A Hybrid Scaffold Induces Chondrogenic Differentiation and Enhances In Vivo Cartilage Regeneration

Abstract

Extensively researched tissue engineering strategies involve incorporating cells into suitable biomaterials, offering promising alternatives to boost tissue repair. In this study, a hybrid scaffold, Gel-DCM, which integrates a photoreactive gelatin–hyaluronic acid hydrogel (Gel) with an oriented porous decellularized cartilage matrix (DCM), was designed to facilitate chondrogenic differentiation and cartilage repair. The Gel-DCM exhibited excellent biocompatibility in vitro, promoting favorable survival and growth of human adipose-derived stem cells (hADSCs) and articular chondrocytes (hACs). Gene expression analysis indicated that the hACs expanded within the Gel-DCM exhibited enhanced chondrogenic phenotype. In addition, Gel-DCM promoted chondrogenesis of hADSCs without the supplementation of exogenous growth factors. Following this, in vivo experiments were conducted where empty Gel-DCM or Gel-DCM loaded with hACs/hADSCs were used and implanted to repair osteochondral defects in a rat model. In the control group, no implants were delivered to the injury site. Interestingly, macroscopic, histological, and microcomputed tomography scanning results revealed superior cartilage restoration and subchondral bone reconstruction in the empty Gel-DCM group compared with the control group. Moreover, both hACs-loaded and hADSCs-loaded Gel-DCM implants exhibited superior repair of hyaline cartilage and successful reconstruction of subchondral bone, whereas defects in the control groups were predominantly filled with fibrous tissue. These observations suggest that the Gel-DCM can provide an appropriate three-dimensional chondrogenic microenvironment, and its combination with reparative cell sources, ACs or ADSCs, holds great potential for facilitating cartilage regeneration.

Impact statement

In this study, we developed a hybrid Gel-DCM scaffold and demonstrated its efficacy in promoting chondrogenic differentiation and facilitating cartilage regeneration. Our findings underscore the potential of this scaffold, especially when combined with adipose-derived stem cells and articular chondrocytes, to enhance the process of cartilage repair. By providing a conducive three-dimensional chondrogenic microenvironment, the Gel-DCM scaffold offers promising prospects for clinical translation in cartilage regeneration therapies. This research lays a solid foundation for further exploration and development of advanced tissue engineering strategies aimed at addressing cartilage defects and improving patient outcomes.