M‐ACI) products for the treatment of large articular cartilage defects of the knee. Methods: A retrospective, registry‐based, matched‐pair analysis was performed, comparing PRO of patients undergoing isolated M‐ACI with either Spherox™, a spheroid‐based ACI (Sb‐ACI), or NOVOCART™ Inject, a hydrogel‐based ACI product (Hb‐ACI), for a focal full‐thickness cartilage defect of the knee ≥4 cm2. Matching parameters included age, sex, body mass index, defect size, defect localization, symptom duration and previous surgeries. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee (IKDC) score were obtained up to the 24‐month follow‐up. The total KOOS response rate and percentage of patients attaining a substantial clinical benefit (SCB) in KOOS subscores were calculated. Results: A total of 45 patients per group were matched. The response rate after 24 months was not significantly different between the groups (Sb‐ACI 64.4% vs. Hb‐ACI 82.2%, p = 0.057). The number of patients with a SCB at 24 months was not significantly different in any KOOS subscore, despite significantly higher improvement of the total KOOS (14.8 ± 16.2 vs. 21.5 ± 15.4, p = 0.047) and KOOS pain in the Hb‐ACI group (12.2 ± 18.6 vs. 20.6 ± 19.1, p = 0.037). The IKDC score in the Hb‐ACI group was significantly higher at the 12‐ and 24‐month follow‐up (60.7 ± 20.2 vs. 70.9 ± 18.0, p = 0.013). Conclusion: The response rate and number of patients achieving an SCB were not significantly different between patients treated with Sb‐ACI or Hb‐ACI. Both procedures can achieve favourable 2‐year PRO. Hb‐ACI was associated with better PRO between 1 and 2 years postoperatively; however, the clinical relevance of this benefit is yet to be proven. Level of Evidence: III, Retrospective comparative study. [ABSTRACT FROM AUTHOR]

Background: Matrix-induced autologous chondrocyte implantation (MACI) is an established cell-based therapy for the treatment of chondral defects of the knee. As long-term outcomes are now being reported in the literature, it is important to systematically review available evidence to better inform clinical practice. Purpose: To report (1) subjective patient-reported outcomes (PROs) and (2) the rate of graft failure, reoperation, and progression to total knee arthroplasty (TKA) after undergoing MACI of the knee at a minimum 10-year follow-up. Study Design: Systematic review; Level of evidence, 4. Methods: A comprehensive search of Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus from 2008 to September 15, 2022, was conducted in the English language. Study eligibility criteria included (1) full-text articles in the English language, (2) patients undergoing a MACI within the knee, (3) clinical outcomes reported, and (4) a minimum 10-year follow-up. Results: In total, 168 patients (99 male, 69 female; mean age, 37 years [range, 15-63 years]; mean body mass index, 26.2 [range, 18.6-39.4]) representing 188 treated chondral defects at a minimum 10-year follow-up after MACI were included in this review. Significant and durable long-term improvements were observed across multiple PRO measures. Follow-up magnetic resonance imaging (MRI), when performed, also demonstrated satisfactory defect fill and an intact graft in the majority of patients. The all-cause reoperation rate was 9.0%, with an overall 7.4% rate of progression to TKA at 10 to 17 years of follow-up. Conclusion: At a minimum 10-year follow-up, patients undergoing MACI for knee chondral defects demonstrated significant and durable improvements in PROs, satisfactory defect fill on MRI-based assessment, and low rates of reoperation and TKA. These data support the use of MACI as a long-term treatment of focal cartilage defects of the knee. [ABSTRACT FROM AUTHOR]

Regenerative cartilage procedures have become increasingly more important in the reconstructive treatment of acute and chronic chondral and osteochondral lesions in the knee joint. Depending on the size and depth of the defect standard methods with high evidence and potential methods with rather low evidence have been established. Long-term results determine the success and failure of the applied procedures and are being discussed in this CME article. [ABSTRACT FROM AUTHOR]

Background: Osteochondral lesions of the knee are difficult to manage. Such lesions can be effectively treated with the matrix-induced autologous chondrocyte implantation (MACI) "sandwich" technique using autologous chondrocytes on porcine collagen membrane in conjuction with autologous cancellous bone grafting (ABG). Few studies have examined this technique to restore the osteochondral unit. Indications: The MACI "Sandwich" procedure is indicated when osteochondral lesions are larger than 2 cm2 in size and deeper than 8 to 10 mm, with symptoms consistent with the location of the lesion. Technique Description: The chondral defect is radically debrided back to healthy bone and cartilage tissue. The base of the bony cavity is drilled to enhance the vascular supply and promote healing. Next, the bony cavity is prepared to slightly undermine the subchondral bone surface around the articular margins, with the depth of the cavity wider than the opening, similar to a dental amalgam. The autologous cancellous bone is subsequently morselized and impacted up to the level of the native subchondral bone plate. The first MACI membrane with the cells facing up is placed directly onto the bone graft site and compressed with a neural patty. The neural patty is removed, and the second MACI membrane is then placed with the cells facing down. The edges are then micro-sutured to ensure stability. Results: The "sandwich" technique has superior survival rates compared with autologous bone grafting alone, with patients reporting decreased pain, improved function, and high satisfaction scores over a mid-term to long-term follow-up. Discussion/Conclusion: The MACI "sandwich" technique is an effective surgical intervention to restore the osteochondral unit and preserve the patient's native knee joint. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication. [ABSTRACT FROM AUTHOR]

Background: There are several techniques for knee exposure in treating chondral defects with restorative procedures. The medial subvastus knee exposure is often overlooked when choosing the surgical approach. When properly performed, the medial subvastus approach can allow for the treatment of a wide range of pathology while preserving the extensor mechanism. Indications: We present a case of an active 40-year-old man with persistent left knee pain noted to have a full-thickness medial femoral condylar articular cartilage defect in an otherwise healthy appearing knee. Technique Description: The rationale and considerations for the medial subvastus knee exposure in treating a chondral defect with an autologous chondrocyte implant are discussed. Careful consideration of the approach, intra-articular exposure, and closure are emphasized to achieve optimal outcomes. Results: At 18 months postoperative, the patient reported no knee pain with improvements made in Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm, and International Knee Documentation Committee (IKDC) scores. These results are consistent with our institutions larger cohort of 26 patients undergoing matrix-induced autologous chondrocyte implantation (MACI) using the subvastus approach. These improvements in patient-reported outcomes are maintained at 2 years postoperative and are consistent with other published outcomes of the MACI procedure. Discussion/Conclusion: Excellent results in addressing chondral pathology about the knee can be achieved by selecting the appropriate surgical access. The subvastus approach has several advantages such as preserving the quadriceps mechanism, improving postoperative quadriceps muscle strength, conservation of the patellar genicular blood supply and possibly reducing postoperative pain that can result in a faster rehabilitation. When performed systematically and carefully, complete exposure of the knee can be achieved to facilitate a wide variety of surgical interventions. In patients undergoing cartilage restoration procedures, the medial subvastus approach should be considered in the surgeon's armamentarium. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication. [ABSTRACT FROM AUTHOR]

Osteochondral lesions of the talus (OLTs) are a difficult pathologic entity to treat. They require a strong plan. Lesion size, location, chronicity, and characteristics such as displacement and the presence of subchondral cysts help dictate the appropriate treatment required to achieve a satisfactory result. In general, operative treatment is reserved for patients with displaced OLTs or for patients who have failed nonoperative treatment for 3 to 6 months. Operative treatments can be broken down into cartilage repair, replacement, and regenerative strategies. There are many promising treatment options, and research is needed to elucidate which are superior to minimize the morbidity from OLTs. [ABSTRACT FROM AUTHOR]

Rehabilitation after knee cartilage repair or restoration can be a challenging and nuanced process. Historically, conservative rehabilitation protocols have been characterized by limited weightbearing and restricted range of motion (ROM) were created to primarily protect the repaired cartilage but did little for progression into higher level activity. Recent literature has supported accelerated protocols in a variety of cartilage procedures ranging from osteochondral allograft (OCA) Osteochondral autograft surgery (OATS) to matrix-based scaffolding procedures such as Matrix Induced Chondrocyte Implantation (MACI) or Denovo procedures. Advances in technology such as blood flow restriction (BFR) and testing equipment with progressive rehabilitation from the acute phase through the return to sport continuum have made it possible to return to a higher level of activity and performance than first thought of for these procedures. This clinical viewpoint discusses the evolution of knee cartilage rehabilitation characterized by early but progressive weightbearing and early ROM while maintaining early homeostasis in the knee, and then its progression to return to sport and performance in the higher-level athlete. [ABSTRACT FROM AUTHOR]

Articular cartilage (AC) tissue repair and regeneration remains an ongoing challenge. One component of the challenge is the limited ability to scale an engineered cartilage graft to clinically relevant sizes while maintaining uniform properties. In this paper, we report on the evaluation of our polyelectrolyte complex microcapsule (PECM) platform technology as a technique for generating cartilage-like spherical modules. Bone marrow-derived mesenchymal stem cells (bMSCs) or primary articular chondrocytes were encapsulated within PECMs composed of methacrylated hyaluronan, collagen I, and chitosan. The formation of cartilage-like tissue in the PECMs over a 90-day culture was characterized. The results showed that chondrocytes exhibited superior growth and matrix deposition compared to either chondrogenically-induced bMSCs or a mixed PECM culture containing both chondrocytes and bMSCs. The chondrocyte-generated matrix filled the PECM and produced substantial increases in capsule compressive strength. The PECM system thus appears to support intracapsular cartilage tissue formation and the capsule approach promotes efficient culture and handling of these micro tissues. Since previous studies have proven the feasibility of fusing such capsules into large tissue constructs, the results suggest that encapsulating primary chondrocytes in PECM modules may be a viable route toward achieving a functional articular cartilage graft. [ABSTRACT FROM AUTHOR]

Objective: Cartilage defect is a common pathology still lacking a unified treating option. The purpose of this retrospective study is to evaluate the safety, efficacy, and clinical and radiological outcome of cartilage restoration of knee joint with allogenic next‐generation Matrix‐Induced Autologous Chondrocyte Implantation (MACI) for the first time, as well as the correlation between postoperative clinical and radiological outcomes and preoperative patient history and demographics. Methods: From July 2014 to August 2020, 15 patients who went through cartilage restoration with allogenic next‐generation MACI were included in this study. Patient demographics and PROM including the International Knee Documentation Committee (IKDC) subjective knee score, Lysholm score, Tegner Activity Scale (TAS), and Knee Injury and Osteoarthritis Outcome Score (KOOS) were obtained preoperatively, at 3, 6, 12 months postoperatively and the last follow‐up using an online questionnaire platform. MOCART 2.0 score was calculated at the last follow‐up. Analysis of variance (ANOVA) was used to compare PROM pre‐ and post‐operation, with two‐tailed p < 0.05 defined as statistical significant. Pearson correlation coefficient was used to evaluate correlation between the PROM and MOCART 2.0 score at the last follow‐up with patients demorgraphics. Results: All patients were followed for an average of 66.47 ± 24.15 months (range, 21–93). All patients were satisfied with the outcome of the surgery and no complication was reported at the end of the study. No significant improvement was observed until 1 year after the implantation, except for IKDC score at 6 months. All PROM showed significant improvement 1 year post‐op except for Lysholm score and TAS, which also increased significantly at the time of the last follow‐up. Pearson correlation coefficient showed that the size of the defect, before or after debridement, was significantly negatively correlated with final KOOS‐Pain (before debridement: r = −0.57, p < 0.05; after debridement: r = −0.54, p < 0.05) and KOOS‐Symptoms score (before debridement: r = −0.66, p < 0.05; after debridement: r = −0.67, p < 0.05). The MOCART 2.0 score was found significantly and negatively correlated with BMI (r = −0.60, p < 0.05), and significantly and positively correlated with Lysholm score (r = 0.70, p < 0.05). Conclusion: The next generation MACI with autologous chondrocyte and allogenic chondrocyte ECM scaffold could be used to treat focal articular cartilage defect in the knee joint safely and efficiently with lasting promising outcomes for more than 5 years. The size of the defects should be considered the most negatively correlated parameters influencing the postoperative clinical outcomes. [ABSTRACT FROM AUTHOR]

Introduction Chondral defects of the knee are common and their management is challenging. Source of data Current scientific literature published in PubMed, Google scholar, Embase and Scopus. Areas of agreement Membrane-induced autologous chondrocyte implantation (mACI) has been used to manage chondral defects of the knee. Areas of controversy Hyaluronic acid membrane provides better outcomes than a collagenic membrane for mACI in the knee at midterm follow-up is controversial. Growing points To investigate whether hyaluronic acid membrane may provide comparable clinical outcomes than collagenic membranes for mACI in focal defects of the knee. Areas timely for developing research Hyaluronic acid membrane yields a lower rate of failures and revision surgeries for mACI in the management of focal articular cartilage defects of the knee compared with collagenic scaffolds at midterm follow-up. No difference was found in patient reported outcome measures (PROMs). Further comparative studies are required to validate these results in a clinical setting. [ABSTRACT FROM AUTHOR]

Introduction Chondral defects of the talus are common and their treatment is challenging. Source of data Recent published literatures. Areas of agreement Membrane-induced Autologous Chondrocyte Implantation (mACI) and Autologous Matrix-Induced Chondrogenesis (AMIC) have been proposed as management for chondral defects of the talus. Areas of controversy It is debated whether AMIC provides greater outcomes compared to mACI for chondral regeneration. Several clinical studies showed controversial results, and the best treatment has not yet been clarified. Growing points To investigate whether AMIC provide superior outcomes than mACI at midterm follow-up. Areas timely for developing research AMIC exhibits similar clinical results to mACI. However, AMIC involves one single surgical procedure, no articular cartilage harvest and hence no morbidity from it, no need for chondrocyte expansion in a separate laboratory setting. For these reasons, AMIC may be preferred to mACI. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a multifactorial disease leading to degeneration of articular cartilage, causing morbidity in approximately 8.5 million of the UK population. As the dense extracellular matrix of articular cartilage is primarily composed of collagen, cartilage repair strategies have exploited the biocompatibility and mechanical strength of bovine and porcine collagen to produce robust scaffolds for procedures such as matrix-induced chondrocyte implantation (MACI). However, mammalian sourced collagens pose safety risks such as bovine spongiform encephalopathy, transmissible spongiform encephalopathy and possible transmission of viral vectors. This study characterised a non-mammalian jellyfish (Rhizostoma pulmo) collagen as an alternative, safer source in scaffold production for clinical use. Jellyfish collagen demonstrated comparable scaffold structural properties and stability when compared to mammalian collagen. Jellyfish collagen also displayed comparable immunogenic responses (platelet and leukocyte activation/cell death) and cytokine release profile in comparison to mammalian collagen in vitro. Further histological analysis of jellyfish collagen revealed bovine chondroprogenitor cell invasion and proliferation in the scaffold structures, where the scaffold supported enhanced chondrogenesis in the presence of TGFβ1. This study highlights the potential of jellyfish collagen as a safe and biocompatible biomaterial for both OA repair and further regenerative medicine applications.

Hyaline articular cartilage is critical for the normal functioning of the knee joint. Untreated focal cartilage defects have the potential to rapidly progress to diffuse osteoarthritis. Over the last several decades, a variety of interventions aiming at preserving articular cartilage and preventing osteoarthritis have been investigated. Reparative cartilage procedures, such as microfracture, penetrate the subchondral bone plate in effort to fill focal cartilage defects with marrow elements and stimulate fibrocartilaginous repair. In contrast, restorative cartilage procedures aim to replace the defective articular surface with autologous or allogeneic hyaline cartilage. This review focuses on the preservation of articular cartilage, and discusses the current reparative and restorative surgical techniques available for treating focal cartilage defects. [ABSTRACT FROM AUTHOR]

Background: Osteochondral lesions of the talus (OLT) are difficult to treat because of the poor intrinsic healing capability of articular cartilage. Matrix-induced autologous chondrocyte implantation (MACI) has been shown to be a reliable method for treating cartilage lesions that fail to respond to traditional microfracture and debridement. The purpose of this study was to assess 7-year clinical follow-up data of this technique and demonstrate midterm success of this implant.Methods: A prospective investigation of MACI was performed on 10 patients with OLTs who had failed previous arthroscopic treatment. In all, 5 male and 5 female patients were included in the study. Of the 10 patients, 9 were available for 7-year follow-up. Functional and clinical evaluations were done at 7 years postoperatively using the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot evaluation and the Short Form Health Survey (SF-36) and compared with preoperative values.Results: SF-36 data at 7 years showed significant improvements in Physical Functioning (P < .01), Lack of Bodily Pain (P < .1), and Social Functioning (P < .001) compared with preoperative data. The mean AOFAS hindfoot scores of the 9 patients at 7 years was 78.3 ± 18.1 (P = .05) compared with their preoperative mean of 61.8 ± 14.3.Conclusions: MACI provides a stable midterm chondral replacement strategy for osteochondral lesions that fail initial microfracture.Levels Of Evidence: Level IV: Prospective case series. [ABSTRACT FROM AUTHOR]

Abstract: Although articular cartilage has extraordinary mechanical properties, able to maintain almost frictionless motion over a lifetime, it is vulnerable to traumatic injury and subsequent degeneration. Poor vascularity and inability to access undifferentiated cell populations that would facilitate a response to injury, are responsible for articular cartilage''s limited ability to self-repair. The creation of cartilage repair tissue hence relies on the implantation or neosynthesis of cartilage matrix elements. This goal is achievable through a variety of repair techniques including marrow stimulation, the use of autologous or synthetic structural grafts or chondrocyte implantation. Although there are substantial differences in the complexity and technical application of each method, they are all united in the endeavour to restore joint function and prevent joint degeneration. The surgeon attempting to treat cartilage defects is required to possess not only a basic understanding of the physiology of cartilage growth, healing and repair, but also of biomechanics and kinematics of the knee, in order to appreciate the forces acting on the joint surfaces. Clinical success or failure will depend on appropriate patient selection, accurate clinical assessment, definition of the root cause and application of the right choice of treatment modality. Any therapy plan must include subsequent treatment options, which may become necessary should the first-line management fail to ameliorate symptoms. [Copyright &y& Elsevier]

Osteoarthritis (OA) is a multifactorial disease leading to degeneration of articular cartilage, causing morbidity in approximately 8.5 million of the UK population. As the dense extracellular matrix of articular cartilage is primarily composed of collagen, cartilage repair strategies have exploited the biocompatibility and mechanical strength of bovine and porcine collagen to produce robust scaffolds for procedures such as matrix-induced chondrocyte implantation (MACI). However, mammalian sourced collagens pose safety risks such as bovine spongiform encephalopathy, transmissible spongiform encephalopathy and possible transmission of viral vectors. This study characterised a non-mammalian jellyfish (Rhizostoma pulmo) collagen as an alternative, safer source in scaffold production for clinical use. Jellyfish collagen demonstrated comparable scaffold structural properties and stability when compared to mammalian collagen. Jellyfish collagen also displayed comparable immunogenic responses (platelet and leukocyte activation/cell death) and cytokine release profile in comparison to mammalian collagen in vitro. Further histological analysis of jellyfish collagen revealed bovine chondroprogenitor cell invasion and proliferation in the scaffold structures, where the scaffold supported enhanced chondrogenesis in the presence of TGFβ1. This study highlights the potential of jellyfish collagen as a safe and biocompatible biomaterial for both OA repair and further regenerative medicine applications. [ABSTRACT FROM AUTHOR]

Matrix-induced autologous chondrocytes implantation (MACI) is a promising technique for the treatment of articular cartilage lesions, but long time outcome have to be established. We developed and optimized specific techniques of histochemical staining to characterize healthy and pathologic osteochondral tissue. Seven different staining protocols were applied to assess tissue architecture, cells morphology, proteoglycan content, and collagen fibers distribution. Potentialities of histochemical staining and histomorphology of biopsies from second look arthroscopy will be presented. [ABSTRACT FROM AUTHOR]