Photochemical 3D Printing of Prototype Medical Devices from Poly(Propylene Fumarate)-Based Copolyesters

Abstract

3D printing has advanced and enabled the fabrication of complex structures with small feature sizes. As the technology continues to improve and the potential for medical advancement has been realized, there has been a call for new biodegradable polymer systems to more closely mimic biological tissue and degrade at faster rates than normal. In vat photopolymerization techniques, a majority of photopolymer resins are crosslinked through strong carbon-carbon linkages that inherently inhibit biodegradability and thus clinical translation. The need for a large system of tunable, biodegradable resins with a wide degree of mechanical property variation is more pressing than ever.Poly(propylene fumarate) (PPF) is an attractive polymer for biodegradation, breaking down into fumaric acid and propylene glycol. Previous efforts to print PPF were limited by the use of diethyl fumarate as a reactive diluent, resulting in stagnant resin formulations and a high degree of covalent crosslinking that left large portions of non-degradable material. Herein, we report a novel thiol-ene click chemistry approach to the rapid 3D printing of PPF stars and ABA triblock copolymers. In both polymer systems, a wide range of mechanical property variation were observed through uniaxial elongation, dynamic mechanical analysis and cyclic testing, among others. Systems were subjected to degradation experiments that varied dependent on the polymer architecture and the crosslinking density. These systems were analyzed and determined to possess mechanical properties relevant to biological tissue. The 10:1 alkene:thiol crosslinking ratio of PPF stars was determined to have similar mechanical properties when compared to cancellous bone. Thus, the polymer was utilized for the fabrication of bone scaffolds to treat critical-sized radial defects in rabbits. In addition to the pure polymer, the resin was enhanced with the addition of 5 wt% hydroxyapatite, a mineral natively found in bone. 3D-printed scaffolds of 50 %, 65 % and 80 % porosity were evaluated for compressive behavior and tensile bars were evaluated using an Instron for analysis. Scaffolds were printed and implanted into critical-sized bone defects in rabbits in order to evaluate bone growth. Further optimization studies to enhance mechanical behavior solely with post-printing conditions were performed in a later study, demonstrating the maximization of mechanical properties through post-curing and post-print bake times and temperatures. The effects of these variables were determined through compression, uniaxial elongation, and dynamic mechanical analysis techniques. An optimized condition for both pure and nanocomposite materials was observed at high drying temperatures and durations. Lastly, a 3D-printed ABA triblock copolymer was investigated for mechanical property loss following in vivo degradation. Mechanical properties were observed to stay in tact after 4 weeks and begin to drop off after 12 weeks. The results of this study launched the investigation of printing coronary artery bypass graft sheaths. Two crosslinking densities and three inner diameters were investigated in this study. Mechanical behavior in a Mylar loop and compression at room temperature and 37 °C were examined. The largest diameter device was subjected to in vitro degradation for 120 days and analyzed for mechanical degradation in this study. These devices were subsequently implanted in vivo for a reinforcement effect to improve long-term success rates following coronary artery bypass graft procedures.