Cartilage Lacuna-inspired Microcarriers Drive Hyaline Neocartilage Regeneration.

Cartilage equivalents from hydrogels containing chondrocytes exhibit excellent potential in hyaline cartilage regeneration, yet current approaches have limited success at reconstituting the architecture to culture nondifferentiated chondrocytes in vitro. In this study, we report specially designed lacunar hyaluronic acid microcarriers (LHAMC) with mechanotransductive conditions that rapidly form stable hyaluronic acid (HA) N-hydroxy succinimide ester (NHS-ester). Specifically, carboxyl-functionalized HA is linked to collagen type I via amide-crosslinking, and gas foaming produced by ammonium bicarbonate form concave surface of the microcarriers. The temporal three-dimensional culture of chondrocytes on LHAMC uniquely remodels the extracellular matrix to induce hyaline cartilaginous microtissue regeneration and prevents an anaerobic-to-aerobic metabolism transition in response to the geometric constraints. Furthermore, by inhibiting the canonical Wnt pathway, LHAMC prevent β-catenin translocation to the nucleus, repressing chondrocyte dedifferentiation. Additionally, the subcutaneous implantation model indicates that LHAMC display favorable cytocompatibility and drive robust hyaline chondrocyte-derived neocartilage formation. Our findings reveal a novel strategy for regulating chondrocyte dedifferentiation. The current study paves the way for a better understanding of geometrical insight clues into mechanotransduction interaction in regulating cell fate, opening new avenues for advancing tissue engineering. This article is protected by copyright. All rights reserved.