Journal article
A Combined In Vitro Imaging and Multi-Scale Modeling System for Studying the Role of Cell Matrix Interactions in Cutaneous Wound Healing
PloS one, Vol.11(2), pp.e0148254-e0148254
2016
DOI: 10.1371/journal.pone.0148254
PMCID: PMC4739727
PMID: 26840835
Abstract
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.
Details
- Title: Subtitle
- A Combined In Vitro Imaging and Multi-Scale Modeling System for Studying the Role of Cell Matrix Interactions in Cutaneous Wound Healing
- Creators
- Aribet M De Jesus - Department of Biomedical Engineering, University of Iowa, Iowa City, IA, United States of AmericaMaziar Aghvami - Department of Biomedical Engineering, University of Iowa, Iowa City, IA, United States of AmericaEdward A Sander - Department of Biomedical Engineering, University of Iowa, Iowa City, IA, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.11(2), pp.e0148254-e0148254
- DOI
- 10.1371/journal.pone.0148254
- PMID
- 26840835
- PMCID
- PMC4739727
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; United States
- Grant note
- R03-AR063967 / NIAMS NIH HHS R03 AR063967 / NIAMS NIH HHS
- Language
- English
- Date published
- 2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Orthopedics and Rehabilitation; Craniofacial Anomalies Research Center; Chemical and Biochemical Engineering
- Record Identifier
- 9984064226602771
Metrics
23 Record Views