Cartilage Lacuna‐Inspired Microcarriers Drive Hyaline Neocartilage Regeneration

• Published in: Advanced materials (Weinheim) Vol. 35; no. 30; pp. e2212114 - n/a
• Main Authors: Ding, Sheng‐Long, Zhao, Xi‐Yuan, Xiong, Wei, Ji, Lin‐Feng, Jia, Min‐Xuan, Liu, Yan‐Yan, Guo, Hai‐Tao, Qu, Feng, Cui, Wenguo, Gu, Qi, Zhang, Ming‐Zhu
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-07-2023
• Subjects: Bicarbonates; Biocompatibility; Cartilage; cartilage tissue engineering; chondrocyte dedifferentiation; Crosslinking; Geometric constraints; Hyaluronic acid; Hydrogels; microcarriers; Regeneration; Tissue engineering; Wnt pathway; geometric constraints; cartilage tissue engineering; chondrocyte dedifferentiation; Wnt pathway; microcarriers
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202212114

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, specially designed lacunar hyaluronic acid microcarriers (LHAMCs) with mechanotransductive conditions that rapidly form stable hyaluronic acid (HA) N‐hydroxy succinimide ester (NHS‐ester) are reported. Specifically, carboxyl‐functionalized HA is linked to collagen type I via amide‐crosslinking, and gas foaming produced by ammonium bicarbonate forms concave surface of the microcarriers. The temporal 3D culture of chondrocytes on LHAMCs 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, LHAMCs prevent β‐catenin translocation to the nucleus, repressing chondrocyte dedifferentiation. Additionally, the subcutaneous implantation model indicates that LHAMCs display favorable cytocompatibility and drive robust hyaline chondrocyte‐derived neocartilage formation. These 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.
Culturing large‐scale chondrocytes with native phenotypes remains a noteworthy challenge for cartilage tissue engineering. In this work, a novel method to fabricate mimicking cartilage lacunar hyaluronic acid microcarriers (LHAMCs) using N‐hydroxy succinimide (NHS)/1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide (EDC) with mechanotransductive conditions is presented. The data show the advanced capabilities of LHAMCs by presenting the uninterrupted, long‐term culture of chondrocytes to generate an enlarged microtissue with robust chondrogenic capacity.