Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
Biomaterials. 2011 Feb;32(5):1327-38. doi: 10.1016/j.biomaterials.2010.10.009. Epub 2010 Nov 10.
Numerous studies have reported generation of cartilage-like tissue from chondrocytes and stem cells, using pellet cultures, bioreactors and various biomaterials, especially hydrogels. However, one of the primary unsolved challenges in the field has been the inability to produce tissue that mimics the highly organized zonal architecture of articular cartilage; specifically its spatially varying mechanical properties and extra-cellular matrix (ECM) composition. Here we show that different combinations of synthetic and natural biopolymers create unique niches that can "direct" a single marrow stem cell (MSC) population to differentiate into the superficial, transitional, or deep zones of articular cartilage. Specifically, incorporating chondroitin sulfate (CS) and matrix metalloproteinase-sensitive peptides (MMP-pep) into PEG hydrogels (PEG:CS:MMP-pep) induced high levels of collagen II and low levels of proteoglycan expression resulting in a low compressive modulus, similar to the superficial zone. PEG:CS hydrogels produced intermediate-levels of both collagen II and proteoglycans, like the transitional zone, while PEG:hyaluronic acid (HA) hydrogels induced high proteoglycan and low collagen II levels leading to high compressive modulus, similar to the deep zone. Additionally, the compressive moduli of these zone-specific matrices following cartilage generation showed similar trend as the corresponding zones of articular cartilage, with PEG:CS:MMP-pep having the lowest compressive modulus, followed by PEG:CS while PEG:HA had the highest modulus. These results underscore the potential for composite scaffold structures incorporating these biomaterial compositions such that a single stem-progenitor cell population can give rise to zonally-organized, functional articular cartilage-like tissue.
许多研究报告称，使用微球培养物、生物反应器和各种生物材料，特别是水凝胶，可从软骨细胞和干细胞生成软骨样组织。然而，该领域尚未解决的主要挑战之一是无法生成模仿关节软骨高度组织化区带结构的组织；具体来说，就是无法生成具有空间变化的机械性能和细胞外基质（ECM）组成的组织。在这里，我们表明，合成和天然生物聚合物的不同组合可以创造独特的小生境，从而“指导”单个骨髓基质细胞（MSC）群体分化为关节软骨的浅层、过渡层或深层。具体来说，将硫酸软骨素（CS）和基质金属蛋白酶敏感肽（MMP-pep）掺入聚乙二醇水凝胶（PEG:CS:MMP-pep）中会诱导高水平的胶原 II 和低水平的蛋白聚糖表达，从而导致低压缩模量，类似于浅层。PEG:CS 水凝胶产生的胶原 II 和蛋白聚糖水平均处于中间水平，类似于过渡层，而 PEG:透明质酸（HA）水凝胶诱导高水平的蛋白聚糖和低水平的胶原 II，导致高压缩模量，类似于深层。此外，软骨生成后这些区带特异性基质的压缩模量表现出与关节软骨相应区带相似的趋势，PEG:CS:MMP-pep 的压缩模量最低，其次是 PEG:CS，而 PEG:HA 的压缩模量最高。这些结果强调了包含这些生物材料组成的复合支架结构的潜力，使得单个干细胞-祖细胞群体可以产生具有区带组织的功能性关节软骨样组织。
