Macroporous Hydrogels Upregulate Osteogenic Signal Expression and Promote Bone Regeneration

被引:59
作者
Betz, Martha W. [1 ]
Yeatts, Andrew B. [1 ]
Richbourg, William J. [1 ]
Caccamese, John F. [2 ]
Coletti, Domenick P. [2 ]
Falco, Erin E. [3 ]
Fisher, John P. [1 ,2 ,3 ]
机构
[1] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA
[2] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA
[3] Univ Maryland, Sch Dent, Dept Oral & Maxillofacial Surg, Baltimore, MD 21201 USA
基金
美国国家科学基金会;
关键词
MESENCHYMAL STEM-CELLS; POLYMER SCAFFOLDS; TISSUE-RESPONSE; IN-VITRO; DIFFERENTIATION; ARCHITECTURE; EXPERIENCE; FRACTURES; CERAMICS; DELIVERY;
D O I
10.1021/bm100061z
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The objective of this work was to investigate the effects of macroporous hydrogel architecture on the osteogenic signal expression and differentiation of human mesenchymal stem cells (hMSCs). In particular, we have proposed a tissue engineering approach for orbital bone repair based on a cyclic acetal biomaterial formed from 5-ethyl-5-(hydroxymethyl)-beta,beta-dimethyl-1,3-dioxane-2-ethanol diacrylate (EHD) and poly(ethylene glycol) diacrylate (PEGDA). The El-ID monomer and PEGDA polymer may be fabricated into macroporous hydrogels by radical polymerization and subsequent porogen leaching, a novel technique for hydrophilic gels. We hypothesized that EH-PEG hydrogel macroporosity facilitates intercellular signaling among hMSCs. To investigate this phenomenon, hMSCs were loaded into El-I-PEG hydrogels with varying pore size and porosity. The viability of hMSCs, the expression of bone morphogenetic protein-2 (BMP-2), BMP receptor type 1A, and BMP receptor type 2 by hMSCs, and the differentiation of hMSCs were then assessed. Results demonstrate that macroporous El-I-PEG hydrogels support hMSCs and that this macroporous environment promotes a dramatic increase in BMP-2 expression by hMSCs. This upregulation of BMP-2 expression is associated by a more rapid hMSC differentiation, as measured by alkaline phosphatase expression. Altering hMSC interactions with the EH-PEG hydrogel surface, by the addition of fibronectin, did not appear to augment BMP-2 expression. We therefore speculate that EH-PEG hydrogel macroporosity facilitates autocrine and paracrine signaling by localizing endogenously expressed factors within the hydrogel's pores and thus promotes hMSC osteoblastic differentiation and bone regeneration.
引用
收藏
页码:1160 / 1168
页数:9
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