Topical Polydeoxyribonucleotide Loaded in Hydrogel Formulation for Wound Healing in Diabetic Rats
Keywords:Polynucleotide, Polydeoxyribonucleotide, Hydrogel, Diabetic foot, Wound healing, Regeneration
Patients with diabetes mellitus experience delayed wound healing because of the uncontrolled glucose level leads to impaired cell proliferative function, poor circulation, decreased production and repair of new blood vessels. Polydeoxyribonucleotide (PDRN) is used in wound healing as a substance that stimulates tissue repair. A hydrogel is a reticular substance generally used as a dressing formulation to accelerate wound healing, and also used as a bio-applicable scaffold or vehicle. The aim of study is to investigate the effects of PDRN loaded in hydrogel on wound healing, in combination and separately, in an animal diabetic wound model.
Methods: We studied the effects of PDRN in diabetes-related healing defect using an incisional skin-wound model produced on the back of male diabetic rats. A total of 36 wounds, were classified into 3 groups: a control group, a hydrogel-only group, a PDRN loaded in hydrogel combined-treatment group. All rats were assessed for changes in wound size and photographed on scheduled dates. The skin specimen sample of diabetic rat wound model were observed on 3, 7, 14 and 21 days after skin injury to measure tissue remodeling through histological evaluation of fibroblasts proliferation, and collagen production, also the number of blood vessels was measured in all specimens.
Results: Differences in the decrease and change in wound size in the PDRN loaded in hydrogel group were more significant than those in the control and hydrogel single-treatment groups. Analysis of the fibroblasts proliferation, collagen production and number of blood vessels through histological examination showed a pattern of increase over time that occurred in PDRN loaded in hydrogel combined-treatment group.
Conclusion: This experiment demonstrated improved wound healing using a PDRN loaded in hydrogel combined treatment compared to either two groups, resulting in a decrease in diabetic wound size and a shortening of the healing period
Plum Analytics Artifact Widget Block
Armstrong DG, Boulton AJ, Bus SA. Diabetic foot ulcers and their recurrence. N Engl J Med. 2017;376(24):2367-75. https://doi.org/10.1056/NEJMra1615439 PMid:28614678 DOI: https://doi.org/10.1056/NEJMra1615439
International Diabetes Federation. IDF Diabetes Atlas. 8th ed. Brussels, Belgium: International Diabetes Federation; 2019.
Frykberg RG, Banks J. Challenges in the treatment of chronic wounds. Adv Wound Care (New Rochelle). 2015;4(9):560-82. https://doi.org/10.1089/wound.2015.0635 PMid:26339534 DOI: https://doi.org/10.1089/wound.2015.0635
Jones RE, Deshka S, Longaker MT. Management of Chronic wounds-2018. JAMA. 2018;320(14):1481. https://doi.org/10.1001/jama.2018.12426 PMid:30326512 DOI: https://doi.org/10.1001/jama.2018.12426
Clark RA. The Molecular and Cellular Biology of Wound Repair, Disorders, Pathophysiology, Pharmacology and Therapeutics: An Update. Germany: Springer; 2013. p. 494-7.
Galkowska H, Wojewodzka U, Olszewski WL. Chemokines, cytokines, and growth factors in keratinocytes and dermal endothelial cells in the margin of chronic diabetic foot ulcers. Wound Repair Regen. 2006;14:558-65. https://doi.org/10.1111/j.1743-6109.2006.00155.x PMid:17014667 DOI: https://doi.org/10.1111/j.1743-6109.2006.00155.x
Falanga V. Wound healing and its impairment in the diabetic foot. Lancet. 2005;366:1736-43. https://doi.org/10.1016/S0140-6736(05)67700-8 PMid:16291068 DOI: https://doi.org/10.1016/S0140-6736(05)67700-8
Kwon TR, Han SW, Kim JH, Lee BC, Kim JM, Hong JY, et al. Polydeoxyribonucleotides improve diabetic wound healing in mouse animal model for experimental validation. Ann Dermatol. 2019;31(4):403-13. https://doi.org/10.5021/ad.2019.31.4.403 PMid:33911618 DOI: https://doi.org/10.5021/ad.2019.31.4.403
Lipsky BA, Aragón-Sánchez J, Diggle M, Embil J, Kono S, Lavery L, et al. IWGDF guidance on the diagnosis and management of foot infections in personswith diabetes. Diabetes Metab Res Rev. 2016;32(1):45-74. https://doi.org/10.1002/dmrr.2699 PMid:26386266 DOI: https://doi.org/10.1002/dmrr.2699
Morgan C, Nigam Y. Naturally derived factors and their role in the promotion of angiogenesis for the healing of chronic wounds. Angiogenesis. 2013;16(3):493-502. https://doi.org/10.1007/s10456-013-9341-1 PMid:23417553 DOI: https://doi.org/10.1007/s10456-013-9341-1
Kolluru GK, Bir SC, Kevil CG. Endothelial dysfunction and diabetes: Effects on angiogenesis, vascular remodeling, and wound healing. Int J Vasc Med. 2012;2012:918267. https://doi.org/10.1155/2012/918267 PMid:22611498 DOI: https://doi.org/10.1155/2012/918267
Squadrito F, Bitto A, Irrera N, Pizzino G, Pallio G, Minutoli L, et al. Pharmacological activity and clinical use of PDRN. Front Pharmacol 2017;8:224. https://doi.org/10.3389/fphar.2017.00224 PMid:28491036 DOI: https://doi.org/10.3389/fphar.2017.00224
Shin J, Park G, Lee J, Bae H. The effect of polydeoxyribonucleotide on chronic non-healing wound of an amputee: A case report. Ann Rehabil Med. 2018;42(4):630-3. https://doi.org/10.5535/arm.2018.42.4.630 PMid:30180535 DOI: https://doi.org/10.5535/arm.2018.42.4.630
Chung KI, Kim HK, Kim WS, Bae TH. The effects of polydeoxyribonucleotide on the survival of random pattern skin flaps in rats. Arch Plast Surg. 2013;40:181-6. https://doi.org/10.5999/aps.2013.40.3.181 PMid:23730590 DOI: https://doi.org/10.5999/aps.2013.40.3.181
Jeong W, Yang CE, Roh TS, Kim JH, Lee JH, Lee WJ. Scar prevention and enhanced wound healing induced by polydeoxyribonucleotide in a rat incisional wound-healing model. Int J Mol Sci. 2017;18(8):1698. https://doi.org/10.3390/ijms18081698 PMid:28771195 DOI: https://doi.org/10.3390/ijms18081698
Lee WY, Park KD, Park Y. The effect of polydeoxyribonucleotide on the treatment of radiating leg pain due to cystic mass lesion in inner aspect of right sciatic foramen: A CARE compliant case report. Medicine. 2018;97(41):e12794. https://doi.org/10.1097/MD.0000000000012794 PMid:30313106 DOI: https://doi.org/10.1097/MD.0000000000012794
Bitto A, Polito F, Irrera N, D’Ascola A, Avenoso A, Nastasi G, et al. Polydeoxyribonucleotide reduces cytokine production and the severity of collagen-induced arthritis by stimulation of adenosine A2A receptor. Arthrit Rheum. 2011;63(11):3364-71. https://doi.org/10.1002/art.30538 PMid:21769841 DOI: https://doi.org/10.1002/art.30538
Kim S, Kim J, Choi J, Jeong W, Kwon S. Polydeoxyribonucleotide improves peripheral tissue oxygenation and accelerates angiogenesis in diabetic foot ulcers. Arch Plast Surg. 2017;44(6):482-9. https://doi.org/10.5999/aps.2017.00801 PMid:29076318 DOI: https://doi.org/10.5999/aps.2017.00801
Guizzardi S, Uggeri J, Belletti S, Cattarini G. Hyaluronate increases polynucleotides effect on human cultured fibroblasts. J Cosmet Dermatol Sci Appl. 2013;3(1):124-8. DOI: https://doi.org/10.4236/jcdsa.2013.31019
Minutoli L, Arena S, Bonvissuto G, Bitto A, Polito F, Irrera N, et al. Activation of adenosine A2A receptors by polydeoxyribonucleotide increases vascular endothelial growth factor and protects against testicular damage induced by experimental varicocele in rats. Fertil Steril. 2011;95(4):1510-3. https://doi.org/10.1016/j.fertnstert.2010.07.1047 PMid:20797711 DOI: https://doi.org/10.1016/j.fertnstert.2010.07.1047
Wang C, Varshney RR, Wang DA. Therapeutic cell delivery and fate control in hydrogels and hydrogel hybrids. Adv Drug Deliv Rev. 2010;62(7-8):699-710. https://doi.org/10.1016/j.addr.2010.02.001 PMid:20138940 DOI: https://doi.org/10.1016/j.addr.2010.02.001
Chattopadhyay S, Raines RT. Collagen-based biomaterials for wound healing. Biopolymers. 2014;101(8):821-33. https://doi.org/10.1002/bip.22486 PMid:24633807 DOI: https://doi.org/10.1002/bip.22486
Chang SC, Zhang L. Cellulose-based hydrogels: Present status and application prospects. J Carbohydrate Polymers. 2011;84(1):40-53. DOI: https://doi.org/10.1016/j.carbpol.2010.12.023
Parenteau-Bareil R, Gauvin R, Berthod F. Collagen-based biomaterials for tissue engineering applications. Materials. 2010;3(3):1863-87. https://doi.org/10.3390/ma3031863 DOI: https://doi.org/10.3390/ma3031863
Laçin NT. Development of biodegradable antibacterial cellulose based hydrogel membranes for wound healing. J. Biol Macromol. 2014;67:22-7. DOI: https://doi.org/10.1016/j.ijbiomac.2014.03.003
Kabir MF, Sikdar PP, Haque B, Bhuiyan MA, Ali A, Islam MN. Cellulose-based hydrogel materials: Chemistry, properties and their prospective applications. Prog Biomater. 2018;7(3):153-74. https://doi.org/10.1007/s40204-018-0095-0 PMid:30182344 DOI: https://doi.org/10.1007/s40204-018-0095-0
Principles of Laboratory Animal Care. United States: NIH Publication; 1985.
Heilborn JD, Nilsson MF, Kratz G, Weber G, Sørensen O, Borregaard N, et al. The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J Invest Dermatol. 2003;120(3):379-89. https://doi.org/10.1046/j.1523-1747.2003.12069.x PMid:12603850 DOI: https://doi.org/10.1046/j.1523-1747.2003.12069.x
Salehi-Lalemarzi H, Shanehbandi D, Shafaghat F, Abbasi- Kenarsari H, Baradaran B, Movassaghpour AA, et al. Cloning and stable expression of cDNA coding for platelet en-dothelial cell adhesion molecule-1 (PECAM-1, CD31) in NIH-3T3 cell line. Adv Pharm Bull. 2015;5(2):247-53. https://doi.org/10.15171/apb.2015.034 PMid:26236664 DOI: https://doi.org/10.15171/apb.2015.034
Hossain M, Qadri SM, Xu N, Su Y, Cayabyab FS, Heit B, et al. Endothelial LSP1 modulates extravascular neutrophil chemotaxis by regu-lating nonhematopoietic vascular PECAM-1 expression. J Immunol. 2015;195(5):2408-16. https://doi.org/10.4049/jimmunol.1402225 PMid:26238489 DOI: https://doi.org/10.4049/jimmunol.1402225
Henning UG, Wang Q, Gee NH, Von Borstel RC. Protection and repair of g-radiation-induced lesions in mice with DNA or deoxyribonucleoside treatments. Mutation Res. 1996;350(1):247-54. https://doi.org/10.1016/0027-5107(95)00109-3 DOI: https://doi.org/10.1016/0027-5107(95)00109-3
Tonello G, Daglio M, Zaccarelli N, Sottofattori E, Mazzei M, Balbi A. Characterization and quantitation of the active polynucleotide fraction (PDRN) from human placenta, a tissue repair stimulating agent. J Pharmacol Biomed Anal. 1996;14(11):1555-60. https://doi.org/10.1016/0731-7085(96)01788-8 PMid:8877863 DOI: https://doi.org/10.1016/0731-7085(96)01788-8
Xi C, Wu Z, Kun Z, Guohui L, Yang S, Ye S, et al. Treatment of chronic ulcer indiabetic rats with self assembling nanofiber gel encapsulated-polydeoxyribonucleotide. Am J Transl Res. 2016;8(7):3067-76. PMid:27508027
Altavilla D, Squadrito F, Polito F, Irrera N, Calò M, Cascio PL, et al. Activation of adenosine A2A receptors restores the altered cell-cycle machinery during impaired wound healing in genetically diabetic mice. Surgery. 2011;149(2):253-61. https://doi.org/10.1016/j.surg.2010.04.024 PMid:20570301 DOI: https://doi.org/10.1016/j.surg.2010.04.024
Galeano M, Bitto A, Altavilla D, Minutoli L, Polito F, Calò M, et al. Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse. Wound Rep Reg. 2008;16(2):208-17. https://doi.org/10.1111/j.1524-475X.2008.00361.x PMid:18318806 DOI: https://doi.org/10.1111/j.1524-475X.2008.00361.x
El-Sherbiny MI, Yacoub HM. Hydrogel scaffolds for tissue engineering: Progress and challenges. Glob Cardiol Sci Pract. 2013;2013(3):316-42. https://doi.org/10.5339/gcsp.2013.38 PMid:24689032 DOI: https://doi.org/10.5339/gcsp.2013.38
Grim C, Marozas IA, Anseth KS. Thiol-ene and photo-cleavage chemistry for controlled presentation of biomolecules in hydrogels. J Control Release. 2015;219:95-106. https://doi.org/10.1016/j.jconrel.2015.08.040 PMid:26315818 DOI: https://doi.org/10.1016/j.jconrel.2015.08.040
de Oliveira Gonzalez C, Costa TF, de Araújo Andrade Z, Medrado AR. Wound healing-a literature review. An Bras Dermatol. 2016; 91:5. https://doi.org/10.1590/abd1806-4841.20164741 PMid:27828635 DOI: https://doi.org/10.1590/abd1806-4841.20164741
How to Cite
Copyright (c) 2022 Mariya Dmitriyeva, Timur Suleimenov, Daulet Yessenbayev, Dulat Turebayev, Saltanat Urazova, Mirsaid Izimbergenov, Saken Kozhakhmetov, Talgat Omarov, Medet Toleubayev (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.