Heseltine, Phoebe; (2022) Advanced Processing and Forming of Polymeric Healthcare Devices. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

An evolving medical device landscape demands highly specialised biomaterials to satisfy functional requirements, patient compatibility, and regulatory approval. Three distinct devices, unique in the materials chosen for their fabrication and processing, were conceptualised, fabricated, and evaluated for their performance. The first part of this work addresses the unmet clinical need for bone tissue engineering scaffolds that can simultaneously facilitate bone cell growth and support the mechanical requirements. Silk has attracted considerable interest in biomedical applications due to its high strength and biocompatibility. Pressurised gyration (PG) was used as a rapid method to manufacture biocompatible silk fibroin (SF) fibres in the micrometre range, using hexafluoroisopropanol (HFIP) solvent. The effect of varying SF concentration and applied PG working pressure, along with the impact on fibre diameter, morphology, and structural composition is reported. Silk fibres in the micrometre diameter range were generated for the first-time using PG. Successful generation of silk fibres in HFIP motivated the transition to spinning SF fibres via PG in a water-based system. Silk was prepared in aqueous form, and was blended with poly(ethylene oxide) (PEO) in ratios of 80:20 and 90:10 and spun into fibres, assisted by a range of applied pressures and heat. PEO, IV SF-HFIP and aqueous SF were prepared for comparison. Aqueous silk did not spin on its own even in high concentrations. The resulting fibres were characterised using scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and Fourier transform infrared (FTIR) spectroscopy. In vitro cell behaviour was analysed using a Live/dead assay and cell proliferation studies were performed with an SaOs-2 human bone osteosarcoma cell line and human foetal osteoblast cells (hFob), in 2D culture conditions. Fibres that were micrometre in their diameter were successfully formed using SF-PEO blends, SF-HFIP and PEO-Aq. Fibre thickness ranged from 0.71 ±0.2 μm to 2.10 ±0.8 μm for blended fibres. FTIR confirmed the presence of SF via Amide I and Amide II bands in the blend fibres, appearing due to change in structural conformation. SaOS-2 cells and hFOb cell studies demonstrated higher cell densities and an increased number of live cells on SF-PEO blends when compared to SF-HFIP. This research indicates a scalable, biocompatible, and greener method of producing SF-based constructs for use in bone-tissue engineering applications. Secondly, the challenge of fabricating a small diameter (<5 mm) blood vessels that recapitulate the tissue structure was addressed. Silk-HFIP was spun at concentrations (1-5 w/v%) onto a flat electrospinning collector set-up, forming fibres above 5 w/v% and at increased flow rates. Then, polycaprolactone (PCL) dissolved in chloroform was electrospun onto a manual collection tube, ~5 mm diameter. Deposited fibres were unable to dry before deposition and clumped together, motivating the design and build of a motorised rotating collector. Tubular PCL constructs of porous fine fibres, with and without beads V were produced at varied concentrations and flow rates, recapitulating the tissue micro-environment. PCL was deemed a suitable material for the outer layer of the vessel. A 60:40 SF-PEO aqueous blend was also spun and collected on the rotating mandrel. Fibres were found to contain larger diameter beads (12.5 ±2.1 μm) with finer fibres (1.7 ±0.4 μm). The work demonstrates the feasibility of producing fibre scaffolds with tuneable morphological properties, towards a biocompatible ≤5 mm diameter tissue engineered vessel. Finally, a passive, ingestible device for sampling upper intestinal tract fluid was conceived, to address the challenge of sampling fluid from specific locations within the gastrointestinal (GI) tract. The device was based on the concept of a hydrogel swelling to draw in a luminal fluid sample. Fused deposition modelling, selective laser sintering and stereolithography were used to fabricate three devices. Stereolithography was deemed the most appropriate method for fabrication due to the high resolutions achieved. BioMed Clear Resin (FormLabs, Berlin, Germany) performed best when subjected to a simulated gut fluid acid-degradation test. An acrylamide and alginate dual- network hydrogel was fabricated and its swelling response and compressive stress in simulated fluid was evaluated. Increased ratio of acrylamide was found to increase swelling ability. Dye absorption studies determined the capsule ability to sample in vitro. This work demonstrates a novel hydrogel- based method for fluid sampling in previously unreachable regions of the GI tract.

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