Facile Construction of Hybrid Hydrogels with High Strength and Biocompatibility for Cranial Bone Regeneration

Abstract

The significant efforts being made towards the utilization of artificial soft materials holds considerable promise for developing tissue engineering scaffolds for bone-related diseases in clinics. However, most of these biomaterials cannot simultaneously satisfy the multiple requirements of high mechanics, good compatibility, and biological osteogenesis. In this study, an osteogenic hybrid hydrogel between the amine-functionalized bioactive glass (ABG) and 4-armed poly(ethylene glycol) succinimidyl glutarate-gelatin network (SGgel) is introduced to flexibly adhere onto the defective tissue and to subsequently guide bone regeneration. Relying on the rapid ammonolysis reaction between amine groups (-NH2) of gelatin and ABG components and N-hydroxysuccinimide (NHS)-ester of tetra-PEG-SG polymer, the hydrogel networks were formed within seconds, offering a multifunctional performance, including easy injection, favorable biocompatibility, biological and mechanical properties (compressive strength: 4.2 MPa; storage modulus: 104 kPa; adhesive strength: 56 kPa), which could facilitate the stem cell viability, proliferation, migration and differentiation into osteocytes. In addition, the integration between the SGgel network and ABG moieties within a nano-scale level enabled the hybrid hydrogel to form adhesion to tissue, maintain the durable osteogenesis and accelerate bone regeneration. Therefore, a robust approach to the simultaneously satisfying tough adhesion onto the tissue defects and high efficiency for bone regeneration on a mouse skull was achieved, which may represent a promising strategy to design therapeutic scaffolds for tissue engineering in clinical applications.