Cell-Based Regenerative Strategies for Knee Cartilage Repair: A Scoping Review of Autologous Cartilage, Mesenchymal Stromal Cells, and Hybrid Approaches

BackgroundCell-based approaches for focal knee cartilage repair include cartilage- and chondrocyte-based procedures, mesenchymal stromal cell (MSC)-based strategies, and combinations of these approaches. However, the amount and type of evidence available for these treatments differ considerably.ObjectiveTo map the clinical and preclinical evidence for cell-based regenerative strategies used for focal chondral and osteochondral defects of the knee, compare cartilage-based, MSC-based, and hybrid approaches, and identify areas where evidence remains limited.MethodsThis scoping review was prospectively registered on the Open Science Framework and reported according to PRISMA-ScR. PubMed, Scopus, and Web of Science were searched for studies published from January 2000 to December 2025. Eligible studies evaluated in vivo cartilage-derived, MSC-based, or hybrid regenerative interventions for focal knee chondral or osteochondral defects. Two reviewers independently screened the records and charted study characteristics and outcomes using a standardized form. Because of substantial heterogeneity in interventions, study designs, models, outcomes, and follow-up periods, the findings were summarized descriptively rather than pooled.ResultsSeventy-five publications met the eligibility criteria. Cartilage-based approaches were evaluated in 29 publications, including 21 clinical and 8 preclinical studies. MSC-based approaches were evaluated in 43 publications, including 12 clinical and 31 preclinical studies. Three publications examined hybrid strategies, including two clinical reports from the same 35-patient cohort and one preclinical study. Cartilage-based evidence was therefore mainly clinical (72.4%), whereas MSC-based evidence was mainly preclinical (72.1%). Clinical studies used a wide range of outcome measures, and comparative studies did not show a consistent advantage of one more complex cell-based approach over another. Evidence for hybrid strategies remained limited to one preclinical study and one clinical programme reported at 18 months and 5 years.ConclusionThe available evidence differs considerably across cartilage-based, MSC-based, and hybrid approaches. Cartilage-based techniques have been studied more extensively in clinical settings, whereas most MSC research remains preclinical. Hybrid cartilage and MSC strategies have been investigated in only a small number of studies. A framework based on structural or chondrogenic input, biological signaling, and the combination of these components may be useful for organizing future research, but it should currently be considered a hypothesis rather than a validated treatment model.