Chung Cindy, Beecham Michael, Mauck Robert L, Burdick Jason A
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104-6321, USA.
Biomaterials. 2009 Sep;30(26):4287-96. doi: 10.1016/j.biomaterials.2009.04.040. Epub 2009 May 22.
The potential of mesenchymal stem cells (MSCs) as a viable cell source for cartilage repair hinges on the development of engineered scaffolds that support adequate cartilage tissue formation. Evolving networks (hydrogels with mesh sizes that change over time due to crosslink degradation) may provide the control needed to enhance overall tissue formation when compared to static scaffolds. In this study, MSCs were photoencapsulated in combinations of hydrolytically and enzymatically degradable hyaluronic acid (HA) hydrogels to investigate the tunability of these hydrogels and the influence of network evolution on neocartilage formation. In MSC-laden HA hydrogels, compressive mechanical properties increased when degradation complemented extracellular matrix deposition and decreased when degradation was too rapid. In addition, dynamic hydrogels that started at a higher wt% and decreased to a lower wt% were not equivalent to static hydrogels that started at the higher or lower wt%. Specifically, evolving 2 wt% hydrogels (2 wt% degrading to 1 wt%) expressed up-regulation of type II collagen and aggrecan, and exhibited increased glycosaminoglycan content over non-evolving 2 and 1 wt% hydrogels. Likewise, mechanical properties and size maintenance were superior in the dynamic system compared to the static 2 wt% and 1 wt% hydrogels, respectively. Thus, hydrogels with dynamic properties may improve engineered tissues and help translate tissue engineering technology to clinical application.
间充质干细胞(MSCs)作为软骨修复可行细胞来源的潜力取决于支持足够软骨组织形成的工程支架的开发。与静态支架相比,动态网络(由于交联降解导致网孔尺寸随时间变化的水凝胶)可能提供增强整体组织形成所需的控制。在本研究中,将MSCs光封装在可水解和可酶解的透明质酸(HA)水凝胶组合中,以研究这些水凝胶的可调性以及网络演化对新软骨形成的影响。在负载MSCs的HA水凝胶中,当降解补充细胞外基质沉积时,压缩力学性能增加,而当降解过快时则降低。此外,起始重量百分比较高并降至较低重量百分比的动态水凝胶与起始重量百分比较高或较低的静态水凝胶不等同。具体而言,从2 wt%降解至1 wt%的动态2 wt%水凝胶表达II型胶原蛋白和聚集蛋白聚糖上调,并且与非动态的2 wt%和1 wt%水凝胶相比,糖胺聚糖含量增加。同样,与静态2 wt%和1 wt%水凝胶相比,动态系统中的力学性能和尺寸维持分别更优。因此,具有动态特性的水凝胶可能改善工程组织,并有助于将组织工程技术转化为临床应用。