開發具有抗菌、消炎、供氧及促使細胞生長特性可注射溫感性水凝膠用於慢性傷口癒合之研究

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姓名

張簡博穎(Bo-Ying, Chang Chien) 查詢紙本館藏

畢業系所

生物醫學工程研究所

論文名稱

開發具有抗菌、消炎、供氧及促使細胞生長特性可注射溫感性水凝膠用於慢性傷口癒合之研究
(Development of Injectable Thermosensitive Hydrogel with Antibacterial, Anti-inflammatory, Oxygen-supply and Enhanced Cell Growth Properties for Chronic Wound Healing)

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至系統瀏覽論文 (2026-11-1以後開放)

摘要(中)

糖尿病是一種葡萄糖代謝異常引起的慢性疾病，它的主要特徵是血液中葡萄糖濃度的升高。而患有糖尿病的患者，其傷口稱為慢性傷口，此傷口擁有較難癒合且易受細菌感染的特性。它不僅要討論傷口中是否存在細菌感染的風險，還必須探討是否擁有促進傷口癒合的能力。在這裡，我們開發了由玻尿酸（HA）結合PEO-PPO-PEO三嵌段共聚物組成的可注射溫感性水凝膠，可改善體外慢性傷口的癒合。將人類表皮生長因子（EGF）奈米粒子、聚六亞甲基雙胍（PHMB）和全氟辛基溴化物（PFOB）奈米乳劑整合到我們的可注射溫感性水凝膠中。通過DLS分析，負載EGF的奈米顆粒和PFOB的奈米乳劑的尺寸約為973.5 ± 63.6 nm和106.16 ± 0.13 nm。為了證明其抗菌效果，選擇了人類皮膚上常見的細菌─金黃色葡萄球菌作為實驗細菌。結果表明，我們的水凝膠具有良好的抗菌能力，同時具有較高的細胞存活率和使細胞生長的能力。透過測量IL-8發炎因子，發現我們的水凝膠具有減緩發炎的能力。而在檢測氧氣的試驗中，也發現PFOB奈米乳劑確實具有攜帶氧氣的能力。總之，在這項研究中開發的可注射溫感性水凝膠在慢性傷口癒合中具有很高的潛力。

摘要(英)

Diabetes is a chronic disease caused by abnormal glucose metabolism. Its main feature is the increase in blood glucose concentration. The wounds of diabetic patients are called chronic wounds, which are difficult to heal and are susceptible to bacterial infections. It must not only discuss whether there is a risk of bacterial infection in the wound, but also the ability to promote wound healing. Here, we developed an injectable thermosensitive hydrogel composed of PEO-PPO-PEO block co-polymer bonded with hyaluronic acid (HA) to improve the chronic wound healing. Incorporating human epidermal growth factor (EGF) nanoparticles, polyhexamethylene biguanide (PHMB) and perfluorooctyl bromide (PFOB) nano-emulsions into our injectable thermosensitive hydrogel. Through the DLS analysis, the sizes of EGF-loaded nanoparticles and PFOB nano-emulsions are about 973.5 ± 63.6 nm and 106.16 ± 0.13 nm, respectively. To demonstrate the antibacterial effect, Staphylococcus aureus, which is common focal microbiome on human skin, was selected as the experimental microorganisms. The results showed that our hydrogels had a good antibacterial ability while it gave a high cell survival rate and enhanced cell growth. By measuring IL-8 inflammatory factors, we found that our hydrogel has the ability to slow down inflammation. In the oxygen test, it was also found that PFOB nano-emulsions actually have the ability to carry oxygen. In summary, the injectable thermosensitive hydrogel developed in this study is highly potential for use in the chronic wound healing.

關鍵字(中)

★ 可注射水凝膠
★ 慢性傷口癒合
★ 抗菌
★ 細胞生長
★ IL-8發炎因子
★ 全氟辛基溴

關鍵字(英)

★ Injectable hydrogel
★ Chronic wound healing
★ Antibacterial
★ Cell growth
★ IL-8 inflammatory factors
★ Perfluorooctyl bromid

論文目次

目錄
摘要 i
Abstract ii
誌謝 iii
圖目錄 ix
表目錄 xii
第一章緒論 1
第二章研究背景 3
2.1 慢性傷口介紹 3
2.1.1 壓瘡(Pressure Ulcer) 3
2.1.2 靜脈潰瘍(Venous Ulcer) 3
2.1.3 動脈潰瘍(Arterial Ulcer) 4
2.1.4 糖尿病足潰瘍(Diabetic Foot Ulcer) 4
2.1.5 慢性傷口之併發症介紹 4
2.1.6 潰瘍(Ulcer) 5
2.1.7 蜂窩性組織炎(Cellulitis) 5
2.1.8 敗血症(Sepsis) 6
2.2 傷口顏色分類系統(Color System) 6
2.2.1 紅色傷口 6
2.2.2 黃色傷口 7
2.2.3 黑色傷口 7
2.3 慢性傷口主要治療方式 7
2.3.1 清創(Debridement) 8
2.3.2 外科清創(Surgical Debridement) 8
2.3.3 酵素清創(Enzymatic Debridement) 8
2.3.4 自溶性清創(Autolytic Debridement) 8
2.3.5 濕到乾清創(Wet to Dry Debridement) 9
2.3.6 高壓氧治療(Hyperbaric Oxygen Therapy) 9
2.3.7 傷口敷料治療(Wound Dressing Treatment) 9
2.4 慢性傷口敷料(Chronic Wound Dressing) 10
2.4.1 傳統紗布 10
2.4.2 薄膜敷料(Films) 11
2.4.3 水膠體敷料(Hydrocolloid) 11
2.4.4 藻酸鹽敷料(Alginates) 12
2.4.5 泡棉敷料(Foams) 13
2.4.6 水凝膠敷料(Hydrogels) 13
2.4.6.1 溫感性水凝膠(Thermosensitive Hydrogels) 14
2.5 傷口癒合機制 14
2.5.1 發炎期(Inflammation) 15
2.5.2 增生期(Proliferation) 15
2.5.3 重塑期(Remodelling) 16
2.6 泊洛沙姆(Pluronic F127, PEO-PPO-PEO) 16
2.7 玻尿酸(Hyaluronic Acid) 17
2.8 Cosmocil CQ (20% Polyhexanide, PHMB) 18
2.9 表皮生長因子(Epidermal Growth Factor, EGF) 19
2.10 全氟辛基溴(Perfluorooctyl Bromide, PFOB) 19
第三章實驗部分 22
3.1 實驗藥品、材料、儀器設備 22
3.1.1 材料及藥品(materials & devices) 22
3.1.2 儀器 24
3.2 檢量線 26
3.2.1 UV-VIS檢測Cosmocil CQ標準線 26
3.2.2 ELISA檢測表皮生長因子標準線 26
3.2.3 ELISA檢測IL-8發炎因子標準線 27
3.3 實驗整體流程 28
3.4 EGF奈米粒子製備 28
3.5 PFOB奈米單層乳劑製備 29
3.6 CTENPs & PFSNEs物理、化學特性分析 30
3.6.1 粒徑分析 30
3.6.2 表面電位分析 31
3.6.3 超高真空場發射掃描式電子顯微鏡(FE-SEM)拍攝 31
3.6.4 包覆率分析 31
3.6.5 負載率分析 31
3.7 製備六亞甲基二異氰酸(HDI)接枝的泊洛沙姆高分子 32
3.8 製備含有CQ、PFSNEs、CTENPs的可注射型水膠 32
3.9 核磁共振光譜(1H NMR)分析HDI-PF127高分子 33
3.10 超高真空場發射掃描式電子顯微鏡(FE-SEM)拍攝 33
3.11 IHG-CPC體外釋放EGF 34
3.12 IHG-CPC體外釋放CQ 34
3.13 IHG-CPC體外釋放氧氣 34
3.14 抗菌測試──細菌點盤 36
3.15 細胞毒性測試 37
3.16 細胞生長試驗 38
3.17 抗發炎反應測試 40
3.18 熱重分析儀(TGA) 41
3.19 流變儀 42
3.20 動物試驗 42
3.21 統計與分析 43
第四章結果與討論 44
4.1 HDI-PF127 1H NMR光譜分析 44
4.2 CTENPs & PFSNEs物理、化學特性分析 45
4.3 CTENPs & PFSNEs之表面形態分析 46
4.4 IHG-CPC之表面形態分析 46
4.5 IHG-CQ之抗菌試驗 47
4.6 IHG-CQ之體外細胞毒性試驗 48
4.7 人類角質形成細胞生長試驗 49
4.8 IHG之抗發炎試驗 51
4.9 IHG-PFSNEs之體外釋放氧氣試驗 52
4.10 IHG-CPC之TGA試驗 53
4.11 IHG-CPC之流變儀試驗 54
4.12 動物試驗 56
第五章結論 59
第六章未來展望 60
第七章參考文獻 61

參考文獻

1. 行政院, https://www.mohw.gov.tw/cp-16-54482-1.html. 2019.
2. Doolittle, R.F., Epidermal Growth-Factor. Science, 1990. 250(4986): p. 1319-1319.
3. Ntwampe, S.K.O., C.C. Williams, and M.S. Sheldon, Water-immiscible dissolved oxygen carriers in combination with Pluronic F 68 in bioreactors. African Journal of Biotechnology, 2010. 9(8): p. 1106-1114.
4. Hubner, N.O. and A. Kramer, Review on the Efficacy, Safety and Clinical Applications of Polihexanide, a Modern Wound Antiseptic. Skin Pharmacology and Physiology, 2010. 23: p. 17-27.
5. Altman, R., et al., Anti-Inflammatory Effects of Intra-Articular Hyaluronic Acid: A Systematic Review. Cartilage, 2019. 10(1): p. 43-52.
6. Han, G. and R. Ceilley, Chronic Wound Healing: A Review of Current Management and Treatments. Advances in Therapy, 2017. 34(3): p. 599-610.
7. Lyder, C.H., Pressure ulcer prevention and management. Jama-Journal of the American Medical Association, 2003. 289(2): p. 223-226.
8. Hess, C.T., Arterial Ulcer Checklist. Advances in Skin & Wound Care, 2010. 23(9): p. 432-432.
9. Boyko, E.J., et al., A prospective study of risk factors for diabetic foot ulcer - The Seattle diabetic foot study. Diabetes Care, 1999. 22(7): p. 1036-1042.
10. Pappalardo, F., et al., Chronic refractory leg ulcers in mosaic Klinefelter′s syndrome: the importance of a prompt diagnosis and appropriate treatment. Italian Journal of Dermatology and Venereology, 2021. 156(1): p. 93-95.
11. CanStockPhoto, https://www.canstockphoto.com/diabetic-foot-medical-vector-58153346.html.
12. Phoenix, G., S. Das, and M. Joshi, Diagnosis and management of cellulitis. Bmj-British Medical Journal, 2012. 345.
13. omicsonline, https://www.omicsonline.org/canada/cellulitis-peer-reviewed-pdf-ppt-articles/.
14. Russell, J.A., Drug therapy: Management of sepsis. New England Journal of Medicine, 2006. 355(16): p. 1699-1713.
15. Falabella, A.F., Debridement and wound bed preparation. Dermatologic Therapy, 2006. 19(6): p. 317-325.
16. Cardinal, M., et al., Serial surgical debridement: A retrospective study on clinical outcomes in chronic lower extremity wounds. Wound Repair and Regeneration, 2009. 17(3): p. 306-311.
17. Ramundo, J. and M. Gray, Collagenase for Enzymatic Debridement A Systematic Review. Journal of Wound Ostomy and Continence Nursing, 2009. 36(6): p. S4-S11.
18. Steed, D.L., Debridement. American Journal of Surgery, 2004. 187(5a): p. 71s-74s.
19. Lau, Y.S. and P. Brooks, Innovative Use of Povidone- Iodine to Guide Burn Wound Debridement and Predict the Success of Biobrane as a Definitive Treatment for Burns. Advances in Skin & Wound Care, 2014. 27(3): p. 111-113.
20. Myers, R.A.M., Hyperbaric oxygen therapy for trauma: Crush injury, compartment syndrome, and other acute traumatic peripheral ischemias. International Anesthesiology Clinics, 2000. 38(1): p. 139-151.
21. Liu, H., et al., A functional chitosan-based hydrogel as a wound dressing and drug delivery system in the treatment of wound healing. Rsc Advances, 2018. 8(14): p. 7533-7549.
22. Fonder, M.A., et al., Treating the chronic wound: A practical approach to the care of nonhealing wounds and wound care dressings. Journal of the American Academy of Dermatology, 2008. 58(2): p. 185-206.
23. https://detail.1688.com/pic/609064353313.html?spm=a261y.7663282.1998411378.
1.47501492WYXI73.
24. Khan, T.A., K.K. Peh, and H.S. Ch′ng, Mechanical, bioadhesive strength and biological evaluations of Chitosan films for wound dressing. Journal of Pharmacy and Pharmaceutical Sciences, 2000. 3(3): p. 303-311.
25. http://icare-inc.com.hk/product.php?pcode=3M1684.
26. Thu, H.E., M.H. Zulfakar, and S.F. Ng, Alginate based bilayer hydrocolloid films as potential slow-release modern wound dressing. International Journal of Pharmaceutics, 2012. 434(1-2): p. 375-383.
27. https://weidian.com/item.html?itemID=2694114512.
28. Machida-Sano, I., et al., Surface characteristics determining the cell compatibility of ionically cross-linked alginate gels. Biomedical Materials, 2014. 9(2).
29. https://tw.mall.yahoo.com/item/%E8%B5%AB%E9%BA%97%E6%95%B7%
E8%97%BB%E9%85%B8%E9%88%A3%E9%B9%BD%E6%95%B7%E6%96%99-%E6%BB%85%E8%8F%8C-10X10cm-10%E7%89%87-%E7%9B%92-p0984197400010.
30. Liu, X.Y., et al., Rapid hemostatic and mild polyurethane-urea foam wound dressing for promoting wound healing. Materials Science & Engineering C-Materials for Biological Applications, 2017. 71: p. 289-297.
31. https://www.anscare.tw/chinese/products/detail.php?cpid=3&dpid=51.
32. Balakrishnan, B., et al., Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatin. Biomaterials, 2005. 26(32): p. 6335-6342.
33. https://www.mountainside-healthcare.com/products/dermacea-aquaflo-hydrogel-wound-dressing-3-diameter-disks.
34. Klouda, L., Thermoresponsive hydrogels in biomedical applications A seven-year update. European Journal of Pharmaceutics and Biopharmaceutics, 2015. 97: p. 338-349.
35. Gong, C., et al., Thermosensitive Polymeric Hydrogels As Drug Delivery Systems. Current Medicinal Chemistry, 2013. 20(1): p. 79-94.
36. Velnar, T., T. Bailey, and V. Smrkoli, The Wound Healing Process: an Overview of the Cellular and Molecular Mechanisms. Journal of International Medical Research, 2009. 37(5): p. 1528-1542.
37. Landen, N.X., D.Q. Li, and M. Stahle, Transition from inflammation to proliferation: a critical step during wound healing. Cellular and Molecular Life Sciences, 2016. 73(20): p. 3861-3885.
38. Nour, S., et al., A review of accelerated wound healing approaches: biomaterial- assisted tissue remodeling. Journal of Materials Science-Materials in Medicine, 2019. 30(10).
39. Chen, Y.Y., et al., Injectable and thermoresponsive self-assembled nanocomposite hydrogel for long-term anticancer drug delivery. Langmuir, 2013. 29(11): p. 3721-9.
40. Chen, Y.Y., et al., Injectable and Thermoresponsive Self-Assembled Nanocomposite Hydrogel for Long-Term Anticancer Drug Delivery. Langmuir, 2013. 29(11): p. 3721-3729.
41. Goa, K.L. and P. Benfield, Hyaluronic-Acid - a Review of Its Pharmacology and Use as a Surgical Aid in Ophthalmology, and Its Therapeutic Potential in Joint Disease and Wound-Healing. Drugs, 1994. 47(3): p. 536-566.
42. Gomes, J.A.P., et al., Sodium hyaluronate (hyaluronic acid) promotes migration of human corneal epithelial cells in vitro. British Journal of Ophthalmology, 2004. 88(6): p. 821-825.
43. Sturmer, J., A. Mermoud, and G.S. Megevand, Trabeculectomy with Mitomycin C Supplemented with Cross-Linking Hyaluronic Acid: A Pilot Study. Klinische Monatsblatter Fur Augenheilkunde, 2010. 227(4): p. 273-276.
44. Hussain, Z., et al., Hyaluronic Acid-Based Biomaterials: A Versatile and Smart Approach to Tissue Regeneration and Treating Traumatic, Surgical, and Chronic Wounds. Polymer Reviews, 2017. 57(4): p. 594-630.
45. Jin, Y.J., et al., Injectable anti-inflammatory hyaluronic acid hydrogel for osteoarthritic cartilage repair. Materials Science & Engineering C-Materials for Biological Applications, 2020. 115.
46. https://www.researchgate.net/figure/Fig-1-The-chemical-structure-of-hyaluronic-acid-HA_fig1_259445695.
47. Kaehn, K., Polihexanide: A Safe and Highly Effective Biocide. Skin Pharmacology and Physiology, 2010. 23: p. 7-16.
48. Zhang, Y.M., J.M. Jiang, and Y.M. Chen, Synthesis and antimicrobial activity of polymeric guanidine and biguanidine salts. Polymer, 1999. 40(22): p. 6189-6198.
49. Eberlein, T. and O. Assadian, Clinical Use of Polihexanide on Acute and Chronic Wounds for Antisepsis and Decontamination. Skin Pharmacology and Physiology, 2010. 23: p. 45-51.
50. https://pubchem.ncbi.nlm.nih.gov/compound/Polihexanide.
51. Carpenter, G. and S. Cohen, Epidermal Growth-Factor. Journal of Biological Chemistry, 1990. 265(14): p. 7709-7712.
52. Heck, D.E., et al., Epidermal Growth-Factor Suppresses Nitric-Oxide and Hydrogen-Peroxide Production by Keratinocytes - Potential Role for Nitric-Oxide in the Regulation of Wound-Healing. Journal of Biological Chemistry, 1992. 267(30): p. 21277-21280.
53. 高點醫護網, 對絲裂原活化蛋白激酶重要生理意義認識.
54. Johnson, G.L. and R. Lapadat, Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science, 2002. 298(5600): p. 1911-1912.
55. Riess, J.G., Oxygen carriers ("blood substitutes") - Raison d′Etre, chemistry, and some physiology. Chemical Reviews, 2001. 101(9): p. 2797-2919.
56. Riess, J.G., Understanding the fundamentals of perfluorocarbons and perfluorocarbon emulsions relevant to in vivo oxygen delivery. Artificial Cells Blood Substitutes and Biotechnology, 2005. 33(1): p. 47-63.
57. Desgranges, S., et al., Micron-sized PFOB liquid core droplets stabilized with tailored-made perfluorinated surfactants as a new class of endovascular sono-sensitizers for focused ultrasound thermotherapy. Journal of Materials Chemistry B, 2019. 7(6): p. 927-939.
58. Arab, A., et al., Oxygenated perfluorochemicals improve cell survival during reoxygenation by pacifying mitochondrial activity. Journal of Pharmacology and Experimental Therapeutics, 2008. 325(2): p. 417-424.
59. Jagers, J., A. Wrobeln, and K.B. Ferenz, Perfluorocarbon-based oxygen carriers: from physics to physiology. Pflugers Archiv-European Journal of Physiology, 2021. 473(2): p. 139-150.
60. Johnson, J.L.H., et al., In Vitro Comparison of Dodecafluoropentane (DDFP), Perfluorodecalin (PFD), and Perfluoroctylbromide (PFOB) in the Facilitation of Oxygen Exchange. Artificial Cells Blood Substitutes and Biotechnology, 2009. 37(4): p. 156-162.
61. Muller, G., T. Koburger, and A. Kramer, Interaction of polyhexamethylene biguanide hydrochloride (PHMB) with phosphatidylcholine containing o/w emulsion and consequences for microbicidal efficacy and cytotoxicity. Chemico-Biological Interactions, 2013. 201(1-3): p. 58-64.
62. Wagner, A.O., et al., Medium Preparation for the Cultivation of Microorganisms under Strictly Anaerobic/Anoxic Conditions. Jove-Journal of Visualized Experiments, 2019(150).
63. Dietrich, N., et al., A new direct technique for visualizing and measuring gas-liquid mass transfer around bubbles moving in a straight millimetric square channel. Chemical Engineering Science, 2013. 100: p. 172-182.
64. Paul, M., et al., Reaction Systems for Bubbly Flows. European Journal of Inorganic Chemistry, 2018(20-21): p. 2101-2124.
65. Litwiniuk, M., A. Krejner, and T. Grzela, Hyaluronic Acid in Inflammation and Tissue Regeneration. Wounds-a Compendium of Clinical Research and Practice, 2016. 28(3): p. 78-88.

指導教授

李宇翔(Yu-Hsiang Lee)

審核日期

2021-10-27

推文