Thermoresponsive Injectable Microparticle-Gel Composites with Recombinant BMP-9 and VEGF Enhance Bone Formation in Rats

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Bone morphogenetic protein-9 (BMP-9) has been shown to be the most osteogenic BMP. Most of these experiments, however, involve an adenovirus-transfection strategy. Here, we used the scaffold-based strategy to study the bone forming ability of recombinant BMP-9 combined with vascular endothelial growth factor (VEGF). A robust, injectable, multicomponent-releasing scaffold in the form of a composite gel was developed by combining chitosan microparticles (MPs) with thermosensitive gel (MPs-gel). The MPs acted as the carriers for BMP-9 and the gel was loaded with VEGF. The developed gel consisted of hydrophobic chains of methyl cellulose (MC) and the cross-linked structures of alginate (Alg) and calcium. Gelation was achieved at physiological temperature and thus facilitated the injection and localization of MPs enabling an increased efficacy of incorporated growth factors at the target site. A release profile of incorporated growth factors over a two-week period showed higher release of VEGF at each time point compared to that of BMP-9. Human mesenchymal stem cells (hMSCs) encapsulated within the MPs-gel maintained their viability. BMP-9 enhanced the proliferation of hMSCs along the surface of MPs. Furthermore, BMP-9 potently induced the osteogenic differentiation of encapsulated hMSCs elucidated by the increased alkaline phosphatase (ALP) activity and the higher expression of ALP

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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