A novel peptide-modified and gene-activated biomimetic bone matrix accelerating bone regeneration
| Autor: | Haitao, Pan, Qixin, Zheng, Shuhua, Yang, Xiaodong, Guo, Bin, Wu, Zhenwei, Zou, Zhixia, Duan |
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| Rok vydání: | 2013 |
| Předmět: |
Transcriptional Activation
Aspartic Acid Bone Regeneration Bone Transplantation Osteocalcin Bone Matrix Mesenchymal Stem Cells Alkaline Phosphatase Collagen Type I Biomechanical Phenomena Polyethylene Glycols Radiography Transforming Growth Factor beta1 Phenotype Polylactic Acid-Polyglycolic Acid Copolymer Biomimetic Materials Osteogenesis Animals Femur Lactic Acid Rabbits Peptides Polyglycolic Acid |
| Zdroj: | Journal of biomedical materials research. Part A. 102(8) |
| ISSN: | 1552-4965 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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