摘要:醫學科技日新月異,生醫植入物的功能與效用從以往機械性質為主的需求,漸漸提升至同時具有生物積極性的方面發展。術後沾黏為外科手術普遍常遇到的問題,例如剖腹產、子宮肌瘤切除手術或腹腔鏡手術等都是常見容易發生術後沾黏的手術類型,術後沾黏的發生,對病患來說不僅可能導致慢性疼痛、不孕、延長住院時間、增加二度手術機率等不便,對醫護人員來說,也會有醫療支出及人力負擔的影響。手術後形成沾黏關鍵多在術後一周後,若發生沾黏則會影響患者癒後狀況,因此若能在手術時採取預防措施,則可大幅降低術後沾黏的風險。本研究計畫希望運用功能性聚對二甲苯鍍膜技術,將目前常用作為預防沾黏的聚丙烯人工網膜,進行表面改質而帶有聚乙二醇(PEG) 與肝素(heparin) 塗層,使其具備抗細胞貼附功能為本計畫研究重點,期待藉此技術避免術後受傷組織處形成不該存在的組織導致沾黏,並降低沾黏後所導致臨床合併症產生的機會。目前現有的表面改質技術均局限於控制單一類型的表面功能,要實現能夠同時控制、且呈現兩種或兩種以上生物分子的改質技術仍具挑戰性。本實驗室發展功能性聚對二甲苯(functionalized parylene) 的發展已有相當成果,進而發展多功能之聚對二甲苯(multifunctional parylene),使鍍膜具備兩種或多種以上的官能基,並利用製程條件來控制不同官能基之間的比例,進而在對等的比例下來固定生物分子,例如:聚合物、抗菌藥物、胜肽蛋白分子等等,讓改質後的材料表面可以同時具備(synergistic presentations) 多種生物分子的特性。本計畫預計以一年時間完成下列二階段之研究工作:一、研究重點將利用化學氣相沉積共聚合技術(CVD copolymerization) 製備多功能性官能基之聚對二甲苯鍍膜,並探討此功能性鍍膜於聚丙烯人工網膜等分子材料的穩定性、黏附力。除此之外,如何利用多官能基聚對二甲苯鍍膜(multifunctional parylene) 鍵結固定聚乙二醇(polyethylene glycol) 及肝素(heparin) 生物分子,再透過各種物理化學分析包括SEM,AFM,FTIR,XPS 與QCM等方法,來驗證第一年鍵結聚乙二醇及抗凝血分子的穩定性與安全性。二、研究重點為生物方法測試包括:血小板沾黏測試、血漿復鈣時間測試、溶血測試與細胞貼附試驗等方法,來驗證第一年鍵結聚乙二醇及抗凝血分子的有效性以及抗貼附之功能性。。本研究利用具備多重官能基的聚對二甲苯對聚丙烯人工網膜進行多功能改質,同時賦予聚丙烯人工網膜植入後需要的兩個重要特性(i)增加血液相容性以及(ii)抗細胞與組織貼附性,並將了解此一多功能改質技術在組織相容與抗貼附效果的實際應用性,並且嘗試解決一般高分子材料之不良反應的發生,具材料前瞻性與共通性,預期研發成果將涵蓋奈米材料科技與生醫科技等,產出豐碩成果與相關專利。
Abstract: Biological interactions are hardly ever unitary and typically involve a complex cascade of immobilizations and simultaneous manipulation of several physical and chemical properties on surfaces. Yet, almost all synthetic surface modification concepts rely on a single type of surface cues; achieving controlled, simultaneous presentation of two or more biomolecules remains challenging. The precise control of multiple surface reactions, while avoiding cross reactivity between the different chemical groups is key to overcome challenges to this field and will benefit applications for advanced biomaterials and sophisticated biomedical devices that all demand defined surface architectures and usually require precise immobilization of multiple biomolecules.Our strategies include less thrombus accumulation and anti-adhesion substance coating on the surface of the PP mesh. In this study, we are synergic modification the plate surface to coat the anti-adhesive substance (PEG, heparin). We eagerly anticipated to block the cell adherence on the mesh and reduced the thrombus formation and accumulation around the surface.In response to this request, this proposal aims to develop a novel synergistic modification process to install multiple biological functions, e.g. anti-adhesive, anti-bacterial, anti-thrombogenic and bactericidal effect, for orthopedic implants. Towards this goal, multifunctional parylene coatings prepared by chemical vapor deposition (CVD) are exceptional candidates for the coating of such implant devices due to the straightforward synthesis process to install multiple functionalities on parylenes; and excellent biocompatibility of parylenes which has gained approval by administrative agencies (e.g., the U.S. Food and Drug Administration (FDA) for several medical implants. We intend to achieve the following specific aims in this proposed research: (i) the development of multifunctional parylene coating via chemical vapor deposition (CVD) polymerization process, and the optimization of CVD conditions. The coating stability and the film adhesion integrity will be tested. In addition, specific conjugations for the co-immobilization of PEG and Heparin molecules on the coating surface will be tested, and the stability of the immobilized PEG and Heparin will be characterized by using a combination of physical and chemical analysis tools including SEM, AFM, XPS, FTIR, and QCM. (ii) the important biological assessments including anti-adhesion test, cytotoxicity, in vitro stability of the anti-adhesion coatings and in vitro inhibition of platelet aggregation, plasma re-calcification time, hemolysis test will be tested.The outcome of this study will support future studies in anti-adehesion related medical implants and the development of more advanced biomaterials. We foresee the practical use of these multifunctional coatings in the regulation of cell behavior, implant biomedical devices, and the development of advanced biological assays and scaffolds for regenerative medicine.