title: Impact of matrix stiffness on fibroblast function.
abstract: Chronic non-healing wounds, caused by impaired production of growth factors and reduced vascularization, represent a significant burden to patients, health care professionals, and health care system. While several wound dressing biomaterials have been developed, the impact of the mechanical properties of the dressings on the residing cells and consequently on the healing of the wounds is largely overlooked. The primary focus of this study is to explore whether manipulation of the substrate mechanics can regulate the function of fibroblasts, particularly in the context of their angiogenic activity. A photocrosslinkable hydrogel platform with orthogonal control over gel modulus and cell adhesive sites was developed to explore the quantitative relationship between ECM compliance and fibroblast function. Increase in matrix stiffness resulted in enhanced fibroblast proliferation and stress fiber formation. However, the angiogenic activity of fibroblasts was found to be optimum when the cells were seeded on compliant matrices. Thus, the observations suggest that the stiffness of the wound dressing material may play an important role in the progression of wound healing.
authors.affiliation: Bioengineering Program, Department of Mechanical Engineering, University of Michigan, Dearborn, 4901 Evergreen Road, Dearborn, MI 48128, United States.
authors.forename: Hichem
authors.initials: H
authors.lastname: El-Mohri
authors.affiliation: Bioengineering Program, Department of Mechanical Engineering, University of Michigan, Dearborn, 4901 Evergreen Road, Dearborn, MI 48128, United States.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Bioengineering Program, Department of Mechanical Engineering, University of Michigan, Dearborn, 4901 Evergreen Road, Dearborn, MI 48128, United States.
authors.forename: Swetaparna
authors.initials: S
authors.lastname: Mohanty
authors.affiliation: Bioengineering Program, Department of Mechanical Engineering, University of Michigan, Dearborn, 4901 Evergreen Road, Dearborn, MI 48128, United States. Electronic address: gargi@umich.edu.
authors.forename: Gargi
authors.initials: G
authors.lastname: Ghosh
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology; D005780:Gelatin / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D008856:Microscopy, Fluorescence; D018919:Neovascularization, Physiologic / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D042461:Vascular Endothelial Growth Factor A; D005780:Gelatin
keywords: Angiogenic activity; Fibroblasts; Matrix stiffness; Wound dressing