研究雙離子單體與高分子對於血小板溶液性質的影響

The effects of zwitterionic monomers and polymers on the solution properties of platelet-rich plasma

謝群(Chun Hsieh)

指導教授 ： 張雍

中原大學/工學院/化學工程研究所/碩士(2019年)

https://doi.org/10.6840/cycu201900515

摘要

輸血醫學在現代醫學的發展中，扮演著促進醫學研究的重要領域，其中包括了免疫醫學、組織再生醫學以及疾病醫學等，而成功且安全的輸血程序往往建立於醫療院所內部的健全制度，並搭配正確的醫療用血觀念以及捐血與血庫管理系統。然而在眾多輸血治療方式中，近幾年來血小板濃厚液由於富含各種生長因子，使其漸漸受到關注，並且被認為具有發展未來自體醫學之潛力，而實際上血小板濃厚液應用不僅在治療血小板缺少症、血友病擁有療效，也在醫療美容、關節炎治療以及各式傷口修復都展現良好的表現。血小板的應用領域及市場規模不斷擴大，並經過統計2016年血小板濃厚液全球市場規模為17.57億美金，並預計以12.8%的年複合成長率不斷擴大，預計到2024年可以成長到49.19億美金的市場規模。 血小板濃厚液在輸血治療的應用上雖然擁有巨大潛力，但是由於血小板濃厚液在體外環境中，血小板會開始不可逆之活化並且失去活性。根據研究文獻報導目前在醫療院所中血小板濃厚液的保存週期大約只有5~7天，這顯示出血小板濃厚液的保存不易，更明顯表示醫療院所可能需要更頻繁的透過捐血得到血小板濃厚液。正因為血小板的需求變多，如何保存血小板就成為一個日趨重要的問題，保存血小板的活性與功能，並且延長保存期限是目前最大的研究目標。根據文獻表示，雙離子高分子可以保存細胞的型態與功能，又能降低蛋白質間的交互作用力。我們假設雙離子高分子在血小板保存時可以提供額外的保護以及減少聚集的效果，所以我們實驗設計在檸檬酸鈉的基礎之上，加入雙離子溶液，預期可以保存血小板的型態及功能，並阻隔血小板與蛋白質間的交互作用力，以降低聚集程度，同時我們以聚集程度、活性及活化程度、凝血功能以及生長因子含量作為血小板保存效果的評估指標。

關鍵字

血小板 ； 雙離子 ； 血小板添加劑

並列摘要

Blood Transfusion plays an important role in modern medicine. Providing a safe and quick way for blood transfusion can depend on different factors such as policies of different medical institutions, correct process of donation, and the usage and management of the blood reserves in blood banks. However, in recent years, the use of platelet rich plasma (PRP) has got significant attention in several blood transfusion therapy procedures because of having rich amounts of growth factors that are can be beneficial in many ways. PRP treatment has a lot of potential for the development of autologous therapy in the future. In fact, PRP treatment is not only used to treat diseases such as thrombocytopenia and hemophilia but also shows a good applicability in beauty, arthritis, and various wound healing applications. The potential applications and the market for PRP are significantly expanding. According to the Transparency Market Research report, the PRP market size now is US$1.92 billion and be predicted that would achieve US$5.435 billion in 2026, progressing at a CAGR of 12.5% therein. PRP treatment has huge potential for blood transfusion application, but platelets will lose their function and encounter irreversible activation in vitro. Based on reports, the shelf time of PRP is between 3 to 7 days. It shows how hard it is to store or preserve PRP, it also means that medical institutions need more frequent blood donation to meet the demand for PRP. Due to more demand of PRP, the challenge on how to preserve PRP efficiently becomes an important issue. The current issue being addressed is to maintain the function and viability of the platelets, and then prolonging the shelf time of PRP. According to literatures, zwitterionic polymers can keep the morphology and function of cells, also they can reduce the interactions between proteins. We assume that adding zwitterionic based solutions into PRP as an additive can provide extra protection to platelets and reduce aggregation between platelets. So, we designed our experiment by adding a zwitterionic monomer and polymer into citrate based PRP. We expect that the zwitterionic monomer/polymer can keep the shape and function of platelets, and also block interactions between platelets and proteins thus prolonging the shelf life of PRP. We measured the degree of aggregation, viability, activation, coagulation ability and the amount of growth factors released as the index of PRP preservation.

並列關鍵字

platelet ； thrombocyte ； zwitterionic polymer ； platelet additive

參考文獻

1. Giangrande, P.L., The history of blood transfusion. British Journal of Haematology, 2000. 110(4): p. 758-767.

2. Grindon, A.J., Chapter 2 - Brief History of Blood Transfusion, in Transfusion Medicine and Hemostasis, C.D. Hillyer, et al., Editors. 2009, Academic Press: San Diego. p. 9-11.

3. Welck, M., P. Borg, and H. Ellis, James Blundell MD Edin FRCP (1790–1877): pioneer of blood transfusion. Journal of medical biography, 2010. 18(4): p. 194-197.

4. Duke, W., The relation of blood platelets to hemorrhagic disease: description of a method for determining the bleeding time and coagulation time and report of three cases of hemorrhagic disease relieved by transfusion. Journal of the American Medical Association, 1910. 55(14): p. 1185-1192.

5. Cohn, E.J., L.E. Strong, W. Hughes, D. Mulford, J. Ashworth, M.e. Melin, and H. Taylor, Preparation and Properties of Serum and Plasma Proteins. IV. A System for the Separation into Fractions of the Protein and Lipoprotein Components of Biological Tissues and Fluids1a, b, c, d. Journal of the American Chemical Society, 1946. 68(3): p. 459-475.