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载有 BMP-2 和 TGF-β1 的可见光固化乙二醇壳聚糖水凝胶的鸡尾酒效应增强大鼠胫骨缺损模型中的骨形成。

The Cocktail Effect of BMP-2 and TGF-β1 Loaded in Visible Light-Cured Glycol Chitosan Hydrogels for the Enhancement of Bone Formation in a Rat Tibial Defect Model.

机构信息

Department of Orthopedic Surgery, Chonbuk National University Hospital, Jeonju 54907, Korea.

Department of Surgery, School of Medicine, The Konkuk University, Seoul 05030, Korea.

出版信息

Mar Drugs. 2018 Sep 25;16(10):351. doi: 10.3390/md16100351.

DOI:10.3390/md16100351
PMID:30257482
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6213427/
Abstract

Bone tissue engineering scaffolds offer the merits of minimal invasion as well as localized and controlled biomolecule release to targeted sites. In this study, we prepared injectable hydrogel systems based on visible light-cured glycol chitosan (GC) hydrogels containing bone morphogenetic protein-2 (BMP-2) and/or transforming growth factor-beta1 (TGF-β1) as scaffolds for bone formation in vitro and in vivo. The hydrogels were characterized by storage modulus, scanning electron microscopy (SEM) and swelling ratio analyses. The developed hydrogel systems showed controlled releases of growth factors in a sustained manner for 30 days. In vitro and in vivo studies revealed that growth factor-loaded GC hydrogels have no cytotoxicity against MC3T3-E1 osteoblast cell line, improved mRNA expressions of alkaline phosphatase (ALP), type I collagen (COL 1) and osteocalcin (OCN), and increased bone volume (BV) and bone mineral density (BMD) in tibia defect sites. Moreover, GC hydrogel containing BMP-2 (10 ng) and TGF-β1 (10 ng) (GC/BMP-2/TGF-β1-10 ng) showed greater bone formation abilities than that containing BMP-2 (5 ng) and TGF-β1 (5 ng) (GC/BMP-2/TGF-β1-5 ng) in vitro and in vivo. Consequently, the injectable GC/BMP-2/TGF-β1-10 ng hydrogel may have clinical potential for dental or orthopedic applications.

摘要

骨组织工程支架具有微创以及局部和控制生物分子释放到靶向部位的优点。在这项研究中，我们制备了基于可见光固化的乙二醇壳聚糖（GC）水凝胶的可注射水凝胶系统，该水凝胶含有骨形态发生蛋白-2（BMP-2）和/或转化生长因子-β1（TGF-β1），作为体外和体内成骨的支架。通过储能模量、扫描电子显微镜（SEM）和溶胀比分析对水凝胶进行了表征。所开发的水凝胶系统以持续的方式表现出生长因子的受控释放，持续 30 天。体外和体内研究表明，负载生长因子的 GC 水凝胶对 MC3T3-E1 成骨细胞系无细胞毒性，可提高碱性磷酸酶（ALP）、I 型胶原（COL 1）和骨钙素（OCN）的 mRNA 表达，并增加胫骨缺损部位的骨体积（BV）和骨密度（BMD）。此外，含有 10ng BMP-2 和 10ng TGF-β1 的 GC 水凝胶（GC/BMP-2/TGF-β1-10ng）比含有 5ng BMP-2 和 5ng TGF-β1 的 GC 水凝胶（GC/BMP-2/TGF-β1-5ng）在体外和体内具有更好的成骨能力。因此，可注射的 GC/BMP-2/TGF-β1-10ng 水凝胶可能具有用于牙科或矫形应用的临床潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/44ff61f37d2a/marinedrugs-16-00351-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/05e1f7265852/marinedrugs-16-00351-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/8318f4392611/marinedrugs-16-00351-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/86ade631a9da/marinedrugs-16-00351-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/db3b2243c98e/marinedrugs-16-00351-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/202819ec15ac/marinedrugs-16-00351-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/20932918b03b/marinedrugs-16-00351-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/93419dc70ed0/marinedrugs-16-00351-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/7d44852e758b/marinedrugs-16-00351-g008a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/44ff61f37d2a/marinedrugs-16-00351-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/05e1f7265852/marinedrugs-16-00351-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/8318f4392611/marinedrugs-16-00351-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/86ade631a9da/marinedrugs-16-00351-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/db3b2243c98e/marinedrugs-16-00351-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/202819ec15ac/marinedrugs-16-00351-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/20932918b03b/marinedrugs-16-00351-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/93419dc70ed0/marinedrugs-16-00351-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/7d44852e758b/marinedrugs-16-00351-g008a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8775/6213427/44ff61f37d2a/marinedrugs-16-00351-g009.jpg

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