Controlled release of transforming growth factor-β3 from cartilage-extra-cellular-matrix-derived scaffolds to promote chondrogenesis of human-joint-tissue-derived stem cells

被引:100
作者
Almeida, Henrique V. [1 ,2 ]
Liu, Yurong [1 ,2 ]
Cunniffe, Grainne M. [1 ,2 ]
Mulhall, Kevin J. [3 ]
Matsiko, Amos [1 ,4 ,5 ,6 ]
Buckley, Conor T. [1 ,2 ]
O'Brien, Fergal J. [1 ,4 ,5 ,6 ]
Kelly, Daniel J. [1 ,2 ,5 ,6 ]
机构
[1] Univ Dublin Trinity Coll, Trinity Biomed Sci Inst, Trinity Ctr Bioengn, Dublin 2, Ireland
[2] Univ Dublin Trinity Coll, Sch Engn, Dept Mech & Mfg Engn, Dublin 2, Ireland
[3] Sports Surg Clin, Dublin 9, Ireland
[4] Royal Coll Surgeons Ireland, Dept Anat, Tissue Engn Res Grp, Dublin 2, Ireland
[5] Univ Dublin Trinity Coll, Adv Mat & Bioengn Res Ctr AMBER, Dublin 2, Ireland
[6] RCSI, Dublin 2, Ireland
基金
欧洲研究理事会;
关键词
Articular cartilage; Extracellular matrix; Tissue engineering; Stem cells; Crosslinking; INFRAPATELLAR FAT PAD; EXTRACELLULAR-MATRIX; BONE-MARROW; IN-VITRO; CROSS-LINKING; ADIPOSE-TISSUE; ENGINEERED CARTILAGE; FUNCTIONAL-PROPERTIES; GELATIN MICROSPHERES; FACTOR DELIVERY;
D O I
10.1016/j.actbio.2014.05.030
中图分类号
R318 [生物医学工程];
学科分类号
100103 [病原生物学];
摘要
The objective of this study was to develop a scaffold derived from cartilaginous extracellular matrix (ECM) that could be used as a growth factor delivery system to promote chondrogenesis of stem cells. Dehydrothermal crosslinked scaffolds were fabricated using a slurry of homogenized porcine articular cartilage, which was then seeded with human infrapatellar-fat-pad-derived stem cells (FPSCs). It was found that these ECM-derived scaffolds promoted superior chondrogenesis of FPSCs when the constructs were additionally stimulated with transforming growth factor (TGF)-beta 3. Cell-mediated contraction of the scaffold was observed, which could be limited by the additional use of 1-ethyl-3-3dimethyl aminopropyl carbodiimide (EDAC) crosslinking without suppressing cartilage-specific matrix accumulation within the construct. To further validate the utility of the ECM-derived scaffold, we next compared its chondro-permissive properties to a biomimetic collagen-hyaluronic acid (HA) scaffold optimized for cartilage tissue engineering (TE) applications. The cartilage-ECM-derived scaffold supported at least comparable chondrogenesis to the collagen-HA scaffold, underwent less contraction and retained a greater proportion of synthesized sulfated glycosaminoglycans. Having developed a promising scaffold for TE, with superior chondrogenesis observed in the presence of exogenously supplied TGF-beta 3, the final phase of the study explored whether this scaffold could be used as a TGF-beta 3 delivery system to promote chondrogenesis of FPSCs. It was found that the majority of TGF-beta 3 that was loaded onto the scaffold was released in a controlled manner over the first 10 days of culture, with comparable long-term chondrogenesis observed in these TGF-beta 3-loaded constructs compared to scaffolds where the TGF-beta 3 was continuously added to the media. The results of this study support the use of cartilage-ECM-derived scaffolds as a growth factor delivery system for use in articular cartilage regeneration. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:4400 / 4409
页数:10
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