Photopolymerization based 3D printing of thermoresponsive hydrogel precursors

Abstract

Thermoresponsive hydrogels, which alter their shape in response to temperature changes, have crucial applications in wound dressings, sensors, and other biomedical contexts due to their responsive collapse behavior, high water content, and biocompatibility. Recent advancements in 3D printing have significantly improved the complexity and precision of hydrogel fabrication beyond traditional casting methods. Bioprinting is the most prevalent method for 3D printing hydrogels but is generally expensive, low-resolution, and restricted to academic settings. One alternative photopolymerization-based 3D printing offers greater accessibility and compatibility with synthetic hydrogel systems, capable of creating micrometer-sized features. However, the mechanical limitations of the printed objects and the temperature fluctuations during polymerization pose challenges for printing thermoresponsive hydrogels. This thesis aims to develop 3D printing methods for thermoresponsive hydrogels using a printed organo-gel precursor, which allows for enhanced mechanical properties without triggering thermoresponsive behaviors during printing. This research targets applications in wound dressings and digital health, facilitating point-of-care fabrication. Mask stereolithography was investigated for creating thermoresponsive hydrogels from poly(N-isopropyl acrylamide) (PNIPAm) and poly(oligoethylene glycol) acrylate, incorporating bio-based polysaccharides as strengthening additives and ionic crosslinkers. The first experimental system used PNIPAm with poloxamers and a double network of sodium alginate, yielding a resin capable of printing precise structures and forming patient-specific wound dressings. This system displayed superior mechanical properties at room temperature and temperature-dependent drug release and adhesion. However, the use of dimethyl sulfoxide (DMSO) and NIPAm’s neurotoxicity prompted a shift to poly(oligoethylene glycol) acrylate-based resins. In the second system, quaternized chitosan/3-sulfopropyl acrylate (QCh:SPA) salts and 2-hydroxyethyl acrylate (HEA) was investigated for producing supramolecular hydrogels along with the use of a cellulose-derived solvent Cyrene to replace DMSO making the process greener. These hydrogels exhibited enhanced elasticity and feature resolution compared to other systems, also showing conductive properties due to ionic interactions. In the third system, the studies were conducted to investigate the incorporation ethylene glycol methyl ether acrylate with HEA and the use of octylamine-grafted cellulose nanofibrils (OA-CNF) and sodium alginate to develop core-shell microparticles. This enhanced the hydrogel's mechanical properties and exhibited broad LCST behavior, offering improved stability and laying the groundwork for future enhancements aimed at refining printability and tuning LCST responses.