針對糖尿病足潰瘍設計並製作一種抗菌且能促進傷口癒合的甲殼素複合式水凝膠之研究

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洪翊玲(Yi-Ling Hong) 查詢紙本館藏

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生物醫學工程研究所

論文名稱

針對糖尿病足潰瘍設計並製作一種抗菌且能促進傷口癒合的甲殼素複合式水凝膠之研究
(Design and Fabrication of an Antimicrobial-Wound Healing-Enhanced Chitosan Complex Hydrogel for Diabetic Foot Ulcer Treatment.)

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摘要(中)

糖尿病中最常見的是第二型糖尿病，屬於一種慢性疾病，它占糖尿病患者總
人口數的 90-95%。通常會有較長的潛伏期，第二型糖尿病患者主要原因是
自身的血液循環較差、新陳代謝異常和炎症時期較長等各種原因，導致傷口
癒合緩慢，嚴重者會影響到患者的生活品質或導致死亡。而本研究中開發一
種包含銀離子和包裹表皮生長因子 (EGF)之奈米粒子的殼聚醣水膠
(CPCHG)，此水膠可以提供抗菌能力也因表皮生長因子的存在幫助傷口癒
合。本研究目前先以牛血清白蛋白(BSA)作為模擬蛋白代替表皮生長因子。
奈米載體的製備方式以聚陰離子三聚磷酸鹽作為交聯劑與殼聚醣進行交聯
製備包覆 BSA 的殼聚醣奈米載體(CTBNPs)。經過 DLS 分析，CTBNPs 的
粒徑大小與表面電荷分別為 265±26 nm 和 30.02±1.42 mV；CTBNPs 在 48
小時的釋放率為 89% 但在 CPCHG 的 BSA 釋放約為 70%。在銀離子釋放
分析中，銀離子在 48 小時中 4°C 和 37°C 的釋放量為 5.11 mg/L 及 6.53
mg/L。此外，在細菌抑制中，使用銀離子濃度為 24 mM 時，對於金黃色葡
萄球菌有顯著抑制的效果；在細胞毒性試驗中，細胞的存活率也可達到 90%。
生長曲線試驗中，將模擬蛋白(BSA)更改成表皮生長因子(EGF)製成的殼聚
醣水膠(CPEHG)。使用不同濃度表皮生長因子(EGF)去測試 NIH-3T3，結果
表明當 EGF 的濃度來到了 60 μg/mL 可讓細胞生長且不受銀離子的影響。
選定水膠(CPEHG)最終配方為 60μg/ mL EGF 和 24 mM 銀離子濃度。在動II
物實驗中，我們使用 Sprague Dawley（SD）大鼠並注射鏈脲佐菌素觀察 2 周
確定為糖尿病大鼠後在大鼠背上製造傷口並且使用敷料治療觀察傷口癒合
情況。結果表明在各組實驗組中 CPEHG 水膠的傷口癒合速度最快、炎症細
胞較少和有較多的膠原蛋白沉積，未來可用於治療糖尿病足傷口敷料。

摘要(英)

Type II diabetes mellitus (T2DM) is the most common form of diabetes,
accounting for 90-95% of diabetics, and is a chronic disease often preceded by a
long asymptomatic period. Most of T2 diabetics suffer with delay wound healing
resulted from poor blood circulation, prolonged inflammation and lack of growth
signal due to disordered metabolism, and it may severely affect patients’ life
quality and even cause death. To overcome the aforementioned issues, a synthetic
chitosan-based hydrogel containing silver ions and growth factor-entrapped
nanoparticles that may provide both antibacterial and would healing-enhanced
functionalities were developed in this study. As being the preliminary
investigation, the bovine serum albumin (BSA) was employed as the model
protein molecule to substitute the practical growth factor protein in this study.
Furthermore, the BSA-encapsulated chitosan nanoparticles were fabricated by
using the polyanion tripolyphosphate as the coacervation crosslink agent.
Through the DLS analysis, the size and surface charge of the BSA-loaded
nanoparticles(CTBNPs) were 265 ± 26 nm and 30.02 ± 1.42 mV, respectively.
The encapsulation efficiency and the loading rate of the BSA in the nanoparticles
were 74± 8.62% and 1.23 ± 0.55%, respectively. Also, the release rate of BSA
from the nanoparticles was 89% within 4 h, while that from the synthetic hydrogel
was about 70% within the same time course. The nanoparticles were successful
insides the chitosan hydrogel. From hydrogel property test, BSA releases were
70% . When the silver ions released in 48 hours, the 4 and 37 degrees release were
5.11 and 6.53 mg/L. Moreover, the bacterial inhibit study, when used 24 mM
silver ions concentration the bacterial inhibit was significant. The hydrogel
toxicity for the cell. In the cell study, we used 24 mM silver ions concentration
the cell viability came to 90 %. In the growth curve study, we decide used
epidermal growth factor with different concentration. However, when EGF came
to 60 μg/mL cell weren′t affected by silver ions. We decided that the final
formulation of the hydrogel was 60 μg/mL EGF and 24 mM silver ion
concentration.In animal experiments, We used Sprague Dawley (SD) rats and
injected with streptozotocin to observe wound healing on rats′ backs after 2 weeks
of diagnosis as diabetic rats and to observe wound healing using dressings. The
results showed that the wound healing rate of CPEHG water gel in each group
was accelerated, inflammatory cell implantation and complication of collagen
deposition, which could be used to treat diabetic foot wound dressing in the future

關鍵字(中)

★ 第二型糖尿病
★ 糖尿病足潰瘍
★ 殼聚醣
★ 銀離子
★ 表皮生長因子
★ 傷口癒合

關鍵字(英)

★ Type 2 diabetes mellitus
★ Diabetic foot ulcer
★ Chitosan
★ Silver ions
★ Epidermal growth factor
★ Wound heling

論文目次

第一章緒論……...……..……………..…….………………………1
1.1 研究背景………………..………………..…...………………1
1.2 研究動機與目的……………..………………..………...……2
第二章文獻回顧………………………..…………………..…...…3
2.1 糖尿病介紹………………..……….….……………….……. 3
2.2 糖尿病主要併發症………………......….…...………..…...…5
2.3 糖尿病足潰瘍(Diabetic foot ulcers)……….....………. …..…7
2.4 糖尿病足潰瘍周邊醫療資源…………......…………..…….. 9
2.5 足部潰瘍等級……………………....……………………...…9
2.6 治療糖尿病足潰瘍方式…………....…………………….…10
2.6.1 足部完全接觸石膏(Total contact casts, TCCs)....…… 10
2.6.2 清創(Debridement)………………….…………………11
2.6.7 酶清創(Enzymatic Debridement)…………….………. 11
2.6.8 自溶性清創(Autolytic Debridement)…….…………....11
2.6.9 生物清創(Biologic Debridement)………………….…. 11
2.6.10 外科手術清創(Surgical Debridement)…….……...…12
2.6.7抗生素治療…………………….….…. ………...…......12
2.6.8 高壓氧治療(Hyperbaric oxygen therapy)…………..…12VI
2.6.9 負壓傷口治療 (Negative Pressure Wound Therapy,
NPWT)..........................................................................................12
2.6.10 敷料治療………………………………………......…13
2.7 傷口癒合機制…………………………………………….…20
2.8 糖尿病足潰瘍常見細菌……………………………….....…22
第三章實驗部分………………………………………………….24
3.1 實驗藥品、材料、儀器設備……………..…………...………24
3.1.1藥品..……………………………………….…………. 24
3.1.2材料……..………………………………………….…. 25
3.1.3 儀器………..…………………………………………..26
3.2 檢量線……………….........…………………………………27
3.3 實驗整體流程………...……..……………..……………..…28
3.4 製備包覆模型蛋白 BSA 奈米載體……………………….. 28
3.5CTBNPs 物理特性分析…………………….…………....…29
3.6 製備銀離子及 CTBNPs 在殼聚醣水凝膠中(CPCHG)…..... 31
3.7 掃描式電子顯微鏡(SEM) 拍攝………………………….... 32
3.8 殼聚醣水膠釋放牛血清白蛋白(BSA)………………..…….32
3.9殼聚醣水膠釋放銀離子………………………………..…... 33
3.10抗菌試驗……………………………………..……………. 33VII
3.16 細胞培養…………………………...…………….……...... 36
3.17CPCHG 中的銀對 NIH-3T3 細胞毒性測試……..…………36
3.18CPCHG 對 NIH-3T3 生長試驗………………….…………37
3.14 製備表皮生長因子奈米載體及銀在殼聚醣水凝膠….......38
3.15CPCHG 對 NIH-3T3 生長試驗……….................................39
第四章結果與討論……………………………………………….43
4.1CTBNPs 物性及化性分析……………..…………………...43
4.2 CTBNPs 之表面形態分析………….………………….……43
4.3 CTBNPs 內 BSA 的包覆率、負載率分析……………..…..44
4.4 BSA 包覆 CTBNPs 之釋放試驗……..…..………..………. 44
4.5 CPCHG之表面分析…………………….....…... ………...…45
4.6CPCHG 釋放試驗……………………..……………………. 46
4.6.1 模擬蛋白(BSA)釋放………………………………..…46
4.6.2銀離子釋放………………………………….. ………..47
4.7CPCHG 中的銀離子對金黃色葡萄球菌抑菌試驗……..…. 48
4.7.1初步抑制圈試驗………………………………..…. ……...48
4.7.2抑菌試驗……………………..…………………………… 49
4.8CPCHG 細胞實驗分析…………………..…………………..51
4.8.1CPCHG 對小鼠胚胎成纖維細胞毒性試驗.. …………51VIII
4.8.2CPCHG 對小鼠胚胎成纖維細胞生長曲線試驗.......…52
4.9 CTENPs 內表皮生長因子包覆率、負載率分析…………...53
4.10CPEHG 體外細胞實驗分析……………………..…………53
4.11 機械性質試驗…………………………………. ………..…55
4.11.1CPCHG 和 CPEHG 延伸率及抗拉強度…………….. 55
4.11.2CPCHG 和 CPEHG 澎潤率及含水率….……………. 56
4.12動物試驗……………………………………..……………. 57
第五章結論……………………………….……………………….61
第六章未來展望………………………………………………….62
參考文獻…………………………………………………………….63

參考文獻

1. Holman, N., Young, B. & Gadsby, R. Current prevalence of type 1 and type
2 diabetes in adults and children in the UK. Diabetic Medicine. 2015; 32,
1119–1120.
2. World Health Organization. DEFINITION AND DIAGNOSIS OF
DIABETES MELLITUS AND INTERMEDIATE HYPERGLYCEMIA.
NLM classification: WK 810.
3. Haileab Fekadu WoldeEmail, Asrat Atsedeweyen, Addisu Jember, Tadesse
Awoke, Malede Mequanent, Adino Tesfahun Tsegaye and Shitaye Alemu.
Predictors of vascular complications among type 2 diabetes mellitus patients
at University of Gondar Referral Hospital: a retrospective follow-up study.
BMC Endocrine Disorders. 2018; 18:52.
4. Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with
diabetes. JAMA. 2005; 293: 217-228.
5. Schirr-Bonnans S, Costa N, Derumeaux-Burel H, Bos J, Lepage B, Garnault
V, Martini J, Hanaire H, Turnin MC, Molinier L. Cost of diabetic eye, renal
and foot complications: a methodological review. European Journal of
Health Economics. 2017; 18:293-312.
6. William J. Jeffcoate, Loretta Vileikyte, Edward J. Boyko, David G.
Armstrong and Andrew J.M. Boulton. Current Challenges and Opportunities
in the Prevention and Management of Diabetic Foot Ulcers. Diabetes Care.
2018; 41(4): 645-652
7. S. Kittler, C. Greulich, J. S. Gebauer, J. Diendorf, L. Treuel, L. Ruiz, J. M.
Gonzales-Calbet, M. Vallet-Regi, R. Zellner, M. Ko¨ller and M. Epple, J.
Mater. Chem., The influence of proteins on the dispersability and cellbiological activity of silver nanoparticles. Royal society of chemistry. 2010;
20, 512–518.
8. Sebastian Grade, Jo¨rg Eberhard, Anne Neumeister, Philipp Wagener,
Andreas Winkel, Meike Stiesch and Stephan Barcikowski. Serum albumin
reduces the antibacterial and cytotoxic effects of hydrogelembedded colloidal
silver nanoparticles. Royal Society of Chemistry. 2012; 2,7190-7196.
9. American Diabetes Association. Diagnosis and Classification of Diabetes
Mellitus. Diabetes Care. 2014; 37(Supplement 1): S81-S90.
10. Jamie Wood, MD, and Anne Peters, MD. The type 1 diabetes self-care manual.
American Diabetes Association. 2018; Z39.48-1992.
11. Medical News Today; Diabetes: The differences between types 1 and 2
https://www.medicalnewstoday.com/articles/7504.php64
12. 知呼你知道胰島素抵抗嗎？
https://zhuanlan.zhihu.com/p/21600119
13. 衛生福利部國民健康署,107 年死因統計分析報告, 2018; p. 1.
14. Caroline Maria Oliveira Volpe, Pedro Henrique Villar-Delfino, Paula Martins
Ferreira dos Anjos, José Augusto Nogueira-Machado. Cellular death, reactive
oxygen species (ROS) and diabetic complications. Cell Death and Disease.
2018; 9:119.
15. Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiol Rev
Suppl. 2013; 93: 137-88.
16. Mohamed Lotfy, Jennifer Adeghate, Huba Kalasz, Jaipaul Singh and Ernest
Adeghate. Chronic Complications of Diabetes Mellitus: A Mini Review.
Current Diabetes Reviews. 2017, 13, 3-10.
17. Fowler MJ. Microvascular and Macrovascular Complications of Diabetes.
Clin Diabetes. 2008; 26: 77-82.
18. Tahergorabi Z, Khazaei M. Imbalance of angiogenesis in diabetic
complications: the mechanisms. Int J Prev Med. 2012; 3: 827-38.
19. X. Chen, W. Zhou, K. Zha, G. Liu, S. Yang, S. Ye, Y. Liu, Y. Xiong and Y.
Wu, Am J Transl Res, 2016, 8, 3067–3076.
20. Richard JL, Schuldiner S. Epidemiology of diabetic foot problems. Rev Med
Interne. 2008; 29 Suppl 2: S222-S230.
21. Hoffstad O, Mitra N, Walsh J, Margolis DJ. Diabetes, lowerextremity
amputation, and death. Diabetes Care. 2015; 38:1852–1857.
22. Armstrong DG, Boulton AJM, Bus SA. Diabetic foot ulcers and their
recurrence. N Engl J Med. 2017; 376: 2367–75.
23. Jorge Berlanga-Acosta, José Fernández-Montequín, Calixto Valdés-Pérez,
William Savigne-Gutiérrez, Yssel Mendoza-Marí, Ariana García-Ojalvo,
Viviana Falcón‐Cama, Diana García del Barco-Herrera, Maday FernándezMayola, Héctor Pérez-Saad, Eulogio Pimentel-Vázquez, Aleida UrquizaRodríguez, Moshe Kulikovsky, and Gerardo Guillén-Nieto. Diabetic Foot
Ulcers and Epidermal Growth Factor: Revisiting the Local Delivery Route
for a Successful Outcome. BioMed Research International. 2017;
2017:2923759.
24. Ren Y, Gu G, Yao M, Driver VR. Role of matrix metalloproteinases in chronic
wound healing: diagnostic and therapeutic implications. Chin Med J (Engl)
2014; 127: 1572–81.65
25. Andrew J.M. Boulton, MD, DSc (Hon), FACP, FRCP,corresponding author,
David G. Armstrong, DPM, MD, PhD,corresponding author, Robert S.
Kirsner, MD, PhD, Christopher E. Attinger, MD, Lawrence A. Lavery, DPM,
MPH, Benjamin A. Lipsky, MD, FACP, FIDSA, FRCP (London), FFPM,
RCPS (Glasg), Joseph L. Mills, Sr., MD, FACS, and John S. Steinberg, DPM,
FACFAS. Diagnosis and Management of Diabetic Foot Complications.
American Diabetes Association. 2018, Oct.
26. Bortoletto MS, de Andrade SM, Matsuo T, Haddad Mdo C, González AD,
Silva AM. Risk factors for foot ulcers--a cross sectional survey from a
primary care setting in Brazil. Prim Care Diabetes. 2014; 8: 71-76.
27. Paquette D, Falanga V. Leg ulcers. Clin Geriatr Med. 2002;18(1):77–88 (vi).
28. Ragnarson Tennvall G, Apelqvist J. Health-economic consequences of
diabetic foot lesions. Clin Infect Dis. 2004; 39 Suppl 2: S132-S139.
29. Oyibo SO, Jude EB, Tarawneh I, Nguyen HC, Harkless LB, Boulton AJ. A
comparison of two diabetic foot ulcer classification systems: the Wagner and
the University of Texas wound classification systems. Diabetes Care. 2001;
24: 84-88.
30. Markowitz JS, Gutterman EM, Magee G, Margolis DJ. Risk of amputation in
patients with diabetic foot ulcers: a claimsbased study. Wound Repair Regen.
2006; 14: 11-17.
31. Markowitz JS, Gutterman EM, Magee G, Margolis DJ. Risk of amputation in
patients with diabetic foot ulcers: a claimsbased study. Wound Repair Regen.
2006; 14: 11-17.
32. Wound care center “Total Contact Casting”
https://www.woundcarecenters.org/article/wound-therapies/total-contact-casting
33. Marrigje H. Nabuurs-Franssen, MD1, Ron Sleegers2, Maya SP Huijberts,
MD, PHD1, Wiel Wijnen2, Antal P. Sanders, MD, PHD3, Geert Walenkamp,
MD, PHD4 and Nicolaas C. Schaper, MD, PHD. Total Contact Casting of the
Diabetic Foot in Daily Practice. Diabetes care. 2005; 28(2):243-247.
34. Guthrie HC, Clasper JC. Historical origins and current concepts of wound
debridement. J R Army Med Corps. 2011;157:130–132.
35. Brodsky JW. The diabetic foot, in Mann RA, Coughlin MJ [eds]: Surgery of
the Foot and Ankle, ed 7. St Louis, MO, Mosby-Year Book, 1999.
36. Lipsky BA, Hoey C. Topical antimicrobial therapy for treating chronic
wounds. Clin Infect Dis. 2009;49(10):1541–9.
37. Taylor SC, Averyhart AN, Heath CR. Postprocedural wound-healing efficacy
following removal of dermatosis papulosa nigra lesions in an African
American population: a comparison of a skin protectant ointment and a66
topical antibiotic. J Am Acad Dermatol. 2011;64(3 Suppl):S30–5.
38. Becker F, Fourgeau P, Carpentier PH, Ouchène A, Thistlethwaite KR,
Finlayson KJ, Cooper PD, Brown B, Bennett MH, Kay G, Stelfox HT,
Brundin-Mather R, Soo A, Parsons Leigh J, Niven DJ, Fiest KM. The
effectiveness of hyperbaric oxygen therapy for healing chronic venous leg
ulcers: A randomized, double‐blind, placebo‐controlled trial. Wound Repair
Regeneration. 2018, volume26, issue4.
39. Dumville JC, Hinchliffe RJ, Cullum N, Game F, Stubbs N, Sweeting M,
Peinemann F. Negative pressure wound therapy for treating foot wounds in
people with diabetes mellitus. Cochrane Database Syst Rev. 2013; 10
CD010318.
40. FDA US Food, Drug Administration. FDA safety communication: update on
serious complications associated with negative pressure wound therapy
systems.2011.
http://www.fda.gov/downloads/drugs/drugsafety/postmarketdrugsafety
informationforpatientsandproviders/ucm 142821.pdf
41. Hansson C. Interactive wound dressings. A practical guide to their use in
older patients. Drugs Aging 1997; 11: 271-284.
42. HEALIOSTM wound solutions
http://www.healioswoundsolutions.com/store/product/hydrogel-dressing/
43. B Braun. Best Practice Guidelines: Wound Management in Diabetic Foot
Ulcers. Wound International. 2013.
44. Eaglstein WH. Moist wound healing with occlusive dressings: a clinical focus.
Dermatol Surg.2001;27(2):175–81.
45. Campbell BG. Dressings, bandages, and splints for wound management in
dogs and cats. Vet Clin North Am Small Anim Pract. 2006;36(4):759–92.
46. Meehan F. Hydrocolloid update. Journal of Community Nursing May
issue.1993.
47. Katakkattu Vijsyan, et al. Choice of wound care in diabetic foot ulcers: A
practical approach. World Journal of Diabetes. 2014; 15;5(4):546-56.
48. KCL an acelity company, NU-DERM™ Hydrocolloid Wound Dressings.
https://www.mykci.com/NU-DERM-Hydrocolloid-Wound-Dressings
49. Yang, J. S., Xie, Y. J., & He, W. Research progress on chemical modification
of alginate: A review. Carbohydrate Polymers. 2011; 84(1), 33-39.
50. Derma Rite, DermaFoam™.
http://dermarite.com/product/dermafoam/
51. HEALTH PRODUCTS FOR YOU, 3M Tegaderm 1624W Transparent Film67
Dressing.
https://www.healthproductsforyou.com/p-a3m-tegaderm-1624w-transparent-film-dressing.html
52. Boateng J.S., Matthews K.H., Stevens H.N. and Eccleston, G.M. Wound
healing dressings and drug delivery systems: a review. J. Pharm. Sci.2008;
97(8): 2892-2923.
53. Okamoto, Y., Yano, R., Miyatake, K., Tomohiro, I., Shigemasa, Y., Minami,
S. Effects of chitin and chitosan on blood coagulation. Carbohydr. Polym.
2003; 53, 337–342.
54. Wang B, Chen K, Jiang S, et al. Chitosan-mediated synthesis of gold
nanoparticles on patterned poly(dimethylsiloxane) surfaces.
Biomacromolecules. 2006;7(4):1203–1209.
55. Singla A.K. and Chawla M. Chitosan: some pharmaceutical and biological
aspects-an update. J. Pharm. Pharmacol. 2001; 53(8):1047-1067.
56. Lin W.C., Lien C.C., Yeh H.J., Yu C.M., Hsu S.H. Bacterial cellulose and
bacterial cellulose-chitosan membranes for wound dressing applications.
Carbohydr. Polym. 2013;94:603–611.
57. Abdel-Rahman R.M., Abdel-Mohsen A.M., Hrdina R., Burgert L., Fohlerova
Z., Pavliňák D., Sayed O.N., Jancar J. Wound dressing based on
chitosan/hyaluronan/nonwoven fabrics: Preparation, characterization and
medical applications. Int. J. Biol. Macromol. 2016;89:725–736.
58. Ceren Alemdarog˘lu , Zelihagu¨l Deg˘im , Nevin C¸ elebi, Fatih Zor, Serdar
O¨ ztu¨rk , Deniz Erdog˘an. An investigation on burn wound healing in rats
with chitosan gel formulation containing epidermal growth
factor.Burns.2006;32(3), 319-327.
59. P. Losi, E. Briganti, C. Errico, A. Lisella, E. Sanguinetti, F. Chiellini, G.
Soldani. Fibrin-based scaffold incorporating VEGF- and bFGF-loaded
nanoparticles stimulates wound healing in diabetic mice. Acta Biomaterialia.
2013; 9(8)7814-7821.
60. Lansdown ABG. A review of the use of silver in wound care: facts and
fallacies. British Journal of Nursing (Tissue Viability Supplement)
2004;13(6):S6–19.
61. Q. L. Feng, J. Wu, G. Q. Chen, F. Z. Cui, T. N. Kim, J. O. Kim. A mechanistic
study of the antibacterial effect of silver ions on Escherichia coli and
Staphylococcus aureus. Research Jourmal of Pharmacognosy and
Phytochemistry. 2018; 23-26.
62. Kinmond K, McGee P, Gough S, Ashford R. Loss of self: a psychosocial
study of the quality of life of adults with diabetic ulceration. Journal of Tissue
Viability. 2003;13(1):6-16.68
63. Department of Urban Engineering, The University of Tokyo, 3-1-7 Hongo
Bunkyo. Effect of Intracellular Resuscitation of Legionella pneumophila in
Acanthamoeba polyphage Cells on the Antimicrobial Properties of Silver and
Copper. Environ. Sci. Technol.2006;40,23,7434-7439.
64. P. Losi, E. Briganti, C. Errico, A. Lisella, E. Sanguinetti, F. Chiellini, G.
Soldani. Fibrin-based scaffold incorporating VEGF- and bFGF-loaded
nanoparticles stimulates wound healing in diabetic mice. Acta Biomaterialia.
2013; 9(8)7814-7821.
65. Iwamoto, R. and Mekada, E. Heparin-binding EGF-like growth factor: a
juxtacrine growth factor. Cytokine Growth Factor Rev. 2000; 11, 335-344.
66. Hong, J. P., Jung, H. D. and Kim, Y. W. Recombinant human epidermal
growth factor (EGF) to enhance healing for diabetic foot ulcers. Annals of
Plastic Surgery.2006; 56, 394-398; discussion 399-400.
67. Tsang MW, Wong WK, Hung CS, Lai KM, Tang W, Cheung EY, et al. Human
epidermal growth factor enhances healing of diabetic foot ulcers. Diabetes
Care. 2003;26:1856–61.
68. MYBioSource.com ; EGF peptide.
https://www.mybiosource.com/egf-rat-elisa-kits/epidermal-growthfactor/723633
69. Saveria Pastore, Francesca Mascia, Valentina Mariani and Giampiero
Girolomoni. The Epidermal Growth Factor Receptor System in Skin Repair
and Inflammation. Journal of Investigative Dermatology. 2008; 128(6):1365-
74.
70. Saveria Pastore, Francesca Mascia, Valentina Mariani and Giampiero
Girolomoni. The Epidermal Growth Factor Receptor System in Skin Repair
and Inflammation. Journal of Investigative Dermatology. 2008; 128(6):1365-
74.
71. Wynn TA, Barron L. Macrophages: master regulators of inflammation and
fibrosis. Semin Liver Dis. 2010; 30(3):245–57.
72. Shied; How Wounds Heal: The 4 Main Phases of Wound Healing.
http://www.shieldhealthcare.com/community/popular/2015/12/18/howwounds-heal-the-4-main-phases-of-wound-healing/
73. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and
regeneration. Nature. 2008;453(7193):314–21.
74. Hunt TK, Hopf HW. Wound healing and wound infection. What surgeons and
anesthesiologists can do. Surg Clin North Am. 1997;77(3):587–606.
75. Armstrong DG, Liswood PJ, Todd WF. Prevalence of mixed infections in the
diabetic pedal wound. Journal of the American Podiatric Medical69
Association. 1995;85(10):533–7.
76. Richard JL, Lavigne JP, Sotto A. Diabetes and foot infection: more than
double trouble. Diabetes Metab Res Rev. 2012;28:46–53.
77. Lipsky BA, Berewdt AR, Cornia PB, Pile JC, Peters EY, Armstrong DG,
Deery HG, Embil JM, Joseph WS, Karchmer HW, Pinzur MS, Sennevilk E.
Infectious Diseases Society of America: infectious Disease Society of
America Clinical Practices guideline for the diagnosis and treatment of
diabetic foot infections. Clin Infect Dis. 2012;2012:e132–73.
78. Brodsky JW. The diabetic foot, in Mann RA, Coughlin MJ (eds): The Diabetic
Foot, St. Louis, MO, Mosby-Year Book.1992, pp 1361-467.
79. Khatib R, Sharma M, Johnson LB et al. Polymicrobial Staphylococcus aureus
bacteremia: Frequency, distinguishing characteristics and outcome. Diagn
Microbiol Infectious Dis. 2016;86:311-315.
80. Madigan, M.T., Martinko, J., Stahl, D., Clark, D., Brock biology of
microorganisms. Benjamin Cummings. 2012.
81. Schierle CF, De la Garza M, Mustoe TA, Galiano RD. Staphylococcal
biofilms 414 impair wound healing by delaying reepithelialization in a
murine cutaneous wound 415 model. Wound Repair Regen. 2009.17:354-9.
82. ENCYCLOPAEDIA BRITANNICA; Staphylococcus aureus
https://www.britannica.com/science/Staphylococcus-aureus
83. Christina Greulich, Dieter Braun, Alexander Peetsch, Jörg Diendorf, Bettina
Siebers, Matthias Epple and Manfred Köller. The toxic effect of silver ions
and silver nanoparticles towards bacteria and human cells occurs in the
same concentration range. Royal society of chemistry. 2012; 2, 6981-6987.
84. Moon-Jung Kim, Roo-Min Jun, Won-Ki Kim, Hoo-Jae Hann, Young Hae
Chong, Hae-Young Park and Jang-Hyun Chung. Optimal concentration of
human epidermal growth factor(hEGF) for epithelial healing in
experimental corneal alkali wounds. Current Eye Research. 2001; Vol
22,(4), 272-279.
85. Corinna Dannert, Bjørn Torger Stokke, and Rita S. Dias NanoparticleHydrogel Composites: From Molecular Interactions to Macroscopic
Behavior. Polymers. 2019; 11(2),275.

指導教授

李宇翔(Yu-Hsiang Lee)

審核日期

2019-10-31

推文