Multiscale design of stiffening and ROS scavenging hydrogels for the augmentation of mandibular bone regeneration

Although biomimetic hydrogels play an essential role in guiding bone remodeling, reconstructing large bone defects is still a significant challenge since bioinspired gels often lack osteoconductive capacity, robust mechanical properties and suitable antioxidant ability for bone regeneration. To address these challenges, we first engineered molecular design of hydrogels (gelatin/polyethylene glycol diacrylate/2-(dimethylamino)ethyl methacrylate, GPEGD), where their mechanical properties were significantly enhanced via introducing trace amounts of additives (0.5 wt%). The novel hybrid hydrogels show high compressive strength (>700 kPa), stiff modulus (>170 kPa) and strong ROS-scavenging ability. Furthermore, to endow the GPEGD hydrogels excellent osteoinductions, novel biocompatible, antioxidant and BMP-2 loaded polydopamine/heparin nanoparticles (BPDAH) were developed for functionalization of the GPEGD gels (BPDAH-GPEGD). In vitro results indicate that the antioxidant BPDAH-GPEGD is able to deplete elevated ROS levels to protect cells viability against ROS damage. More importantly, the BPDAH-GPEGD hydrogels have good biocompatibility and promote the osteo differentiation of preosteoblasts and bone regenerations. At 4 and 8 weeks after implantation of the hydrogels in a mandibular bone defect, Micro-computed tomography and histology results show greater bone volume and enhancements in the quality and rate of bone regeneration in the BPDAH-GPEGD hydrogels. Thus, the multiscale design of stiffening and ROS scavenging hydrogels could serve as a promising material for bone regeneration applications.