MSC–Hydrogel Composite Systems for Knee Cartilage Repair and Osteoarthritis: A Systematic Review

Yerik Raimagambetov, Birzhan Suiindik, Meruyert Makhmetova, Dina Saginova, Ulunay Kanatlı, Gulzhanat Korganbekova

Gels, 2026

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DOI 10.3390/gels12080715
Data confidence 70 medium
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Abstract

Background: MSC–hydrogel composite systems were developed to overcome the poor cell retention and limited durability of conventional marrow stimulation and suspension-based MSC delivery. A rigorous synthesis of the clinical evidence is lacking. Objectives: To evaluate the safety and efficacy of MSC–hydrogel composite therapy for focal knee cartilage defects and knee osteoarthritis, and to assess the certainty of evidence using the GRADE framework. Methods: PROSPERO-registered systematic review (CRD420261393525), conducted and reported per PRISMA 2020 and SWiM. Five databases (Embase, PubMed/MEDLINE, Cochrane CENTRAL, Scopus, Web of Science) were searched in May 2026 without date, language, or design restrictions. Adults receiving MSCs co-delivered in a hydrogel carrier for knee cartilage pathology were eligible. Risk of bias was assessed using RoB 2 (RCTs) and ROBINS-I (non-randomized studies). Narrative synthesis following Popay et al. was the primary method; GRADE certainty was assessed per outcome domain. Results: Ten studies (N = 521) were identified. Eight studies fulfilled the predefined eligibility criteria for MSC–hydrogel composite interventions and formed the primary evidence synthesis. Two additional studies were retained as contextual comparators because they evaluated either hydrogel-based therapy without MSC administration or MSC therapy without a structured hydrogel carrier. Surgical MSC–hydrogel implantation was associated with improvements in cartilage repair. Intra-articular injection without a hydrogel scaffold produced synovitis reduction but no detectable structural regeneration at six months. No serious treatment-related adverse events were recorded. Risk of bias was serious or critical in seven of nine assessable studies; GRADE certainty was low to very low across all outcome domains. Conclusions: MSC–hydrogel composite implantation may provide favorable safety signals and directionally positive effects on cartilage repair, pain, and function, with seven-year follow-up data suggesting a possible durability advantage over marrow stimulation. However, adverse-event reporting was inconsistent, and certainty of evidence remains low or very low because most studies were non-randomized, single-center, and concentrated around one commercial platform. These findings are relevant to international cartilage-regeneration research because they identify key methodological limitations and trial-design priorities for translating MSC–hydrogel systems across different clinical and regulatory settings.