Author(s):
Seema Yadav, Narahari N. Palei
Email(s):
narahari.palei@gmail.com
DOI:
10.52711/0974-360X.2024.00784 
Address:
Seema Yadav, Narahari N. Palei*
Amity Institute of Pharmacy, Lucknow, Amity University, Uttar Pradesh, Sector 125, Noida, 201313.
*Corresponding Author
Published In:
Volume - 17,
Issue - 10,
Year - 2024
ABSTRACT:
Several materials are used to promote wound healing. However, natural polymers work better than synthetic polymers for wound healing. Chitosan is a naturally occurring biopolymer that has several beneficial biological properties, such as biocompatibility and biodegradability, that make it helpful for wound healing applications. Chitosan is a biomaterial obtained from deacetylated chitin. Because of their ease of acquisition, hemostatic, antibacterial properties, and ability to promote skin regeneration, chitosan hasgained significant research on skin wound repair. In this review, we have discussed the mechanisms of wound healing of skin by chitosan promoting haemostasis, anti-inflammation, and proliferation of granulation. This review discussed the various applications of chitosan in wound healing process. We also provided latest information of chitosan playing the major role in preclinical studies, theranostic applications, and clinical trials for wound healing process.
Cite this article:
Seema Yadav, Narahari N. Palei. Chitosan as Biomaterial for Wound healing: Mechanisms and Various applications. Research Journal of Pharmacy and Technology. 2024; 17(10):5102-2. doi: 10.52711/0974-360X.2024.00784
Cite(Electronic):
Seema Yadav, Narahari N. Palei. Chitosan as Biomaterial for Wound healing: Mechanisms and Various applications. Research Journal of Pharmacy and Technology. 2024; 17(10):5102-2. doi: 10.52711/0974-360X.2024.00784 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2024-17-10-69
REFERENCES:
1. Bura AR. Effect of Wound Healing Potential of Plumeria obtusa (Champa) Spray. Asian J Pharm Res. 2018; 8(4): 231. doi:10.5958/2231-5691.2018.00039.4
2. Jacob J, Haponiuk JT, Thomas S, Gopi S. Biopolymer based nanomaterials in drug delivery systems: A review. Mater Today Chem. 2018; 9: 43-55. doi:https://doi.org/10.1016/j.mtchem.2018.05.002
3. Thiruchelvi R, Priyadharshini S, Mugunthan P, Rajakumari K. Collagen–Zinc Oxide Nanoparticles (ZnO NPs) Composites for Wound Healing–A Review. Res J Pharm Technol. 2022; 15(6): 2838-2844. http://dx.doi.org/10.52711/0974-360X.2022.00474
4. Gobinath T, Kaviya K, Ravichandran S. Chitosan/Ulva lactuca polysaccharide Hydrogel containing copper (II) beneficial for Biofilm-associated wound infection: Formulation Characterizations and in vitro study. Res J Pharm Technol. 2020; 13(9): 4224-4230. http://dx.doi.org/10.5958/0974-360X.2020.00746.5
5. Hamzah ML. Formulation and evaluation of Flurbiprofen nanogel. Res J Pharm Technol. 2020; 13(11): 5183-5188. http://dx.doi.org/10.5958/0974-360X.2020.00906.3
6. Ratnaparkhi MP, Andhale RS, Karnawat GR. Nanofibers-a newer technology. Res J Pharm Technol. 2021; 14(4): 2321-2327. http://dx.doi.org/10.52711/0974-360X.2021.00410.
7. Paswan SK, Srivastava S, Rao CV. Incision wound healing, anti-inflammatory and analgesic activity of amaranthus spinonous in wistar rats. Res J Pharm Technol. 2020; 13(5): 2439-2444. doi:10.5958/0974-360X.2020.00437.0
8. Beanes SR, Dang C, Soo C, Ting K. Skin repair and scar formation: the central role of TGF-β. Expert Rev Mol Med. 2003; 5(8): 1-22. https://doi.org/10.1017/S1462399403005817.
9. Budhy TI, Rahayu RP, Prathama FA. Potential of Anadara granosa Nanoparticles to improve the Expression of the Fibroblast Growth Factor-2 (FGF-2) in Chronic wound of Hyperglycemia conditions. Res J Pharm Technol. 2022; 15(12): 5757-5760.http://dx.doi.org/10.52711/0974-360X.2022.00971.
10. Feng P, Luo Y, Ke C, et al. Chitosan-Based Functional Materials for Skin Wound Repair: Mechanisms and Applications. Front Bioeng Biotechnol. 2021; 9(February). doi:10.3389/fbioe.2021.650598
11. Kalaivani C, Kuppusamy G, Karri VVSR. Simvastatin loaded polycaprolactone-collagen scaffolds for the treatment of diabetic foot ulcer. Res J Pharm Technol. 2019; 12(6): 2637-2644. http://dx.doi.org/10.5958/0974-360X.2019.00441.4.
12. Salva E, Alan S, Karakoyun B, Çakalağaoğlu F, Özbaş S, Akbuğa J. Investigation of therapeutic effects in the wound healing of chitosan/pGM-CSF complexes. Brazilian J Pharm Sci. 2022; 58: 1-15. doi:10.1590/s2175-97902022e19668
13. Jangde RK, Khute S. Design and Development of Ciprofloxacin Lipid Polymer Hybrid Nanoparticle by Response Surface Methodology. Res J Pharm Technol. 2020; 13(7): 3249-3256. http://dx.doi.org/10.5958/0974-360X.2020.00576.4.
14. Liu H, Wang C, Li C, et al. A functional chitosan-based hydrogel as a wound dressing and drug delivery system in the treatment of wound healing. RSC Adv. 2018; 8(14): 7533-7549. doi:10.1039/c7ra13510f
15. Hu J, Lin Y, Cui C, et al. Clinical efficacy of wet dressing combined with chitosan wound dressing in the treatment of deep second-degree burn wounds: A prospective, randomised, single-blind, positive control clinical trial. Int Wound J. 2023; 20(3): 699-705. doi:10.1111/iwj.13911
16. Liu H, Ding J, Wang C, et al. Intra-articular transplantation of allogeneic BMMSCs rehabilitates cartilage injury of antigen-induced arthritis. Tissue Eng Part A. 2015; 21(21-22): 2733-2743. https://doi.org/10.1089/ten.tea.2014.0666.
17. Huang X, Zhang Y, Zhang X, Xu L, Chen X, Wei S. Influence of radiation crosslinked carboxymethyl-chitosan/gelatin hydrogel on cutaneous wound healing. Mater Sci Eng C. 2013; 33(8): 4816-4824. https://doi.org/10.1016/j.msec.2013.07.044.
18. Lin Y, Lin J, Li T, et al. Dressing with epigallocatechin gallate nanoparticles for wound regeneration. Wound Repair Regen. 2016; 24(2): 287-301.https://doi.org/10.1111/wrr.12372.
19. Sharma D, Rajput J, Kaith BS, Kaur M, Sharma S. Synthesis of ZnO nanoparticles and study of their antibacterial and antifungal properties. Thin Solid Films. 2010; 519(3): 1224-1229.https://doi.org/10.1016/j.tsf.2010.08.073.
20. Diegelmann RF, Dunn JD, Lindblad WJ, Cohen IK. Analysis of the effects of chitosan on inflammation, angiogenesis, fibroplasia, and collagen deposition in polyvinyl alcohol sponge implants in rat wounds. Wound Repair Regen. 1996; 4(1): 48-52. https://doi.org/10.1046/j.1524-475X.1996.40109.x
21. Kozen BG, Kircher SJ, Henao J, Godinez FS, Johnson AS. An alternative hemostatic dressing: comparison of CELOX, HemCon, and QuikClot. Acad Emerg Med. 2008; 15(1): 74-81. https://doi.org/10.1111/j.1553-2712.2007.00009.x.
22. Millner RWJ, Lockhart AS, Bird H, Alexiou C. A New Hemostatic Agent: Initial Life-Saving Experience With Celox (Chitosan) in Cardiothoracic Surgery. Ann Thorac Surg. 2009; 87(2): e13-e14. doi:10.1016/j.athoracsur.2008.09.046
23. Ueno H, Mori T, Fujinaga T. Topical formulations and wound healing applications of chitosan. Adv Drug Deliv Rev. 2001; 52(2): 105-115.https://doi.org/10.1016/S0169-409X(01)00189-2
24. Ong SY, Wu J, Moochhala SM, Tan MH, Lu J. Development of a chitosan-based wound dressing with improved hemostatic and antimicrobial properties. Biomaterials. 2008; 29(32): 4323-4332. doi:10.1016/j.biomaterials.2008.07.034
25. Feng P, Luo Y, Ke C, et al. Chitosan-based functional materials for skin wound repair: Mechanisms and applications. Front Bioeng Biotechnol. 2021; 9: 650598. https://doi.org/10.3389/fbioe.2021.650598.
26. Howling GI, Dettmar PW, Goddard PA, Hampson FC, Dornish M, Wood EJ. The effect of chitin and chitosan on the proliferation of human skin fibroblasts and keratinocytes in vitro. Biomaterials. 2001; 22(22): 2959-2966. doi:https://doi.org/10.1016/S0142-9612(01)00042-4
27. Dvorak HF. Vascular permeability to plasma, plasma proteins, and cells: an update. Curr Opin Hematol. 2010; 17(3): 225. https://doi.org/10.1097%2FMOH.0b013e3283386638.
28. Nedelec B, De Oliveira A, Saint-Cyr M, Garrel DR. Differential effect of burn injury on fibroblasts from wounds and normal skin. Plast Reconstr Surg. 2007; 119(7): 2101-2109. https://doi.org/ 10.1097/01.prs.0000260592.31969.06
29. Guo S al, DiPietro LA. Factors affecting wound healing. J Dent Res. 2010; 89(3): 219-229. https://doi.org/10.1177/0022034509359125
30. Moura LIF, Dias AMA, Carvalho E, de Sousa HC. Recent advances on the development of wound dressings for diabetic foot ulcer treatment—A review. Acta Biomater. 2013; 9(7): 7093-7114. https://doi.org/10.1016/j.actbio.2013.03.033
31. Montazeri S, Rastegari A, Mohammadi Z, et al. Chitosan nanoparticle loaded by epidermal growth factor as a potential protein carrier for wound healing: In vitro and in vivo studies. IET nanobiotechnology. 2023; 17(3): 204-211. doi:10.1049/nbt2.12116
32. Mishra A, Sahu G, Kumar A, et al. Underlining the pharmaceutical aspects associated with the development of pH responsive hydrogel. Res J Pharm Technol. 2017; 10(4): 1261-1268. http://dx.doi.org/10.5958/0974-360X.2017.00224.4.
33. Vijayan A, Sabareeswaran A, Kumar GSV. PEG grafted chitosan scaffold for dual growth factor delivery for enhanced wound healing. Sci Rep. 2019; 9(1): 1-12. doi:10.1038/s41598-019-55214-7
34. Amsden B. Novel biodegradable polymers for local growth factor delivery. Eur J Pharm Biopharm. 2015; 97: 318-328. https://doi.org/10.1016/j.ejpb.2015.06.008.
35. Pulat M, Kahraman AS, Tan N, Gümüşderelioğlu M. Sequential antibiotic and growth factor releasing chitosan-PAAm semi-IPN hydrogel as a novel wound dressing. J Biomater Sci Polym Ed. 2013; 24(7): 807-819. https://doi.org/10.1080/09205063.2012.718613.
36. Hajimiri M, Shahverdi S, Esfandiari MA, et al. Preparation of hydrogel embedded polymer-growth factor conjugated nanoparticles as a diabetic wound dressing. Drug Dev Ind Pharm. 2016; 42(5): 707-719. https://doi.org/10.3109/03639045.2015.1075030.
37. Sukumar N, Ramachandran T, Kalaiarasi H, Sengottuvelu S. Characterization and in vivo evaluation of silk hydrogel with enhancement of dextrin, rhEGF, and alginate beads for diabetic Wistar Albino wounded rats. J Text Inst. 2015; 106(2): 133-140. https://doi.org/10.1080/00405000.2014.906100.
38. Choi JS, Yoo HS. Pluronic/chitosan hydrogels containing epidermal growth factor with wound‐adhesive and photo‐crosslinkable properties. J Biomed Mater Res Part A. 2010; 95(2): 564-573. https://doi.org/10.1002/jbm.a.32848.
39. Park CJ, Clark SG, Lichtensteiger CA, Jamison RD, Johnson AJW. Accelerated wound closure of pressure ulcers in aged mice by chitosan scaffolds with and without bFGF. Acta Biomater. 2009; 5(6): 1926-1936. https://doi.org/10.1016/j.actbio.2009.03.002.
40. Wang W, Lin S, Xiao Y, et al. Acceleration of diabetic wound healing with chitosan-crosslinked collagen sponge containing recombinant human acidic fibroblast growth factor in healing-impaired STZ diabetic rats. Life Sci. 2008; 82(3-4): 190-204. https://doi.org/10.1016/j.lfs.2007.11.009.
41. Obara K, Ishihara M, Fujita M, et al. Acceleration of wound healing in healing‐impaired db/db mice with a photocrosslinkable chitosan hydrogel containing fibroblast growth factor‐2. Wound repair Regen. 2005; 13(4): 390-397. https://doi.org/10.1111/j.1067-1927.2005.130406.x.
42. Guo L, Wang W, Chen Z, Zhou R, Liu Y, Yuan Z. Promotion of microvasculature formation in alginate composite hydrogels by an immobilized peptide GYIGSRG. Sci China Chem. 2012; 55: 1781-1787. https://doi.org/10.1007/s11426-012-4513-1.
43. Ribeiro MP, Morgado PI, Miguel SP, Coutinho P, Correia IJ. Dextran-based hydrogel containing chitosan microparticles loaded with growth factors to be used in wound healing. Mater Sci Eng C. 2013; 33(5): 2958-2966. https://doi.org/10.1016/j.msec.2013.03.025.
44. Kiwanuka E, Junker J, Eriksson E. Harnessing growth factors to influence wound healing. Clin Plast Surg. 2012; 39(3): 239-248. https://doi.org/10.1016/j.cps.2012.04.003
45. Behm B, Babilas P, Landthaler M, Schreml S. Cytokines, chemokines and growth factors in wound healing. J Eur Acad Dermatology Venereol. 2012; 26(7): 812-820.https://doi.org/10.1111/j.1468-3083.2011.04415.x.
46. Gainza G, Villullas S, Pedraz JL, Hernandez RM, Igartua M. Advances in drug delivery systems (DDSs) to release growth factors for wound healing and skin regeneration. Nanomedicine Nanotechnology, Biol Med. 2015; 11(6): 1551-1573. https://doi.org/10.1016/j.nano.2015.03.002.
47. Dai T, Tanaka M, Huang YY, Hamblin MR. Chitosan preparations for wounds and burns: antimicrobial and wound-healing effects. Expert Rev Anti Infect Ther. 2011; 9(7): 857-879. doi:10.1586/eri.11.59
48. Santos TC, Marques AP, Silva SS, et al. In vitro evaluation of the behaviour of human polymorphonuclear neutrophils in direct contact with chitosan-based membranes. J Biotechnol. 2007; 132(2): 218-226. doi:https://doi.org/10.1016/j.jbiotec.2007.07.497
49. Kojima K, Okamoto Y, Kojima K, et al. Effects of chitin and chitosan on collagen synthesis in wound healing. J Vet Med Sci. 2004; 66(12): 1595-1598.https://doi.org/10.1292/jvms.66.1595.
50. Minagawa T, Okamura Y, Shigemasa Y, Minami S, Okamoto Y. Effects of molecular weight and deacetylation degree of chitin/chitosan on wound healing. Carbohydr Polym. 2007; 67(4): 640-644.https://doi.org/10.1016/j.carbpol.2006.07.007.
51. Alsarra IA. Chitosan topical gel formulation in the management of burn wounds. Int J Biol Macromol. 2009; 45(1): 16-21. doi:10.1016/j.ijbiomac.2009.03.010
52. Alsarra IA. Chitosan topical gel formulation in the management of burn wounds. Int J Biol Macromol. 2009; 45(1): 16-21. https://doi.org/10.1016/j.ijbiomac.2009.03.010.
53. Azad AK, Sermsintham N, Chandrkrachang S, Stevens WF. Chitosan membrane as a wound‐healing dressing: characterization and clinical application. J Biomed Mater Res Part B Appl Biomater An Off J Soc Biomater Japanese Soc Biomater Aust Soc Biomater Korean Soc Biomater. 2004; 69(2): 216-222. https://doi.org/10.1002/jbm.b.30000.
54. Ahmed S, Ikram S. Chitosan & its derivatives: a review in recent innovations. Int J Pharm Sci Res. 2015; 6(1): 14-30. http://dx.doi.org/10.13040/IJPSR.0975-8232.6(1).14-30.
55. Jayakumar R, Prabaharan M, Nair S V, Tamura H. Novel chitin and chitosan nanofibers in biomedical applications. Biotechnol Adv. 2010; 28(1): 142-150. https://doi.org/10.1016/j.biotechadv.2009.11.001.
56. Boateng JS, Matthews KH, Stevens HNE, Eccleston GM. Wound healing dressings and drug delivery systems: a review. J Pharm Sci. 2008; 97(8): 2892-2923. https://doi.org/10.1002/jps.21210.
57. Pourseif T, Ghafelehbashi R, Abdihaji M, et al. Chitosan -based nanoniosome for potential wound healing applications: Synergy of controlled drug release and antibacterial activity. Int J Biol Macromol. 2023; 230: 123185. doi:https://doi.org/10.1016/j.ijbiomac.2023.123185
58. Pasquina LW, Santa Maria JP, Walker S. Teichoic acid biosynthesis as an antibiotic target. Curr Opin Microbiol. 2013; 16(5): 531-537. https://doi.org/10.1016/j.mib.2013.06.014.
59. Severino R, Ferrari G, Vu KD, Donsì F, Salmieri S, Lacroix M. Antimicrobial effects of modified chitosan based coating containing nanoemulsion of essential oils, modified atmosphere packaging and gamma irradiation against Escherichia coli O157: H7 and Salmonella Typhimurium on green beans. Food Control. 2015; 50: 215-222. https://doi.org/10.1016/j.foodcont.2014.08.029
60. Tamara FR, Lin C, Mi FL, Ho YC. Antibacterial effects of chitosan/cationic peptide nanoparticles. Nanomaterials. 2018; 8(2): 88. https://doi.org/10.3390/nano8020088
61. Beck BH, Yildirim‐Aksoy M, Shoemaker CA, Fuller SA, Peatman E. Antimicrobial activity of the biopolymer chitosan against Streptococcus iniae. J Fish Dis. 2019; 42(3): 371-377. https://doi.org/10.1111/jfd.12938.
62. Archana D, Singh BK, Dutta J, Dutta PK. Chitosan-PVP-nano silver oxide wound dressing: in vitro and in vivo evaluation. Int J Biol Macromol. 2015; 73: 49-57.
63. Chien RC, Yen MT, Mau JL. Antimicrobial and antitumor activities of chitosan from shiitake stipes, compared to commercial chitosan from crab shells. Carbohydr Polym. 2016; 138: 259-264. https://doi.org/10.1016/j.carbpol.2015.11.061.
64. Tayel AA, Moussa S, Opwis K, Knittel D, Schollmeyer E, Nickisch-Hartfiel A. Inhibition of microbial pathogens by fungal chitosan. Int J Biol Macromol. 2010; 47(1): 10-14.https://doi.org/10.1016/j.ijbiomac.2010.04.005
65. Devi N, Dutta J. Preparation and characterization of chitosan-bentonite nanocomposite films for wound healing application. Int J Biol Macromol. 2017;104:1897-1904.https://doi.org/10.1016/j.ijbiomac.2017.02.080
66. Okamoto Y, Kawakami K, Miyatake K, Morimoto M, Shigemasa Y, Minami S. Analgesic effects of chitin and chitosan. Carbohydr Polym. 2002; 49(3): 249-252.https://doi.org/10.1016/S0144-8617(01)00316-2.
67. Aoyagi S, Onishi H, Machida Y. Novel chitosan wound dressing loaded with minocycline for the treatment of severe burn wounds. Int J Pharm. 2007; 330(1-2): 138-145. https://doi.org/10.1016/j.ijpharm.2006.09.016.
68. Kim MS, Sung MJ, Seo SB, Yoo SJ, Lim WK, Kim HM. Water-soluble chitosan inhibits the production of pro-inflammatory cytokine in human astrocytoma cells activated by amyloid β peptide and interleukin-1β. Neurosci Lett. 2002; 321(1-2): 105-109. https://doi.org/10.1016/S0304-3940(02)00066-6
69. Spindola H, Fernandes J, De Sousa V, et al. Anti-inflammatory effect of chitosan oligomers. N Biotechnol. 2009; 25: S9. https://doi.org/10.1016/j.nbt.2009.06.025
70. Mutlu N, Liverani L, Kurtuldu F, Galusek D, Boccaccini AR. Zinc improves antibacterial, anti-inflammatory and cell motility activity of chitosan for wound healing applications. Int J Biol Macromol. 2022; 213: 845-857. doi:https://doi.org/10.1016/j.ijbiomac.2022.05.199
71. Li F, Shi Y, Liang J, Zhao L. Curcumin-loaded chitosan nanoparticles promote diabetic wound healing via attenuating inflammation in a diabetic rat model. J Biomater Appl. 2019;34(4):476-486. https://doi.org/10.1177/0885328219860929
72. Nahar K, Hossain K, Khan TA. Alginates: The Wonder Molecule and its Gelling Techniques. Res J Pharm Technol. 2017; 10(9): 3195-3204.http://dx.doi.org/10.5958/0974-360X.2017.00568.6
73. Oliviya CR. Production of ecofriendly silver nanoparticle and evaluation of its potential antimicrobial activity. Res J Pharm Technol. 2015; 8(10): 1374-1378.http://dx.doi.org/10.5958/0974-360X.2015.00246.2.
74. Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res Eur Chir Forschung Rech Chir Eur. 2012; 49(1): 35-43. doi:10.1159/000339613
75. Singh R, Shitiz K, Singh A. Chitin and chitosan: biopolymers for wound management. Int Wound J. 2017; 14(6): 1276-1289. doi:10.1111/iwj.12797
76. Kulling D, Vournakis JN, Woo S, et al. Endoscopic injection of bleeding esophageal varices with a poly-N-acetyl glucosamine gel formulation in the canine portal hypertension model. Gastrointest Endosc. 1999; 49(6): 764-771. https://doi.org/10.1016/S0016-5107(99)70298-1
77. Patrulea V, Ostafe V, Borchard G, Jordan O. Chitosan as a starting material for wound healing applications. Eur J Pharm Biopharm. 2015; 97: 417-426. doi:10.1016/j.ejpb.2015.08.004
78. Jiang Q, zhou W, Wang J, Tang R, Zhang D, Wang X. Hypromellose succinate-crosslinked chitosan hydrogel films for potential wound dressing. Int J Biol Macromol. 2016; 91: 85-91. doi:10.1016/j.ijbiomac.2016.05.077
79. Zhao R, Li X, Sun B, et al. Electrospun chitosan/sericin composite nanofibers with antibacterial property as potential wound dressings. Int J Biol Macromol. 2014; 68: 92-97. https://doi.org/10.1016/j.ijbiomac.2014.04.029
80. Ahmed S, Ikram S. Chitosan Based Scaffolds and Their Applications in Wound Healing. Achiev Life Sci. 2016; 10(1): 27-37. doi:https://doi.org/10.1016/j.als.2016.04.001
81. Miguel SP, Moreira AF, Correia IJ. Chitosan based-asymmetric membranes for wound healing: A review. Int J Biol Macromol. 2019; 127: 460-475. doi:10.1016/j.ijbiomac.2019.01.072
82. Feng W, Wang Z. Shear-thinning and self-healing chitosan-graphene oxide hydrogel for hemostasis and wound healing. Carbohydr Polym. 2022; 294: 119824. doi:https://doi.org/10.1016/j.carbpol.2022.119824
83. Hu S, Bi S, Yan D, et al. Preparation of composite hydroxybutyl chitosan sponge and its role in promoting wound healing. Carbohydr Polym. 2018; 184: 154-163. doi:https://doi.org/10.1016/j.carbpol.2017.12.033
84. Bektas N, Şenel B, Yenilmez E, Özatik O, Arslan R. Evaluation of wound healing effect of chitosan-based gel formulation containing vitexin. Saudi Pharm J. 2020; 28(1): 87-94. doi:https://doi.org/10.1016/j.jsps.2019.11.008
85. Wang D, Zhang N, Meng G, He J, Wu F. The effect of form of carboxymethyl-chitosan dressings on biological properties in wound healing. Colloids Surfaces B Biointerfaces. 2020; 194: 111191. doi:https://doi.org/10.1016/j.colsurfb.2020.111191
86. Zhou L, Zhao X, Li M, et al. Antibacterial and wound healing–promoting effect of sponge-like chitosan-loaded silver nanoparticles biosynthesized by iturin. Int J Biol Macromol. 2021; 181: 1183-1195. doi:https://doi.org/10.1016/j.ijbiomac.2021.04.119
87. Algandaby MM, Esmat A, Nasrullah MZ, et al. LC-MS based metabolic profiling and wound healing activity of a chitosan nanoparticle-loaded formula of Teucrium polium in diabetic rats. Biomed Pharmacother. 2023; 168: 115626. https://doi.org/10.1016/j.biopha.2023.115626
88. Cui Y, Duan W, Jin Y, Wo F, Xi F, Wu J. Graphene quantum dot-decorated luminescent porous silicon dressing for theranostics of diabetic wounds. Acta Biomater. 2021; 131: 544-554. doi:https://doi.org/10.1016/j.actbio.2021.07.018
89. Zhang S, Liu Y, Zhang X, et al. Prostaglandin E(2) hydrogel improves cutaneous wound healing via M2 macrophages polarization. Theranostics. 2018; 8(19): 5348-5361. doi:10.7150/thno.27385
90. Zheng K, Tong Y, Zhang S, et al. Flexible bicolorimetric polyacrylamide/chitosan hydrogels for smart real‐time monitoring and promotion of wound healing. Adv Funct Mater. 2021; 31(34): 2102599. https://doi.org/10.1002/adfm.202102599
91. Wang CH, Cherng JH, Liu CC, et al. Procoagulant and Antimicrobial Effects of Chitosan in Wound Healing. Int J Mol Sci. 2021; 22(13). doi:10.3390/ijms22137067
92. Vescovali C, Damour O, Shahabedin L, et al. Epidermalization of an artificial dermis made of collagen. Ann Mediterrian Burn Club. 1989; 2: 137139.
93. Shivakumar P, Gupta MS, Jayakumar R, Gowda DV. Prospection of chitosan and its derivatives in wound healing: Proof of patent analysis (2010–2020). Int J Biol Macromol. 2021; 184(May): 701-712. doi:10.1016/j.ijbiomac.2021.06.086
94. Damour O, Gueugniaud PY, Berthin-Maghit M, et al. A dermal substrate made of collagen-GA-chitosan for deep burn coverage: first clinical uses. Clin Mater. 1994; 15(4): 273-276. https://doi.org/10.1016/0267-6605(94)90057-4
95. Zhang C, Yang X, Hu W, Han X, Fan L, Tao S. Preparation and characterization of carboxymethyl chitosan/collagen peptide/oxidized konjac composite hydrogel. Int J Biol Macromol. 2020; 149: 31-40. https://doi.org/10.1016/j.ijbiomac.2020.01.127
96. Mo X, Cen J, Gibson E, Wang R, Percival SL. An open multicenter comparative randomized clinical study on chitosan. Wound repair Regen Off Publ Wound Heal Soc [and] Eur Tissue Repair Soc. 2015; 23(4): 518-524. doi:10.1111/wrr.12298
97. Shaik J, Garlapati R, Nagesh B, Sujana V, Jayaprakash T, Naidu S. Comparative evaluation of antimicrobial efficacy of triple antibiotic paste and calcium hydroxide using chitosan as carrier against Candida albicans and Enterococcus faecalis: An in vitro study. J Conserv Dent. 2014; 17(4): 335-339. doi:10.4103/0972-0707.136444
98. Liu J, Shen H. Clinical efficacy of chitosan-based hydrocolloid dressing in the treatment of chronic refractory wounds. Int Wound J. 2022; 19(8): 2012-2018. doi:10.1111/iwj.13801
99. Shao Y, Zhou H. Clinical evaluation of an oral mucoadhesive film containing chitosan for the treatment of recurrent aphthous stomatitis: a randomized, double-blind study. J Dermatolog Treat. 2020; 31(7): 739-743. doi:10.1080/09546634.2019.1610548
100. Valentine R, Athanasiadis T, Moratti S, Hanton L, Robinson S, Wormald PJ. The efficacy of a novel chitosan gel on hemostasis and wound healing after endoscopic sinus surgery. Am J Rhinol Allergy. 2010; 24(1): 70-75. doi:10.2500/ajra.2010.24.3422