Injectable microgel for soft tissue repair

用于软组织修复的可注射微凝胶

• 批准号: 8586070
• 负责人: Joseph C. Salamone
• 金额: $ 15万
• 依托单位: ROCHAL INDUSTRIES, LLP
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8586070
• 关键词: Adipose tissue; Affect; Area; Autologous; Behavior; Biocompatible; Biocompatible Materials; Biological Assay; Biopolymers; Cell Adhesion; Cell Survival; Cell Transplants; Cell-Cell Adhesion; Cell-Matrix Junction; Cells; Characteristics; Clinical; Defect; Development; Evaluation; Exhibits; Fibrinogen; Filler; Gel; Goals; Government; Growth Factor; Human; Hydration status; Hydrogels; In Vitro; Incubated; Industry; Injectable; Injection of therapeutic agent; Investigation; Left; Liquid substance; Mechanics; Microscopy; Operating Rooms; Operative Surgical Procedures; Patients; Persons; Phase; Physiological; Powder dose form; Preparation; Process; Property; Prunella vulgaris; Recovery; Research; Rheology; Simulate; Solutions; Staining method; Stains; Stem cells; Sterility; Surface; Swelling; System; Testing; Time; Tissues; Toxic effect; Weight; Wound Healing; angiogenesis; aqueous; base; cell behavior; cell growth; cell motility; clinical practice; commercial application; commercialization; crosslink; cytotoxicity; design; in vivo; innovation; paracrine; particle; protein expression; public health relevance; scaffold; self assembly; soft tissue; technological innovation; tissue regeneration; tissue repair; uptake; wound

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.

描述（由申请人提供）：临床迫切需要一种可注射基质来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保护自体细胞同时促进软组织修复 或伤口愈合。该领域取得进展的一个关键障碍是，没有支架的细胞注射会导致细胞快速离开注射点，并且由于注射过程，细胞表现出活力降低。为了克服这一障碍，设计了一种生物衍生基质，用于注射细胞以进行软组织修复和伤口愈合。所提出的产品具有创新性，因为该系统提供了一种简单的机制，可以在注射之前在手术室中将患者的自体细胞与血管生成的生物相容性生物材料混合。该系统的水合行为使得注射变得容易，然后立即自组装以填充缺​​陷。该项目的总体目标是生产一种可注射的自愈系统，以便将自体干细胞轻松输送到软组织缺陷或伤口。该系统应促进血管生成、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。第二个目标是表征再水化材料的流体吸收、降解速率和流变特性。材料的溶胀能力评价为 以及它们在模拟生理条件下的降解率。流变学将用于确定它们的粘弹性特性，以量化溶液特性、凝胶状行为和变形恢复。第三个具体目标是确定与系统一起孵育和注射时的细胞粘附、增殖、细胞毒性和蛋白质表达。人类脂肪干细胞将与这些材料一起孵育，并通过染色和显微镜检查来确定细胞粘附、活力和增殖。还将评估细胞的血管生成标记物的表达。注射过程对充满细胞的材料的影响也将在体外进行评估。通过优化细胞附着和活力，将选择注射产品的最终成分进行 II 期测试。该系统的设计可以轻松地融入临床实践，并且本研究的可注射基质的商业化应该增强伤口愈合和组织修复的临床策略。