Fabrication and evaluation of a BMP-2/dexamethasone co-loaded gelatin sponge scaffold for rapid bone regeneration

Qi Gan; Hao Pan; Wenjing Zhang; Yuan Yuan; Jiangchao Qian; Changsheng Liu

doi:10.1093/rb/rbac008

Fabrication and evaluation of a BMP-2/dexamethasone co-loaded gelatin sponge scaffold for rapid bone regeneration

Regen Biomater. 2022 Feb 16:9:rbac008. doi: 10.1093/rb/rbac008. eCollection 2022.

Authors

Qi Gan^{1

2}, Hao Pan³, Wenjing Zhang³, Yuan Yuan¹, Jiangchao Qian², Changsheng Liu^{1

3

4}

Affiliations

¹ Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.
² The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China.
³ Engineering Research Center for Biomedical Materials of the Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.
⁴ Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai 200237, PR China.

Abstract

Improving the osteogenic activity of BMP-2 in vivo has significant clinical application value. In this research, we use a clinical gelatin sponge scaffold loaded with BMP-2 and dexamethasone (Dex) to evaluate the osteogenic activity of dual drugs via ectopic osteogenesis in vivo. We also investigate the mechanism of osteogenesis induced by BMP-2 and Dex with C2C12, a multipotent muscle-derived progenitor cell. The results show that the gelatin scaffold with Dex and BMP-2 can significantly accelerate osteogenesis in vivo. It is indicated that compared with the BMP-2 or Dex alone, 100 nM of Dex can dramatically enhance the BMP-2-induced alkaline phosphatase activity (ALP), ALP mRNA expression and mineralization. Further studies show that 100 nM of Dex can maintain the secondary structure of BMP-2 and facilitate recognition of BMP-2 with its receptors on the surface of C2C12 cells. We also find that in C2C12, Dex has no obvious effect on the BMP-2-induced Smad1/5/8 protein expression and the STAT3-dependent pathway, but Runx2-dependent pathway is involved in the Dex-stimulated osteoblast differentiation of BMP-2 both in vitro and in vivo. Based on these results, a potential mechanism model about the synergistic osteoinductive effect of Dex and BMP-2 in C2C12 cells via Runx2 activation is proposed. This may provide a theoretical basis for the pre-clinical application of Dex and BMP-2 for bone regeneration.

Keywords: BMP-2; Runx2; bone regeneration; dexamethasone; pre-clinical.