Almeida Henrique V, Dikina Anna D, Mulhall Kevin J, O'Brien Fergal J, Alsberg Eben, Kelly Daniel J
Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse Street, Dublin 2, Ireland.
Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, College Green, Dublin 2, Ireland.
ACS Biomater Sci Eng. 2017 Jun 12;3(6):1075-1082. doi: 10.1021/acsbiomaterials.7b00019. Epub 2017 Apr 28.
ECM-derived scaffolds have previously been developed from devitalized native cartilage and successfully used in tissue engineering. Such ECM-based biomaterials are commonly derived from animal tissue, which may not represent the ideal source for applications in human. Native human ECM can be used as an alternative to xenogeneic tissue; however, its supply may be limited, leading to the need for a more readily available source of such biomaterials. The objective of this study was to compare devitalized native and tissue engineered cartilaginous ECM as chondro-permissive scaffolds for tissue engineering. To this end, porous scaffolds were produced using ECM derived from porcine articular cartilage and cartilaginous sheets engineered using human bone marrow stem cells. An identical process was used to produce scaffolds from three different types of devitalized ECMs, namely that derived from porcine cartilage (Native), human engineered cartilaginous sheets (Eng), and human engineered cartilaginous sheets generated in the presence of growth factor releasing microspheres (Eng-MS). Scaffolds produced using both devitalized engineered and native ECM possessed similar mechanical properties, pore size and GAG content, although were compositionally distinct. After being seeded with human infrapatellar fat pad stem cells, the engineered ECM-derived scaffolds (no Microspheres) supported less robust cartilage matrix deposition than native ECM scaffolds. However, more chondro-permissive scaffolds could be generated using cartilaginous ECM engineered in the presence of TGF-β1 releasing microspheres. Eng-MS scaffolds supported comparable levels of GAG synthesis to native ECM scaffolds. These results demonstrate that engineered ECM can be used to produce scaffolds for cartilage tissue engineering, overcoming stock limitations and other barriers associated with native autogeneic, allogeneic, and xenogeneic tissues. Such engineered ECM holds significant promise as an off-the-shelf chondro-permissive scaffold for articular cartilage repair.
基于细胞外基质（ECM）的支架先前已由失活的天然软骨开发而来，并成功应用于组织工程。这种基于ECM的生物材料通常来自动物组织，这可能并非人类应用的理想来源。天然人类ECM可作为异种组织的替代品；然而，其供应可能有限，因此需要一种更容易获得的此类生物材料来源。本研究的目的是比较失活的天然软骨和组织工程软骨ECM作为用于组织工程的软骨允许性支架。为此，使用从猪关节软骨衍生的ECM和用人骨髓干细胞工程化的软骨片制备了多孔支架。采用相同的工艺从三种不同类型的失活ECM制备支架，即来自猪软骨的ECM（天然）、人工程化软骨片（工程化）以及在存在释放生长因子的微球的情况下生成的人工程化软骨片（工程化-微球）。使用失活的工程化和天然ECM制备的支架具有相似的机械性能、孔径和糖胺聚糖（GAG）含量，尽管在组成上有所不同。接种人髌下脂肪垫干细胞后，工程化ECM衍生的支架（无微球）支持的软骨基质沉积不如天然ECM支架强劲。然而，使用在存在释放转化生长因子-β1（TGF-β1）的微球的情况下工程化的软骨ECM可以生成更具软骨允许性的支架。工程化-微球支架支持的GAG合成水平与天然ECM支架相当。这些结果表明，工程化ECM可用于制备软骨组织工程支架，克服与天然自体、异体和异种组织相关的库存限制和其他障碍。这种工程化ECM作为用于关节软骨修复的现成软骨允许性支架具有巨大潜力。
