Minimum 10-Year Outcomes of Matrix-Induced Autologous Chondrocyte Implantation in the Knee: A Systematic Review.

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.

Republication of "Osteochondral Lesions of the Talus: Current Concepts in Diagnosis and Treatment".

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.

The Evolution of Rehabilitation and Return to Sport Following Cartilage Surgery.

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. Level of evidence: V.

Rate of Conversion to Matrix-Induced Autologous Chondrocyte Implantation After a Biopsy: A Multisurgeon Study.

Background: Autologous chondrocyte implantation (ACI) and matrix-induced autologous chondrocyte implantation (MACI) are performed to treat focal chondral defects (FCDs); both are 2-step procedures involving a biopsy, followed by transplantation. There is little published research evaluating ACI/MACI in patients who undergo a biopsy alone. Purpose: To determine (1) the value of ACI/MACI cartilage biopsies and concomitant procedures in patients with FCDs of the knee and (2) the conversion rate to cartilage transplantation as well as the rate of reoperation. Study Design: Case series; Level of evidence, 4. Methods: A retrospective review was performed of 46 patients (63% female) who underwent a MACI (or ACI) biopsy between January 2013 and January 2018. Preoperative data, intraoperative data, and postoperative outcomes were assessed at a minimum of 2 years after the biopsy. The conversion rate from a biopsy to transplantation and the reoperation rate were calculated and analyzed. Results: Among the 46 patients included, 17 (37.0%) underwent subsequent surgery, with only 12 undergoing cartilage restoration surgery, for an overall transplantation rate of 26.1%. Of these 12 patients, 9 underwent MACI/ACI, 2 underwent osteochondral allograft transplantation (OCA), and 1 underwent particulated juvenile articular cartilage implantation at 7.2 ± 7.5 months after the biopsy. The reoperation rate was 16.7% (1 patient after MACI/ACI and 1 patient after OCA) at 13.5 ± 2.3 months after transplantation. Conclusion: Arthroscopic surgery with debridement, chondroplasty, loose body removal, meniscectomy/meniscal repair, and other treatment approaches of knee compartment abnormalities at the time of a biopsy appeared to be sufficient in improving function and reducing pain in patients with knee FCDs.

Long-Term Culture Performance of a Polyelectrolyte Complex Microcapsule Platform for Hyaline Cartilage Repair.

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.

Cost-effectiveness of a new ACI technique for the treatment of articular cartilage defects of the knee compared to regularly used ACI technique and microfracture.

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.

Mid- to Long-Term Clinical Outcomes of Cartilage Restoration of Knee Joint with Allogenic Next-Generation Matrix-Induced Autologous Chondrocyte Implantation (MACI).

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.

Correlation between the quality of cartilage repair tissue and patellofemoral osteoarthritis after matrix-induced autologous chondrocyte implantation at three-year follow-up: a cross-sectional study.

PURPOSE: To investigate whether the quality of cartilage repair tissue is associated with patellofemoral osteoarthritis (PFOA) at a three year follow-up after matrix-induced autologous chondrocyte implantation (MACI). METHODS: This retrospective study included 32 patients who underwent MACI between October 2014 and May 2018 at our institute. The Lysholm score and Visual Analog Scale (VAS) score were assessed. The magnetic resonance observation of cartilage repair tissue (MOCART) 2.0 score and T2* relaxation time of repair tissue were used to evaluate cartilage repair tissue quality. A modified MRI Osteoarthritis Knee Score (mMOAKS) was used to evaluate PFOA. RESULTS: Compared with pre-operative scores, the final Lysholm score (50.71 ± 2.22 vs 89.70 ± 1.18; t = 15.5, P < 0.0001) and VAS score (4.67 ± 0.47 vs 0.92 ± 0.64; t = 22.62, P < 0.0001) were improved at 3 years after MACI. At the three year follow-up, the mean MOCART 2.0 score was 61.56 ± 18.11, and the T2* relaxation time of the repair tissue was significantly lower than that in the healthy control region (24.11 ± 6.38 vs 34.39 ± 1.33, t = - 8.635, P < 0.0001). The mean mMOAKS score was 9.16 ± 4.51. On univariate analysis, the MOCART 2.0 score and T2* relaxation time were negatively associated with the mMOAKS score. CONCLUSION: MACI can lead to significant pain relief and restoration of knee joint function, and good quality cartilage repair tissue was a protective factor against PFOA at the three year follow-up.

Surgical strategies for chondral defects of the patellofemoral joint: a systematic review.

BACKGROUND: The management of chondral defects of the patellofemoral joint is debated, and definitive evidence is lacking. This study systematically updated and summarised the current literature on the surgical management of isolated chondral defects of the patellofemoral joint, discussing techniques, outcome, pitfalls, and new frontiers. METHODS: This systematic review was conducted according to the 2020 PRISMA statement. In August 2022, PubMed, Web of Science, Google Scholar, and Embase databases were accessed with no time constrain. All the clinical studies investigating the surgical management of chondral defects of the patellofemoral joint were retrieved. Articles which reported data on patients with advanced to severe osteoarthritis were not eligible. Only studies with a minimum 24 months follow-up were considered. Studies which mixed results of patellofemoral and tibiofemoral joints were not considered. RESULTS: Data from 10 studies (692 procedures) were retrieved. The mean follow-up was 46.9 ± 18.2 months. The mean age of the patients was 34.0 ± 6.1 years, and the mean BMI was 25.9 ± 0.8 kg/m2. The mean duration of symptoms before the index surgery was 81.0 ± 24.0 months. The mean defect size was 3.8 ± 0.8 cm2. All the PROMs improved from baseline to last follow-up: VAS 0-10 (P = 0.04), Tegner (P = 0.02), Lysholm (P = 0.03), and International Knee Documentation Committee (P = 0.03). The rate of hypertrophy was 5.6% (14 of 251), the rate of progression to total knee arthroplasty was 2.4% (2 of 83), the rate of revision was 16.9% (29 of 136), and the rate of failure was 13.0% (16 of 123). CONCLUSION: Current surgical strategies may be effective to improve symptoms deriving from chondral defects of the patellofemoral joint. The limited and heterogeneous data included for analysis impact negatively the results of the present study. Further clinical studies are strongly required to define surgical indications and outcomes, and the most suitable technique.

Personalidad en adolescentes en muestra general y clínica / Personality in adolescents in a general and clinical sample

El objetivo principal del estudio fue analizar las diferencias entre muestra general y clínica en los prototipos de personalidad (PRP) del “Inventario clínico para adolescentes de Millón” (MACI). La metodología incluyó un diseño observacional y analítico, utilizando un muestreo de participantes (13-17 años) aleatorio polietápico, estratificado y proporcional por conglomerados en muestra general (n= 461) y un muestreo consecutivo en muestra clínica (n= 219). Encontramos que los PRP introvertido, inhibido, pesimista, rudo, oposicionista, autopunitivo y límite presentan una media significativamente mayor en muestra clínica y los PRP histriónico y conformista en muestra general. Se observa ausencia de diferencias significativas en los PRP egocéntrico, sumiso y rebelde. En la variable sexo observamos más diferencias significativas de PRP en muestra clínica que en la general y en la variable edad encontramos una tendencia lineal significativa descendente en los PRP sumiso o conformista y ascendente en los PRP rebelde y rudo en muestra general. El clínico debe estar alerta ante la interpretación de los PRP del MACI que no diferencian entre muestra general y clínica. (AU)

The main objective of the study was to analyze the differences between samples from general and clinical sample in personality prototypes (PRP), derived from the Millon Adolescent Clinical Inventory (MACI). The methodology included an analytical and observational design with a random, multi-stage, stratified and proportional cluster sampling in general sample (n= 461) and consecutive sampling of clinical sample (n= 219), in adolescents between 13 and 17 years of age. We found introvert, inhibited, doleful, forceful, oppositional, self-demeaning and borderline PRP in the clinical sample and dramatizing and conforming PRP in the general sample present a significantly higher mean. There is a relevant absence of significant differences in egotistic, submissive and unruly PRP. By sex, more significant differences in PRP are observed in the clinical sample. By age, a significant downward linear trend in the submissive and conforming PRP is observed, as well as an upward trend in the unruly and forceful PRP in the general sample. The clinician must be alert in the interpretation of the MACI PRP that do not differentiate between general and clinical samples. (AU)

Four cases report: Treatment of knee joint cartilage defects using autologous chondrocyte patch implantation.

Introduction: Autologous chondrocyte implantation (ACI) is a crucial method for the treatment of defects in articular cartilage. However, the extant methods for the preparation of autologous chondrocyte patch are relatively complicated and money-consuming. Therefore, an efficient, reliable, easy-to-follow, and cost-effective technique is needed to overcome constraints. This case report aims to introduce an autologous chondrocyte patch fabrication technique to repair knee joint cartilage defects and report our typical cases with a 2-year follow-up. Case presentation: We described four cases in which patients complained of knee joint pain. According to radiological examination, the patients were diagnosed as knee joint cartilage defect. Arthroscopy and autologous chondrocyte patch implantation were performed as well as a 2-year follow up of patients. The autologous chondrocyte patch for knee joint cartilage repair was fabricated using a "sandwich" technique. The preoperative and postoperative knee function was evaluated by four subjective evaluation systems. MRI was performed for all patients to achieve more intuitionistic observation of the postoperative radiological changes of defect sites. The quality of repaired tissue was evaluated by Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART). Postoperative follow-up showed improvement in clinical and MOCART scores for all patients. However, one patient complained of knee joint pain after walking for a long time or recreational activities from 12- to 18-month postoperatively. The location of pain for this patient was not in accordance with the location of cartilage defect. Conclusion: The patients undergoing autologous chondrocyte patch implantation demonstrated clinical improvement and good quality of repaired tissue postoperatively. The procedure is an efficient and cost-effective treatment for knee joint cartilage defect in this report. In addition, patients with osteoarthritis carry the risk of a poor outcome after the procedure, and whether to have a procedure should be considered carefully.

Fixation of the Membrane during Matrix-Induced Autologous Chondrocyte Implantation in the Knee: A Systematic Review.

Introduction: It is unclear whether the type of membrane used for matrix-assisted autologous chondrocyte implantation (mACI) influences results. A systematic review was conducted to investigate the midterm results of the three most common types of membrane fixation for mACI. Methods: This systematic review was conducted according to the 2020 PRISMA checklist. PubMed, Google Scholar, Embase, and Scopus online databases were accessed in August 2022. All the prospective clinical trials reporting outcomes of mACI in the knee were considered. Studies that describe the modality of membrane fixation (glued, glued, and sutured, no fixation) used for mACI were eligible. Studies that conducted a minimum of 12 months of follow-up were considered. The outcomes of interest were the Tegner Activity Scale and International Knee Documentation Committee (IKDC) score. The rate of failure and revisions were also collected. Results: Data from 26 studies (1539 procedures; 554 of 1539 (36%) were women) were retrieved. The mean follow-up was 42.6 (12 to 84) months. No difference between the groups was found in terms of mean duration of symptoms, age, BMI, gender, and defect size (P > 0.1). No difference was found in terms of the Tegner score (P = 0.3). When no fixation was used, a statistically significant higher IKDC compared to the other groups (P = 0.02) was evidenced. No difference was found in the rate of failure (P = 0.1). The no-fixation group evidenced a statistically significant lower rate of revisions (P = 0.02). Conclusions: No membrane fixation for mACI in the knee scored better than the fastening techniques at the midterm follow-up.

Matrix-induced autologous chondrocyte implantation (mACI) versus autologous matrix-induced chondrogenesis (AMIC) for chondral defects of the knee: a systematic review.

INTRODUCTION: Chondral defects of the knee are common and their treatment is challenging. SOURCE OF DATA: PubMed, Google scholar, Embase and Scopus databases. AREAS OF AGREEMENT: Both autologous matrix-induced chondrogenesis (AMIC) and membrane-induced autologous chondrocyte implantation (mACI) have been used to manage chondral defects of the knee. AREAS OF CONTROVERSY: It is debated whether AMIC and mACI provide equivalent outcomes for the management of chondral defects in the knee at midterm follow-up. Despite the large number of clinical studies, the optimal treatment is still controversial. GROWING POINTS: To investigate whether AMIC provide superior outcomes than mACI at midterm follow-up. AREAS TIMELY FOR DEVELOPING RESEARCH: AMIC may provide better outcomes than mACI for chondral defects of the knee. Further studies are required to verify these results in a clinical setting.

Freeze-Dried Curdlan/Whey Protein Isolate-Based Biomaterial as Promising Scaffold for Matrix-Associated Autologous Chondrocyte Transplantation-A Pilot In-Vitro Study.

The purpose of this pilot study was to establish whether a novel freeze-dried curdlan/whey protein isolate-based biomaterial may be taken into consideration as a potential scaffold for matrix-associated autologous chondrocyte transplantation. For this reason, this biomaterial was initially characterized by the visualization of its micro- and macrostructures as well as evaluation of its mechanical stability, and its ability to undergo enzymatic degradation in vitro. Subsequently, the cytocompatibility of the biomaterial towards human chondrocytes (isolated from an orthopaedic patient) was assessed. It was demonstrated that the novel freeze-dried curdlan/whey protein isolate-based biomaterial possessed a porous structure and a Young's modulus close to those of the superficial and middle zones of cartilage. It also exhibited controllable degradability in collagenase II solution over nine weeks. Most importantly, this biomaterial supported the viability and proliferation of human chondrocytes, which maintained their characteristic phenotype. Moreover, quantitative reverse transcription PCR analysis and confocal microscope observations revealed that the biomaterial may protect chondrocytes from dedifferentiation towards fibroblast-like cells during 12-day culture. Thus, in conclusion, this pilot study demonstrated that novel freeze-dried curdlan/whey protein isolate-based biomaterial may be considered as a potential scaffold for matrix-associated autologous chondrocyte transplantation.

Management of Chondral Defects Associated with Patella Instability.

Cartilage defects of the patellofemoral joint are commonly found in association with patellar instability owing to abnormal biomechanics. Strategies to address chondral defects of the patellofemoral joint secondary to instability should first address causes of recurrent instability. Most patellofemoral chondral defects associated with instability are less than 2 cm2 and do not generally require intervention beyond chondroplasty. Larger defects of the patella and/or the trochlea can be repaired with osteochondral or surface cartilage repair.

Membrane scaffolds for matrix-induced autologous chondrocyte implantation in the knee: a systematic review.

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.

Jellyfish Collagen: A Biocompatible Collagen Source for 3D Scaffold Fabrication and Enhanced Chondrogenicity.

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 TGFß1. This study highlights the potential of jellyfish collagen as a safe and biocompatible biomaterial for both OA repair and further regenerative medicine applications.

Alginate-Agarose Hydrogels Improve the In Vitro Differentiation of Human Dental Pulp Stem Cells in Chondrocytes. A Histological Study.

Matrix-assisted autologous chondrocyte implantation (MACI) has shown promising results for cartilage repair, combining cultured chondrocytes and hydrogels, including alginate. The ability of chondrocytes for MACI is limited by different factors including donor site morbidity, dedifferentiation, limited lifespan or poor proliferation in vitro. Mesenchymal stem cells could represent an alternative for cartilage regeneration. In this study, we propose a MACI scaffold consisting of a mixed alginate-agarose hydrogel in combination with human dental pulp stem cells (hDPSCs), suitable for cartilage regeneration. Scaffolds were characterized according to their rheological properties, and their histomorphometric and molecular biology results. Agarose significantly improved the biomechanical behavior of the alginate scaffolds. Large scaffolds were manufactured, and a homogeneous distribution of cells was observed within them. Although primary chondrocytes showed a greater capacity for chondrogenic differentiation, hDPSCs cultured in the scaffolds formed large aggregates of cells, acquired a rounded morphology and expressed high amounts of type II collagen and aggrecan. Cells cultured in the scaffolds expressed not only chondral matrix-related genes, but also remodeling proteins and chondrocyte differentiation factors. The degree of differentiation of cells was proportional to the number and size of the cell aggregates that were formed in the hydrogels.

Arthroscopy versus mini-arthrotomy approach for matrix-induced autologous chondrocyte implantation in the knee: a systematic review.

BACKGROUND: Matrix-induced autologous chondrocyte implantation (mACI) can be performed in a full arthroscopic or mini-open fashion. A systematic review was conducted to investigate whether arthroscopy provides better surgical outcomes compared with the mini-open approach for mACI in the knee at midterm follow-up. METHODS: This systematic review was conducted following the PRISMA guidelines. The literature search was performed in May 2021. All the prospective studies reporting outcomes after mACI chondral defects of the knee were accessed. Only studies that clearly stated the surgical approach (arthroscopic or mini-open) were included. Only studies reporting a follow-up longer than 12 months were eligible. Studies reporting data from combined surgeries were not eligible, nor were those combining mACI with less committed cells (e.g., mesenchymal stem cells). RESULTS: Sixteen studies were included, and 770 patients were retrieved: 421 in the arthroscopy group, 349 in the mini-open. The mean follow-up was 44.3 (12-60) months. No difference between the two groups was found in terms of mean duration of symptoms, age, body mass index (BMI), gender, defect size (P > 0.1). No difference was found in terms of Tegner Score (P = 0.3), Lysholm Score (P = 0.2), and International Knee Documentation Committee (IKDC) Score (P = 0.1). No difference was found in the rate of failures (P = 0.2) and revisions (P = 0.06). CONCLUSION: Arthroscopy and mini-arthrotomy approaches for mACI in knee achieve similar outcomes at midterm follow-up. LEVEL OF EVIDENCE: II, systematic review of prospective studies.

Matrix-induced autologous chondrocyte implantation versus autologous matrix-induced chondrogenesis for chondral defects of the talus: a systematic review.

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.