McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Tissue Eng Part A. 2011 May;17(9-10):1445-55. doi: 10.1089/ten.TEA.2010.0535. Epub 2011 Mar 3.
Fibrocartilaginous tissues such as the meniscus serve critical load-bearing roles, relying on arrays of collagen fibers to resist tensile loads experienced with normal activity. As these structures are frequently injured and possess limited healing capacity, there exists great demand for tissue-engineered replacements. Toward recreating the structural features of these anisotropic tissues in vitro, we employ scaffolds composed of co-aligned nanofibers that direct mesenchymal stem cell (MSC) orientation and the formation of organized extracellular matrix (ECM). Concomitant with ECM synthesis, the mechanical properties of constructs increase with free-swelling culture, but ultimately failed to achieve equivalence with meniscal fibrocartilage. As mechanical forces are essential to the development and maintenance of musculoskeletal tissues, this work examined the effect of cyclic tensile loading on MSC-laden nanofibrous constructs. We hypothesized that loading would modulate the transcriptional behavior of MSCs, spur the deposition of ECM, and lead to enhancements in construct mechanical properties compared to free-swelling controls. Fiber-aligned scaffolds were seeded with MSCs and dynamically loaded daily in tension or maintained as nonloaded controls for 4 weeks. With mechanical stimulation, fibrous gene expression increased, collagen deposition increased, and the tensile modulus increased by 16% relative to controls. These results show that dynamic tensile loading enhances the maturation of MSC-laden aligned nanofibrous constructs, suggesting that recapitulation of the structural and mechanical environment of load-bearing tissues results in increases in functional properties that can be exploited for tissue engineering applications.
纤维软骨组织，如半月板，起着至关重要的承载作用，依靠胶原纤维阵列来抵抗正常活动中所经历的拉伸载荷。由于这些结构经常受伤且具有有限的愈合能力，因此对组织工程替代品的需求很大。为了在体外重现这些各向异性组织的结构特征，我们采用由共取向纳米纤维组成的支架，这些纳米纤维可以指导间充质干细胞（MSC）的取向和有组织的细胞外基质（ECM）的形成。伴随着 ECM 的合成，构建体的机械性能随着自由膨胀培养而增加，但最终未能达到半月板纤维软骨的等效水平。由于机械力对于肌肉骨骼组织的发育和维持至关重要，因此这项工作研究了循环拉伸载荷对负载 MSC 的纳米纤维构建体的影响。我们假设加载会调节 MSC 的转录行为，刺激 ECM 的沉积，并导致构建体的机械性能相对于自由膨胀对照得到增强。纤维对齐的支架用 MSC 接种，并在张力下每天动态加载或保持未加载对照 4 周。通过机械刺激，纤维基因表达增加，胶原蛋白沉积增加，与对照相比，拉伸模量增加了 16%。这些结果表明，动态拉伸加载可增强负载 MSC 的纤维状纳米纤维构建体的成熟度，这表明重现承载组织的结构和机械环境可导致功能特性的增加，可用于组织工程应用。
