3D列印製備生物相容性及溫感性水膠應用於人工角膜

Abstract

本研究開發一種可運用於3D列印方法製造的生物相容性高分子水膠作為仿生人工角膜。透過使用不同分子量的泊洛沙姆高分子(Poloxamer 407, Poloxamer 188)做為水膠主要材料。基於泊洛沙姆高分子具有低臨界溶液溫度(lower critical solution temperature, LCST)之特性，其在低溫時能於水互溶，而當溶液溫度升高時則由液態轉換成凝膠態，故可透過改變溫度從而調整水膠溶液黏度使其可應用於3D列印以客製化製造仿生人工角膜。本實驗透過改質泊洛沙姆高分子使其末端接上丙烯醯基團，讓高分子具有光感性，能在紫外光的作用產生自由基並進行自由基聚合反應形成一個三維的網路結構。

由於泊洛沙姆水膠的機械強度不是最理想的，本實驗透過調整不同分子量的泊洛沙姆高分子的比例使水膠具有相當強度，並在水膠當中分別加入海藻酸或明膠，透過將海藻酸或明膠進一步交聯形成複合型水膠，使水膠的機械強度增加及生物相容性提高。隨後便對水膠進行透光度、含水量、機械強度、細胞貼附能力進行測試，根據水膠的物性評估是否適合作為人眼角膜。根據實驗結果發現此水膠具有與人眼角膜相似的物性而且細胞貼附方面也有所改善，為一具有潛力的仿生人工角膜材料。

In this study, a novel biocompatible polymer hydrogel for biomimetic artificial cornea that can be manufactured by 3D printing method is developed. The main components of the hydrogel consists of mixture of Poloxamer with different molecular weights. Based on the lower critical solution temperature (LCST) properties of the polymer solution, the viscosity of the polymer solution can be adjusted by changing the temperature in order to be extruded from a 3D printing nozzle to manufacture biomimetic artificial cornea with desired curvature and thickness. The terminal hydroxyl group of Poloxamer are further modified to carry acrylated function groups, such that the modified polymers can be crosslinked by using free radical polymerization to from a hydrogel network under the exposure of ultraviolet light. Since the mechanical properties of pristine Poloxamer hydrogel is suboptimal, hydrogels with better mechanical properties were first made by preparing hydrogel mixtures of various ratios of Poloxamers with different molecular weights. Moreover, alginate as well as gelatin were incorporated into the hydrogel mixture to further enhancing their mechanical property and biocompatibility. The hybrid hydrogels thus made were tested for their transmittance, water content, mechanical strength and cell adhesion properties for the evaluation for uses in artificial cornea. The resulting optimized hydrogels have similar physical properties similar to those of human cornea and show high biocompatibility, demonstrating their potentials to be used in future artificial cornea applications.