利用氮氣為主的常壓電漿束增進3T3 細胞對蜂巢型高分子材料的貼附與增生之實驗與多重尺度模擬研究

Abstract

近幾年來，蜂窩狀孔洞的高分子聚合物(以下簡稱「蜂窩狀膜」)已經在世界各地引起極大的關注。細 胞在蜂窩狀膜上的貼附能力會隨著孔洞的大小、孔洞的分布而改變。但是，將這種蜂窩狀膜真正應用 在生物材料的例子並不多，因此還有許多待研究開發之處。本團隊近年來初步的研究成果顯示，經過 以氮氣為主的兩段式常壓介電質放電電漿束(DBD-APPJ)處理後，可以於極短時間內(5-10 分鐘)順利將 氨基摻入平板PLA表面層，進而大幅提高(PLA)的生物相容性；然而，PLA表面與電漿產生的活性粒 子的化學反應機制卻尚未釐清。因此，在我們提出的三年計畫中，我們將以實驗和多重尺度數值模擬 方式進行研究結合兩段式DBD-APPJ 處理來增強蜂窩狀膜的細胞貼附性與增生能力。在實驗的部分包 括：1)發展一套經由旋轉塗佈可調變PLA膜的孔洞大小和分布的方法；2)經由以氮氣為主的兩段式 DBD-APPJ(N2/O2 + N2/NH3)處理平板式PLA 和蜂窩狀PLA後，再觀察細胞在材料上的貼附和生長情 況來斷定材料生物相容性的改變情形；3)分析電漿束氣相性質(利用OES)與PLA表面性質(利用XPS、 FTIR、AFM)。另外，在多重尺度數值模擬部分包括：1) 融合已發展的平行化程式： Navier-Stokes (NS) equation solver 和電漿流體模型(FM)以模擬真實二維DBD-APPJ 的流場分布以及電漿物理化學；2)結 合分子動力學(MD)模擬以及第一原理量子化學之計算去模擬電漿產生之高活性粒子與PLA表面兩者 之間的表面反應。希望透過實驗和模擬的結合，能有利於了解增加表面親水性和摻入氨基(amino)的詳 細機制，並期待可以協助我們製造具有高生物相容性的PLA材料。

Honeycomb patterned polymers have attracted much attention in several disciplines of research more than a decade. With proper control of the size and distribution of the pores, they can be used to enhance cell attachment. However, its potential in biomaterial applications has yet to be fully explored. Recently, in our group we have shown that we can greatly enhance the biocompability of flat Polylactic acid (PLA) in a very short period of time (5-10 minutes) by a two-step nitrogen-based DBD-APPJ treatment procedure (dielectric barrier discharge – atmospheric-pressure plasma jet) for incorporation of amino functional group. However, the detailed surface reaction mechanism of plasma generated reactive species with PLA surface is not clear. Thus, in this three-year project, we would like to propose a study consisting of a series of experiments and multiscale simulations of enhancing the cell attachment and proliferation of honeycomb patterned polymers using a two-step nitrogen-based DBD-APPJ treatment procedure. On one hand, in the experimental part, we are interested in: 1) developing a technique for preparing a uniform honeycomb patterned PLA with controllable size and distribution of the pores using a spin coating method; 2) applying a two-step nitrogen-based (N2/O2 + N2/NH3) DBD-APPJ treatment on a flat and patterned PLA to enhance its biocompatibility in terms of observation of cell attachment and cell proliferation; and 3) conducting several gas-phase (OES) and surface measurements (XPS, FTIR and AFM). On the other hand, in the multiscale simulation part, we are interested in: 1) synthesizing two previously developed parallel simulation codes: Navier-Stokes (NS) equation solver and parallel plasma fluid modeling (FM) code for simulating the flow field and plasma physics of practical DBD-APPJ; 2) conducting molecular dynamics (MD) simulations and 1st principle quantum chemistry calculations for the plasma generated reactive species with PLA surface. By combining the experiments and multiscale simulations, we can understand the fundamental mechanism leading to enhancing hydrophilic properties and incorporation of amino functional groups of the plasma treated patterned PLA surface, which could possibly lead to a better approach in preparing a highly biocompatible material using honeycomb patterned PLA material.