探討延長冷凍保存對氣管重建中主動脈移植物的影響並評估豬主動脈替代品之適用性

Abstract

目前已有成功臨床案例顯示，氣管重建手術可透過冷凍保存的同種異體主動脈進行置換。本研究旨在評估延長冷凍保存時間對主動脈移植物的影響，同時探討豬主動脈作為替代品之適用性，期能尋求更多可供氣管重建的替代移植物。結果顯示，人類主動脈在攝氏負80度的條件下可冷凍保存長達十二個月，並且其生物力學特性並無明顯下降，能夠支持其在氣管重建中的應用且無機械失效風險。細胞實驗證實，新鮮和冷凍保存的人類主動脈均能支持人類脂肪幹細胞的生長，但在二維模型中無法誘導其分化為軟骨。關於豬主動脈替代品，使用Triton X-100/EDTA和SDS的去細胞方法效果不佳，而氰溴化物（CNBr）去細胞方法雖能有效去除細胞，卻破壞了組織的生物力學強度。然而，實驗結果指向透過0.625%的戊二醛處理後的豬主動脈，其減弱的生物力學強度仍在可接受範圍內，並成功掩蓋了α-半乳糖苷寡糖（alphaGal）表位，凸顯經戊二醛處理的豬主動脈作為臨床替代品的可能。這項研究確立了使用冷凍保存的人類主動脈和經特殊處理的豬主動脈在氣管重建中的可行性，為再生醫學的進步指引出一條可行途徑。

Cryopreserved allogenic aorta has proven effective in tracheal reconstruction, demonstrating clinical success. This study aims to enhance the availability of aortic grafts for tracheal reconstruction by evaluating the biomechanical properties and biological viability of prolonged cryopreservation, as well as exploring porcine aortas as alternatives. Human aortas were cryopreserved at -80℃ for up to twelve months, revealing no significant biomechanical degradation, thereby supporting their use in tracheal reconstruction without risk of mechanical failure. In vitro studies indicated that both fresh and cryopreserved human aortas support the growth of human adipose-derived stem cells but do not induce chondrogenic differentiation in a 2D model. Regarding porcine aortic alternatives, decellularization methods using Triton X-100/EDTA and SDS were inadequate, while cyanogen bromide (CNBr) decellularization compromised biomechanical integrity despite effective cell removal. However, glutaraldehyde treatment at 0.625% resulted in acceptable biomechanical properties and successful masking of alpha-galactose-1,3-galactose (alphaGal) epitopes, highlighting the potential of glutaraldehyde-treated porcine aortas as clinical alternatives. This research underscores the feasibility of utilizing cryopreserved human aortas and treated porcine aortas in tracheal reconstruction, offering insights for advancements in regenerative medicine.