期刊
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
卷 107, 期 10, 页码 2222-2234出版社
WILEY
DOI: 10.1002/jbm.a.36731
关键词
cartilage; decellularization; extracellular matrix; immune response; scaffold; tissue engineering
资金
- Enterprise Ireland [CF/2014/4325]
- European Regional Development Fund
- H2020 European Research Council [ANCHOR - 779909, 647004, 258463]
- Science Foundation Ireland [12/IA/1554]
- Science Foundation Ireland (SFI) [12/IA/1554] Funding Source: Science Foundation Ireland (SFI)
- European Research Council (ERC) [647004] Funding Source: European Research Council (ERC)
Extracellular matrix (ECM)-derived implants hold great promise for tissue repair, but new strategies are required to produce efficiently decellularized scaffolds with the necessary porosity and mechanical properties to facilitate regeneration. In this study, we demonstrate that it is possible to produce highly porous, elastic, articular cartilage (AC) ECM-derived scaffolds that are efficiently decellularized, nonimmunogenic, and chondro-permissive. Pepsin solubilized porcine AC was cross-linked with glyoxal, lyophilized and then subjected to dehydrothermal treatment. The resulting scaffolds were predominantly collagenous in nature, with the majority of sulphated glycosaminoglycan (sGAG) and DNA removed during scaffold fabrication. Four scaffold variants were produced to examine the effect of both ECM (10 or 20 mg/mL) and glyoxal (5 or 10 mM) concentration on the mechanical and biological properties of the resulting construct. When seeded with human infrapatellar fat pad-derived stromal cells, the scaffolds with the lowest concentration of both ECM and glyoxal were found to promote the development of a more hyaline-like cartilage tissue, as evident by increased sGAG and type II collagen deposition. Furthermore, when cultured in the presence of human macrophages, it was found that these ECM-derived scaffolds did not induce the production of key proinflammatory cytokines, which is critical to success of an implantable biomaterial. Together these findings demonstrate that the novel combination of solubilized AC ECM and glyoxal crosslinking can be used to produce highly porous scaffolds that are sufficiently decellularized, highly elastic, chondro-permissive and do not illicit a detrimental immune response when cultured in the presence of human macrophages.
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