以分子動力模擬探討WDPU的自組裝行為以及力學性質

Abstract

生物降解水凝膠已成為許多生物應用的熱門材料。它們不僅具有與天然軟組織相似的機械性能，而且還具有在其使用壽命後在水性環境中降解的能力。最近，一種新型水性生物降解聚氨酯（WDPU）已經被合成並顯示出在生物醫學應用中具有很大的潛力。此材料具有優良的生物相容性，生物降解能力和機械性質。此外，最近已被作為3D印刷墨水，並成功製造出生物相容的支架。 由於透過3D列印技術能夠創造複雜的結構，生物降解水凝膠和3D列印技術的應用為設計生物相容性支架提供了巨大的可能性。然而，水性聚氨脂的自組裝過程的分子機制以及軟鍊段的化學成分與生物降解性水凝膠性質之間的關係尚不清楚。 本研究旨在透過全原子尺度分子動力模擬探討WDPU的基本機制。我們使用分子模擬來研究聚合物相互作用的分子機制。為了解自組裝行為，我們分析了三種以PCL和PLA為主要軟鏈成份之奈米顆粒的迴轉半徑，偏心率，表面積，端對端距離和氫鍵，以瞭解WDPU水凝膠分子特性與其性質的關聯性。本研究也透過單軸拉伸試驗量測WDPU無定形聚合物的彈性係數，以及以奈米壓印試驗量測WDPU奈米顆粒的機械性質。 單軸拉伸試驗中，我們考慮不同數量的鍊和應變率，以研究楊氏係數以及練與應變率的關係，並比較不同WDPU的差異。而在壓印試驗包括加載和卸載階段，並且考慮不同的壓印深度，以研究壓印深度和楊氏係數之間的關係，以及不同WDPU奈米顆粒的差異。我們的研究結果指出，生物可降解水凝膠的材料性質可以通過調整WDPU中聚合物鏈段的分子量和化學成分來設計。模擬結果顯示，PCL80LL20 奈米顆粒尺寸大於PCL100 奈米顆粒尺寸，且PCL80LL20顆粒的結構也較為鬆散，此結果與實驗結果一致。此外，我們發現影響奈米顆粒的形狀和尺寸的關鍵因素是PLA的旋光度，這將影響WDPU中氫鍵的數量。PCL75DL25的氫鍵數量較PCL75LL25多，具有PDLA作為軟鏈段的WDPU的結構較為展開，PDLA和PCL明顯斥開。而以PLLA作為軟鏈段的WDPU中，PLLA和PCL並無斥開且聚合良好，因此我們認為PLLA會抑制PCL中氫鍵的發生。對於未來的3D列印應用，本研究可以為WDPU奈米顆粒的機械性能提供根本的見解，有助於設計生物相容性水凝膠的材料性能。

Biodegradable hydrogels have become promising materials for many biological applications in the past years. They not only exhibit similar mechanical properties as natural soft tissues but also have the ability to be degraded in an aqueous environment after their useful lifetime. Recently, a novel waterborne biodegradable polyurethane (WDPU) has been synthesized and shown to have great potential in biomedical applications. It is synthesized by a green water-based process, and has great biocompatibility, biodegradability, and mechanical properties. Furthermore, it has been used as a 3D printing ink recently to enable the fabrication of biocompatible scaffolds. The integration of biodegradable hydrogel and 3D printing technology has open great opportunities for the design of smart biocompatible scaffolds for many applications due to the ability to access complex internal structures. However, the molecular mechanisms of the self-assembly process of WDPUs and the relationship between the chemical compositions of the polymer segments and the material properties of the biodegradable hydrogels at macro-scale are still not clear. In this study, we aim to explore the fundamental mechanisms of WDPU through a full atomistic simulation approach. We use molecular simulations to study the molecular mechanisms of polymer interactions. For self-assembly, we analyze the radius of gyration, eccentricity, surface area, end to end distance and hydrogen bonds of different WDPU nanoparticles, including PCL100, PCL75DL25 and PCL75LL25, for the purpose of predicting WDPU hydrogel properties at macro-scale. By considering different number of chains and strain rate, we perform uniaxial tensile test to measure the Young’s modulus of each bulk WDPU. For WDPU nanoparticles, we considered different indentation depth and performed molecular dynamics simulation of a full indentation cycle, which includes the loading and unloading stages. The relationships between the indentation depth and reduced Young’s modulus are also investigated. Our results show that the material properties of the biodegradable hydrogel can be designed by tuning the molecular weights and the chemical compositions of the polymer segments in the WDPU. Our simulation results found that PCL80LL20 NP size is larger than PCL100 NP size, also the structure of PCL80LL20 particle is relatively loose, and these results are consistent with experiment results. Moreover, we found that the key factor of shape and size of nanoparticles is the optical rotation of PLA, which would affect the number of hydrogen bond in WDPUPCL section, the structure of WDPU with PDLA as soft segments is more extended, while PLLA and PCL are close, which inhibit the occurrence of hydrogen bonding in PCL. For future 3D printing applications, this study can provide fundamental insights into the mechanical performances of WDPU nanoparticles and help enabling the design of material properties of biocompatible hydrogel.