Slow-release human recombinant bone morphogenetic protein-2 embedded within electrospun scaffolds for regeneration of bone defect: in vitro and in vivo evaluation.
The design of mat-like scaffolds slow-releasing bone morphogenetic protein-2 (BMP-2) retaining bone regeneration functions has been a major challenge in tissue engineering. This study aimed to develop core-shell fiber scaffolds releasing BMP-2 to support bone regeneration. BMP-2 was incorporated in an aqueous core solution of poly(ethylene oxide), whereas the shell solution was made of polycaprolactone blended with poly(ethylene glycol). This blending induced pores in the shell, which pronouncedly affected the movement of proteins out of the fibers. BMP-2 release profiles were monitored. In vitro bioactivity of BMP-2 released from the scaffolds was assessed using human mesenchymal stem cells by measuring alkaline phosphatase activity. Bone regeneration capabilities were demonstrated by implanting the BMP-2-embedded scaffolds in rat cranial defect model followed by micro-computed tomography analysis. The degree of fiber's shell porosity, highly correlative with the slow- and fast-release patterns of BMP-2, were found to be dependent on the relative amount of poly(ethylene glycol) within the shell. In vitro assays of scaffolds manifesting the slow-release pattern have revealed significant (∼9-fold) increase in alkaline phosphatase activity, compared to fast BMP-2 releasing scaffolds. Likewise, in vivo studies have revealed significant bone regeneration in cranial defects of scaffold implants with recombinant human BMP-2 with slow-release pattern.
Srouji
Samer
S
Department of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. mdsamer@tx.technion.ac.il
Ben-David
Dror
D
Lotan
Rona
R
Livne
Erella
E
Avrahami
Ron
R
Zussman
Eyal
E
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000737:chemistry*; D001861:Bone Regeneration / Q000187:drug effects*; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000138:chemical synthesis*; D004563:Electrochemistry / Q000379:methods; D004867:Equipment Design; D019544:Equipment Failure Analysis; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry; D012399:Rotation; D012887:Skull Fractures / Q000000981:diagnostic imaging / Q000601:surgery*; D054457:Tissue Scaffolds; D016896:Treatment Outcome
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D003692:Delayed-Action Preparations; D011994:Recombinant Proteins