title: Influence of the stiffness of three-dimensional alginate/collagen-I interpenetrating networks on fibroblast biology.
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.
authors.affiliation: 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.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Branco da Cunha
authors.affiliation: 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.
authors.forename: Darinka D
authors.initials: DD
authors.lastname: Klumpers
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
authors.forename: Weiwei A
authors.initials: WA
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Sandeep T
authors.initials: ST
authors.lastname: Koshy
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Weaver
authors.affiliation: Department of Mechanical Engineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Ovijit
authors.initials: O
authors.lastname: Chaudhuri
authors.affiliation: 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.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Granja
authors.affiliation: 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.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
mesh_terms: D000464:Alginates / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry*; D001684:Biological Dressings; D002448:Cell Adhesion; D002478:Cells, Cultured; D024042:Collagen Type I / Q000737:chemistry*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D011108:Polymers; D012038:Regeneration; D054457:Tissue Scaffolds; D015854:Up-Regulation; D014945:Wound Healing
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D024042:Collagen Type I; D006603:Hexuronic Acids; D011108:Polymers; D016753:Interleukin-10; D020723:Glucuronic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: ECM (extracellular matrix); Inflammation; Interpenetrating networks (IPNs); Mechanical properties; Wound dressing biomaterial; Wound healing