Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: Implications for cartilage tissue repair
Self-assembling peptide hydrogel fosters chondrocyte extracellular matrix production and cell division: Implications for cartilage tissue repair
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DOI：
10.1073/pnas.142309999
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发表时间：
2002-07-23
影响因子：
11.1
通讯作者：
Grodzinsky, AJ
中科院分区：
文献类型：
--
作者：
Kisiday, J;Jin, M;Grodzinsky, AJ
用于关节软骨的有效和持久修复的新兴医疗技术包括将细胞或细胞接种的支架递送到缺损部位以启动从头组织再生。生物相容性支架有助于为三维几何结构中的细胞分布和细胞外基质（ECM）积累提供模板。选择合适的软骨修复支架的一个主要挑战是鉴定一种材料，该材料可以同时刺激高速率的细胞分裂和高速率的细胞合成表型特异性ECM大分子，直到修复演变成稳态组织维持。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型胶原的软骨样ECM，表明稳定的软骨细胞表型。这种ECM的时间依赖性积累被材料硬度的增加所抑制，这表明机械功能性新组织的沉积。总之，这些结果证明了自组装肽水凝胶作为用于软骨组织修复的三维细胞培养物内的真软骨样ECM的合成和积累的支架的潜力。
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.