Building Osteogenic Microenvironments with a Double-Network Composite Hydrogel for Bone Repair

Abstract

The critical factor determining the in vivo effect of bone repair materials is the microenvironment, which greatly depends on their abilities to promote vascularization and bone formation. However, implant materials are far from ideal candidates for guiding bone regeneration due to their deficient angiogenic and osteogenic microenvironments. Herein, a double-network composite hydrogel combining vascular endothelial growth factor (VEGF)-mimetic peptide with hydroxyapatite (HA) precursor was developed to build an osteogenic microenvironment for bone repair. The hydrogel was prepared by mixing acrylated β-cyclodextrins and octacalcium phosphate (OCP), an HA precursor, with gelatin solution, followed by ultraviolet photo-crosslinking. To improve the angiogenic potential of the hydrogel, QK, a VEGF-mimicking peptide, was loaded in acrylated β-cyclodextrins. The QK-loaded hydrogel promoted tube formation of human umbilical vein endothelial cells and upregulated the expression of angiogenesis-related genes, such as Flt1 , Kdr , and VEGF , in bone marrow mesenchymal stem cells. Moreover, QK could recruit bone marrow mesenchymal stem cells. Furthermore, OCP in the composite hydrogel could be transformed into HA and release calcium ions facilitating bone regeneration. The double-network composite hydrogel integrated QK and OCP showed obvious osteoinductive activity. The results of animal experiments showed that the composite hydrogel enhanced bone regeneration in skull defects of rats, due to perfect synergistic effects of QK and OCP on vascularized bone regeneration. In summary, improving the angiogenic and osteogenic microenvironments by our double-network composite hydrogel shows promising prospects for bone repair.

Engineered cyclodextrin-based supramolecular hydrogels for biomedical applications

“…8C). 197 OCP (an HA precursor that releases Ca 2+ ) and QK (a VEGF-mimetic peptide) were simultaneously added into the hydrogel to further enhance its osteoconductive properties, angiogenic capacity and mechanical properties. It was demonstrated that the integration of QK and OCP into the dual-network hydrogel could synergistically contribute to the regeneration of skull bone defects via the construction of angiogenic and osteogenic microenvironments, indicating promising application prospects in the field of bone repair.…”

Enzyme‐Photodynamic Adaptive Bionic Periosteum for Bone Revitalization

“…These results confirm that the implanted bionic periosteum adaptively releases QK to promote angiogenesis based on the high expression of MMP-2 in the vicinity of the fracture and further synergistically promotes new bone formation by releasing BFP on demand after active NIR irradiation. [17,29] Importantly, the bionic periosteum effectively mimicked the dynamic function of the native periosteum at different stages of promoting bone healing was customized to specific spatiotemporal needs of bone healing process.…”

Smart Hydrogels for Bone Reconstruction via Modulating the Microenvironment

“…In biomedicine, photo-crosslinked hydrogels are commonly prepared by introducing light-responsive groups, such as acrylamide, norbornene, and methacryloyl [ 115 ]. The photo-crosslinked groups incorporated in the light-sensitive hydrogels enable the gelation process.…”