Hydrolytically degradable poly(ethylene glycol) hydrogel scaffolds as a cell delivery vehicle: characterization of PC12 cell response.
Hydrolytically degradable poly(ethylene glycol) hydrogel scaffolds as a cell delivery vehicle: characterization of PC12 cell response.
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DOI：
10.1002/btpr.1761
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发表时间：
2013-09
影响因子：
2.9
通讯作者：
Leach, Jennie B.
中科院分区：
文献类型：
--
作者：
Zustiak, Silviya P.;Pubill, Stephanie;Ribeiro, Andreia;Leach, Jennie B.
中枢神经系统（CNS）在损伤和疾病后具有较低的内在再生潜力，但神经干/祖细胞（NPC）移植显示出在这种复杂的组织环境中提供动态治疗的前景。此外，生物材料支架可以通过促进细胞活力和引导细胞反应来改善基于NPC的治疗的成功。我们假设，水凝胶支架可以提供一个临时的神经源性环境，支持细胞在封装过程中的生存，并在时间控制的方式完全降解，以允许动态的细胞过程，如神经突延伸的进展。我们利用PC 12细胞作为具有可诱导神经元表型的模型细胞系，以定义可水解降解的聚（乙二醇）水凝胶支架的关键特性，这些特性在从降解的水凝胶释放后影响细胞活力和分化。需要粘附肽配体（RGDS、IKVAV或YIGSR）在包封期间维持细胞活力;与YIGSR相比，RGDS和IKVAV配体与较高百分比的在从水凝胶释放后分化成神经元表型的PC 12细胞相关。此外，在检查的水凝胶性质中（例如，配体类型、浓度），水凝胶内的总聚合物密度对细胞活力具有最显著的影响，高于15%w/v的密度可能由于较高的剪切模量而导致细胞活力降低。因此，通过确定可降解水凝胶的关键特性，影响细胞活力和分化后，从水凝胶释放，我们奠定了基础，该系统的应用对未来的应用支架作为神经细胞的运载工具。
The central nervous system (CNS) has a low intrinsic potential for regeneration following injury and disease, yet neural stem/progenitor cell (NPC) transplants show promise to provide a dynamic therapeutic in this complex tissue environment. Moreover, biomaterial scaffolds may improve the success of NPC-based therapeutics by promoting cell viability and guiding cell response. We hypothesized that a hydrogel scaffold could provide a temporary neurogenic environment that supports cell survival during encapsulation, and degrades completely in a temporally controlled manner to allow progression of dynamic cellular processes such as neurite extension. We utilized PC12 cells as a model cell line with an inducible neuronal phenotype to define key properties of hydrolytically-degradable poly(ethylene glycol) hydrogel scaffolds that impact cell viability and differentiation following release from the degraded hydrogel. Adhesive peptide ligands (RGDS, IKVAV or YIGSR), were required to maintain cell viability during encapsulation; as compared to YIGSR, the RGDS and IKVAV ligands were associated with a higher percentage of PC12 cells that differentiated to the neuronal phenotype following release from the hydrogel. Moreover, among the hydrogel properties examined (e.g., ligand type, concentration), total polymer density within the hydrogel had the most prominent effect on cell viability, with densities above 15% w/v leading to decreased cell viability likely due to a higher shear modulus. Thus, by identifying key properties of degradable hydrogels that affect cell viability and differentiation following release from the hydrogel, we lay the foundation for application of this system towards future applications of the scaffold as a neural cell delivery vehicle.
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