Versatile hydrogel facilitating angiogenesis and cell recruitments for enhanced calvarial bone regeneration

Abstract

The repair of large-size cranial bone defects caused by traumatic brain injury (TBI) remains a substantial clinical challenge. On one hand, traditional bone implants with intrinsic brittle and poor recovery features hinder their immediate implantation for cranioplasty applications. On the other hand, using exogenous growth factors to enhance the osteo-bioactivity of bone implants often leads to efficacy, safety, and cost concerns. Thus far, the authors develop a growth factor-free pliable hydrogel with multiple functions for mediating endogenous growth factor production and stem cell functions in cranioplasty. The pliable hydrogels are based on GelMA networks, in which the mechanical properties and protein affinity were strengthened by the crosslinked poly (ethylene glycol) disuccinimidyl succinate (PEG-(SS)2), while the antioxidant capability and osteoinductivity were remarkedly enhanced through the decoration of magnesium-seamed C-propylpyrogallol[4]arene cages (PgC3Mg). In vitro and in vivo results confirmed that the versatile hydrogel with excellent biocompatibility and biodegradability can improve osteogenic differentiation and cranial bone regeneration by facilitating growth factor production, endogenous cell recruitment and angiogenesis. These findings indicate that the versatile hydrogels represent a potential avenue for developing growth factor-free pliable scaffolds in cranioplasty after TBI.