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Substrate modulus of 3D-printed scaffolds regulates the regenerative response in subcutaneous implants through the macrophage phenotype and Wnt signaling.
- Source :
-
Biomaterials [Biomaterials] 2015 Dec; Vol. 73, pp. 85-95. Date of Electronic Publication: 2015 Sep 11. - Publication Year :
- 2015
-
Abstract
- The growing need for therapies to treat large cutaneous defects has driven recent interest in the design of scaffolds that stimulate regenerative wound healing. While many studies have investigated local delivery of biologics as a restorative approach, an increasing body of evidence highlights the contribution of the mechanical properties of implanted scaffolds to wound healing. In the present study, we designed poly(ester urethane) scaffolds using a templated-Fused Deposition Modeling (t-FDM) process to test the hypothesis that scaffolds with substrate modulus comparable to that of collagen fibers enhance a regenerative versus a fibrotic response. We fabricated t-FDM scaffolds with substrate moduli varying from 5 to 266 MPa to investigate the effects of substrate modulus on healing in a rat subcutaneous implant model. Angiogenesis, cellular infiltration, collagen deposition, and directional variance of collagen fibers were maximized for wounds treated with scaffolds having a substrate modulus (Ks = 24 MPa) comparable to that of collagen fibers. The enhanced regenerative response in these scaffolds was correlated with down-regulation of Wnt/β-catenin signaling in fibroblasts, as well as increased polarization of macrophages toward the restorative M2 phenotype. These observations highlight the substrate modulus of the scaffold as a key parameter regulating the regenerative versus scarring phenotype in wound healing. Our findings further point to the potential use of scaffolds with substrate moduli tuned to that of the native matrix as a therapeutic approach to improve cutaneous healing.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Cells, Cultured
Collagen chemistry
Down-Regulation
Fibroblasts metabolism
Humans
Intercellular Signaling Peptides and Proteins metabolism
Kinetics
Male
Neovascularization, Pathologic
Phenotype
Porosity
Pressure
Printing, Three-Dimensional
Rats
Rats, Sprague-Dawley
Tissue Engineering
Wnt Proteins metabolism
Wound Healing
beta Catenin metabolism
Macrophages pathology
Regeneration physiology
Tissue Scaffolds chemistry
Wnt Signaling Pathway
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5905
- Volume :
- 73
- Database :
- MEDLINE
- Journal :
- Biomaterials
- Publication Type :
- Academic Journal
- Accession number :
- 26406449
- Full Text :
- https://doi.org/10.1016/j.biomaterials.2015.09.005