Biomimetic Hydrogels as the Inductive Endochondral Ossification Template for Promoting bone Regeneration.

Repairing critical size bone defects (CSBD) is a major clinical challenge and requires effective intervention by biomaterial scaffolds. Inspired by the fact that the cartilaginous template-based endochondral ossification (ECO) process is crucial to bone healing and development, developing biomimetic biomaterials to promote ECO is recognized as a promising approach for repairing CSBD. With the unique highly hydrated 3D polymeric network, hydrogels can be designed to closely emulate the physiochemical properties of cartilage matrix to facilitate ECO. In this review, we first introduce the various preparation methods of hydrogels possessing the specific physiochemical properties required for promoting ECO. We further summarize the materiobiological impacts of the physicochemical properties of hydrogels, such as mechanical properties, topographical structures and chemical compositions on ECO and the associated molecular mechanisms related to the BMP, Wnt, TGF-β, HIF-1α, FGF and RhoA signaling pathways. This review provides a detailed coverage on the materiobiological insights required for the design and preparation of hydrogel-based biomaterials to facilitate bone regeneration. This article is protected by copyright. All rights reserved.