title: Development and functional evaluation of biomimetic silicone surfaces with hierarchical micro/nano-topographical features demonstrates favourable in vitro foreign body response of breast-derived fibroblasts.
abstract: Reproducing extracellular matrix topographical cues, such as those present within acellular dermal matrix (ADM), in synthetic implant surfaces, may augment cellular responses, independent of surface chemistry. This could lead to enhanced implant integration and performance while reducing complications. In this work, the hierarchical micro and nanoscale features of ADM were accurately and reproducibly replicated in polydimethylsiloxane (PDMS), using an innovative maskless 3D grayscale fabrication process not previously reported. Human breast derived fibroblasts (n=5) were cultured on PDMS surfaces and compared to commercially available smooth and textured silicone implant surfaces, for up to one week. Cell attachment, proliferation and cytotoxicity, in addition to immunofluorescence staining, SEM imaging, qRT-PCR and cytokine array were performed. ADM PDMS surfaces promoted cell adhesion, proliferation and survival (p=<0.05), in addition to increased focal contact formation and spread fibroblast morphology when compared to commercially available implant surfaces. PCNA, vinculin and collagen 1 were up-regulated in fibroblasts on biomimetic surfaces while IL8, TNFα, TGFβ1 and HSP60 were down-regulated (p=<0.05). A reduced inflammatory cytokine response was also observed (p=<0.05). This study represents a novel approach to the development of functionalised biomimetic prosthetic implant surfaces which were demonstrated to significantly attenuate the acute in vitro foreign body reaction to silicone.
authors.affiliation: Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK; School of Computer Science, Centre for Mesoscience and Nanotechnology, The University of Manchester, Manchester, UK.
authors.forename: Daniel J T
authors.initials: DJ
authors.lastname: Kyle
authors.affiliation: School of Computer Science, Centre for Mesoscience and Nanotechnology, The University of Manchester, Manchester, UK.
authors.forename: Antonios
authors.initials: A
authors.lastname: Oikonomou
authors.affiliation: School of Computer Science, Centre for Mesoscience and Nanotechnology, The University of Manchester, Manchester, UK.
authors.forename: Ernie
authors.initials: E
authors.lastname: Hill
authors.affiliation: Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK. Electronic address: Ardeshir.Bayat@manchester.ac.uk.
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Bayat
mesh_terms: D000328:Adult; D040761:Biomimetic Materials / Q000737:chemistry*; D032701:Biomimetics / Q000379:methods; D001940:Breast / Q000166:cytology* / Q000276:immunology; D018427:Breast Implants / Q000009:adverse effects*; D002448:Cell Adhesion; D002478:Cells, Cultured; D004129:Dimethylpolysiloxanes / Q000737:chemistry*; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000276:immunology; D005549:Foreign-Body Reaction / Q000209:etiology* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000276:immunology; D008875:Middle Aged; D012828:Silicones / Q000737:chemistry; D013499:Surface Properties
chemical_list: D004129:Dimethylpolysiloxanes; D012828:Silicones; C013830:baysilon
keywords: Acellular dermal matrix (ADM); Biomimetic topography; Capsular contracture; Cell-implant interface; Micro and nano patterning; Silicone breast implant