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Mechanosensitive synthetic cell-regulatable hydrogels for tissue engineering

用于组织工程的机械敏感合成细胞调节水凝胶

基本信息

批准号：
10570918
负责人：
Eben Alsberg
金额：
$ 20.04万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-15 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10570918
关键词：
Acceleration Address Affect Alginates Automobile Driving Biochemical Biocompatible Materials Biology Calcium Cartilage Cell Proliferation Cell Size Cell Survival Cell Transplantation Cell physiology Cells Chelating Agents Congenital Abnormality Coupled Cues Defect Development Dextrans Disease Dyes Elements Encapsulated Engineering Environment Enzymes Extracellular Matrix Fluorescence Fluorescence Microscopy Glutathione Human Hydrogels Injury Light Lipid Bilayers Mechanical Stress Mechanics Mediating Medical Membrane Mesenchymal Stem Cells Metalloproteases Microfluidics Modeling Organ Osmolar Concentration Physical Chemistry Physical environment Play Process Production Proliferating Property Proteins Reaction Reader Regulation Reporting Research Rheology Rhodamine Role Stimulus Stress Supporting Cell Swelling System Technology Testing Therapeutic Thinness Time Tissue Engineering Tissues Vesicle Work biodegradable scaffold biomaterial compatibility bioscaffold bone cell behavior cell growth constriction crosslink design disulfide bond experience extracellular healing implantation improved in vivo inhibitor interest mechanical force mechanical properties mechanical signal mechanical stimulus mechanotransduction migration physical property physical state release factor repaired replacement tissue response restoration scaffold sensor spatiotemporal synthetic biology tissue regeneration

项目摘要

Abstract There is great need for engineered functional tissues to address currently unmet medical need for replacement or restoration of damaged tissues and organs due to disease, injury and congenital defects. Biomaterial scaffolds can play a key role in engineering tissues because they not only provide mechanical support and deliver bioactive molecules and/or cells, but they also degrade to provide new space to support cell growth and extracellular matrix production. It is desirable for the scaffold to degrade in concert with the rate of new tissue formation. Scaffold degradation also dynamically affects its mechanical properties, which has been shown to regulate host and transplanted cell behaviors, such as spreading, proliferation, migration and differentiation. Although attempts have been made to predict and tailor the degradation rate of employed biodegradable scaffolds prior to implantation for specific tissue regeneration applications, it is currently difficult to control their degradation after implantation. To regulate scaffold degradation in a triggered fashion, exogenous or external stimuli, such as enzymes, pH, and light, have been employed. Few have considered forces as a trigger input. Biochemical molecules, such as enzymes secreted from hosted/transplanted cells, have already been reported in efforts to control the degradation rate of biomaterial scaffolds. However, there are still challenges regarding regulating the production amount of those molecules at a rate and level needed to match scaffold degradation profile with engineered tissue formation while providing a minimal loss in mechanical support. Therefore, dynamic regulation of the degradation of a tissue engineering scaffold via its response to its mechanical environment may allow for design of smart biomaterials that resorb as the newly formed tissue is able to support the required loads. A synthetic biology approach to create mechanosensitive synthetic cells (MSSCs) harboring mechanosensitive channels for mimicking the ability of cells to secrete biochemicals for dynamically degrading biomaterial scaffolds in response to environment mechanical signals is proposed. Synthetic cells are cell-sized lipid bilayer vesicles encapsulating cell-free expression system expressing proteins of interest. MSSCs loaded with different sized cargos will be created and their capability to release the payloads under compressive stress will be examined (Aim 1). The MSSCs will then be encapsulated in a hydrogel system for examining the capacity of external compressive stress-mediated payload release from MSSCs to regulate hydrogel degradation (Aim 2). Lastly, the capacity of external compressive stress-controlled hydrogel degradation in driving the function of hydrogel co-encapsulated cells will be examined (Aim 3). This work will create a new class of hydrogels with a distinct mechanism of mechanoresponsiveness that dynamically react to their physical environment and are anticipated to be valuable for engineering a wide range of tissues.

摘要