International Journal of Nanomedicine (Oct 2018)
Argon plasma improves the tissue integration and angiogenesis of subcutaneous implants by modifying surface chemistry and topography
Abstract
Michelle Griffin,1–3 Robert Palgrave,4 Víctor G Baldovino-Medrano,5 Peter E Butler,1–3 Deepak M Kalaskar1,6 1UCL Centre for Nanotechnology and Regenerative Medicine, Division of Surgery and Interventional Science, University College London, London, UK; 2Royal Free London NHS Foundation Trust Hospital, London, UK; 3The Charles Wolfson Center for Reconstructive Surgery, Royal Free London NHS Foundation Trust Hospital, London, UK; 4Department of Chemistry, University College London, London, UK; 5Laboratory of Surface Science (SurfLab), School of Chemical Engineering, Piedecuesta, Colombia; 6UCL Institute of Orthopaedics and Musculoskeletal Science, Division of Surgery and Interventional Science, University College London, London, UK Background: Tissue integration and vessel formation are important criteria for the successful implantation of synthetic biomaterials for subcutaneous implantation. Objective: We report the optimization of plasma surface modification (PSM) using argon (Ar), oxygen (O2) and nitrogen (N2) gases of a polyurethane polymer to enhance tissue integration and angiogenesis. Methods: The scaffold’s bulk and surface characteristics were compared before and after PSM with either Ar, O2 and N2. The viability and adhesion of human dermal fibroblasts (HDFs) on the modified scaffolds were compared. The formation of extracellular matrix by the HDFs on the modified scaffolds was evaluated. Scaffolds were subcutaneously implanted in a mouse model for 3 months to analyze tissue integration, angiogenesis and capsule formation. Results: Surface analysis demonstrated that interfacial modification (chemistry, topography and wettability) achieved by PSM is unique and varies according to the gas used. O2 plasma led to extensive changes in interfacial properties, whereas Ar treatment caused moderate changes. N2 plasma caused the least effect on surface chemistry of the polymer. PSM-treated scaffolds significantly (P<0.05) enhanced HDF activity and growth over 21 days. Among all three gases, Ar modification showed the highest protein adsorption. Ar-modified scaffolds also showed a significant upregulation of adhesion-related proteins (vinculin, focal adhesion kinase, talin and paxillin; P<0.05) and extracellular matrix marker genes (collagen type I, fibronectin, laminin and elastin) and deposition of associated proteins by the HDFs. Subcutaneous implantation after 3 months demonstrated the highest tissue integration and angiogenesis and the lowest capsule formation on Ar-modified scaffolds compared with O2- and N2-modified scaffolds. Conclusion: PSM using Ar is a cost-effective and efficient method to improve the tissue integration and angiogenesis of subcutaneous implants. Keywords: tissue integration, angiogenesis, surface modification, biomaterials, implants
