title: A novel peptide-modified and gene-activated biomimetic bone matrix accelerating bone regeneration.
abstract: The osteogenic differentiation of bone marrow stromal cells (BMSCs) can be regulated by systemic or local growth factor, especially by transforming growth factor beta 1 (TGF-β1). However, how to maintain the bioactivity of exogenous TGF-β1 is a great challenge due to its short half-life time. The most promising solution is to transfer TGF-β1 gene into seed cells through transgenic technology and then transgenic cells to continuously secret endogenous TGF-β1 protein via gene expression. In this study, a novel non-viral vector (K)16GRGDSPC was chemically linked to bioactive bone matrices PLGA-[ASP-PEG]n using cross-linker to construct a novel non-viral gene transfer system. TGF-β1 gene was incubated with this system and subsequently rabbit-derived BMSCs were co-cultured with this gene-activated PLGA-[ASP-PEG]n, while co-cultured with PLGA-[ASP-PEG]n modified with (K)16GRGDSPC only and original PLGA-[ASP-PEG]n as control. Thus we fabricated three kinds of composites: Group A (BMSCs-TGF-β1DNA-(K)16GRGDSPC-PLGA-[ASP-PEG]n composite); Group B (BMSCs-(K)16GRGDSPC-PLGA-[ASP-PEG]n composite); and Group C (BMSCs-PLGA-[ASP-PEG]n composite). TGF-β1 and other osteogenic phenotype markers of alkaline phosphatase, osteocalcin, osteopontin and type I collagen in Group A were all significantly higher than the other two groups ex vivo. In vivo, 15-mm long segmental rabbit bone defects were created and randomly implanted the aforementioned composites separately, and then fixed with plate-screws. The results demonstrated that the implants in Group A significantly accelerated bone regeneration compared with the other implants based on X-rays, histological and biomechanical examinations. Therefore, we conclude this novel peptide-modified and gene-activated biomimetic bone matrix of TGF-β1DNA-(K)16GRGDSPC-PLGA-[ASP-PEG]n is a very promising scaffold biomaterial for accelerating bone regeneration.
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Pan
authors.forename: Qixin
authors.initials: Q
authors.lastname: Zheng
authors.forename: Shuhua
authors.initials: S
authors.lastname: Yang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Guo
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Zou
authors.forename: Zhixia
authors.initials: Z
authors.lastname: Duan
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry; D001696:Biomechanical Phenomena / Q000187:drug effects; D040761:Biomimetic Materials; D001857:Bone Matrix / Q000187:drug effects / Q000378:metabolism*; D001861:Bone Regeneration / Q000187:drug effects*; D016025:Bone Transplantation; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology / Q000601:surgery; D019344:Lactic Acid / Q000737:chemistry; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000201:enzymology; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D010455:Peptides / Q000494:pharmacology*; D010641:Phenotype; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D011859:Radiography; D015533:Transcriptional Activation / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D010455:Peptides; D053773:Transforming Growth Factor beta1; D015675:Osteocalcin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D001224:Aspartic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D000469:Alkaline Phosphatase
keywords: bone regeneration; gene-acivated matrix; osteogenic differentiation; peptide modification; transforming growth factor beta 1