臺灣博碩士論文加值系統

　　傷口的產生，代表組織遭受連續性的破壞，並需要依照傷口的深淺、位置、面積以及病人的生理狀態，採取適當之處理方式以達到最佳的治癒效果。傷口癒合的發炎期和細胞增生期間，由於作為物理性屏障之表皮受到破壞，許多外界的因子和傷口本身的狀態，都會影響傷口癒合的快慢、發炎期的長短以及最終留下疤痕與否。
　　而傷口敷料的使用，則可以降低諸如傷口感染、缺乏水分和滲液過多等問題造成之傷害。傳統使用的乾式敷料，諸如紗布與棉花，雖然能夠有效阻隔外界的機械傷害，卻沒辦法維持一個適合體液流通的理想環境，使免疫細胞交流、皮膚細胞進行新生。更因為容易沾黏、更換不易而造成使用上的困難，進一步的增加復原的時間和留下疤痕的機會。
　　相較於乾式敷料，濕式敷料的問世時間較短。從六零年代開始，世人才發現當傷口處於濕潤的狀態下，會癒合得較為快速，留下疤痕的機率也顯著降低。除了可以讓患部血管新生速度增快，濕式敷料更具有保濕、不易沾黏、易更換、可大面積使用等優點。常見的濕式敷料包括膠原蛋白(collagen)、褐藻酸 (alginate)、聚氨酯泡棉 (polyurethane foam) 和水凝膠 (hydrogel)。
　　水凝膠是一種具有立體結構的物質，可以在結構穩定的狀態下吸收大量的水分，物理性和化學性的交聯都可以維持其立體狀態。大自然中的膠原蛋白、幾丁質 (chitin)、褐藻酸和瓊脂醣 (agarose) 都可形成水凝膠。近幾年來，水凝膠因為具有良好的敷材特性，更可進行藥物釋放，故被廣泛地運用在傷口敷材上。本篇研究將會利用三種高生物可相容性的物質，研發出理想之傷口敷料。分別為具有高保水性的聚乙烯醇 (poly (vinyl alcohol))、可促進傷口癒合的右旋醣酐 (dextran)以及具有抗菌效果的甲殼素 (chitosan)，並利用以戊二醛 (glutaraldehyde，GA) 進行交聯。
　首先，考量日後敷料製成與使用的方便性，選擇6% 的PVA製作水凝膠來進行後續實驗。抗菌的效果為影響傷口感染與否的決定因素，運用接觸型抗菌實驗，發現0.25% chitosan之添加組別具有最佳之抗菌效果。透過細胞毒性實驗，確定水膠製程中並不會有過量GA之殘留，造成對細胞的傷害；另一方面，細胞增生實驗的結果也顯示出4% dextran可以提升細胞初期的附著。在後續的材料特性分析中，更發現chitosan和dextran的添加，可以增進水凝膠的熱穩定度、機械性質、水分含量和保水程度。故未來發展成水凝膠敷材時，將可達到促進傷口癒合的效果。

　As the wounds appear, it means that the skin is under continuous destruction. The best treatments should be adjusted according to the depth, location, size and the medical conditions of the wounds. In the period of inflammation and cell-proliferation, the efficiency of recovery, duration of the inflammation, and the final fate of the scars are determined mainly by various external factors and the condition of the wounds.
　Applications of wound-dressings could prevent further impairments, such as pathogen infection, dehydration and excessive exudate. Traditional dry wound dressings, like cotton and gauze, have the ability to block external mechanical invasions, but could not provide an ideal environment for communication of leukocytes within the liquid and proliferation of epidermal cells. Furthermore, since dry wound dressings are easily adhesive to the wounds, it causes difficulty in changing and increases the duration of recovery and the potentials of permanent scars.
　Moisture-retentive dressings have not been used for a very long time. In the 60’s, it was discovered that the period of recovery and possibility of permanent scar significantly reduced when the wound was in a moist environment. The moisture-retentive dressings not only elevate the cell proliferation rate, but also have many advantages, such as moisturizing and non-sticky texture, less difficulty in changing, and flexible dressing-size. Collagen, alginate, polyurethane foam, and hydrogel, are commonly used as moisture-retentive dressings.
　Hydrogel is a three-dimensional structure with hydrophilic polymer chain, having the ability in absorbing water in great amount. Either physical or chemical cross-links could contribute to its three-dimensional structure. Naturally-occured collagen, chitin alginate and agarose could form hydrogel. Due to its splendid characters, hydrogel could be used in not only wound-dressings but also drug-delivers. Three components with high bio-capability are integrated to produce ideal wound-dressing. These components are poly (vinyl alcohol) with high water-content, dextran with the ability in promoting wound-recovery and chitosan with anti-microbial characteristic, when glutaraldehyde is used as the cross-linker.
　In this study, 6% PVA hydrogel was chosen owing to its texture and further applications. In the anti-microbial test, 0.25% chitosan was found to provide the best anti-microbial ability. In the cell-toxicity test, it has shown that no residue of glutaraldehyde, which might undermine the growth of cells, was remained in our hydrogel-making procedure. In the cell-proliferation test, the greatest cell-proliferation happened to be on the hydrogel with 4% dextran. In the following physical analyses, the addition of chitosan and dextran was appeared to promote the thermo-stability, mechanical properties, water retention and moisturizing ability in the PVA hydrogel. In conclusion, the PVA/chitosan/dextran hydrogel has a promising potential as a wound dressing in the future.

摘要 VII
Abstract IX
一、前言 1
二、文獻探討 3
2-1 傷口種類 3
2-2傷口癒合 4
2-2-1 癒合階段 4
2-2-2 影響癒合之因子 5
2-2-3傷口敷料選擇 6
7
2-3水凝膠敷料之特性與應用 8
2-3-1水凝膠物化特性簡介 8
2-3-2 水凝膠的物理性交聯 9
2-3-3 水凝膠的化學性交聯 11
2-3 PVA之特性與運用 13
2-4 Dextran之特性與運用 14
2-4-1 Dextran之化學特性 14
2-4-2 Dextran之應用 14
2-5 Chitosan之特性與應用 17
2-5-1 Chitosan之化學特性 17
2-5-2 Chitosan的抗菌能力 18
2-5-3 Chitosan在傷口敷料之應用 19
2-6 PVA/ dextran/ chitosan水凝膠之應用 20
三、材料與方法 22
3-1 實驗步驟與流程 22
3-2 實驗材料 22
3-2-1 樣品製備 22
3-2-2 抗菌分析 24
3-2-3細胞實驗 25
3-3儀器設備 26
3-4 抗菌分析 27
3-5細胞實驗 28
3-5-1 細胞生長曲線 (cell growth curve) 28
3-5-2細胞毒性分析(cell cytotoxicity) 28
3-5-3 細胞附著及增生實驗 (cell adhesion and proliferation test) 28
3-6材料特性分析 28
3-6-1 水氣穿透 (water vapor transmission rates) 28
3-6-2 掃描式顯微鏡 (scanning electron microscopy) 29
3-6-3 熱重量分析法 (thermogravimetric analysis) 29
3-6-4 保水量分析 (water retention analysis) 29
3-6-5 機械性質分析 (mechanical property analysis) 29
3-7 統計分析 30
四、結果與討論 31
4-1水膠型態 31
4-2 抗菌實驗 33
4-3細胞實驗 38
4-3-1 細胞毒性 38
4-3-2細胞附著與增生 40
4-4 掃描式電子顯微鏡 42
4-5 熱重分析儀 45
4-6 機械性質 47
4-7 保水性測定 49
4-8 水氣穿透 51
五、結論 53
六、未來與展望 56
七、文獻來源 57
八、附錄 67
九、簡歷 70

Abd El-Kader, F.H., S.A. Gaafer, and M.F. Abd El-Kader. 2014. Characterization and optical studies of 90/10 (wt/wt%) PVA/beta-chitin blend irradiated with gamma-rays. Spectrochimica Acta. Part A, Molecular and biomolecular Spectroscopy. 131:564-570.
Abdou, E.S., K.S. Nagy, and M.Z. Elsabee. 2008. Extraction and characterization of chitin and chitosan from local sources. Bioresource Technology. 99:1359-1367.
Abou Taleb, M.F., H.L. Abd El-Mohdy, and H.A. Abd El-Rehim. 2009. Radiation preparation of PVA/CMC copolymers and their application in removal of dyes. Journal of Hazardous Materials. 168:68-75.
Akiyoshi, K., S. Kobayashi, S. Shichibe, D. Mix, M. Baudys, S.W. Kim, and J. Sunamoto. 1998. Self-assembled hydrogel nanoparticle of cholesterol-bearing pullulan as a carrier of protein drugs: complexation and stabilization of insulin. Journal of Control Release. 54:313-320.
Andres, Y., L. Giraud, C. Gerente, and P. Le Cloirec. 2007. Antibacterial effects of chitosan powder: mechanisms of action. Environmental Technology. 28:1357-1363.
Anseth, K.S., C.N. Bowman, and L. Brannon-Peppas. 1996. Mechanical properties of hydrogels and their experimental determination. Biomaterials. 17:1647-1657.
Azad, A.K., N. Sermsintham, S. Chandrkrachang, and W.F. Stevens. 2004. Chitosan membrane as a wound-healing dressing: characterization and clinical application. Journal of Biomedical Material Research Part B: Applied Biomaterials. 69:216-222.
Aziz, M.A., J.D. Cabral, H.J. Brooks, S.C. Moratti, and L.R. Hanton. 2012. Antimicrobial properties of a chitosan dextran-based hydrogel for surgical use. Antimicrobial Agents Chemotherapy. 56:280-287.
Benahmed, A., M. Ranger, and J.C. Leroux. 2001. Novel polymeric micelles based on the amphiphilic diblock copolymer poly (N-vinyl-2-pyrrolidone)-block-poly (D,L-lactide). Pharmacy Research. 18:323-328.
Bredow, J., J. Oppermann, K. Hoffmann, M. Hellmich, B. Wenk, M. Simons, P. Eysel, and K. Zarghooni. 2015. Clinical trial to evaluate the performance of a flexible self-adherent absorbent dressing coated with a soft silicone layer compared to a standard wound dressing after orthopedic or spinal surgery: study protocol for a randomized controlled trial. Trials. 16:81.
Bullough, L., S. Johnson, and R. Forder. 2015. Evaluation of a foam dressing for acute and chronic wound exudate management. British Journal of Community Nursing Supplied Wound Care:S17-18, S20, S22-14.
Buranachai, T., N. Praphairaksit, and N. Muangsin. 2010. Chitosan/polyethylene glycol beads crosslinked with tripolyphosphate and glutaraldehyde for gastrointestinal drug delivery. AAPS Pharmacy Science Technology. 11:1128-1137.
Cadee, J.A., M.J. van Luyn, L.A. Brouwer, J.A. Plantinga, P.B. van Wachem, C.J. de Groot, W. den Otter, and W.E. Hennink. 2000. In vivo biocompatibility of dextran-based hydrogels. J Biomedical Material Research. 50:397-404.
Ceccarini, C., and H. Eagle. 1971. pH as a determinant of cellular growth and contact inhibition. Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences of the United States 68:229-233.
Chen, F., Z. Wu, and Y. Jin. 2005. Application research on dextran-based hydrogel and its drug controlled release. Chinese journal of reparative and reconstructive surgery. 19:919-922.
Chuang, W.Y., T.H. Young, C.H. Yao, and W.Y. Chiu. 1999. Properties of the poly (vinyl alcohol)/chitosan blend and its effect on the culture of fibroblast in vitro. Biomaterials. 20:1479-1487.
Chung, Y.C., and C.Y. Chen. 2008. Antibacterial characteristics and activity of acid-soluble chitosan. Bioresource Technology. 99:2806-2814.
Chvapil, M., T.A. Chvapil, and J.A. Owen. 1987. Comparative study of four wound dressings on epithelization of partial-thickness wounds in pigs. Journal of Trauma. 27:278-282.
Cuero, R.G. 1999. Antimicrobial action of exogenous chitosan. Experientia Supplementum. 87:315-333.
Cutting, K.F. 2003. Wound exudate: composition and functions. British of Journal Community Nursing supplication 4-9.
de Jong, S.J., S.C. De Smedt, J. Demeester, C.F. van Nostrum, J.J. Kettenes-van den Bosch, and W.E. Hennink. 2001. Biodegradable hydrogels based on stereocomplex formation between lactic acid oligomers grafted to dextran. Journal of Control Release. 72:47-56.
Devi, N., and T.K. Maji. 2010. Microencapsulation of isoniazid in genipin-crosslinked gelatin-A-kappa-carrageenan polyelectrolyte complex. Drug Development Industry Pharmacy. 36:56-63.
Diegelmann, R.F., and M.C. Evans. 2004. Wound healing: an overview of acute, fibrotic and delayed healing. Front Bioscience. 9:283-289.
Draye, J.P., B. Delaey, A. Van de Voorde, A. Van Den Bulcke, B. Bogdanov, and E. Schacht. 1998. In vitro release characteristics of bioactive molecules from dextran dialdehyde cross-linked gelatin hydrogel films. Biomaterials. 19:99-107.
Fanucci, D., and J. Seese. 1991. Multi-faceted use of calcium alginates. A painless, cost-effective alternative for wound care management. Ostomy Wound Manage. 37:16-22.
Galle, S., C. Schwab, E. Arendt, and M. Ganzle. 2010. Exopolysaccharide-forming Weissella strains as starter cultures for sorghum and wheat sourdoughs. Journal of Agricultural and Food Chemistry. 58:5834-5841.
Geeraerd, A.H., V.P. Valdramidis, F. Devlieghere, H. Bernaert, J. Debevere, and J.F. Van Impe. 2004. Development of a novel approach for secondary modelling in predictive microbiology: incorporation of microbiological knowledge in black box polynomial modelling. International Journal of Food Microbiology. 91:229-244.
Gilchrist, T., and A.M. Martin. 1983. Wound treatment with Sorbsan--an alginate fibre dressing. Biomaterials. 4:317-320.
Gommes, C.J., and A.P. Roberts. 2008. Structure development of resorcinol-formaldehyde gels: microphase separation or colloid aggregation. Physical Review E. 77:041409.
Goosen, M.F., G.M. O''Shea, H.M. Gharapetian, S. Chou, and A.M. Sun. 1985. Optimization of microencapsulation parameters: Semipermeable microcapsules as a bioartificial pancreas. Biotechnology and Bioengineering. 27:146-150.
Gough, J.E., C.A. Scotchford, and S. Downes. 2002. Cytotoxicity of glutaraldehyde crosslinked collagen/poly (vinyl alcohol) films is by the mechanism of apoptosis. J Biomedical Material Research. 61:121-130.
Gu, Z.Q., J.M. Xiao, and X.H. Zhang. 1998. The development of artificial articular cartilage--PVA-hydrogel. Biomedical Material Engineer. 8:75-81.
Helander, I.M., E.L. Nurmiaho-Lassila, R. Ahvenainen, J. Rhoades, and S. Roller. 2001. Chitosan disrupts the barrier properties of the outer membrane of gram-negative bacteria. International Journal of Food Microbiology. 71:235-244.
Heng, M.C. 2011. Wound healing in adult skin: aiming for perfect regeneration. International Journal of Dermatology. 50:1058-1066.
Hennink, W.E., S.J. De Jong, G.W. Bos, T.F. Veldhuis, and C.F. van Nostrum. 2004. Biodegradable dextran hydrogels crosslinked by stereocomplex formation for the controlled release of pharmaceutical proteins. International Journal of Pharmacy. 277:99-104.
Hennink, W.E., and C.F. van Nostrum. 2002. Novel crosslinking methods to design hydrogels. Advanced Drug Deliver Review. 54:13-36.
Hoffman, A.S. 2002. Hydrogels for biomedical applications. Advanced Drug Deliver Review. 54:3-12.
Hoffman, A.S. 2014. A novel approach for preparation of pH-sensitive hydrogels for enteric drug delivery, 1991. Journal of Control Release. 190:36-40.
Hwang, M.R., J.O. Kim, J.H. Lee, Y.I. Kim, J.H. Kim, S.W. Chang, S.G. Jin, J.A. Kim, W.S. Lyoo, S.S. Han, S.K. Ku, C.S. Yong, and H.G. Choi. 2010. Gentamicin-loaded wound dressing with polyvinyl alcohol/dextran hydrogel: gel characterization and in vivo healing evaluation. AAPS Pharmacy Science Technology. 11:1092-1103.
Ito, K., A. Saito, T. Fujie, K. Nishiwaki, H. Miyazaki, M. Kinoshita, D. Saitoh, S. Ohtsubo, and S. Takeoka. 2015. Sustainable antimicrobial effect of silver sulfadiazine-loaded nanosheets on infection in a mouse model of partial-thickness burn injury. Acta Biomaterialiaialia. 24:87-95.
Jameela, S.R., and A. Jayakrishnan. 1995. Glutaraldehyde cross-linked chitosan microspheres as a long acting biodegradable drug delivery vehicle: studies on the in vitro release of mitoxantrone and in vivo degradation of microspheres in rat muscle. Biomaterials. 16:769-775.
Jen, A.C., M.C. Wake, and A.G. Mikos. 1996. Review: Hydrogels for cell immobilization. Biotechnology and Bioengineering. 50:357-364.
Jiang, H., Y. Zuo, L. Zhang, J. Li, A. Zhang, Y. Li, and X. Yang. 2014. Property-based design: optimization and characterization of polyvinyl alcohol (PVA) hydrogel and PVA-matrix composite for artificial cornea. Journal of Materials Science: Materials in Medicine. 25:941-952.
Jiang, S., S. Liu, and W. Feng. 2011. PVA hydrogel properties for biomedical application. Biomedical MaterialsJournal of the Mechanical Behavior of Biomedical Materials. 4:1228-1233.
Jing, Y.J., Y.J. Hao, H. Qu, Y. Shan, D.S. Li, and R.Q. Du. 2007. Studies on the antibacterial activities and mechanisms of chitosan obtained from cuticles of housefly larvae. Acta Biologica Cracoviensia Series Botanica Hung. 58:75-86.
Khalid, M.N., F. Agnely, N. Yagoubi, J.L. Grossiord, and G. Couarraze. 2002. Water state characterization, swelling behavior, thermal and mechanical properties of chitosan based networks. European Journal of Pharmaceutical Sciences. 15:425-432.
Kickhofen, B., H. Wokalek, D. Scheel, and H. Ruh. 1986. Chemical and physical properties of a hydrogel wound dressing. Biomaterials. 7:67-72.
Kloppenberg, F.W., G.I. Beerthuizen, and H.J. ten Duis. 2001. Perfusion of burn wounds assessed by laser doppler imaging is related to burn depth and healing time. Burns. 27:359-363.
Kofinas, P., V. Athanassiou, and E.W. Merrill. 1996. Hydrogels prepared by electron irradiation of poly (ethylene oxide) in water solution: unexpected dependence of cross-link density and protein diffusion coefficients on initial PEO molecular weight. Biomaterials. 17:1547-1550.
Kong, M., X.G. Chen, K. Xing, and H.J. Park. 2010. Antimicrobial properties of chitosan and mode of action: a state of the art review. International Journal of Food Microbiology.144:51-63.
Kuo, K.C., R.Z. Lin, H.W. Tien, P.Y. Wu, Y.C. Li, J.M. Melero-Martin, and Y.C. Chen. 2015. Bioengineering vascularized tissue constructs using an injectable cell-laden enzymatically crosslinked collagen hydrogel derived from dermal extracellular matrix. Acta Biomaterialia. 27:151-166.
Lee, K.Y., and D.J. Mooney. 2001. Hydrogels for tissue engineering. Chemistry Review. 101:1869-1879.
Lisman, A., B. Butruk, I. Wasiak, and T. Ciach. 2014. Dextran/Albumin hydrogel sealant for Dacron (R) vascular prosthesis. Journal of Biomaterials Applications. 28:1386-1396.
Liu, D., Y. Wei, P. Yao, and L. Jiang. 2006. Determination of the degree of acetylation of chitosan by UV spectrophotometry using dual standards. Carbohydrate Research. 341:782-785.
Liu, J., S. Lin, L. Li, and E. Liu. 2005. Release of theophylline from polymer blend hydrogels. International Journal of Pharmacy. 298:117-125.
Liu, Q., Y. Zheng, Y. Wang, and G. Wu. 2003. Review of poly (vinyl alcohol) hydrogel and its compounds in the application of artificial cartilage materials. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 20:742-745.
Liu, Y., and M.B. Chan-Park. 2009. Hydrogel based on interpenetrating polymer networks of dextran and gelatin for vascular tissue engineering. Biomaterials. 30:196-207.
Lovvorn, H.N., 3rd, D.T. Cheung, M.E. Nimni, N. Perelman, J.M. Estes, and N.S. Adzick. 1999. Relative distribution and crosslinking of collagen distinguish fetal from adult sheep wound repair. Journal of Pediatric Surgery. 34:218-223.
Mahadik, B.P., S. Pedron Haba, L.J. Skertich, and B.A. Harley. 2015. The use of covalently immobilized stem cell factor to selectively affect hematopoietic stem cell activity within a gelatin hydrogel. Biomaterials. 67:297-307.
Martins, A.F., S.P. Facchi, H.D. Follmann, A.G. Pereira, A.F. Rubira, and E.C. Muniz. 2014. Antimicrobial activity of chitosan derivatives containing N-quaternized moieties in its backbone: a review. International Journal of Molecular Sciences. 15:20800-20832.
McGuckin, M., R. Goldman, L. Bolton, and R. Salcido. 2003. The clinical relevance of microbiology in acute and chronic wounds. Advances in Skin & Wound Care. 16:12-23; quiz 24-15.
Miguel, S.P., M.P. Ribeiro, H. Brancal, P. Coutinho, and I.J. Correia. 2014. Thermoresponsive chitosan-agarose hydrogel for skin regeneration. Carbohydrate Polymers. 111:366-373.
Miyata, T., N. Asami, and T. Uragami. 1999. A reversibly antigen-responsive hydrogel. Nature. 399:766-769.
Morales-Hurtado, M., X. Zeng, P. Gonzalez-Rodriguez, J.E. Ten Elshof, and E. van der Heide. 2015. A new water absorbable mechanical Epidermal skin equivalent: the combination of hydrophobic PDMS and hydrophilic PVA hydrogel. Journal of the Mechanical Behavior of Biomedical Materials. 46:305-317.
Nacer Khodja, A., M. Mahlous, D. Tahtat, S. Benamer, S. Larbi Youcef, H. Chader, L. Mouhoub, M. Sedgelmaci, N. Ammi, M.B. Mansouri, and S. Mameri. 2013. Evaluation of healing activity of PVA/chitosan hydrogels on deep second degree burn. Burns. 39:98-104.
Nam, K., A. Murakoshi, T. Kimura, T. Fujisato, S. Kitamura, and A. Kishida. 2009. Study on the physical properties of tissue-engineered blood vessels made by chemical cross-linking and polymer-tissue cross-linking. Journal of Artificial Organs. 12:47-54.
Negishi, J., K. Nam, T. Kimura, Y. Hashimoto, S. Funamoto, T. Higami, T. Fujisato, and A. Kishida. 2014. Fabrication of a heparin-PVA complex hydrogel for application as a vascular access. Journal of Biomedical Material Research Part B: Applied Biomaterials. 102:1426-1433.
Nugent, M.J., and C.L. Higginbotham. 2007. Preparation of a novel freeze thawed poly (vinyl alcohol) composite hydrogel for drug delivery applications. European Journal of Pharmaceutics and Biopharmaceutics. 67:377-386.
Opalenik, S.R., and J.M. Davidson. 2005. Fibroblast differentiation of bone marrow-derived cells during wound repair. Federation of American Societies for Experimental Biology. 19:1561-1563.
Patel, S., N. Kasoju, U. Bora, and A. Goyal. 2010. Structural analysis and biomedical applications of dextran produced by a new isolate Pediococcus pentosaceus screened from biodiversity hot spot Assam. Bioresource Technology. 101:6852-6855.
Peppas, N.A., and R.E. Benner, Jr. 1980. Proposed method of intracordal injection and gelation of poly (vinyl alcohol) solution in vocal cords: polymer considerations. Biomaterials. 1:158-162.
Petka, W.A., J.L. Harden, K.P. McGrath, D. Wirtz, and D.A. Tirrell. 1998. Reversible hydrogels from self-assembling artificial proteins. Science. 281:389-392.
Prescott, L.M. 2002. Highlights of the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). The Body Positive. 15:6-9.
Rassu, G., A. Salis, E.P. Porcu, P. Giunchedi, M. Roldo, and E. Gavini. 2016. Composite chitosan/alginate hydrogel for controlled release of deferoxamine: A system to potentially treat iron dysregulation diseases. Carbohydrate Polymers. 136:1338-1347.
Refojo, M.F. 1967. Hydrophobic interaction in poly (2-hydroxyethyl methacrylate) homogeneous hydrogel. J Polymer Science. 5:3103-3113.
Ribeiro, M.P., A. Espiga, D. Silva, P. Baptista, J. Henriques, C. Ferreira, J.C. Silva, J.P. Borges, E. Pires, P. Chaves, and I.J. Correia. 2009. Development of a new chitosan hydrogel for wound dressing. Wound Repair Regeneration. 17:817-824.
Rosenblatt, K.M., and H. Bunjes. 2009. Poly (vinyl alcohol) as emulsifier stabilizes solid triglyceride drug carrier nanoparticles in the alpha-modification. Molecular Pharmacy . 6:105-120.
Rouzes, C., R. Gref, M. Leonard, A. De Sousa Delgado, and E. Dellacherie. 2000. Surface modification of poly (lactic acid) nanospheres using hydrophobically modified dextrans as stabilizers in an o/w emulsion/evaporation technique. Journal of Biomedical Material Research. 50:557-565.
Rovee, D.T., C.A. Kurowsky, and J. Labun. 1972. Local wound environment and epidermal healing. Mitotic response. Archives of Dermatology Journal. 106:330-334.
Runarsson, O.V., C. Malainer, J. Holappa, S.T. Sigurdsson, and M. Masson. 2008. tert-Butyldimethylsilyl O-protected chitosan and chitooligosaccharides: useful precursors for N-modifications in common organic solvents. Carbohydrate Research. 343:2576-2582.
Sen, M., and E.N. Avci. 2005. Radiation synthesis of poly (N-vinyl-2-pyrrolidone)-kappa-carrageenan hydrogels and their use in wound dressing applications. I. Preliminary laboratory tests. Journal of Biomedical Material Research . 74:187-196.
Shepherd, R., S. Reader, and A. Falshaw. 1997. Chitosan functional properties. Glycoconjugate Journal. 14:535-542.
Simons, C., S.E. Walsh, J.Y. Maillard, and A.D. Russell. 2000. Ortho-phthalaldehyde: proposed mechanism of action of a new antimicrobial agent. Letters in Applied Microbiology. 31:299-302.
Singh, B., and L. Pal. 2011. Radiation crosslinking polymerization of sterculia polysaccharide-PVA-PVP for making hydrogel wound dressings. International Journal of Biological Macromolecules. 48:501-510.
Singh, B., and L. Pal. 2012. Sterculia crosslinked PVA and PVA-poly (AAm) hydrogel wound dressings for slow drug delivery: mechanical, mucoadhesive, biocompatible and permeability properties. Journal of the Mechanical Behavior of Biomedical Materials. 9:9-21.
Stenekes, R.J., and W.E. Hennink. 1999. Equilibrium water content of microspheres based on cross-linked dextran. International Journal of Pharmacy. 189:131-135.
Sun, G., X. Zhang, Y.I. Shen, R. Sebastian, L.E. Dickinson, K. Fox-Talbot, M. Reinblatt, C. Steenbergen, J.W. Harmon, and S. Gerecht. 2011. Dextran hydrogel scaffolds enhance angiogenic responses and promote complete skin regeneration during burn wound healing. Proceedings of the National Academy of Sciences of the United States. 108:20976-20981.
Sung, J.H., M.R. Hwang, J.O. Kim, J.H. Lee, Y.I. Kim, J.H. Kim, S.W. Chang, S.G. Jin, J.A. Kim, W.S. Lyoo, S.S. Han, S.K. Ku, C.S. Yong, and H.G. Choi. 2010. Gel characterisation and in vivo evaluation of minocycline-loaded wound dressing with enhanced wound healing using polyvinyl alcohol and chitosan. International Journal of Pharmacy. 392:232-240.
Suzuki, Y., M. Tanihara, Y. Nishimura, K. Suzuki, Y. Kakimaru, and Y. Shimizu. 1997. A novel wound dressing with an antibiotic delivery system stimulated by microbial infection. American Society for Artificial Internal Organs. 43:M854-857.
Szabowski, A., N. Maas-Szabowski, S. Andrecht, A. Kolbus, M. Schorpp-Kistner, N.E. Fusenig, and P. Angel. 2000. c-Jun and JunB antagonistically control cytokine-regulated mesenchymal-epidermal interaction in skin. Cell. 103:745-755.
Tahtat, D., M. Mahlous, S. Benamer, A.N. Khodja, H. Oussedik-Oumehdi, and F. Laraba-Djebari. 2013. Oral delivery of insulin from alginate/chitosan crosslinked by glutaraldehyde. International Journal of Biological Macromolecules. 58:160-168.
Tingirikari, J.M., D. Kothari, R. Shukla, and A. Goyal. 2014. Structural and biocompatibility properties of dextran from Weissella cibaria JAG8 as food additive. International journal of food sciences and nutrition. 65:686-691.
Tsai, G.J., S.L. Zhang, and P.L. Shieh. 2004. Antimicrobial activity of a low-molecular-weight chitosan obtained from cellulase digestion of chitosan. Journal of Food Protection. 67:396-398.
Van Tomme, S.R., M.J. van Steenbergen, S.C. De Smedt, C.F. van Nostrum, and W.E. Hennink. 2005. Self-gelling hydrogels based on oppositely charged dextran microspheres. Biomaterials. 26:2129-2135.
Vandor, E., P. Mozsary, and A. Reffy. 1980. A critical study on the preparation and application of gelatin-resorcinol tissue adhesive crosslinked by formaldehyde. Transplant Kunstliche Organe Journal. 13:43-51.
Velnar, T., T. Bailey, and V. Smrkolj. 2009. The wound healing process: an overview of the cellular and molecular mechanisms. Journal of International Medical Research. 37:1528-1542.
Vishu Kumar, A.B., M.C. Varadaraj, L.R. Gowda, and R.N. Tharanathan. 2005. Characterization of chito-oligosaccharides prepared by chitosanolysis with the aid of papain and Pronase, and their bactericidal action against Bacillus cereus and Escherichia coli. The Biochemical Journal. 391:167-175.
Vogt, P.M., C. Andree, K. Breuing, P.Y. Liu, J. Slama, G. Helo, and E. Eriksson. 1995. Dry, moist, and wet skin wound repair. Annals of Plastic Surgery. 34:493-499; discussion 499-500.
Wang, C., R.J. Stewart, and J. Kopecek. 1999. Hybrid hydrogels assembled from synthetic polymers and coiled-coil protein domains. Nature. 397:417-420.
Werner, S., and R. Grose. 2003. Regulation of wound healing by growth factors and cytokines. Physiology Review. 83:835-870.
White, M.J., I. Kohno, A.L. Rubin, K.H. Stenzel, and T. Miyata. 1973. Collagen films: effect of cross-linking on physical and biological properties. Biomaterials for Medical Devices Artificial Organs. 1:703-715.
Winter, G.D. 1975. Epidermal wound healing under a new polyurethane foam dressing (Lyofoam). Plastic and Reconstructive Surgery. 56:531-537.
Winter, G.D. 1995. Formation of the scab and the rate of epithelisation of superficial wounds in the skin of the young domestic pig. 1962. Journal of Wound Care. 4:366-367; discussion 368-371.
Wu, T., S. Zivanovic, F.A. Draughon, and C.E. Sams. 2004. Chitin and chitosan--value-added products from mushroom waste. Journal of Agricultural Food Chemistry. 52:7905-7910.
Wu, Z., Z. Sheng, T. Sun, M. Geng, J. Li, Y. Yao, and Z. Huang. 2003. Preparation of collagen-based materials for wound dressing. Chinese Medical Journal. 116:419-423.
Xing, L., C. Dawei, X. Liping, and Z. Rongqing. 2003. Oral colon-specific drug delivery for bee venom peptide: development of a coated calcium alginate gel beads-entrapped liposome. Journal of Control Release. 93:293-300.
Younes, I., S. Hajji, V. Frachet, M. Rinaudo, K. Jellouli, and M. Nasri. 2014. Chitin extraction from shrimp shell using enzymatic treatment. Antitumor, antioxidant and antimicrobial activities of chitosan. International Journal of Biological Macromolecules. 69:489-498.
Yuksel, N., and L. Beba. 2009. Preparation and optimization of superabsorbent hydrogel micromatrices based on poly (acrylic acid), partly sodium salt-g-poly (ethylene oxide) for modified release of indomethacin. Drug Development and Industrial Pharmacy. 35:756-767.
Zhang, X.G., D.Y. Teng, Z.M. Wu, X. Wang, Z. Wang, D.M. Yu, and C.X. Li. 2008. PEG-grafted chitosan nanoparticles as an injectable carrier for sustained protein release. Journal of Materials Science: Materials in Medicine. 19:3525-3533.
Zhu, D., S. Damodaran, and J.A. Lucey. 2010. Physicochemical and emulsifying properties of whey protein isolate (WPI)-dextran conjugates produced in aqueous solution. Journal of Agricultural Food Chemistry. 58:2988-2994.
Zuo, Q., J. Lu, A. Hong, D. Zhong, S. Xie, Q. Liu, Y. Huang, Y. Shi, L. He, and W. Xue. 2012. Preparation and characterization of PEM-coated alginate microgels for controlled release of protein. Biomedical Materials. 7:035012