CURRENT TECHNOLOGIES IN WOUND DRESSINGS AND PHARMACEUTICAL CHARACTERIZATION METHODS

Öz

Objective: This review aims to evaluate studies on wound dressings by comparatively analyzing wound care principles, ideal wound dressing properties, classifications of wound dressings, preparation methods, and characterization studies of wound dressings. Additionally, it seeks to investigate the latest technologies in wound dressing production. Result and Discussion: An ideal wound dressing must meet the fundamental principles of wound care. Numerous studies have been performed from past to present to facilitate and accelerate the wound healing process. With the advancement of modern technologies, traditional wound dressings such as gauze have been replaced by modern wound dressings made from natural and synthetic polymers or their combinations. Modern polymer-based wound dressings enable the development of products that can carry drugs facilitating and accelerating wound healing and can be adapted into various physical forms. In this review, modern wound dressings are classified into films and hydrogels, nanofibers, foams and sponges, composites and scaffolds, bioactive wound dressings, and biological wound dressings. Preparation methods, advantages, disadvantages, and examples of approved market preparations are discussed. The characterization studies of wound dressings regarding their stability and efficacy are also evaluated. As a result of our studies on the subject, although a single ideal wound dressing suitable for different wound types cannot be identified, it has been determined that mass-produced therapeutic systems can be customized where wound dressings can be prepared according to the size of patient-specific chronic wounds thanks to the use of technologies that can almost exactly mimic the skin such as 3D printing, nanofiber technologies, or use of sprayable-particulate wound dressing systems.

Anahtar Kelimeler

• Biomaterial
• polymeric drug delivery systems
• wound healing
• wound dressing
• wound management
• in vitro characterization

YARA ÖRTÜLERİNDE GÜNCEL TEKNOLOJİLER VE FARMASÖTİK KARAKTERİZASYON YÖNTEMLERİ

Öz

Amaç: Bu derlemede yara örtüsü üzerine yapılan çalışmalar incelenerek yara bakım prensipleri, ideal yara örtüsü özellikleri, yara örtülerinin sınıflandırmaları, hazırlanma yöntemleri ve yara örtülerinde yapılan karakterizasyon çalışmaları karşılaştırmalı olarak değerlendirerek en güncel yara örtüsü üretim teknolojilerinin araştırılması amaçlanmıştır. Sonuç ve Tartışma: İdeal bir yara örtüsü temel yara bakım prensiplerini karşılamalıdır. Yara iyileşme sürecini kolaylaştırmak ve hızlandırmak için geçmişten günümüze dek pek çok çalışma yapılmıştır. Günümüzde modern teknolojilerin gelişmesiyle birlikte, gazlı bezler gibi geleneksel örtüler yerine doğal ve sentetik polimerler ve bunların kombinasyonlarından oluşan modern yara örtüleri kullanılmaya başlamıştır. Temeli polimerlere dayanan modern yara örtüleri sayesinde, bünyesinde yara iyileşmesini kolaylaştıran ve hızlandıran etkin maddeleri taşıyabilen ve farklı fiziksel formlarda uyarlanabilen yara örtüleri geliştirilmiştir. Bu derlemede modern yara örtüleri filmler ve hidrojeller, nanolifler, köpükler ve süngerler, kompozitler ve iskeleler, biyoaktif yara örtüleri ve biyolojik yara örtüleri olarak sınıflandırılmıştır. Hazırlama yöntemleri, çeşitli avantajları ve dezavantajları, onaylı piyasa preparatlarından örnekler verilerek açıklanmıştır. Hem stabilite hem etkinlik açısından yara örtülerinden beklenen özelliklerin karakterizasyon çalışmaları değerlendirilmiştir. Konuyla ilgili incelemelerimiz sonucunda, farklı yara türlerine uygun ideal tek bir yara örtüsünden bahsedilemese de özellikle hastaya özgü kronik yaraların boyutuna uygun yara örtülerinin hazırlanabildiği 3B baskı, nanolif teknolojileri gibi deriyi neredeyse birebir taklit edebilen teknolojilerin veya püskürtülebilir-partiküler yara örtüsü sistemlerinin kullanımı sayesinde kitlesel olarak üretilen terapötik sistemlerin kişiye özel hale getirilebileceği tespit edilmiştir.

Anahtar Kelimeler

• Biyomateryal
• polimerik ilaç taşıyıcı sistemler
• yara iyileşmesi
• yara örtüsü
• yara yönetimi
• in vitro karakterizasyon

Kaynakça

1. 1. Liu, M., Wei, X., Zheng, Z., Li, Y., Li, M., Lin, J., Yang, L. (2023). Recent advances in nano-drug delivery systems for the treatment of diabetic wound healing. International Journal of Nanomedicine, 18, 1537-1560. [CrossRef]
2. 2. Nguyen, H.M., Ngoc Le, T.T., Nguyen, A.T., Thien Le, H.N., Pham, T.T. (2023). Biomedical materials for wound dressing: Recent advances and applications. RSC Advances, 13(8), 5509-5528. [CrossRef]
3. 3. Tiwari, N., Kumar, D., Priyadarshani, A., Jain, G.K., Mittal, G., Kesharwani, P., Aggarwal, G. (2023). Recent progress in polymeric biomaterials and their potential applications in skin regeneration and wound care management. Journal of Drug Delivery Science and Technology, 82, 104319. [CrossRef]
4. 4. Fonder, M.A., Lazarus, G.S., Cowan, D.A., Aronson-Cook, B., Kohli, A.R., Mamelak, A.J. (2008). Treating the chronic wound: A practical approach to the care of nonhealing wounds and wound care dressings. Journal of the American Academy of Dermatology, 58(2), 185-206. [CrossRef]
5. 5. Kamoun, E.A., Kenawy, E.S., Chen, X. (2017). A review on polymeric hydrogel membranes for wound dressing applications: Pva-based hydrogel dressings. Journal of Advanced Research, 8(3), 217-233. [CrossRef]
6. 6. Simoes, D., Miguel, S.P., Ribeiro, M.P., Coutinho, P., Mendonca, A.G., Correia, I.J. (2018). Recent advances on antimicrobial wound dressing: A review. European Journal of Pharmaceutics and Biopharmaceutics, 127, 130-141. [CrossRef]
7. 7. Dabiri, G., Damstetter, E., Phillips, T. (2016). Choosing a wound dressing based on common wound characteristics. Advances in Wound Care, 5(1), 32-41. [CrossRef]
8. 8. Tandara, A.A., Mustoe, T.A. (2004). Oxygen in wound healing-more than a nutrient. World Journal of Surgery, 28(3), 294-300. [CrossRef]

9. 9. Egozi, D., Baranes-Zeevi, M., Ullmann, Y., Gilhar, A., Keren, A., Matanes, E., Berdicevsky, I., Krivoy, N., Zilberman, M. (2015). Biodegradable soy wound dressings with controlled release of antibiotics: Results from a guinea pig burn model. Burns, 41(7), 1459-1467. [CrossRef]
10. 10. Dhivya, S., Padma, V.V., Santhini, E. (2015). Wound dressings-A review. BioMedicine, 5(4), 22-28.
11. 11. Saghazadeh, S., Rinoldi, C., Schot, M., Kashaf, S.S., Sharifi, F., Jalilian, E., Nuutila, K., Giatsidis, G., Mostafalu, P., Derakhshandeh, H., Yue, K., Swieszkowski, W., Memic, A., Tamayol, A., Khademhosseini, A. (2018). Drug delivery systems and materials for wound healing applications. Advanced Drug Delivery Reviews, 127, 138-166. [CrossRef]
12. 12. Richetta, A.G., Cantisani, C., Li, V.W., Mattozzi, C., Melis, L., De Gado, F., Giancristoforo, S., Silvestri, E., Calvieri, S. (2011). Hydrofiber dressing and wound repair: Review of the literature and new patents. Recent Patents on Inflammation & Allergy Drug Discovery, 5(2), 150-154. [CrossRef]
13. 13. Grip, J., Engstad, R.E., Skjaeveland, I., Skalko-Basnet, N., Holsaeter, A.M. (2017). Sprayable carbopol hydrogel with soluble beta-1,3/1,6-glucan as an active ingredient for wound healing-development and in-vivo evaluation. European Journal of Pharmaceutical Sciences, 107, 24-31. [CrossRef]
14. 14. Yoon, D.S., Lee, Y., Ryu, H.A., Jang, Y., Lee, K.M., Choi, Y., Choi, W.J., Lee, M., Park, K.M., Park, K.D., Lee, J.W. (2016). Cell recruiting chemokine-loaded sprayable gelatin hydrogel dressings for diabetic wound healing. Acta Biomaterialia, 38, 59-68. [CrossRef]
15. 15. Balakrishnan, B., Mohanty, M., Umashankar, P.R., Jayakrishnan, A. (2005). Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatin. Biomaterials, 26(32), 6335-6342. [CrossRef]
16. 16. Cheng, H., Shi, Z., Yue, K., Huang, X., Xu, Y., Gao, C., Yao, Z., Zhang, Y.S., Wang, J. (2021). Sprayable hydrogel dressing accelerates wound healing with combined reactive oxygen species-scavenging and antibacterial abilities. Acta Biomaterialia, 124, 219-232. [CrossRef]
17. 17. Annabi, N., Rana, D., Shirzaei Sani, E., Portillo-Lara, R., Gifford, J.L., Fares, M.M., Mithieux, S.M., Weiss, A.S. (2017). Engineering a sprayable and elastic hydrogel adhesive with antimicrobial properties for wound healing. Biomaterials, 139, 229-243. [CrossRef]
18. 18. Qu, J., Zhao, X., Liang, Y., Zhang, T., Ma, P.X., Guo, B. (2018). Antibacterial adhesive injectable hydrogels with rapid self-healing, extensibility and compressibility as wound dressing for joints skin wound healing. Biomaterials, 183, 185-199. [CrossRef]
19. 19. Kilicarslan, M., Ilhan, M., Inal, O., Orhan, K. (2018). Preparation and evaluation of clindamycin phosphate loaded chitosan/alginate polyelectrolyte complex film as mucoadhesive drug delivery system for periodontal therapy. European Journal of Pharmaceutical Sciences, 123, 441-451. [CrossRef]
20. 20. Kılıçarslan, M., Büke, A.N., Nekük, Ö. (2023). 3B Baskı Teknolojisi ve Çok Katmanlı Farmasötik Filmler. In: A. Bozkır and İ. Yıldız (Eds.), Eczacılıkta Yenilikler 4, (pp. 381-397). Ankara, Ankara Üniversitesi Basımevi.
21. 21. Kariduraganavar, M.Y., Kittur, A.A., Kamble, R.R. (2014). Polymer Synthesis and Processing. In: S.G. Kumbar, L. C.T., and M. Deng (Eds.), Natural and Synthetic Biomedical Polymers, (pp. 1-31). USA, Elsevier.
22. 22. Khan, M.I., Islam, J.M., Kabir, W., Rahman, A., Mizan, M., Rahman, M.F., Amin, J., Khan, M.A. (2016). Development of hydrocolloid bi-layer dressing with bio-adhesive and non-adhesive properties. Materials Science and Engineering C, 69, 609-615. [CrossRef]
23. 23. Gomes Neto, R.J., Genevro, G.M., Paulo, L.A., Lopes, P.S., de Moraes, M.A., Beppu, M.M. (2019). Characterization and in vitro evaluation of chitosan/konjac glucomannan bilayer film as a wound dressing. Carbohydrate Polymers, 212, 59-66. [CrossRef]
24. 24. Repka, M.A., Gerding, T.G., Repka, S.L., McGinity, J.W. (1999). Influence of plasticizers and drugs on the physical-mechanical properties of hydroxypropylcellulose films prepared by hot melt extrusion. Drug Development and Industrial Pharmacy, 25(5), 625-633. [CrossRef]
25. 25. Kilicarslan, M., Gencel, C.N. (2020). İlaç Üretiminde Üç Boyutlu Baskı Teknolojileri. In: G. Özçelikay and İ. Yıldız (Eds.), Eczacılıkta Yenilikler 3, (pp. 371-390). Ankara, Ankara Üniversitesi Basımevi.
26. 26. Hafezi, F., Scoutaris, N., Douroumis, D., Boateng, J. (2019). 3d printed chitosan dressing crosslinked with genipin for potential healing of chronic wounds. International Journal of Pharmaceutics, 560, 406-415. [CrossRef]
27. 27. Goyanes, A., Det-Amornrat, U., Wang, J., Basit, A.W., Gaisford, S. (2016). 3d scanning and 3d printing as innovative technologies for fabricating personalized topical drug delivery systems. Journal of Controlled Release, 234, 41-48. [CrossRef]
28. 28. Muwaffak, Z., Goyanes, A., Clark, V., Basit, A.W., Hilton, S.T., Gaisford, S. (2017). Patient-specific 3d scanned and 3d printed antimicrobial polycaprolactone wound dressings. International Journal of Pharmaceutics, 527(1-2), 161-170. [CrossRef]
29. 29. Intini, C., Elviri, L., Cabral, J., Mros, S., Bergonzi, C., Bianchera, A., Flammini, L., Govoni, P., Barocelli, E., Bettini, R., McConnell, M. (2018). 3d-printed chitosan-based scaffolds: An in vitro study of human skin cell growth and an in-vivo wound healing evaluation in experimental diabetes in rats. Carbohydrate Polymers, 199, 593-602. [CrossRef]
30. 30. Alven, S., Peter, S., Mbese, Z., Aderibigbe, B.A. (2022). Polymer-based wound dressing materials loaded with bioactive agents: Potential materials for the treatment of diabetic wounds. Polymers, 14, 1-35. [CrossRef]
31. 31. Pillay, V., Dott, C., Choonara, Y.E., Tyagi, C., Tomar, L., Kumar, P., du Toit, L.C., Ndesendo, V.M.K. (2013). A review of the effect of processing variables on the fabrication of electrospun nanofibers for drug delivery applications. Journal of Nanomaterials, 2013, 1-22. [CrossRef]
32. 32. Zaman, H.U., Islam, J.M., Khan, M.A., Khan, R.A. (2011). Physico-mechanical properties of wound dressing material and its biomedical application. Journal of the Mechanical Behavior of Biomedical Materials, 4(7), 1369-1375. [CrossRef]
33. 33. Miguel, S.P., Figueira, D.R., Simoes, D., Ribeiro, M.P., Coutinho, P., Ferreira, P., Correia, I.J. (2018). Electrospun polymeric nanofibres as wound dressings: A review. Colloids Surf B Biointerfaces, 169, 60-71. [CrossRef]
34. 34. Maver, T., Smrke, D.M., Kurecic, M., Gradisnik, L., Maver, U., Kleinschek, K.S. (2018). Combining 3d printing and electrospinning for preparation of pain-relieving wound-dressing materials. Journal of Sol-Gel Science and Technology, 88, 33-48. [CrossRef]
35. 35. Ignatova, M., Manolova, N., Markova, N., Rashkov, I. (2009). Electrospun non-woven nanofibrous hybrid mats based on chitosan and pla for wound-dressing applications. Macromolecular Bioscience, 9(1), 102-111. [CrossRef]
36. 36. Naseri, N., Algan, C., Jacobs, V., John, M., Oksman, K., Mathew, A.P. (2014). Electrospun chitosan-based nanocomposite mats reinforced with chitin nanocrystals for wound dressing. Carbohydrate Polymers, 109, 7-15. [CrossRef]
37. 37. Pourhojat, F., Sohrabi, M., Shariati, S., Mahdavi, H., Asadpour, L. (2016). Evaluation of poly ε-caprolactone electrospun nanofibers loaded with hypericum perforatum extract as a wound dressing. Research on Chemical Intermediates, 43, 297-320. [CrossRef]
38. 38. Ulubayram, K., Nur Cakar, A., Korkusuz, P., Ertan, C., Hasirci, N. (2001). Egf containing gelatin-based wound dressings. Biomaterials, 22(11), 1345-1356. [CrossRef]
39. 39. Kondo, S., Kuroyanagi, Y. (2012). Development of a wound dressing composed of hyaluronic acid and collagen sponge with epidermal growth factor. Journal of Biomaterials Science, Polymer Edition, 23(5), 629-643. [CrossRef]
40. 40. Öztürk, E., Ağalar, C., Keçeci, K., Denkba, E.B. (2006). Preparation and characterization of ciprofloxacin-loaded alginate/chitosan sponge as a wound dressing material. Journal of Applied Polymer Science, 101(3), 1602-1609. [CrossRef]
41. 41. Berce, C., Muresan, M.S., Soritau, O., Petrushev, B., Tefas, L., Rigo, I., Ungureanu, G., Catoi, C., Irimie, A., Tomuleasa, C. (2018). Cutaneous wound healing using polymeric surgical dressings based on chitosan, sodium hyaluronate and resveratrol. A preclinical experimental study. Colloids Surf B Biointerfaces, 163, 155-166. [CrossRef]
42. 42. Maver, T., Maver, U., Mostegel, F., Griesser, T., Spirk, S., Smrke, D.M., Stana-Kleinschek, K. (2015). Cellulose based thin films as a platform for drug release studies to mimick wound dressing materials. Cellulose, 22, 749-761. [CrossRef]
43. 43. Wathoni, N., Motoyama, K., Higashi, T., Okajima, M., Kaneko, T., Arima, H. (2016). Physically crosslinked-sacran hydrogel films for wound dressing application. International Journal of Biological Macromolecules, 89, 465-470. [CrossRef]
44. 44. Dai, C., Shih, S., Khachemoune, A. (2020). Skin substitutes for acute and chronic wound healing: An updated review. Journal of Dermatological Treatment, 31(6), 639-648. [CrossRef]
45. 45. Suntar, I.P., Akkol, E.K., Yilmazer, D., Baykal, T., Kirmizibekmez, H., Alper, M., Yesilada, E. (2010). Investigations on the in vivo wound healing potential of hypericum perforatum l. Journal of Ethnopharmacology, 127(2), 468-477. [CrossRef]
46. 46. Azad, A.K., Sermsintham, N., Chandrkrachang, S., Stevens, W.F. (2004). Chitosan membrane as a wound-healing dressing, characterization and clinical application. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 69B(2), 216-222. [CrossRef]
47. 47. Li, X., Chen, S., Zhang, B., Li, M., Diao, K., Zhang, Z., Li, J., Xu, Y., Wang, X., Chen, H. (2012). In situ injectable nano-composite hydrogel composed of curcumin, n,o-carboxymethyl chitosan and oxidized alginate for wound healing application. International Journal of Pharmaceutics, 437(1-2), 110-119. [CrossRef]
48. 48. Dadashzadeh, A., Imani, R., Moghassemi, S., Omidfar, K., Abolfathi, N. (2019). Study of hybrid alginate/gelatin hydrogel-incorporated niosomal aloe vera capable of sustained release of Aloe vera as potential skin wound dressing. Polymer Bulletin, 77, 387-403. [CrossRef]
49. 49. Sohrabi, S., Haeri, A., Mahboubi, A., Mortazavi, A., Dadashzadeh, S. (2016). Chitosan gel-embedded moxifloxacin niosomes: An efficient antimicrobial hybrid system for burn infection. International Journal of Biological Macromolecules, 85, 625-633. [CrossRef]
50. 50. Gainza, G., Chu, W.S., Guy, R.H., Pedraz, J.L., Hernandez, R.M., Delgado-Charro, B., Igartua, M. (2015). Development and in vitro evaluation of lipid nanoparticle-based dressings for topical treatment of chronic wounds. International Journal of Pharmaceutics, 490(1-2), 404-411. [CrossRef]
51. 51. Lin, T.F., Huang, Y.J., Liu, Y.J., Peng, C.M., Juan, C.J., Yeh, S.H., Chou, R.H. (2022). 3d-printed surgical wound dressing for prolonged 5-fluorouracil delivery from pluronic blending composites. Materials Today Communications, 33, 104284. [CrossRef]
52. 52. Shi, G., Wang, Y., Derakhshanfar, S., Xu, K., Zhong, W., Luo, G., Liu, T., Wang, Y., Wu, J., Xing, M. (2019). Biomimicry of oil infused layer on 3d printed poly(dimethylsiloxane): Non-fouling, antibacterial and promoting infected wound healing. Materials Science and Engineering C, 100, 915-927. [CrossRef]
53. 53. Teoh, J.H., Tay, S.M., Fuh, J., Wang, C.H. (2022). Fabricating scalable, personalized wound dressings with customizable drug loadings via 3d printing. Journal of Controlled Release, 341, 80-94. [CrossRef]
54. 54. El Hosary, R., El-Mancy, S.M.S., El Deeb, K.S., Eid, H.H., El Tantawy, M.E., Shams, M.M., Samir, R., Assar, N.H., Sleem, A.A. (2020). Efficient wound healing composite hydrogel using egyptian Avena sativa L. polysaccharide containing beta-glucan. International Journal of Biological Macromolecules, 149, 1331-1338. [CrossRef]
55. 55. Roy, N., Saha, N., Kitano, T., Saha, P. (2010). Development and characterization of novel medicated hydrogels for wound dressing. Soft Materials, 8(2), 130-148. [CrossRef]
56. 56. Ahmed, A.S., Mandal, U.K., Taher, M., Susanti, D., Jaffri, J.M. (2018). Pva-peg physically cross-linked hydrogel film as a wound dressing: Experimental design and optimization. Pharmaceutical Development and Technology, 23(8), 751-760. [CrossRef]
57. 57. Liakos, I., Rizzello, L., Scurr, D.J., Pompa, P.P., Bayer, I.S., Athanassiou, A. (2014). All-natural composite wound dressing films of essential oils encapsulated in sodium alginate with antimicrobial properties. International Journal of Pharmaceutics, 463(2), 137-145. [CrossRef]
58. 58. Peles, Z., Binderman, I., Berdicevsky, I., Zilberman, M. (2013). Soy protein films for wound-healing applications: Antibiotic release, bacterial inhibition and cellular response. Journal of Tissue Engineering And Regenerative Medicine, 7(5), 401-412. [CrossRef]
59. 59. Jiang, Q., Zhou, W., Wang, J., Tang, R., Zhang, D., Wang, X. (2016). Hypromellose succinate-crosslinked chitosan hydrogel films for potential wound dressing. International Journal of Biological Macromolecules, 91, 85-91. [CrossRef]
60. 60. Fan, Z.J., Liu, B., Wang, J.Q., Zhang, S.Y., Lin, Q.Q., Gong, P.W., Ma, L.M., Yang, S.R. (2014). A novel wound dressing based on ag/graphene polymer hydrogel: Effectively kill bacteria and accelerate wound healing. Advanced Functional Materials, 24(25), 3933-3943. [CrossRef]
61. 61. Sandri, G., Bonferoni, M.C., D'Autilia, F., Rossi, S., Ferrari, F., Grisoli, P., Sorrenti, M., Catenacci, L., Del Fante, C., Perotti, C., Caramella, C. (2013). Wound dressings based on silver sulfadiazine solid lipid nanoparticles for tissue repairing. European Journal of Pharmaceutics and Biopharmaceutics, 84(1), 84-90. [CrossRef]
62. 62. Gunes, S., Tihminlioglu, F. (2017). Hypericum perforatum incorporated chitosan films as potential bioactive wound dressing material. International Journal of Biological Macromolecules, 102, 933-943. [CrossRef]
63. 63. Pagano, C., Marinozzi, M., Baiocchi, C., Beccari, T., Calarco, P., Ceccarini, M.R., Chielli, M., Orabona, C., Orecchini, E., Ortenzi, R., Ricci, M., Scuota, S., Tiralti, M.C., Perioli, L. (2020). Bioadhesive polymeric films based on red onion skins extract for wound treatment: An innovative and eco-friendly formulation. Molecules, 25(2), 318. [CrossRef]
64. 64. Sung, J.H., Hwang, M.R., Kim, J.O., Lee, J.H., Kim, Y.I., Kim, J.H., Chang, S.W., Jin, S.G., Kim, J.A., Lyoo, W.S., Han, S.S., Ku, S.K., Yong, C.S., Choi, H.G. (2010). Gel characterisation and in vivo evaluation of minocycline-loaded wound dressing with enhanced wound healing using polyvinyl alcohol and chitosan. International Journal of Pharmaceutics, 392(1-2), 232-240. [CrossRef]
65. 65. Kaur, P., Gondil, V.S., Chhibber, S. (2019). A novel wound dressing consisting of pva-sa hybrid hydrogel membrane for topical delivery of bacteriophages and antibiotics. International Journal of Pharmaceutics, 572, 118779. [CrossRef]
66. 66. Hurler, J., Berg, O.A., Skar, M., Conradi, A.H., Johnsen, P.J., Skalko-Basnet, N. (2012). Improved burns therapy: Liposomes-in-hydrogel delivery system for mupirocin. Journal of Pharmaceutical Sciences, 101(10), 3906-3915. [CrossRef]
67. 67. Choi, J.S., Kim, D.W., Kim, D.S., Kim, J.O., Yong, C.S., Cho, K.H., Youn, Y.S., Jin, S.G., Choi, H.G. (2016). Novel neomycin sulfate-loaded hydrogel dressing with enhanced physical dressing properties and wound-curing effect. Drug Delivery, 23(8), 2806-2812. [CrossRef]
68. 68. Kim, J.O., Park, J.K., Kim, J.H., Jin, S.G., Yong, C.S., Li, D.X., Choi, J.Y., Woo, J.S., Yoo, B.K., Lyoo, W.S., Kim, J.A., Choi, H.G. (2008). Development of polyvinyl alcohol-sodium alginate gel-matrix-based wound dressing system containing nitrofurazone. International Journal of Pharmaceutics, 359(1-2), 79-86. [CrossRef]
69. 69. Jin, S.G., Kim, K.S., Kim, D.W., Kim, D.S., Seo, Y.G., Go, T.G., Youn, Y.S., Kim, J.O., Yong, C.S., Choi, H.G. (2016). Development of a novel sodium fusidate-loaded triple polymer hydrogel wound dressing: Mechanical properties and effects on wound repair. International Journal of Pharmaceutics, 497(1-2), 114-122. [CrossRef]
70. 70. Singh, B., Pal, L. (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. [CrossRef]
71. 71. Ahmady, A.R., Razmjooee, K., Saber-Samandari, S., Toghraie, D. (2022). Fabrication of chitosan-gelatin films incorporated with thymol-loaded alginate microparticles for controlled drug delivery, antibacterial activity and wound healing: In-vitro and in-vivo studies. International Journal of Biological Macromolecules, 223(Part A), 567-582. [CrossRef]
72. 72. Nunes, P.S., Albuquerque, R.L., Jr., Cavalcante, D.R., Dantas, M.D., Cardoso, J.C., Bezerra, M.S., Souza, J.C., Serafini, M.R., Quitans, L.J., Jr., Bonjardim, L.R., Araujo, A.A. (2011). Collagen-based films containing liposome-loaded usnic acid as dressing for dermal burn healing. Journal of Biomedicine and Biotechnology, 2011(1), 761593. [CrossRef]
73. 73. Nunes, P.S., Rabelo, A.S., Souza, J.C., Santana, B.V., da Silva, T.M., Serafini, M.R., Dos Passos Menezes, P., Dos Santos Lima, B., Cardoso, J.C., Alves, J.C., Frank, L.A., Guterres, S.S., Pohlmann, A.R., Pinheiro, M.S., de Albuquerque, R.L.J., Araujo, A.A. (2016). Gelatin-based membrane containing usnic acid-loaded liposome improves dermal burn healing in a porcine model. International Journal of Pharmaceutics, 513(1-2), 473-482. [CrossRef]
74. 74. Pagano, C., Ceccarini, M.R., Calarco, P., Scuota, S., Conte, C., Primavilla, S., Ricci, M., Perioli, L. (2019). Bioadhesive polymeric films based on usnic acid for burn wound treatment: Antibacterial and cytotoxicity studies. Colloids and Surfaces B: Biointerfaces, 178, 488-499. [CrossRef]
75. 75. Monteiro, N., Martins, M., Martins, A., Fonseca, N.A., Moreira, J.N., Reis, R.L., Neves, N.M. (2015). Antibacterial activity of chitosan nanofiber meshes with liposomes immobilized releasing gentamicin. Acta Biomaterialia, 18, 196-205. [CrossRef]
76. 76. Almukainzi, M., El-Masry, T.A., Negm, W.A., Elekhnawy, E., Saleh, A., Sayed, A.E., Ahmed, H.M., Abdelkader, D.H. (2022). Co-delivery of gentiopicroside and thymoquinone using electrospun m-peg/pvp nanofibers: In-vitro and in vivo studies for antibacterial wound dressing in diabetic rats. International Journal of Pharmaceutics, 625, 122106. [CrossRef]
77. 77. Daristotle, J.L., Lau, L.W., Erdi, M., Hunter, J., Djoum, A., Jr., Srinivasan, P., Wu, X., Basu, M., Ayyub, O.B., Sandler, A.D., Kofinas, P. (2020). Sprayable and biodegradable, intrinsically adhesive wound dressing with antimicrobial properties. Bioengineering & Translational Medicine, 5(1), e10149. [CrossRef]
78. 78. Ahtzaz, S., Sher Waris, T., Shahzadi, L., Anwar Chaudhry, A., Ur Rehman, I., Yar, M. (2019). Boron for tissue regeneration-it’s loading into chitosan/collagen hydrogels and testing on chorioallantoic membrane to study the effect on angiogenesis. International Journal of Polymeric Materials and Polymeric Biomaterials, 69(8), 525-534. [CrossRef]
79. 79. Ali, M., Motaal, A.A., Ahmed, M.A., Alsayari, A., El-Gazayerly, O.N. (2018). An in vivo study of Hypericum perforatum in a niosomal topical drug delivery system. Drug Delivery, 25(1), 417-425. [CrossRef]
80. 80. Yadollah-Damavandi, S., Chavoshi-Nejad, M., Jangholi, E., Nekouyian, N., Hosseini, S., Seifaee, A., Rafiee, S., Karimi, H., Ashkani-Esfahani, S., Parsa, Y., Mohsenikia, M. (2015). Topical Hypericum perforatum improves tissue regeneration in full-thickness excisional wounds in diabetic rat model. Evidence-Based Complementary and Alternative Medicine, 2015(1), 245328. [CrossRef]
81. 81. Kıyan, S., Uyanıkgil, Y., Altuncı, Y.A., Cavusoglu, T., Cetin Uyanikgil, E.O., Karabey, F. (2015). Investigation of acute effects of Hypericum perforatum (st. John's wort-kantaron) treatment in experimental thermal burns and comparison with silver sulfadiazine treatment. Ulusal Travma ve Acil Cerrahi Dergisi, 21(5), 323-336.
82. 82. Hurler, J., Skalko-Basnet, N. (2012). Potentials of chitosan-based delivery systems in wound therapy: Bioadhesion study. Journal of Functional Biomaterials, 3(1), 37-48. [CrossRef]
83. 83. Gong, C., Wu, Q., Wang, Y., Zhang, D., Luo, F., Zhao, X., Wei, Y., Qian, Z. (2013). A biodegradable hydrogel system containing curcumin encapsulated in micelles for cutaneous wound healing. Biomaterials, 34(27), 6377-6387. [CrossRef]
84. 84. Hurler, J., Zakelj, S., Mravljak, J., Pajk, S., Kristl, A., Schubert, R., Skalko-Basnet, N. (2013). The effect of lipid composition and liposome size on the release properties of liposomes-in-hydrogel. International Journal of Pharmaceutics, 456(1), 49-57. [CrossRef]
85. 85. Tran, N.Q., Joung, Y.K., Lih, E., Park, K.D. (2011). In situ forming and rutin-releasing chitosan hydrogels as injectable dressings for dermal wound healing. Biomacromolecules, 12(8), 2872-2880. [CrossRef]
86. 86. Dogan, A., Demirci, S., Caglayan, A.B., Kilic, E., Gunal, M.Y., Uslu, U., Cumbul, A., Sahin, F. (2014). Sodium pentaborate pentahydrate and pluronic containing hydrogel increases cutaneous wound healing in vitro and in vivo. Biological Trace Element Research, 162, 72-79. [CrossRef]
87. 87. Demirci, S., Dogan, A., Aydin, S., Dulger, E.C., Sahin, F. (2016). Boron promotes streptozotocin-induced diabetic wound healing: Roles in cell proliferation and migration, growth factor expression, and inflammation. Molecular and Cellular Biochemistry, 417, 119-133. [CrossRef]
88. 88. Demirci, S., Dogan, A., Karakus, E., Halici, Z., Topcu, A., Demirci, E., Sahin, F. (2015). Boron and poloxamer (f68 and f127) containing hydrogel formulation for burn wound healing. Biological Trace Element Research, 168, 169-180. [CrossRef]
89. 89. Dharashivkar, S.S., Sahasrabuddhe, S.H., Saoji, A.N. (2015). Niosomally encapsulated silver sulfadiazine gel for burn treatment. Journal of Microencapsulation, 32(2), 137-142. [CrossRef]
90. 90. Xu, W., Gao, X., Tan, H., Li, S., Zhou, T., Li, J., Chen, Y. (2022). Covalent and biodegradable chitosan-cellulose hydrogel dressing containing microspheres for drug delivery and wound healing. Materials Today Communications, 33, 104163. [CrossRef]
91. 91. Li, W., Wang, B., Zhang, M., Wu, Z., Wei, J., Jiang, Y., Sheng, N., Liang, Q., Zhang, D., Chen, S. (2020). All-natural injectable hydrogel with self-healing and antibacterial properties for wound dressing. Cellulose, 27, 2637-2650. [CrossRef]
92. 92. Elsner, J.J., Egozi, D., Ullmann, Y., Berdicevsky, I., Shefy-Peleg, A., Zilberman, M. (2011). Novel biodegradable composite wound dressings with controlled release of antibiotics: Results in a guinea pig burn model. Burns, 37(5), 896-904. [CrossRef]
93. 93. Hong, H.J., Jin, S.E., Park, J.S., Ahn, W.S., Kim, C.K. (2008). Accelerated wound healing by smad3 antisense oligonucleotides-impregnated chitosan/alginate polyelectrolyte complex. Biomaterials, 29(36), 4831-4837. [CrossRef]
94. 94. Coyne, J., Zhao, N., Olubode, A., Menon, M., Wang, Y. (2020). Development of hydrogel-like biomaterials via nanoparticle assembly and solid-hydrogel transformation. Journal of Controlled Release, 318, 185-196. [CrossRef]
95. 95. Romic, M.D., Klaric, M.S., Lovric, J., Pepic, I., Cetina-Cizmek, B., Filipovic-Grcic, J., Hafner, A. (2016). Melatonin-loaded chitosan/pluronic(r) f127 microspheres as in situ forming hydrogel: An innovative antimicrobial wound dressing. European Journal of Pharmaceutics and Biopharmaceutics 107, 67-79. [CrossRef]
96. 96. De Cicco, F., Porta, A., Sansone, F., Aquino, R.P., Del Gaudio, P. (2014). Nanospray technology for an in situ gelling nanoparticulate powder as a wound dressing. International Journal of Pharmaceutics, 473(1-2), 30-37. [CrossRef]
97. 97. Basha, M., AbouSamra, M.M., Awad, G.A., Mansy, S.S. (2018). A potential antibacterial wound dressing of cefadroxil chitosan nanoparticles in situ gel, Fabrication, in vitro optimization and in vivo evaluation. International Journal of Pharmaceutics, 544(1), 129-140. [CrossRef]
98. 98. Devi, N., Dutta, J. (2017). Preparation and characterization of chitosan-bentonite nanocomposite films for wound healing application. International Journal of Biological Macromolecules, 104(Part B), 1897-1904. [CrossRef]
99. 99. Kilicarslan, M., Ilhan, M., Orhan, K. (2020). Micro-computed tomography (Micro-CT) analysis as a new approach for characterization of drug delivery systems. In: K. Orhan (Ed.), Micro-Computed Tomography (Micro-Ct) in Medicine and Engineering, (pp. 213-223). Switzerland: Springer Nature.
100. 100. Parvez, S., Rahman, M.M., Khan, M.A., Khan, M.A.H., Islam, J.M.M., Ahmed, M., Rahman, M.F., Ahmed, B. (2012). Preparation and characterization of artificial skin using chitosan and gelatin composites for potential biomedical application. Polymer Bulletin, 69, 715-731. [CrossRef]