title: RhBMP-2-loaded calcium silicate/calcium phosphate cement scaffold with hierarchically porous structure for enhanced bone tissue regeneration.
abstract: Calcium phosphate cement scaffold (CPC) has been widely used as bone graft substitutes, but undesirable osteoinductivity and slow degradability greatly hamper their clinic application. To address these problems, a recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded calcium silicate/calcium phosphate cement scaffold (CSPC) with hierarchical pores was developed in this study. The CSPC scaffold with both interconnected macropores on the order of 200-500 μm and micropores of 2-5 μm was synthesized from CPC and calcium silicate (CS) by a NaCl particulate-leaching method. In vitro cell culture with C2C12 model cells, in vivo ectopic bone formation and rabbit femur cavity defect repair were performed to evaluate the osteogeneic capacity of the CSPC/rhBMP-2 scaffold. CPC, CSPC and CPC/rhBMP-2 scaffolds were parallelly investigated for comparison. The results demonstrated that the hierarchical macro/microporous structure, whether in presence of CS or rhBMP-2, highly favored the adhesion of C2C12 cells and bone in-growth into the CPC-based scaffolds. But, in comparison to the CPC-based scaffolds with CS or rhBMP-2 alone, the CSPC/rhBMP-2 scaffold strongly promoted osteogenic differentiation in vitro and osteogenetic efficacy in vivo. Further studies demonstrated that Si ions derived from CSPC contributed mainly to maintain the conformation of rhBMP-2 and thus stimulate the synergistic action of CS and rhBMP-2 in osteogenic differentiation and osteoinductivity. Additionally, the incorporation of CS was also beneficial for the dissolution of the scaffold. Those results suggest that the CSPC has superior properties for incorporation of rhBMP-2 and our developed CSPC/rhBMP-2 scaffold have great potential for future use in bone tissue regeneration.
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China; Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China; Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Huanjun
authors.initials: H
authors.lastname: Zhou
authors.forename: Kai
authors.initials: K
authors.lastname: Yang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Changsheng
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D001843:Bone Cements / Q000737:chemistry*; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000627:therapeutic use; D001861:Bone Regeneration / Q000187:drug effects*; D017610:Calcium Compounds / Q000737:chemistry*; D002130:Calcium Phosphates / Q000737:chemistry*; D002448:Cell Adhesion; D002460:Cell Line; D005269:Femur / Q000293:injuries; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology; D016062:Porosity; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D017640:Silicates / Q000737:chemistry*; D054457:Tissue Scaffolds / Q000737:chemistry*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D001843:Bone Cements; D055396:Bone Morphogenetic Protein 2; D017610:Calcium Compounds; D002130:Calcium Phosphates; D011994:Recombinant Proteins; D017640:Silicates; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C020243:calcium phosphate; C031293:calcium silicate
keywords: Bone regeneration; Calcium silicate/calcium phosphate cement; Hierarchical porosity; rhBMP-2