Microenvironment engineering with injectable hydrogel-based biofunctional scaffolds for augmenting bone defect regeneration

Bone defects are common injuries in the clinic that often require the use of bone grafts to facilitate bone regeneration. However, the application of bone grafts is challenged by invasive surgeries, insufficient bone regeneration capability and limited availability, necessitating the development of substituting materials with enhanced safety, osteogenic capacity and large-scale applicability. Interestingly, injectable hydrogels emerge as a promising candidate for bone defect repair on account of their intrinsic biocompatibility, biomimetic structures, in-situ morphological malleability and versatile functionality. Herein, a comprehensive account is provided on the development of injectable hydrogel-based biomaterials and their application as scaffolds for supporting and guiding bone defect healing, focusing on the gelling mechanisms as well as their potential osteoinductive properties through (1) establishing osteoinductive microenvironment and (2) localized delivery of osteogenic therapeutics for boosting osteogenesis. Furthermore, existing challenges and potential breakthroughs in injectable hydrogel-based biofunctional scaffolds for bone defect treatment are discussed in-depth, focusing on the leveraging their therapeutic persistence and degradability, cost-effectiveness and dynamic material-biointeractions. It is anticipated that the insights in this review may provide new opportunities for minimally invasive bone defect treatment in the clinic.