Dual physical dynamic bond-based injectable and biodegradable hydrogel for tissue regeneration

A biodegradable and injectable hydrogel was designed using dual physical dynamic bonds based on host-guest chemistry and electrostatic interactions to build up the network structure. The material was synthesized by simultaneously coupling mono-carboxylic acid terminated poly(ethylene glycol) and arginine to poly(ethylene aspartate diglyceride) to yield a mPEG-grafted poly(ethylene argininylaspartate diglyceride) (mPEG-g-PEAD). When mixing this polymer with α-cyclodextrin and a natural polyanion (heparin), the supramolecular network was formed in a quick gelation with shear thinning properties. The in vitro cytotoxicity was evaluated using primary baboon arterial smooth muscle cells (BaSMCs) and the results showed that cell membrane integrity, viability and metabolism were not compromised by this synthetic polycation at concentrations as high as 10 mg mL^-1, a 1000-fold lower toxicity than commercial PEI. The in vitro biocompatibility of the as-made hydrogel was also evaluated using BaSMCs. Neither the hydrogel nor the hydrogel components altered cell behavior in the assays. Fibroblast growth factor 2 was incorporated into the hydrogel and sustainably released at a nearly stable rate up to 16 days without initial burst release, suggesting potential applications in wound healing and ischemic tissue regeneration, among others.