Collagen fibril-like injectable hydrogels from self-assembled nanoparticles for promoting wound healing

Soft hydrogels are excellent candidate materials for repairing various tissue defects, yet the mechanical strength, anti-swelling properties, and biocompatibility of many soft hydrogels need to be improved. Herein, inspired by the nanostructure of collagen fibrils, we developed a strategy toward achieving a soft but tough, anti-swelling nanofibrillar hydrogel by combining the self-assembly and chemical crosslinking of nanoparticles. Specifically, the collagen fibril-like injectable hydrogel was subtly designed and fabricated by self-assembling methylacrylyl hydroxypropyl chitosan (HM) with laponite (LAP) to form nanoparticles, followed by the inter-nanoparticle bonding through photo-crosslinking. The assembly mechanism of nanoparticles was elucidated by both experimental and simulation techniques. Due to the unique structure of the crosslinked nanoparticles, the nanocomposite hydrogels exhibited low stiffness (G'< 2 kPa), high compressive strength (709 kPa), and anti-swelling (swelling ratio of 1.07 in PBS) properties. Additionally, by harnessing the photo-crosslinking ability of the nanoparticles, the nanocomposite hydrogels were processed as microgels, which can be three-dimensionally (3D) printed into complex shapes. Furthermore, we demonstrated that these nanocomposite hydrogels are highly biocompatible, biodegradability, and can effectively promote fibroblast migration and accelerate blood vessel formation during wound healing. This work presents a promising approach to develop biomimetic, nanofibrillar soft hydrogels for regenerative medicine applications.