Sustained delivery of recombinant human bone morphogenetic protein‐2 from perlecan domain I ‐ functionalized electrospun poly (ε‐caprolactone) scaffolds for bone regeneration

Abstract

Abstract Background Biomaterial scaffolds that deliver growth factors such as recombinant human bone morphogenetic proteins‐2 (rhBMP‐2) have improved clinical bone tissue engineering by enhancing bone tissue regeneration. This approach could be further improved if the controlled delivery of bioactive rhBMP‐2 were sustained throughout the duration of osteogenesis from fibrous scaffolds that provide control over dose and bioactivity of rhBMP‐2. In nature, heparan sulfate attached to core proteoglycans serves as the co‐receptor that delivers growth factors to support tissue morphogenesis. Methods To mimic this behavior, we conjugated heparan sulfate decorated recombinant domain I of perlecan/HSPG2 onto an electrospun poly(ε‐caprolactone) (PCL) scaffold, hypothesizing that the heparan sulfate chains will enhance rhBMP‐2 loading onto the scaffold and preserve delivered rhBMP‐2 bioactivity. Results In this study, we demonstrated that covalently conjugated perlecan domain I increased loading capacity of rhBMP‐2 onto PCL scaffolds when compared to control unconjugated scaffolds. Additionally, rhBMP‐2 released from the modified scaffolds enhanced alkaline phosphatase activity in W20–17 mouse bone marrow stromal cells, indicating the preservation of rhBMP‐2 bioactivity indicative of osteogenesis. Conclusions We conclude that this platform provides a sophisticated and efficient approach to deliver bioactive rhBMP‐2 for bone tissue regeneration applications.

Keywords

• Heparan sulfate
• Poly(ε‐caprolactone)
• Bone morphogenetic protein
• Alkaline phosphatase
• Perlecan/HSPG2
• Bone regeneration