可降解形狀記憶水性聚胺酯彈性體於骨科組織工程之應用

Abstract

可降解形狀記憶高分子材料為生醫器材和組織工程支架的最佳候選材料，超順磁氧化鐵奈米粒子 (Superparamagnetic iron oxide nanoparticles, SPIO NPs) 在近年被報導可以促進人類間葉幹細胞的硬骨化。在本篇研究我們合成生物可降解形狀記憶水性聚胺酯 (shape memory polyurethane, 簡稱PU) 作為三維列印 (Three-dimensional printing, 3D printing) 墨水之主要成分製造3D列印支架，並包覆500 ppm之SPIO NPs以促進間葉幹細胞之硬骨誘導以及支架之形狀固定。此外，3D列印墨水包含聚乙二醇 (polyethylene oxide, PEO) 或gelatin作為增黏劑增加墨水之列印性，支架製作以低溫熔融沉積製造 (low-temperature fuse deposition manufacturing, LFDM) 平台列印，並進行24小時之真空乾燥。形狀記憶性質評估於50C空氣以及37C水浴，PU-PEO支架較PU-gelatin支架有更好的形狀固定與回復，且水中之形狀記憶性質優於空氣。人類間葉幹細胞培養於3D列印支架以評估硬骨化能力：以膠原蛋白含量分析，細胞在PU/PEO/SPIO支架上之硬骨沉積為PU/PEO支架的2.7倍；PU/gelatin/SPIO支架上之硬骨沉積為PU/gelatin支架的1.5倍。因此，本篇製作的3D列印可降解形狀記憶支架可作為客製化硬骨組織填充物，以微創手術方式應用於硬骨組織工程。

The biodegradable shape memory polymers are candidate materials for making biomedical devices and scaffolds for tissue engineering. Superparamagnetic iron oxide nanoparticles (SPIO NPs) have been reported to promote the osteogenesis of human mesenchymal stem cells (hMSCs). In this study, we synthesize water-based biodegradable shape memory polyurethane (PU) as the main component of the 3D printing ink for fabricating bone scaffolds. The 3D printing ink contains 500 ppm SPIO NPs to promote osteogenic induction and shape fixity, and it also contains polyethylene oxide (PEO) or gelatin for the improvement of printability. Scaffolds are printed by the microextrusion-based low-temperature fuse deposition manufacturing platform. Shape memory properties are evaluated in 50C air and 37C water. PU-PEO scaffolds show better shape fixity and recovery than PU-gelatin scaffolds, while the shape memory properties in water are better than those in air. hMSCs are seeded for evaluation of bone regeneration. With SPIO in the scaffolds, the osteogenesis increases 2.7 times for PU/PEO and 1.5 times for PU/gelatin scaffolds based on the collagen content. We conclude that 3D printed PU scaffolds with shape memory properties, biodegradability and osteogenic effect may be employed as customized-bone substitutes for bone tissue engineering.