Injectable microgel for soft tissue repair

描述(由申请人提供)：临床上迫切需要一种可注射的基质，以安全地将自体干细胞输送到体内进行组织修复。目前有 没有临床上有用的产品可以在保护自体细胞的同时促进软组织修复 或者伤口愈合。在这一领域取得进展的一个关键障碍是，细胞注射在没有裂口的情况下会导致细胞迅速离开注射点，细胞的生存能力因注射过程而减弱。为了克服这一障碍，设计了一种生物衍生基质，用于注射用于软组织修复和伤口愈合的细胞。拟议的产品是创新的，因为该系统提供了一种简单的机制，可以在注射前在手术室将患者的自体细胞与血管生成、生物兼容的生物材料混合。该系统的水合行为使其能够轻松注射，然后立即进行自我组装，以填补缺陷。该项目的总体目标是制造一种可注射的自我修复系统，以方便地将自体干细胞输送到软组织缺陷或伤口。该系统应该促进血管生成、细胞存活和伤口愈合。第一个具体目标是开发用于制备形成可注射基质的生物聚合物的合成工艺。第二个目标将描述复水材料的流体吸收率、降解率和流变性。材料的溶胀能力将被评估为 以及在模拟生理条件下的降解率。流变学将用来确定它们的粘弹性性质，以量化溶液性质、凝胶行为和从变形中恢复。第三个特定目标将确定与该系统孵育和注射时的细胞黏附、增殖、细胞毒性和蛋白质表达。人类脂肪干细胞将与材料孵育，细胞黏附、活性和增殖将通过染色和显微镜来确定。还将对细胞进行血管生成标记物的表达评估。注射过程对载细胞材料的影响也将在体外进行评估。可注射产品的最终成分将通过优化细胞附着和活性来选择进行第二阶段测试。该系统的设计允许轻松地结合到临床实践中，这项研究的可注射基质的商业化应该会加强伤口愈合和组织修复的临床策略。

DESCRIPTION (provided by applicant): There is a critical clinical need for an injectable matrix to safely deliver autologous stem cells into the body for tissue repair. Currently there are no clinically useful products that will protect autologous cells while promoting soft tissue repair or wound healing. A critical barrier to progress in the field is that cell injection without a scafold leads to the cells leaving the point of injection rapidly with cells exhibiting diminished viabilit due to the injection process. To overcome this barrier, a biologically derived matrix has been designed for injection of cells for soft tissue repair and wound healing. The proposed product is innovative because the system provides an easy mechanism for mixing a patient's autologous cells with an angiogenic, biocompatible biomaterial in the operating room just prior to injection. The hydrated behavior of the system enables easy injection followed by immediate self-assembly for filling a defect. The overall goal of this project is to produce an injectable self-healing system for facile delivery of autologous stem cells to soft tissue defects or wounds. The system should promote angiogenesis, cell survival, and wound healing. The first specific aim is to develop the synthetic process for preparation of the biopolymer that forms an injectable matrix. The second aim will characterize the fluid uptake, degradation rate, and rheological characteristics of rehydrated materials. The swelling ability of the materials will be evaluated as well as their degradation rate under simulated physiological conditions. Rheology will be used to determine their viscoelastic properties to quantify solution properties, gel- like behavior, and recovery from deformation. The third specific aim will determine cell adhesion, proliferation, cytotoxicity, and protein expression when incubated with the system and upon injection. Human adipose derived stem cells will be incubated with the materials, and cell adhesion, viability, and proliferation will be determined by staining and microscopy. Cells will also be evaluated for expression of angiogenic markers. The effects of the injection process on the cell-laden materials will also be evaluated in vitro. The final composition of the injectable product will be selected for Phase II testing by optimizing cell attachment and viability. The design of the system allows for facile incorporation into clinical practice, and commercialization of the injectable matrix of this research should enhance clinical strategies for wound healing and tissue repair.