Tailored biomimetic hydrogel based on a photopolymerised DMP1/MCF/gelatin hybrid system for calvarial bone regeneration

Abstract

Searching for effective osteoinduction factors with higher specificity and biosafety for the preparation of biomimetic materials, which mimic the natural bone extracellular matrix (ECM), seems to be an optimum strategy for achieving ideal bone regeneration. Dentin matrix protein 1 (DMP1) seems to be a highly promising candidate due to its pleiotropic bio-regulation roles in several bone formation processes including osteoinduction, osteogenesis and biomineralization. In this study, we first generated a novel meso/macro-structured photopolymerised hybrid hydrogel system, in which DMP1 was loaded in mesocellular silica foam (MCF) and then evenly embedded in the photopolymerised gelatin hydrogel. This DMP1-loaded hybrid system (DMP1/MCF/gel) exhibited a hierarchical porous structure according to the surface area and pore size distribution analysis, TEM and SEM. Protein loading quantification and release kinetics experiments demonstrated that DMP1 is well protected and stably released for a longer duration in the DMP1/MCF/gel system. The expression levels of bone markers in the BMSCs under the co-treatment of both Si ion and DMP1 suggested there was a synergistic effect between Si ion and DMP1, both of which could be released from DMP1/MCF/gel system. Further in vitro osteoinductive experiments of bone marrow stem cells (BMSCs) showed that the DMP1/MCF/gel system enhanced the activity of alkaline phosphatase (ALP), promoted the formation of mineralized bone nodules, and up-regulated the expression levels of several osteogenic markers (including Runx2, Osx, Bsp, Ocn, Opn, and Dmp1). In addition, both µ-CT and histological studies suggested that the in vivo repair of rat calvarial defects using the DMP1/MCF/gel system led to accelerated bone regeneration with better mineralization and higher quality. In summary, this work generated a tailored biomimetic hydrogel based on a photopolymerised DMP1/MCF/gel hybrid system, which mimicked the non-mineralized bone ECM and resulted in improved bone regeneration.