A Combined In Vitro Imaging and Multi-Scale Modeling System for Studying the Role of Cell Matrix Interactions in Cutaneous Wound Healing.
A Combined In Vitro Imaging and Multi-Scale Modeling System for Studying the Role of Cell Matrix Interactions in Cutaneous Wound Healing.
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DOI：
10.1371/journal.pone.0148254
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Sander EA
中科院分区：
文献类型：
--
作者：
De Jesus AM;Aghvami M;Sander EA
许多类型的细胞重塑它们所居住的组织的细胞外基质，以响应广泛的环境刺激，包括机械刺激。这是皮肤伤口愈合的情况，其中成纤维细胞以复杂的方式迁移到临时纤维蛋白基质中并重塑临时纤维蛋白基质，该方式部分取决于局部机械环境和系统的演变的多尺度机械相互作用。在这项研究中，我们报告了一种基于图像的多尺度力学模型的发展，该模型预测了成纤维细胞对纤维蛋白凝胶的短期（24小时）结构重组。这些预测模型基于体外实验系统，其中成纤维细胞簇（即，外植体）在空间上排列成三角形几何形状到纤维蛋白凝胶的表面上，所述纤维蛋白凝胶经受固定或自由的平面内机械约束。实验上，短期结构重塑和细胞迁移的区域差异，观察两种凝胶边界条件。初步实验表明，纤维蛋白凝胶短期重塑中的这些小差异转化为长期（4周）重塑中的实质性差异，特别是在胶原蛋白产生方面。多尺度模型能够预测两种边界条件下重塑的一些区域差异和定性相似的重组模式。然而，该模型的其他方面，如凝胶的变形的幅度和速率，与实验不符。模型和实验之间的这些差异为挑战模型假设和设计新的实验提供了肥沃的土壤，以增强我们对这个多尺度系统如何运作的理解。这些努力将最终改善重塑过程的预测，特别是因为它涉及到皮肤伤口愈合和减少患者疤痕。此类模型可用于根据伤口几何形状、位置、年龄和健康状况等参数推荐患者特定的基于机械的治疗。
Many cell types remodel the extracellular matrix of the tissues they inhabit in response to a wide range of environmental stimuli, including mechanical cues. Such is the case in dermal wound healing, where fibroblast migrate into and remodel the provisional fibrin matrix in a complex manner that depends in part on the local mechanical environment and the evolving multi-scale mechanical interactions of the system. In this study, we report on the development of an image-based multi-scale mechanical model that predicts the short-term (24 hours), structural reorganization of a fibrin gel by fibroblasts. These predictive models are based on an in vitro experimental system where clusters of fibroblasts (i.e., explants) were spatially arranged into a triangular geometry onto the surface of fibrin gels that were subjected to either Fixed or Free in-plane mechanical constraints. Experimentally, regional differences in short-term structural remodeling and cell migration were observed for the two gel boundary conditions. A pilot experiment indicated that these small differences in the short-term remodeling of the fibrin gel translate into substantial differences in long-term (4 weeks) remodeling, particularly in terms of collagen production. The multi-scale models were able to predict some regional differences in remodeling and qualitatively similar reorganization patterns for the two boundary conditions. However, other aspects of the model, such as the magnitudes and rates of deformation of gel, did not match the experiments. These discrepancies between model and experiment provide fertile ground for challenging model assumptions and devising new experiments to enhance our understanding of how this multi-scale system functions. These efforts will ultimately improve the predictions of the remodeling process, particularly as it relates to dermal wound healing and the reduction of patient scarring. Such models could be used to recommend patient-specific mechanical-based treatment dependent on parameters such as wound geometry, location, age, and health.