受創傷時，如無給予適當的保護及治療，傷口則容易造成感染，並導致傷口發炎化膿，而在更換敷料的同時可能對患部造成二次傷害，我們為了減輕敷料在更換時對傷口所造成的疼痛感與新生組織被剝除的風險，將選用具有抗沾黏特性的材料作為敷料基材進行混紡開發。雖然市面上有許多不同種類的敷料，但仍有缺點的存在，如：不沾黏紗布雖使用容易且價格低，但於更換的過程中會產生些許沾黏及會造成傷口乾燥，增加更換時的疼痛感。本研究將利用靜電紡絲的多孔隙結構以及材料的組成特性將傳統敷料的缺點加以改進，並以天然高分子蠶絲蛋白為基底，加入人工高分子聚乙烯醇(Poly(vinyl alcohol), PVA)、聚乙二醇(Polyethylene glycol, PEG)、聚環氧乙烷(Polyethylene oxide, PEO)予以共混，再利用靜電紡絲技術將其共混液製作成電紡纖維薄膜，並評估其對於傷口沾黏之程度。研究包含物化特性、孔徑及孔洞大小量測、細胞毒性測試、抗發炎能力測試、體外抗貼附成分釋放、體外降解測試以及創傷動物模式之傷口沾黏等試驗與評估。本研究結果顯示，於研究中所製作出的電紡薄膜皆具有良好的生物相容性、無引發發炎之副作用，且不具有細胞毒性，其中在纖維母細胞抗貼附測試中PVA/SFP(5/5)電紡薄膜具有較好的抗貼附能力，並且具有生物可降解性。於體內試驗方面PVA/SFP(5/5)不僅能促進傷口癒合，並具有最佳抗沾黏的能力。結果顯示，PVA/SFP(5/5)具有有效降低組織沾黏的形成。

Wound tissue adhesion causes secondary damage to the wound when changing the wound dressing, while commercial anti-adhesion wound dressing cannot completely prevent wound tissue adhesions. This study was designed to evaluate the silk fibroin protein-based materials for using as anti-adhesion dressings on nonwoven mats. We use the electrospun of silk fibroin protein (SFP)/polyvinyl alcohol (PVA), silk fibroin protein (SFP)/polyethylene glycol (PEG), silk fibroin protein (SFP)/polyethylene oxide (PEO) blended solution to fabricate a silk fibroin protein-based nonwoven mat as a wound anti-adhesion dressing. Their materials characterization and mechanical properties were evaluated by SEM surface characterization, FT-IR, biodegradation rate, and so forth. Biocompatibility was observed by in vitro experiments of cell proliferation using the MTT assay in fibroblast model. The result shows that PVA/SFP (5/5) membrane has good biocompatibility, non-cytotoxicity and anti-adhesion ability. In vivo, the fabricated PVA/SFP and SFP membranes was covered on an wound area of a mouse model and changed the membranes five days a time to compare their tissue adhesion extent with that of the control group. The mice was sacrificed after fully wound closure. The PVA/SFP (5/5) membrane significantly reduced the degree of adhesion and showed to be a potential candidate for the anti-adhesion application.

1. 林瑞萍, 傷口敷料之介紹與護理應用. 台北榮總傷造口護理師, 2016.
2. 于博芮, et al., 最新傷口護理學, ed. 于博芮. 2012, 華杏機構.
3. Sekine, T., et al., A novel method for preparing oil-in-water-in-oil type multiple emulsions using organophilic montmorillonite clay mineral. Journal of Surfactants and Detergents, 1999. 2(3 July 1999): p. 309-315.
4. Rafique, A., et al., Chitosan functionalized poly(vinyl alcohol) for prospects biomedical and industrial applications: A review. Int J Biol Macromol, 2016. 87: p. 141-54.
5. Lih, E., et al., Polymers for cell/tissue anti-adhesion. Progress in Polymer Science, 2015. 44: p. 28-61.
6. Vepari, C. and D.L. Kaplan, Silk as a Biomaterial. Progress in polymer science, 2007. 32(8-9): p. 991-1007.
7. 洪詩涵, 多醣類基材之敷料研究. 國立陽明大學醫學工程研究所碩士論文, 2007.
8. Falanga, V., Wound healing and its impairment in the diabetic foot. The Lancet, 2005. 366(9498): p. 1736-1743.
9. Barrientos, S., et al., Growth factors and cytokines in wound healing. Wound Repair Regen, 2008. 16(5): p. 585-601.
10. Witte, M.B. and A. Barbul, General principles of wound healing. Surg Clin North Am, 1997. 77(3): p. 509-28.
11. Singer, A.J. and R.A. Clark, Cutaneous wound healing. The New England Journal of Medicine, 1999. 341(10): p. 738-746.
12. Martin, P., Wound Healing--Aiming for Perfect Skin Regeneration. Science, 1997. 276(5309): p. 75-81.
13. Hubner, G., et al., Differential regulation of pro-inflammatory cytokines during wound healing in normal and glucocorticoid-treated mice. Cytokine, 1996. 8(7): p. 548-56.
14. Chang, H.Y., et al., Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds. PLoS Biol, 2004. 2(2): p. E7.
15. Midwood, K.S., L.V. Williams, and J.E. Schwarzbauer, Tissue repair and the dynamics of the extracellular matrix. The International Journal of Biochemistry & Cell Biology, 2004. 36(6): p. 1031-1037.
16. Ahmed, N., Advanced glycation endproducts--role in pathology of diabetic complications. Diabetes Res Clin Pract, 2005. 67(1): p. 3-21.
17. Conway, K.P. and K.G. Harding, CHAPTER 15 - WOUND HEALING IN THE DIABETIC FOOT A2 - Bowker, John H, in Levin and O'Neal's The Diabetic Foot (Seventh Edition), M.A. Pfeifer, Editor. 2008, Mosby: Philadelphia. p. 319-327.
18. 靳燕芬, 傷口換藥疼痛護理. 護理雜誌, 2007. 54(3): p. 87-91.
19. 蘇紹宇, 用於傷口敷料之藻酸鹽/幾丁聚醣組合物的製備與性質探討. 嘉南藥理科技大學藥物科技研究所碩士論文, 2010.
20. 徐翊庭 and 翁清松, 醫療用傷口照護材之全球產業規模及競爭力分析. 先進工程學刊, 2011. 6(3): p. 193-199.
21. Kammerlander, G. and T. Eberlein, Nurses' views about pain and trauma at dressing changes: a central European perspective. J Wound Care, 2002. 11(2): p. 76-79.
22. Yang, X., et al., Cytotoxicity and wound healing properties of PVA/ws-chitosan/glycerol hydrogels made by irradiation followed by freeze–thawing. Radiation Physics and Chemistry, 2010. 79(5): p. 606-611.
23. Nacer Khodja, A., et al., Evaluation of healing activity of PVA/chitosan hydrogels on deep second degree burn: pharmacological and toxicological tests. Burns, 2013. 39(1): p. 98-104.
24. Bai, M.-Y., et al., The effect of active ingredient-containing chitosan/polycaprolactone nonwoven mat on wound healing: In vitro and in vivo studies. Journal of Biomedical Materials Research Part A, 2014. 102(7): p. 2324-2333.
25. Wang, B.-l., et al., Chitosan/poly (vinyl pyrollidone) coatings improve the antibacterial properties of poly(ethylene terephthalate). Applied Surface Science, 2012. 258(20): p. 7801-7808.
26. Jayakumar, R., et al., Biomaterials based on chitin and chitosan in wound dressing applications. Biotechnol Adv, 2011. 29(3): p. 322-337.
27. Sarkar, S.D., et al., Chitosan–collagen scaffolds with nano/microfibrous architecture for skin tissue engineering. Journal of Biomedical Materials Research Part A, 2013. 101(12): p. 3482-3492.
28. Lee, K.Y. and D.J. Mooney, Alginate: properties and biomedical applications. Prog Polym Sci, 2012. 37(1): p. 106-126.
29. Qiu, Y., et al., Bacterial cellulose and bacterial cellulose-vaccarin membranes for wound healing. Mater Sci Eng C Mater Biol Appl, 2016. 59: p. 303-309.
30. Czaja, W., et al., Microbial cellulose—the natural power to heal wounds. Biomaterials, 2006. 27(2): p. 145-151.
31. 陳克紹, et al., 感溫性水膠/多孔性gelatin雙層組織工程支架之製備及細胞貼附研究. 9th Conf. Biochemical Engineering and Sym. Agri. Bioindustry, 2004: p. 88.
32. Boateng, J.S., et al., Wound healing dressings and drug delivery systems: a review. J Pharm Sci, 2008. 97(8): p. 2892-2923.
33. Bhattarai, S.R., et al., Novel biodegradable electrospun membrane: scaffold for tissue engineering. Biomaterials, 2004. 25(13): p. 2595-2602.
34. Khil, M.S., et al., Electrospun nanofibrous polyurethane membrane as wound dressing. J Biomed Mater Res B Appl Biomater, 2003. 67(2): p. 675-679.
35. Chen, J.-P., G.-Y. Chang, and J.-K. Chen, Electrospun collagen/chitosan nanofibrous membrane as wound dressing. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2008. 313-314: p. 183-188.
36. 張惠甄, et al., 比較新型敷料與傳統敷料對第二, 三級壓瘡傷口 癒合的成效. 2012.
37. Yang, D.-J., et al., Tissue anti-adhesion potential of biodegradable PELA electrospun membranes. Acta Biomaterialia, 2009. 5(7): p. 2467-2474.
38. 蔡婷芳 and 戴玉慈, 傷口照護與敷料運用. 榮總護理, 2007. 24(1): p. 69-75.
39. Lee, J.H., et al., Tissue anti-adhesion potential of ibuprofen-loaded PLLA–PEG diblock copolymer films. Biomaterials, 2005. 26(6): p. 671-678.
40. Niwa, D., et al., Application of nanosheets as an anti‐adhesion barrier in partial hepatectomy. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2013. 101(7): p. 1251-1258.
41. Chang, J.-J., et al., Electrospun anti-adhesion barrier made of chitosan alginate for reducing peritoneal adhesions. Carbohydrate Polymers, 2012. 88(4): p. 1304-1312.
42. Ko, J.E., et al., Nanofiber mats composed of a chitosan-poly(d,l-lactic-co-glycolic acid)-poly(ethylene oxide) blend as a postoperative anti-adhesion agent. J Biomed Mater Res B Appl Biomater, 2016.
43. Weis, C., et al., Poly(vinyl alcohol) membranes for adhesion prevention. J Biomed Mater Res B Appl Biomater, 2004. 70(2): p. 191-202.
44. Bae, S.H., et al., Evaluation of the potential anti‐adhesion effect of the PVA/Gelatin membrane. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2014. 102(4): p. 840-849.
45. Xia, Q., et al., A Biodegradable Trilayered Barrier Membrane Composed of Sponge and Electrospun Layers: Hemostasis and Antiadhesion. Biomacromolecules, 2015. 16(9): p. 3083-3092.
46. Wang, H., et al., Multiple targeted drugs carrying biodegradable membrane barrier: anti-adhesion, hemostasis, and anti-infection. Biomacromolecules, 2013. 14(4): p. 954-961.
47. Yang, B., et al., Preventing postoperative abdominal adhesions in a rat model with PEG-PCL-PEG hydrogel. Int J Nanomedicine, 2012. 7: p. 547-557.
48. Zhu, L. and Y.Q. Zhang, Postoperative anti-adhesion ability of a novel carboxymethyl chitosan from silkworm pupa in a rat cecal abrasion model. Mater Sci Eng C Mater Biol Appl, 2016. 61: p. 387-395.
49. Tsujimoto, H., et al., The anti-adhesive effect of thermally cross-linked gelatin film and its influence on the intestinal anastomosis in canine models. J Biomed Mater Res B Appl Biomater, 2013. 101(1): p. 99-109.
50. 蔡俊宏, 利用靜電紡絲製備嗜鹽菌聚羥基丁酯戊酯共聚物(PHBV)中空纖維薄膜. 大同大學生物工程學所碩士論文 2013.
51. Li, W.J., et al., Electrospun nanofibrous structure: a novel scaffold for tissue engineering. Journal of biomedical materials research, 2002. 60(4): p. 613-621.
52. 蔡晟豪, 靜電紡絲PVDF混摻F127複合膜作為生醫基材之探討. 國立台灣科技大學高分子工程研究所碩士學位論文, 2009.
53. Brown, T.D., P.D. Dalton, and D.W. Hutmacher, Melt electrospinning today: An opportune time for an emerging polymer process. Progress in Polymer Science, 2016. 56: p. 116-166.
54. Zong, X., et al., Structure and process relationship of electrospun bioabsorbable nanofiber membranes. Polymer, 2002. 43(16): p. 4403-4412.
55. Lee, Y.J. and W.S. Lyoo, Preparation and Characterization of High-Molecular-Weight Atactic Poly(vinyl alcohol)/Sodium Alginate/Silver Nanocomposite by Electrospinning. Journal of Polymer Science Part B-Polymer Physics, 2009. 47(19): p. 1916-1926.
56. Chen, W. and W. Weng, Ultrafine lauric–myristic acid eutectic/poly (meta-phenylene isophthalamide) form-stable phase change fibers for thermal energy storage by electrospinning. Applied Energy, 2016. 173: p. 168-176.
57. Larsen, G. and M. Skotak, Co-solvent mediated fiber diameter and fiber morphology control in electrospinning of sol–gel formulations. Journal of Non-Crystalline Solids, 2008. 354(52–54): p. 5547-5554.
58. von Reitzenstein, N.H., et al., Morphology, structure, and properties of metal oxide/polymer nanocomposite electrospun mats. Journal of Applied Polymer Science, 2016. 133(33).
59. Moheman, A., M.S. Alam, and A. Mohammad, Recent trends in electrospinning of polymer nanofibers and their applications in ultra thin layer chromatography. Advances in Colloid and Interface Science, 2016. 229: p. 1-24.
60. Lu, P. and B. Ding, Applications of electrospun fibers. Recent patents on nanotechnology, 2008. 2(3): p. 169-182.
61. Torres-Giner, S., R. Pérez-Masiá, and J.M. Lagaron, A review on electrospun polymer nanostructures as advanced bioactive platforms. Polymer Engineering & Science, 2016. 56(5): p. 500-527.
62. 陳麗妃, 微脂粒包覆蠶絲蛋白之製備與功能性評估. 樹德科技大學應用設計研究所碩士論文, 2007.
63. 毛文霖, 蠶絲絲膠蛋白之純化與應用及其奈米乳化之製備. 大葉大學環境工程學系碩士班碩士論文, 2011.
64. Kim, U.J., et al., Structure and properties of silk hydrogels. Biomacromolecules, 2004. 5(3): p. 786-792.
65. Yoo, M.K., et al., Preparation of semi-interpenetrating polymer networks composed of silk fibroin and poloxamer macromer. Int J Biol Macromol, 2004. 34(4): p. 263-270.
66. Mori, H. and M. Tsukada, New silk protein: modification of silk protein by gene engineering for production of biomaterials. J Biotechnol, 2000. 74(2): p. 95-103.
67. Horan, R.L., et al., In vitro degradation of silk fibroin. Biomaterials, 2005. 26(17): p. 3385-3393.
68. Mauney, J.R., et al., Engineering adipose-like tissue in vitro and in vivo utilizing human bone marrow and adipose-derived mesenchymal stem cells with silk fibroin 3D scaffolds. Biomaterials, 2007. 28(35): p. 5280-5290.
69. Liu, T.-L., et al., Cytocompatibility of Regenerated Silk Fibroin Film: A Medical Biomaterial Applicable to Wound Healing. Journal of Zhejiang University Science, 2010. 11B(1): p. 10-16.
70. Vasconcelos, A., A.C. Gomes, and A. Cavaco-Paulo, Novel silk fibroin/elastin wound dressings. Acta Biomater, 2012. 8(8): p. 3049-3060.
71. Liang, J., et al., Molecular-Level Dispersion of Graphene into Poly(vinyl alcohol) and Effective Reinforcement of their Nanocomposites. Advanced Functional Materials, 2009. 19(14): p. 2297-2302.
72. Ino, J.M., et al., Plasma functionalization of poly(vinyl alcohol) hydrogel for cell adhesion enhancement. Biomatter, 2013. 3(4).
73. Cutiongco, M.F.A., et al., In vitro and ex vivo hemocompatibility of off-the-shelf modified poly(vinyl alcohol) vascular grafts. Acta Biomaterialia, 2015. 25: p. 97-108.
74. Palacio, J., N.A. Agudelo, and B.L. Lopez, PEGylation of PLA nanoparticles to improve mucus-penetration and colloidal stability for oral delivery systems. Current Opinion in Chemical Engineering, 2016. 11: p. 14-19.
75. Le, T.T.D., et al., Evaluation of anti-HER2 scFv-conjugated PLGA–PEG nanoparticles on 3D tumor spheroids of BT474 and HCT116 cancer cells. Advances in Natural Sciences: Nanoscience and Nanotechnology, 2016. 7(2): p. 025004.
76. Fasehee, H., et al., The inhibitory effect of disulfiram encapsulated PLGA NPs on tumor growth: Different administration routes. Mater Sci Eng C Mater Biol Appl, 2016. 63: p. 587-595.
77. Xin, H., et al., Anti-glioblastoma efficacy and safety of paclitaxel-loading Angiopep-conjugated dual targeting PEG-PCL nanoparticles. Biomaterials, 2012. 33(32): p. 8167-8176.
78. 李玉寶, in 奈米生醫材料. 2006: 五南圖書.
79. Shi, H., et al., Effect of polyethylene glycol on the antibacterial properties of polyurethane/carbon nanotube electrospun nanofibers. RSC Advances, 2016. 6(23): p. 19238-19244.
80. Ali, I.H., I.A. Khalil, and I.M. El-Sherbiny, Single-Dose Electrospun Nanoparticles-in-Nanofibers Wound Dressings with Enhanced Epithelialization, Collagen Deposition, and Granulation Properties. ACS Appl Mater Interfaces, 2016. 8(23): p. 14453-14469.
81. Rieger, K.A., N.P. Birch, and J.D. Schiffman, Electrospinning chitosan/poly(ethylene oxide) solutions with essential oils: Correlating solution rheology to nanofiber formation. Carbohydr Polym, 2016. 139: p. 131-138.
82. Dubey, P., et al., Silver-nanoparticle-incorporated composite nanofibers for potential wound-dressing applications. Journal of Applied Polymer Science, 2015. 132(35).
83. 楊智元, 以靜電紡織製備藥物釋放纖維薄膜之研究. 崑山科技大學綠色材料研究所碩士論文 2010.
84. Haryanto, et al., Poly(ethylene glycol) dicarboxylate/poly(ethylene oxide) hydrogel film co-crosslinked by electron beam irradiation as an anti-adhesion barrier. Materials Science and Engineering: C, 2015. 46: p. 195-201.
85. Peng, L., B. Wang, and P. Ren, Reduction of MTT by flavonoids in the absence of cells. Colloids and Surfaces B: Biointerfaces, 2005. 45(2): p. 108-111.
86. Green, S.J., et al., Cellular mechanisms of nonspecific immunity to intracellular infection: Cytokine-induced synthesis of toxic nitrogen oxides from l-arginine by macrophages and hepatocytes. Immunology Letters, 1990. 25(1): p. 15-19.
87. Schmalzl, M., et al., VizieR Online Data Catalog: CB17 dust emission (100-500um), N (H) and T maps (Schmalzl+, 2014). VizieR Online Data Catalog, 2014. 356: p. 90007.
88. Smalley, I., K. O'hara-Dhand, and S. McLaren. The nature and formation of aeolian mineral dust material. in EGU General Assembly Conference Abstracts. 2013.
89. Williams, C., Who are you calling simple? New Scientist, 2011. 211(2821): p. 38-41.
90. Schulz, H.N. and B.B. Jrgensen, Big Bacteria. Annual Review of Microbiology, 2001. 55(1): p. 105-137.
91. Sampaio, S., et al., Enzymatic grafting of chitosan onto Bombyx mori silk fibroin: kinetic and IR vibrational studies. J Biotechnol, 2005. 116(1): p. 21-33.
92. Ling, S., et al., Synchrotron FTIR microspectroscopy of single natural silk fibers. Biomacromolecules, 2011. 12(9): p. 3344-3349.
93. Reis, E.F.d., et al., Synthesis and characterization of poly (vinyl alcohol) hydrogels and hybrids for rMPB70 protein adsorption. Materials Research, 2006. 9(2): p. 185-191.
94. Mohamed Saat, A. and M.R. Johan, The Surface Structure and Thermal Properties of Novel Polymer Composite Films Based on Partially Phosphorylated Poly (vinyl alcohol) with Aluminum Phosphate. The Scientific World Journal, 2014. 2014.
95. Wang, Y., I. Ramos, and J.J. Santiago-Aviles, Diversity of Nanofibers from Electrospinning: from Graphitic Carbons to Ternary Oxides. 2010: INTECH Open Access Publisher.
96. Ranjbar-Mohammadi, M. and S.H. Bahrami, Development of nanofibrous scaffolds containing gum tragacanth/poly (epsilon-caprolactone) for application as skin scaffolds. Mater Sci Eng C Mater Biol Appl, 2015. 48: p. 71-79.
97. Schnüriger, B., et al., Prevention of postoperative peritoneal adhesions: a review of the literature. The American Journal of Surgery, 2011. 201(1): p. 111-121.
98. 童寶玲, 惱人的手術後沾黏! 健康世界, 2013. 335: p. 56-58.
99. Kobayashi, M., J. Toguchida, and M. Oka, Development of the shields for tendon injury repair using polyvinyl alcohol—hydrogel (PVA‐H). Journal of biomedical materials research, 2001. 58(4): p. 344-351.
100. Haney, A. and E. Doty, A barrier composed of chemically cross-linked hyaluronic acid (Incert) reduces postoperative adhesion formation. Fertility and sterility, 1998. 70(1): p. 145-151.
101. Yamaoka, T., et al., Novel adhesion prevention membrane based on a bioresorbable copoly (ester‐ether) comprised of poly‐L‐lactide and Pluronic®: In vitro and in vivo evaluations. Journal of biomedical materials research, 2001. 54(4): p. 470-479.
102. Rodgers, K., et al., Evaluation of polyethylene glycol/polylactic acid films in the prevention of adhesions in the rabbit adhesion formation and reformation sidewall models. Fertility and sterility, 1998. 69(3): p. 403-408.
103. Sahbaz, A., et al., Bromelain: a natural proteolytic for intra-abdominal adhesion prevention. Int J Surg, 2015. 14: p. 7-11.
104. Li, L., et al., Biodegradable and injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for postoperative adhesion prevention. Biomaterials, 2014. 35(12): p. 3903-3917.