Development of novel bioresponsive photopolymerizable hydrogel scaffolds for chondrogenesis of monkey-derived stem cells

急性或慢性关节软骨损伤的有限自发修复是有文献记载的，似乎是由于软骨细胞结构支撑的改变、软骨的无血管性质以及随后对损伤缺乏生理性炎症反应所致。治疗干预的目标是通过提高细胞募集和修复能力来应对这些生物挑战。在这一应用中，我们寻求开发新型的生物响应性光聚合水凝胶支架，以适应不同类型干细胞的软骨形成。因此，我们评估了一种假说，即具有与细胞分化和基质形成相关的降解动力学的植入物将促进再生软骨组织的产生。此外，这些可适应的支架的可用性提供了为不同的干细胞类型量身定做它们的手段。我们选择了四种细胞类型来代表潜在的治疗候选细胞类型：关节软骨细胞、骨髓源干细胞、体细胞核移植来源的胚胎干细胞和诱导的多能干细胞。所有这些细胞类型都来自恒河猴，这使我们能够在临床相关的动物模型中进行体内实验和测试干细胞负载的支架。

The limited spontaneous repair of acute or chronic articular cartilage injury is well documented and appears to result from alterations in the structural support for chondrocytes, the avascular nature of cartilage and subsequent lack of physiologic inflammatory response to injury. The goals of therapeutic interventions are to meet these biologic challenges by improving cell recruitment and repair capacity. In this application we seek to develop novel bioresponsive photopolymerizable hydrogel scaffolds that will adapt to chondrogenesis of different stem cell types. Therefore we evaluate the hypothesis that implants with degradation kinetics linked to cellular differentiation and matrix elaboration will facilitate the production of a regenerative cartilaginous tissue. In addition the availability of these adaptable scaffolds provides the means to tailor them for different stem cell types. We have selected four cell types that are representative of the range of potentially therapeutic candidate cell types: articular cartilage chondrocytes, bone marrow-derived stem cells, somatic cell nuclear transfer-derived embryonic stem cells and induced pluripotent stem cells. All of these cell types are derived from the rhesus macaque which offers us the ability to perform and test the stem cell loaded scaffolds in in vivo experiments in a clinically relevant animal model.