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）：临床上迫切需要一种可注射基质，以安全地将自体干细胞输送到体内进行组织修复。目前有 没有在促进软组织修复的同时保护自体细胞的临床有用产品 或伤口愈合。本领域进展的关键障碍是，没有支架的细胞注射导致细胞快速离开注射点，细胞由于注射过程而表现出降低的活力。为了克服这一障碍，生物衍生基质已被设计用于注射用于软组织修复和伤口愈合的细胞。申报产品具有创新性，因为该系统提供了一种简单的机制，可在注射前在手术室中将患者的自体细胞与血管生成生物相容性生物材料混合。该系统的水合行为使得易于注射，随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，用于将自体干细胞轻松输送到软组织缺损或伤口。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方法。第二个目标将表征再水化材料的流体吸收、降解速率和流变特性。材料的溶胀能力将评价为： 以及在模拟生理条件下的降解速率。流变学将用于确定其粘弹性，以量化溶液性质、凝胶样行为和从变形中恢复。第三个具体目标将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。将人脂肪来源的干细胞与材料一起孵育，并通过染色和显微镜检查确定细胞粘附、活力和增殖。还将评价细胞的血管生成标志物的表达。还将在体外评价注射工艺对载有细胞的材料的影响。通过优化细胞附着和活力，选择注射产品的最终组成用于II期试验。该系统的设计允许容易地并入临床实践，并且本研究的可注射基质的商业化应增强伤口愈合和组织修复的临床策略。