A novel smart injectable hydrogel prepared by microbial transglutaminase and human-like collagen: Its characterization and biocompatibility

Various tissue scaffold materials are increasingly used to repair skin defects by cross-linking because of the ability to fill and implant in any form via operation. However, crosslinker residues cannot be easily removed from scaffold materials prepared by chemical crosslinking methods, limiting their use for skin tissue engineering. Here, microbial transglutaminase (MTGase), a nontoxic crosslinker with high specific activity and reaction rate under mild conditions, was employed crosslinks in human-like collagen (HLC) to yield novel smart MTGase crosslinked with human-like collagen (MTGH) hydrogels, which are sensitive to temperature and/or enzymes. Various ratios of MTGase/HLC were performed, and their physicochemical properties were characterized, including the swelling ratio, the elastic modulus, the morphology and the porosity. The degradation behavior and mechanism of MTGase in concentration-dependent manner involved in formation hydrogels were identifying in vitro. The cell attachment in vitro and biocompatibility in vivo were also investigated. The results demonstrated that the use of different concentrations of MTGase to crosslink HLC produced products with different degradation times and biocompatibilities. The 50 U/g MTGase-prepared MTGH hydrogels had a higher density of crosslinks, which made them more resistant to degradation by collagenase I and collagenase II. However, 40 U/g MTGase-prepared MTGH hydrogels were more suitable for cell attachment. In addition, compared with the Collagen Implant I® (SUM) used in animal experiments, the 40 U/g MTGase-prepared MTGH hydrogels had a lower toxicity and better biocompatibility. Therefore, 40 U/g MTGase crosslinked with HLC should be used to prepare MTGH hydrogels for potential application as soft materials for skin tissue engineering.