Nayyer, L; (2014) Design and Development of a Synthetic POSS-Nanocomposite Implant for Auricular Reconstruction. Doctoral thesis , UCL (University College London).

Abstract

Auricular reconstruction using sculpted autologous costal cartilage following congenital microtia, trauma and cancer is effective, but complex, time consuming and may incur donor site morbidity. Current conventional synthetic alternatives are associated with infection and extrusion. A novel nanocomposite polymer based on polyhedral oligomeric silsesquioxane (POSS) covalently bonded to poly(carbonate-urea-urethane) (PCU), has developed and patented in our laboratory and displayed promising clinical applications in first-in-human. POSS-PCU has been utilised to develop synthetic 3D auricle construct for use as auricular cartilage replacement, which aims to reduce extrusion rates by mimicking the mechanical properties of human ears and by encouraging desirable cellular interactions. Methods & Material: A novel custom-made ear-shaped 3D negative glass-mould was fabricated from positive 3D-printing ear model of a CT scan obtained from the external part of the human ear. This glass-mould was used to manufacture 3D auricular scaffolds using POSS-PCU materials. Two novel fabrication techniques solvent-evaporation/porogen-leaching (POSS-PCUs) and phase-separation/porogen-leaching (POSS-PCUc) were developed to produce nanocomposite scaffolds. The fabrication, physicochemical properties (including nanoscale topography) and in-vitro cellular interactions of these novel fabricated nanocomposites were extensively studied and compared to current commercially available synthetic material (Medpor®). Further cell-material interactions were completed on the optimized POSS-PCUs and Medpor® to examine the angiogenic and inflammatory responses to these materials using human fibroblasts and macrophages. Finally, POSS-PCUs scaffolds with two different pore sizes ranging from 50-100µm & 150-250µm were subcutaneously evaluated compared with Medpor® in-vivo in a rodent model for up-to 3 months. Results: The glass-mould design using 3D-printing technology allowed the manufacture of customised auricular POSS-PCU scaffolds that replicated the original human auricle. Two different polymeric fabrication methods resulted in the production of two types of nanocomposite scaffolds with same average pore size (150µm) but different porosity (63.47±1.35% in POSS-PCUs & 85.21±1.19% in POSS-PCUc). POSS-PCUs had similar elastic modulus (5.73±0.17 MPa) to human ear cartilage (5.02±0.17 MPa) compared with POSS-PCUc (0.58±0.12 MPa) and Medpor® (140.9±0.04 MPa) elastic modulus which were significantly different (P<0.001). Optimised POSS-PCUs nanocompoiste showed greater protein adsorption, and subsequently increased fibroblast adhesion, growth, and collagen production in vitro, compared to Medpor®. A higher volume fraction of fibrotic tissue ingrowth with negligible capsular formation was achieved in vivo in POSS-PCUs with pore-sizes of 150-250µm than Medpor®. No evidence of chronic inflammation was observed in the implanted scaffolds. Conclusion: These findings as well as other clinical studies in man suggest that POSS-PCUs nanocomposite can be a promising biomaterial for auricular reconstruction.

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