Engineering Morphogenetic Microenvironments: Biomaterial‐Driven Reprogramming of Cartilage Regeneration

ABSTRACT Articular cartilage is avascular, aneural, and sparsely cellular, so it has very limited capacity for self‐repair and its regeneration remains a major clinical challenge. Conventional treatments rarely restore native zonal architecture and function; instead, they often generate mechanically inferior fibrocartilage with poor long‐term durability. In this review, we advance a morphogenetic biomaterial strategy in which materials are engineered not as passive scaffolds but as organizers of endogenous signals. Framing biomaterials as morphogenetic organizers shifts the focus from static replacement toward dynamic, development‐inspired programming of tissue repair. By constructing morphogen‐enriched biomimetic microenvironments, these systems are designed to recruit endogenous or implanted stem/progenitor cells, guide their migration, and support chondrogenic differentiation toward more stable cartilage‐like phenotypes. We systematically summarize recent advances in hydrogels, 3D‐printed scaffolds, decellularized extracellular matrix, nanomaterials, and immunomodulatory platforms, emphasizing how their physical structure, chemical functionality, and biological cues can be tuned to mimic morphogenetic centers in developing cartilage. We highlight their roles in controlling morphogen presentation, mediating mechanotransduction and shaping immune responses, and discuss emerging translational considerations. Finally, we outline design principles and future research directions for morphogenetic microenvironments that seek to bridge the gap between short‐term structural repair and durable, functionally restored cartilage.