Effect of Local Sustainable Release of BMP2-VEGF from Nano-Cellulose Loaded in Sponge Biphasic Calcium Phosphate on Bone Regeneration

Abstract

Bone regeneration is a coordinated process mainly regulated by multiple growth factors. Vascular endothelial growth factor (VEGF) stimulates angiogenesis and bone morphogenetic proteins (BMPs) induce osteogenesis during bone healing process. The aim of this study was to investigate how these growth factors released locally and sustainably from nano-cellulose (NC) simultaneously effect bone formation. A biphasic calcium phosphate (BCP)-NC-BMP2-VEGF (BNBV) scaffold was fabricated for this purpose. The sponge BCP scaffold was prepared by replica method and then loaded with 0.5% NC containing BMP2-VEGF. Growth factors were released from NC in a sustainable manner from 1 to 30 days. BNBV scaffolds showed higher cell attachment and proliferation behavior than the other scaffolds loaded with single growth factors. Bare BCP scaffolds and BNBV scaffolds seeded with rat bone marrow mesenchymal stem cells were implanted ectopically and orthotopically in nude mice for 4 weeks. No typical bone formation was exhibited in BNBV scaffolds in ectopic sites. BMP2 and VEGF showed positive effects on new bone formation in BNBV scaffolds, with and without seeded stem cells, in the orthotopic defects. This study demonstrated that the BNBV scaffold could be beneficial for improved bone regeneration. Stem cell incorporation into this scaffold could further enhance the bone healing process.

A biphasic calcium phosphate ceramic scaffold loaded with oxidized cellulose nanofiber–gelatin hydrogel with immobilized simvastatin drug for osteogenic differentiation

“…The rest of the drug was released slowly, based on the slow degradation rate of the scaffold. The degradation rate of the scaffold was slow due to the lower degradation characteristics of cellulose nanofiber (Sukul, Nguyen, Min, Lee, & Lee, ). Drug delivery from the composite system depends on degradation, cross‐linking, and chemical bonding of the different types of polymers and ceramic system used.…”

Effects of platelet‐rich plasma on biological activity and bone regeneration of brushite‐based calcium phosphate cement

“…Moreover, multiple growth factors are involved in the angiogenesis signaling reaction. 37,43,44 Sukul et al 45 reported that incorporating multiple growth factors into the osteoconductive scaffold stimulated more angiogenesis and osteogenesis during bone healing than did incorporating a single growth factor. Adding PRP to the B-P3 introduced multiple growth factors, which enhanced osteogenic cell recruitment and increased vascularization to the repair site compared with B0.…”

Biomaterials for Craniofacial Bone Regeneration

“…Many growth factors (GFs) have been clinically proven to play a key role in craniofacial growth and development, including TGF-β, FGF, VEGF, PDGF, IGFs and BMPs (BMP-2 and BMP-7) [85],[86],[87]. For example, recombinant human BMPs (rhBMPs), [88] one of the widely investigated FDA approved growth factors, are involved in various developmental processes critical for the formation of soft and hard callus, cranial neural crest, facial primordia, tooth, lip and palate.…”