Bioinspired dual dynamic network hydrogels promote cartilage regeneration through regulating BMSC chondrogenic differentiation

How to improve the therapeutic efficacy of cell delivery during mechanical injection has been a great challenge for tissue engineering. Here, we present a facile strategy based on dynamic chemistry to prepare injectable hydrogels for efficient stem cell delivery using hyaluronic acid (HA) and poly(gamma-glutamic acid) (gamma-PGA). The combination of the guest-host (GH) complexation and dynamic hydrazone bonds enable the HA/gamma-PGA hydrogels with physical and chemical dual dynamic network and endow hydrogels a stable structure, rapid self-healing ability, and injectability. The mechanical properties, self-healing ability, and adaptability can be programmed by changing the ratio of GH network to hydrazine bond cross-linked network. Benefitting from the dynamic cross-linking networks, mild preparation process, and cytocompatibility of HA/gamma-PGA hydrogels, bone marrow mesenchymal stem cells (BMSCs) show high cell viability in this system following mechanical injection. Moreover, HA/gamma-PGA hydrogels can promote BMSC proliferation and upregulate the expression of cartilage-critical genes. Notably, in a rabbit auricular cartilage defect model, BMSC-laden HA/gamma-PGA hydrogels can effectively promote cartilage regeneration. Together, we propose a general strategy to develop injectable self-healing HA/gamma-PGA hydrogels for effective stem cell delivery in cartilage tissue engineering. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

A facile strategy based on dynamic chemistry was presented to prepare injectable hydrogels using hyaluronic acid and poly(gamma-glutamic acid), enabling efficient stem cell delivery. The hydrogels showed stable structure, rapid self-healing ability, and injectability with dual dynamic networks. Remarkably, the hydrogels promoted stem cell viability, proliferation, and cartilage regeneration in preclinical models.