Biophysical Cues and Corneal Wound Healing

生物物理线索和角膜伤口愈合

基本信息

批准号：
8585852
负责人：
CHRISTOPHER John MURPHY
金额：
$ 37.73万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-12-01 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8585852
关键词：
Actins Address Adhesions Affect Apoptosis Apoptotic Atomic Force Microscopy Beds Behavior Blindness Cell Culture Techniques Cells Cellular biology Collagen Cornea Corneal Injury Crosslinker Cues Cytochalasin D Data Development Elements Engineering Environment Excision Extracellular Matrix Fibroblasts Gene Proteins Healed Hydrogels Impairment In Vitro Laboratories Lead Measures Methods Modeling Myofibroblast Oryctolagus cuniculus Outcome Pathway interactions Patients Phase Phenotype Play Process Production Prosthesis Research Personnel Riboflavin Role Signal Transduction Signaling Molecule Smooth Muscle Actin Staining Method Stem cells Stromal Cells Testing Therapeutic Time Tissue Engineering Visual Acuity Work Wound Healing biophysical properties body system cell behavior cellular engineering corneal scar crosslink experience extracellular healing improved in vivo migration prevent research study response therapeutic target wound

项目摘要

ABSTRACT Dysregulated wound healing in the cornea can lead to corneal scars and corneal haze resulting in a loss of visual acuity. While many elements of corneal wound healing are well characterized, the biophysical attributes of the wound space and the impact of these on cellular activities critical to wound healing have not been adequately investigated. Along with soluble signaling molecules present in the extracellular milieu, biophysical cues are emerging as key factors in determining cell behaviors. We propose to quantitatively analyze the alterations in stromal topography and compliance throughout the wound healing process. Our hypothesis is that the biophysical cues in the wound space alter throughout wound healing and that these directly influence the transition of keratocytes to myofibroblasts in the corneal stromal layer. The myofibroblasts, in turn, would alter the compliance of the wound microenvironment through active contraction. Ultimately, the change in the biophysical cues in the wound bed would activate apoptotic pathways, promoting removal of the myofibroblasts and an optically clear cornea would return. Using the measured alterations in the biophysical environment as a guide, we will fabricate hydrogel substrates with similar biophysical properties (of compliance and topography) to determine the cellular consequences of these alterations on myofibroblast behavior in vitro. The information that we obtain about the cellular behaviors and gene and protein alterations could enable the therapeutic targeting of biophysical cues during wound healing. Attributes of the wound bed could be directly modulated, such as the contractile elements of the corneal stromal cells, to improve wound healing outcomes.

抽象的角膜伤口愈合失调会导致角膜疤痕和角膜混浊，从而导致角膜丧失视力。虽然角膜伤口愈合的许多要素已得到很好的表征，但生物物理属性伤口空间的变化以及这些对伤口愈合至关重要的细胞活动的影响尚未得到证实充分调查。除了细胞外环境中存在的可溶性信号分子外，生物物理线索正在成为决定细胞行为的关键因素。我们建议定量分析在整个伤口愈合过程中基质地形和顺应性的改变。我们的假设是伤口空间的生物物理线索在伤口愈合过程中发生变化，并且这些直接影响角膜基质层中角膜细胞向肌成纤维细胞的转变。反过来，肌成纤维细胞会通过主动收缩改变伤口微环境的顺应性。最终，改变在伤口床中的生物物理信号会激活细胞凋亡途径，促进肌成纤维细胞的去除并且光学透明的角膜将会恢复。使用测量到的生物物理环境的变化作为指南中，我们将制造具有相似生物物理特性（顺应性和形貌）的水凝胶基材以确定这些改变对体外肌成纤维细胞行为的细胞影响。信息我们获得的有关细胞行为以及基因和蛋白质改变的信息可以使治疗成为可能在伤口愈合过程中针对生物物理线索。可以直接调节创面床的属性，例如角膜基质细胞的收缩成分，以改善伤口愈合效果。