Sridhar Balaji V, Brock John L, Silver Jason S, Leight Jennifer L, Randolph Mark A, Anseth Kristi S
Department of Chemical and Biological Engineering and the Biofrontiers Institute, University of Colorado, 596 UCB, Boulder, CO, 80303-0596, USA.
Adv Healthc Mater. 2015 Apr 2;4(5):702-13. doi: 10.1002/adhm.201400695. Epub 2015 Jan 21.
Healing articular cartilage remains a significant clinical challenge because of its limited self-healing capacity. While delivery of autologous chondrocytes to cartilage defects has received growing interest, combining cell-based therapies with scaffolds that capture aspects of native tissue and promote cell-mediated remodeling could improve outcomes. Currently, scaffold-based therapies with encapsulated chondrocytes permit matrix production; however, resorption of the scaffold does not match the rate of production by cells leading to generally low extracellular matrix outputs. Here, a poly (ethylene glycol) (PEG) norbornene hydrogel is functionalized with thiolated transforming growth factor (TGF-β1) and cross-linked by an MMP-degradable peptide. Chondrocytes are co-encapsulated with a smaller population of mesenchymal stem cells, with the goal of stimulating matrix production and increasing bulk mechanical properties of the scaffold. The co-encapsulated cells cleave the MMP-degradable target sequence more readily than either cell population alone. Relative to non-degradable gels, cellularly degraded materials show significantly increased glycosaminoglycan and collagen deposition over just 14 d of culture, while maintaining high levels of viability and producing a more widely-distributed matrix. These results indicate the potential of an enzymatically degradable, peptide-functionalized PEG hydrogel to locally influence and promote cartilage matrix production over a short period. Scaffolds that permit cell-mediated remodeling may be useful in designing treatment options for cartilage tissue engineering applications.
由于关节软骨自身修复能力有限，修复关节软骨仍是一项重大的临床挑战。虽然将自体软骨细胞输送到软骨缺损处已越来越受到关注，但将基于细胞的疗法与能够模拟天然组织特性并促进细胞介导的重塑的支架相结合，可能会改善治疗效果。目前，含有包封软骨细胞的支架疗法能够促进基质生成；然而，支架的吸收速度与细胞的生成速度不匹配，导致细胞外基质的总体产出较低。在此，一种聚（乙二醇）（PEG）降冰片烯水凝胶用硫醇化转化生长因子（TGF-β1）进行功能化，并通过基质金属蛋白酶（MMP）可降解肽交联。软骨细胞与少量间充质干细胞共同封装，目的是刺激基质生成并提高支架的整体力学性能。与单独的任何一种细胞群体相比，共同封装的细胞更容易切割MMP可降解的靶序列。相对于不可降解的水凝胶，在仅14天的培养过程中，细胞降解的材料显示出糖胺聚糖和胶原蛋白沉积显著增加，同时保持高活力水平并产生分布更广泛的基质。这些结果表明，一种可酶促降解、肽功能化的PEG水凝胶在短期内局部影响和促进软骨基质生成方面具有潜力。允许细胞介导重塑的支架可能有助于设计软骨组织工程应用的治疗方案。
