Construction of injectable collagen-microgel/tannic acid/nano-hydroxyapatite granular hydrogel and evaluation of its potential in wound healing

Granular hydrogel is a kind of hydrogel assembled from micro-particles, possessing micro-porous structure that advanced in terms of exudate absorption, mass exchange and cell migration during wound healing. The present study fabricated an injectable granular hydrogel based on tannic acid (TA) connected collagen (COL)-microparticles and hydroxyapatite nanoparticles (nHA). Through the coordination of calcium and phenolic hydroxyl groups, TA was bound on nHA surface to form TA modified nano-hydroxyapatite, TA@nHA. The content of TA bound on nHA surface was as high as 30%. TA@nHA as high as 20% was used as giant crosslinking component to connect COL microgels (COLmg) via hydrogen bond, forming COLmg@TA@nHA granular hydrogel. The size of COL microgels could be controlled via adjusting stirring speed. The larger COL microgels assembled granular hydrogel possessed higher porosity. While the smaller COL microgels assembled granular hydrogel was more stable, showing better self-healing ability in rheological test. Due to the dynamically reversible interactions, COLmg@TA@nHA granular hydrogel was injectable, which could be applied to the skin wound, exhibiting the ability to inhibit inflammatory response, while enhance alpha-SMA expression, promoting wound healing. The method to fabricate granular hydrogel introduced in this study has a broad scalability toward repairing various tissues.