Braided Nanofibrous Scaffold for Tendon and Ligament Tissue Engineering
Braided Nanofibrous Scaffold for Tendon and Ligament Tissue Engineering
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DOI：
10.1089/ten.tea.2010.0538
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发表时间：
2013-06-01
影响因子：
4.1
通讯作者：
Li, Wan-Ju
中科院分区：
文献类型：
--
作者：
Barber, John G.;Handorf, Andrew M.;Li, Wan-Ju
肌腱和韧带损伤(T/L)由于其固有的较差的愈合能力，是一个重要的临床挑战。自然愈合通常会导致形成机械性能较差的疤痕样组织。因此，组织工程学作为T/L修复的一种有前景的替代方法受到了广泛的关注。在本研究中，我们制备了编织纳米纤维支架(BNFSS)作为T/L组织工程的潜在构建材料。支架是通过编织3、4或5束电纺聚(L-乳酸)纳米纤维制成的，从而引入了额外的柔韧性来改变单个支架的力学性能。我们观察到，与4束和5束BNFSS相比，3束BNFSS的杨氏模量、屈服应力和极限应力都有所增加。有趣的是，脱细胞的BNFSS模拟了自然肌腱和韧带(T/L)在加载过程中的正常三相力学行为。当在BNFS上培养时，人间充质干细胞(HMSCs)附着，平行于纳米纤维的长度排列，并伴随着肌动蛋白细胞骨架的重新排列。此外，BNFSS还支持hMSC的增殖，并诱导关键多能性基因的表达上调。当hMSCs在含有张力生长因子的BNFSS上培养时，在循环拉伸应变的刺激下，hMSCs分化为张力系，最显著的证据是Skeraxis基因的表达显著上调。这些结果表明，BNFSS为T/L组织工程应用提供了一种支持干细胞扩增和分化的多功能支架。
Tendon and ligament (T/L) injuries present an important clinical challenge due to their intrinsically poor healing capacity. Natural healing typically leads to the formation of scar-like tissue possessing inferior mechanical properties. Therefore, tissue engineering has gained considerable attention as a promising alternative for T/L repair. In this study, we fabricated braided nanofibrous scaffolds (BNFSs) as a potential construct for T/L tissue engineering. Scaffolds were fabricated by braiding 3, 4, or 5 aligned bundles of electrospun poly(l-lactic acid) nanofibers, thus introducing an additional degree of flexibility to alter the mechanical properties of individual scaffolds. We observed that the Young's modulus, yield stress, and ultimate stress were all increased in the 3-bundle compared to the 4- and 5-bundle BNFSs. Interestingly, acellular BNFSs mimicked the normal tri-phasic mechanical behavior of native tendon and ligament (T/L) during loading. When cultured on the BNFSs, human mesenchymal stem cells (hMSCs) adhered, aligned parallel to the length of the nanofibers, and displayed a concomitant realignment of the actin cytoskeleton. In addition, the BNFSs supported hMSC proliferation and induced an upregulation in the expression of key pluripotency genes. When cultured on BNFSs in the presence of tenogenic growth factors and stimulated with cyclic tensile strain, hMSCs differentiated into the tenogenic lineage, evidenced most notably by the significant upregulation of Scleraxis gene expression. These results demonstrate that BNFSs provide a versatile scaffold capable of supporting both stem cell expansion and differentiation for T/L tissue engineering applications.