Highly bioactive peptide-HA photo-crosslinking hydrogel for sustained promoting bone regeneration

Peptides provide promising application prospects for clinical therapy with their higher bioactivity and specificity. However, the rapid degradation and short half-life hinder the further application of the peptides in vivo. In this study, a novel peptide hydrogel (HA-c-CGRP) was constructed by calcitonin gene-related peptide (CGRP) grafted photo-crosslinking hyaluronic acid (HA) hydrogel template. This peptide hydrogel could sustained release the highly bioactive CGRP through the dynamic covalent bonds, promote the bone marrow stem cell (BMSCs) proliferation and induce osteoblast differentiation. The gene and protein expression of osteogenic markers ALP, Runx2, and OCN were significantly increased in vitro, compared to the control. Besides, the co-crosslinking HA-c-CGRP hydrogel could accelerate the new bone formation process with the highly bioactive peptide. Furthermore, the HA-c-CGRP hydrogel could function as an excellent biological scaffold with maintaining the defect site's three-dimensional space for the ingrowth of bone tissues by Micro-CT analysis, Van Gieson, Hematoxylin-Eosin (HE), Masson staining, and Immunochemistry analysis of the new bone. The HA-c-CGRP hydrogel was formed with transient UV light in situ, which could also avoid a rapid releasing of CGRP and maintain the high bioactivity of CGRP. Therefore, this novel peptide hydrogel has a promising prospect for healing the defected bone tissue.