Abstract
BackgroundTissue integration and vessel formation are important criteria for the successful implantation of synthetic biomaterials for subcutaneous implantation.ObjectiveWe 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.MethodsThe 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.ResultsSurface 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.ConclusionPSM using Ar is a cost-effective and efficient method to improve the tissue integration and angiogenesis of subcutaneous implants.
Highlights
Subcutaneous synthetic implants are being used in several surgical settings surgery to restore anatomy following surgical resection including breast, facial, abdominal and pelvic reconstruction
Even though the usefulness of plasma surface modification (PSM) has been widely documented, there is a lack of information on the efficiency of various gases used in PSM and optimal process parameters, which can be used to enhance tissue integration and angiogenesis of synthetic implants
This is in agreement with previous reports, which suggest, that PSM has no effect on the bulk properties of materials.[11,42,43]
Summary
Subcutaneous synthetic implants are being used in several surgical settings surgery to restore anatomy following surgical resection including breast, facial, abdominal and pelvic reconstruction. To improve the outcome of synthetic biomaterials, the substrate should aim to guide desired cell responses by mimicking the extracellular matrix (ECM). With the recent advancements in nanotechnology, nanocomposites offer substrates with a dimension that mimics the native ECM, improving their biocompatibility.[4,5,6,7,8] Our group is currently developing a subcutaneous implant using a nanocomposite polyurethane.[4,5] This polyurethane polymer has been extensively tested and meets international standards (ISO 10993) for biocompatibility. Tissue integration and vessel formation are important criteria for the successful implantation of synthetic biomaterials for subcutaneous implantation
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