title: Novel micropatterns mechanically control fibrotic reactions at the surface of silicone implants.
abstract: Over the past decade, various implantable devices have been developed to treat diseases that were previously difficult to manage such diabetes, chronic pain, and neurodegenerative disorders. However, translation of these novel technologies into clinical practice is often difficult because fibrotic encapsulation and/or rejection impairs device function after body implantation. Ideally, cells of the host tissue should perceive the surface of the implant being similar to the normal extracellular matrix. Here, we developed an innovative approach to provide implant surfaces with adhesive protein micropatterns. The patterns were designed to promote adhesion of fibroblasts and macrophages by simultaneously suppressing fibrogenic activation of both cell types. In a rat model, subcutaneously implanted silicone pads provided with the novel micropatterns caused 6-fold lower formation of inflammatory giant cells compared with clinical grade, uncoated, or collagen-coated silicone implants. We further show that micropatterning of implants resulted in 2-3-fold reduced numbers of pro-fibrotic myofibroblast by inhibiting their mechanical activation. Our novel approach allows controlled cell attachment to implant surfaces, representing a critical advance for enhanced biointegration of implantable medical devices.
authors.affiliation: Biomechanical Orthopedics Laboratory, Ecole Polytechnique Fédérale de Lausanne, Switzerland; Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospitals of Lausanne, Switzerland; Laboratory of Cell Biophysics, Ecole Polytechnique Fédérale de Lausanne, Switzerland.
authors.forename: Hicham
authors.initials: H
authors.lastname: Majd
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospitals of Lausanne, Switzerland.
authors.forename: Saja S
authors.initials: SS
authors.lastname: Scherer
authors.affiliation: Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Canada.
authors.forename: Stellar
authors.initials: S
authors.lastname: Boo
authors.affiliation: Biomechanical Orthopedics Laboratory, Ecole Polytechnique Fédérale de Lausanne, Switzerland.
authors.forename: Silvio
authors.initials: S
authors.lastname: Ramondetti
authors.affiliation: Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cambridge
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospitals of Lausanne, Switzerland.
authors.forename: Wassim
authors.initials: W
authors.lastname: Raffoul
authors.affiliation: Laboratory of Cell Biophysics, Ecole Polytechnique Fédérale de Lausanne, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Friedrich
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospitals and Faculty of Medicine of Geneva, Switzerland.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Pittet
authors.affiliation: Biomechanical Orthopedics Laboratory, Ecole Polytechnique Fédérale de Lausanne, Switzerland.
authors.forename: Dominique
authors.initials: D
authors.lastname: Pioletti
authors.affiliation: Laboratory of Tissue Repair and Regeneration, Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Canada. Electronic address: boris.hinz@utoronto.ca.
authors.forename: Boris
authors.initials: B
authors.lastname: Hinz
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospitals of Lausanne, Switzerland. Electronic address: gpietramaggiori@gmail.com.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pietramaggiori
mesh_terms: D000818:Animals; D019544:Equipment Failure Analysis; D005355:Fibrosis / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D019736:Prostheses and Implants / Q000009:adverse effects*; D011474:Prosthesis Design; D051381:Rats; D017208:Rats, Wistar; D012825:Silicon / Q000009:adverse effects* / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D012825:Silicon
keywords: Collagen; Contracture; Fibrosis; Foreign body reaction; Mechanobiology; Myofibroblast