Programmed Sustained Release of Recombinant Human Bone Morphogenetic Protein-2 and Inorganic Ion Composite Hydrogel as Artificial Periosteum

Abstract

Recombinant human bone morphogenetic protein-2 (rhBMP-2) and bioceramic are the widely used bioactive factors in treatment of bone defects, but these easily cause side effects because of uncontrollable local concentration. In this study, rhBMP-2 was grafted on the surface of mesoporous bioglass nanoparticles (MBGNs) with an amide bond and then photo-cross-linked together with methacrylate gelatin (GelMA); in this way, a GelMA/MBGNs-rhBMP-2 hydrogel membrane was fabricated to release rhBMP-2 in a controllable program during the early bone regeneration period and then release calcium and silicon ions to keep promoting osteogenesis instead of rhBMP-2 in a long term. In this way, rhBMP-2 can keep releasing for 4 weeks and then the ions keep releasing after 4 weeks; this process is matched to early and late osteogenesis procedures. In vitro study demonstrated that the early release of rhBMP-2 can effectively promote local cell osteogenic differentiation in a short period, and then, the inorganic ions can promote cell adhesion not only in the early stage but also keep promoting osteogenic differentiation for a long period. Finally, the GelMA/MBGNs-rhBMP-2 hydrogel shows a superior capacity in long-term osteogenesis and promoting bone tissue regeneration in rat calvarial critical size defect. This GelMA/MBGNs-rhBMP-2 hydrogel demonstrated a promising strategy for the controllable and safer use of bioactive factors such as rhBMP-2 in artificial periosteum to accelerate bone repairing.

3D Bioprinting Photo-Crosslinkable Hydrogels for Bone and Cartilage Repair

“…In another study, Xin et al . prepared recombinant human BMP-2 (rhBMP-2)-laden GelMA hydrogel to accelerate bone repair[ 69 ]. rhBMP-2 can localize BMSCs to the site of bone injury, promoting proliferation, and osteogenic differentiation.…”

Biomedical application of photo-crosslinked gelatin hydrogels

“…Benefiting from the adjustable mechanical properties of GelMA (which can meet the mechanical requirements of load-bearing tissues) and good bio-compatibility (reducing the inflammatory response in the damaged area), it has been paid significant attention in the field of bone tissue repair and more and more researchers have also begun to explore its application in bone tissue repair. Various types of scaffolds, such as GelMA/PEGDA [68,77], GelMA/MBG [69,75,76], GeLMA/liposome [70,86] et al have been developed for bone defect regeneration and the recent applications of GelMA in the field of bone tissue are summarized in Table 3. 3D printing technology has received much attention in recent years.…”

Periosteal Tissue Engineering: Current Developments and Perspectives

“…Xin et al. [ 94 ] grafted recombinant human BMP‐2 onto bioglass nanoparticles through an amide bond, then used photo‐crosslinking with methacrylate gelatin to develop TEP. The resulting recombinant human BMP‐2 exhibited continuous release for 4 weeks.…”

“…Gelatin [ 91,92 ] and GelMA, [ 93–95 ] which are common materials for developing implanting scaffolds, present excellent biocompatibility and biodegradability properties. They are modified to improve their degradation rate and to allow the incorporation of biomolecules and other cell‐adhesion ligands effectively, thus increasing their application in gene networks, cell networks, and drug delivery.…”