Influence of the stiffness of three-dimensional alginate/collagen-I interpenetrating networks on fibroblast biology

Cristiana Branco da Cunha; Darinka D Klumpers; Weiwei A Li; Sandeep T Koshy; James C Weaver; Ovijit Chaudhuri; Pedro L Granja; David J Mooney

doi:10.1016/j.biomaterials.2014.06.047

Influence of the stiffness of three-dimensional alginate/collagen-I interpenetrating networks on fibroblast biology

Biomaterials. 2014 Oct;35(32):8927-36. doi: 10.1016/j.biomaterials.2014.06.047. Epub 2014 Jul 19.

Authors

Cristiana Branco da Cunha¹, Darinka D Klumpers², Weiwei A Li³, Sandeep T Koshy⁴, James C Weaver⁵, Ovijit Chaudhuri⁶, Pedro L Granja⁷, David J Mooney⁸

Affiliations

¹ School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-465 Porto, Portugal; Instituto de Engenharia Biomédica da Universidade do Porto (INEB), 4150-180 Porto, Portugal; Faculdade de Medicina da Universidade do Porto (FMUP)/Hospital S. João, 4200-319 Porto, Portugal.
² School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; Dept. Orthopedic Surgery, Research Institute MOVE, VU University Medical Center, 1081 HV, Amsterdam, The Netherlands.
³ School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
⁴ School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 10239, USA.
⁵ Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
⁶ Department of Mechanical Engineering, Stanford University, Stanford, CA 94305, USA.
⁷ Instituto de Engenharia Biomédica da Universidade do Porto (INEB), 4150-180 Porto, Portugal; Departamento de Engenharia Metalúrgica e Materiais, Faculdade de Engenharia da Universidade do Porto (FEUP), 4200-465 Porto, Portugal; Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto (ICBAS), 4050-313 Porto, Portugal.
⁸ School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA. Electronic address: mooneyd@seas.harvard.edu.

PMID: 25047628
DOI: 10.1016/j.biomaterials.2014.06.047

Abstract

Wound dressing biomaterials are increasingly being designed to incorporate bioactive molecules to promote healing, but the impact of matrix mechanical properties on the biology of resident cells orchestrating skin repair and regeneration remains to be fully understood. This study investigated whether tuning the stiffness of a model wound dressing biomaterial could control the behavior of dermal fibroblasts. Fully interpenetrating networks (IPNs) of collagen-I and alginate were fabricated to enable gel stiffness to be tuned independently of gel architecture, polymer concentration or adhesion ligand density. Three-dimensional cultures of dermal fibroblasts encapsulated within matrices of different stiffness were shown to promote dramatically different cell morphologies, and enhanced stiffness resulted in upregulation of key-mediators of inflammation such as IL-10 and COX-2. These findings suggest that simply modulating the matrix mechanical properties of a given wound dressing biomaterial deposited at the wound site could regulate the progression of wound healing.

Keywords: ECM (extracellular matrix); Inflammation; Interpenetrating networks (IPNs); Mechanical properties; Wound dressing biomaterial; Wound healing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alginates / chemistry*
Biocompatible Materials / chemistry*
Biological Dressings*
Cell Adhesion
Cells, Cultured
Collagen Type I / chemistry*
Cyclooxygenase 2 / genetics
Cyclooxygenase 2 / metabolism
Fibroblasts / chemistry*
Glucuronic Acid / chemistry
Hexuronic Acids / chemistry
Humans
Interleukin-10 / genetics
Interleukin-10 / metabolism
Microscopy, Electron, Scanning
Polymers
Regeneration
Tissue Scaffolds
Up-Regulation
Wound Healing*

Substances

Alginates
Biocompatible Materials
Collagen Type I
Hexuronic Acids
Polymers
Interleukin-10
Glucuronic Acid
Cyclooxygenase 2
PTGS2 protein, human

Grants and funding

Howard Hughes Medical Institute/United States