Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Biomaterials. 2010 Dec;31(35):9232-43. doi: 10.1016/j.biomaterials.2010.08.056. Epub 2010 Sep 22.
One of the key challenges in tissue engineering is to understand the host response to scaffolds and engineered constructs. We present a study in which two collagen-based scaffolds developed for bone repair: a collagen-glycosaminoglycan (CG) and biomimetic collagen-calcium phosphate (CCP) scaffold, are evaluated in rat cranial defects, both cell-free and when cultured with MSCs prior to implantation. The results demonstrate that both cell-free scaffolds showed excellent healing relative to the empty defect controls and somewhat surprisingly, to the tissue engineered (MSC-seeded) constructs. Immunological analysis of the healing response showed higher M1 macrophage activity in the cell-seeded scaffolds. However, when the M2 macrophage response was analysed, both groups (MSC-seeded and non-seeded scaffolds) showed significant activity of these cells which are associated with an immunomodulatory and tissue remodelling response. Interestingly, the location of this response was confined to the construct periphery, where a capsule had formed, in the MSC-seeded groups as opposed to areas of new bone formation in the non-seeded groups. This suggests that matrix deposited by MSCs during in vitro culture may adversely affect healing by acting as a barrier to macrophage-led remodelling when implanted in vivo. This study thus improves our understanding of host response in bone tissue engineering.
组织工程面临的一个关键挑战是了解宿主对支架和工程结构的反应。我们进行了一项研究，评估了两种用于骨修复的基于胶原的支架：一种是胶原-糖胺聚糖（CG）支架，另一种是仿生胶原-磷酸钙（CCP）支架，这两种支架都在大鼠颅缺损中进行了研究，包括无细胞支架和在植入前与 MSC 共培养的支架。结果表明，与空缺陷对照相比，这两种无细胞支架的愈合效果都非常好，而且与组织工程（MSC 接种）构建体相比，有些出人意料。对愈合反应的免疫分析表明，接种细胞的支架中 M1 巨噬细胞的活性更高。然而，当分析 M2 巨噬细胞反应时，两组（MSC 接种和非接种支架）均表现出这些细胞的显著活性，这些细胞与免疫调节和组织重塑反应有关。有趣的是，这种反应的位置局限于 MSC 接种组中形成的胶囊的构建体周围，而在非接种组中则局限于新骨形成的区域。这表明，MSC 在体外培养过程中沉积的基质可能通过在体内植入时充当巨噬细胞主导的重塑的屏障，从而对骨组织工程中的愈合产生不利影响。因此，这项研究提高了我们对骨组织工程中宿主反应的理解。
