Injuries to the avascular region of the knee meniscus—the inner “white–white” zone—pose a significant therapeutic challenge due to its lack of vascular supply and limited intrinsic healing capacity. While conventional meniscal repair techniques often fail in this region, recent advances in regenerative medicine have turned to explant culture systems as a bridge between simple cell cultures and complex in vivo models. This review synthesizes the current literature on the role of explant cultures in understanding and advancing avascular meniscus repair. Explant cultures maintain native extracellular matrix structure and provide a controlled three-dimensional environment to study cellular responses to injury. Within these systems, a distinct subpopulation of cells termed migratory meniscus cells emerge from the tissue edge, exhibiting progenitor-like features, including clonogenicity, multipotency, and responsiveness to transforming growth factor-β signaling. These cells have demonstrated the capacity to infiltrate defect zones, remodel extracellular matrix, and synthesize reparative fibrocartilaginous tissue. Experimental manipulations within explant models, including fibrin scaffolds, enzymatic border conditioning, sequential growth factor delivery, mechanical loading, and electrical stimulation, have shown promise in enhancing integration strength and tissue quality. These studies underscore the importance of biochemical and biophysical cues in orchestrating effective repair in avascular regions. Current explant systems, however, are constrained by limited culture durations, the absence of vascular and immune components, and species-specific differences in matrix biology, thereby limiting their ultimate utility in translational research. Despite these limitations, explant models remain essential for dissecting the mechanistic basis of meniscal repair and for evaluating candidate therapies in a reproducible, hypothesis-driven manner. Looking ahead, next-generation platforms incorporating perfusion bioreactors, immune cocultures, and validated integration assays will be critical to better replicate in vivo physiology. Personalized strategies targeting patient-specific tear characteristics and cellular profiles, including autologous progenitor cell delivery and biomaterial-based signaling systems, hold potential for transforming the clinical management of avascular meniscus injuries. This review highlights the central role of explant cultures in shaping such innovations and guiding their translation into meaningful orthopedic therapies. Impact Statement This review summarizes the current state of meniscal explant culture models for avascular-zone repair and explains how they can serve as a practical, translational bridge between cell studies and in vivo models. This will help guide development of true meniscus-preserving therapies that will eventually lead to deliverable solutions that will revolutionize meniscus injury care.
Ekundayo et al. (Sat,) studied this question.