Injectable microgel for soft tissue repair

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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.