Kisiday J, Jin M, Kurz B, Hung H, Semino C, Zhang S, Grodzinsky A J
Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, MA 02139-4307, USA.
Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9996-10001. doi: 10.1073/pnas.142309999. Epub 2002 Jul 15.
Emerging medical technologies for effective and lasting repair of articular cartilage include delivery of cells or cell-seeded scaffolds to a defect site to initiate de novo tissue regeneration. Biocompatible scaffolds assist in providing a template for cell distribution and extracellular matrix (ECM) accumulation in a three-dimensional geometry. A major challenge in choosing an appropriate scaffold for cartilage repair is the identification of a material that can simultaneously stimulate high rates of cell division and high rates of cell synthesis of phenotypically specific ECM macromolecules until repair evolves into steady-state tissue maintenance. We have devised a self-assembling peptide hydrogel scaffold for cartilage repair and developed a method to encapsulate chondrocytes within the peptide hydrogel. During 4 weeks of culture in vitro, chondrocytes seeded within the peptide hydrogel retained their morphology and developed a cartilage-like ECM rich in proteoglycans and type II collagen, indicative of a stable chondrocyte phenotype. Time-dependent accumulation of this ECM was paralleled by increases in material stiffness, indicative of deposition of mechanically functional neo-tissue. Taken together, these results demonstrate the potential of a self-assembling peptide hydrogel as a scaffold for the synthesis and accumulation of a true cartilage-like ECM within a three-dimensional cell culture for cartilage tissue repair.
用于有效且持久修复关节软骨的新兴医学技术包括将细胞或接种细胞的支架递送至缺损部位,以启动新的组织再生。生物相容性支架有助于在三维结构中为细胞分布和细胞外基质(ECM)积累提供模板。为软骨修复选择合适支架的一个主要挑战是确定一种材料,该材料能够同时刺激高细胞分裂率以及高表型特异性ECM大分子的细胞合成率,直到修复演变为稳态组织维持。我们设计了一种用于软骨修复的自组装肽水凝胶支架,并开发了一种将软骨细胞包封在肽水凝胶内的方法。在体外培养4周期间,接种在肽水凝胶内的软骨细胞保持其形态,并形成富含蛋白聚糖和II型胶原的类软骨ECM,这表明软骨细胞表型稳定。这种ECM的时间依赖性积累与材料硬度的增加同时出现,表明机械功能新组织的沉积。综上所述,这些结果证明了自组装肽水凝胶作为一种支架在三维细胞培养中用于软骨组织修复时合成和积累真正类软骨ECM的潜力。