title: Sustained delivery of BMP-2 enhanced osteoblastic differentiation of BMSCs based on surface hydroxyapatite nanostructure in chitosan-HAp scaffold.
abstract: The surface characteristics of biomaterials, especially regarding the sustained delivery of bone morphogenetic protein-2 (BMP-2), can possibly provide a novel and effective drug delivery system that can enhance osteogenesis. In this study, we evaluated the BMP-2 adsorption and release ability of the surface biomimetic hydroxyapatite (HAp) nanostructure on a new HAp-coated genipin-chitosan conjugation scaffold (HGCCS), and the resulting osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. HGCCS exhibited a loading efficiency of 65% (1.30 μg), which is significantly higher than 28% (0.56 μg, p < 0.01) for the genipin cross-linked chitosan framework, as quantified by an enzyme-linked immunosorbent assay. More importantly, we found that the release of BMP-2 from HGGCS sustained for at least 14 days in simulated body fluid in vitro, which is much better than the burst release within 3 days for CGF. Moreover, the BMP-2 release from HGCCS induced an increase in alkaline phosphatase activity as an indicator of osteogenic differentiation of seeded BMSCs for 14 days in vitro. HGCCS also stimulated a high mRNA expression of osteogenic differentiation makers, runt-related transcription factor 2 for 14 days, osteopontin for 3 days, and osteocalcin for 14 days. The results of this study suggest that the surface biomimetic HAp nanostructure of HGCCS used as a delivery system for BMP-2 is capable of promoting osteogenic differentiation in vitro. These findings demonstrated that HAp nanostructure assembled on organic porous scaffold could work as both calcium source and absorption/release platform, which opened a new research avenue for cell growth factor release, and provided a promising strategy for design and preparation of bioactive scaffold for bone tissue engineering.
authors.affiliation: a The Technology Research and Development Centre , Shandong Energy Group Co., Ltd , No. 10777, Jingshi Road, Jinan 250014 , P.R. China.
authors.forename: Guancong
authors.initials: G
authors.lastname: Wang
authors.forename: Jichuan
authors.initials: J
authors.lastname: Qiu
authors.forename: Lin
authors.initials: L
authors.lastname: Zheng
authors.forename: Na
authors.initials: N
authors.lastname: Ren
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Junying
authors.initials: J
authors.lastname: Miao
mesh_terms: D000327:Adsorption; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018786:Bone Substitutes / Q000737:chemistry; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry; D003692:Delayed-Action Preparations; D017886:Durapatite / Q000737:chemistry; D005269:Femur / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006133:Growth Substances / Q000008:administration & dosage* / Q000493:pharmacokinetics; D039823:Iridoids / Q000737:chemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D049329:Nanostructures / Q000737:chemistry*; D010012:Osteogenesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D013977:Tibia / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D003692:Delayed-Action Preparations; D006133:Growth Substances; D039823:Iridoids; D012333:RNA, Messenger; D048271:Chitosan; D017886:Durapatite; C007834:genipin; D000469:Alkaline Phosphatase
keywords: BMP-2; chitosan; hydroxyapatite nanostructure; osteoblastic differentiation; sustained release