پیشرفت‌های اخیر فناوری زیستی در تهیه پانسمان‌های زخم برای افراد دیابتی

محورهای موضوعی : فصلنامه زیست شناسی جانوری

سید رسول ذاکر ¹ (مرکز پژوهشی فرآورده های طبیعی و زیستی دارویی، دانشگاه اصفهان، اصفهان، ایران)
سیده شهربانو جعفری ² (گروه زیست شناسی، دانشکده علوم و فناوری های زیستی، دانشگاه اصفهان، اصفهان، ایران)
رحمان امام زاده ³ (گروه زیست شناسی، دانشکده علوم و فناوری های زیستی، دانشگاه اصفهان، اصفهان، ایران)

تاریخ دریافت : 1402/01/25 تاریخ پذیرش : 1402/03/12 تاریخ انتشار : 1402/12/01

کلید واژه: پانسمان زخم پیشرفته, پلیمرهای طبیعی, سیتم تحویل دارویی, فناوری زیستی‌, زخم پای دیابتی,

چکیده مقاله :

دردو دهه اخیر با توجه به اهمیت داروهای حاصل از فناوری زیستی‌ و نقش مهم آن‌ها در درمان زخم‌های مزمن، مطالعات پیش‌بینی کرده‌اند که بازار مراقبت از زخم پیشرفته خصوصا زخم‌های جراحی و زخم‌های مزمن احتمالاً تا سال 2024 به 15 تا 22 میلیارد دلار خواهد رسید. بنابراین در مطالعه حاضر پیشرفت‌های اخیر فناوری زیستی در زمینه‌ی تهیه پانسمان زخم از ترکیبات حاصل از گیاهان و جانوران برای افراد مبتلا به زخم پای دیابتی بحث شده است. در این تحقیق روش‌ها و رویکردهای تحویل عوامل درمانی برای درمان DFUs و در واقع نتایج اخیر مطالعات برون تنی و درون تنی، با تأکید بر پتانسیل منحصربه‌ فرد پانسمان‌های زخم مبتنی بر پلیمرهای طبیعی در درمان DFUs، جمع آوری و مورد بررسی قرار گرفته است. مروری بر چالش‌های پیش‌رو در درمان زخم‌های مزمن، ناکافی بودن اثربخشی برخی از محصولات مراقبت از زخم را نشان می‌دهد که بیانگر این است که خانواده‌ها و دولت باید با چالش‌های پزشکی برای دوره‌های طولانی‌تری مبارزه کنند. زخم پای دیابت نوعی زخم مزمن است که می‌تواند باعث عفونت‌های شدید و حتی قطع عضو شود. مواد زیستی که در حال حاضر به عنوان ماتریکس برای ترمیم زخم استفاده می‌شوند را می‌توان با توجه به منشاء آنها به انواع طبیعی و مصنوعی طبقه‌بندی کرد. با توجه به ویژگی‌های تخریب آسان، زیست سازگاری قابل توجه، کاهش پاسخ‌های التهابی و ماهیت غیر ایمنی‌زا، مواد زیستی طبیعی مانند، کیتوزان، الژینات، سلولز، اسید هیالورونیک، فیبروئین ابریشم، کلاژن به طور گسترده‌ای برای ترمیم زخم پای دیابتی توصیه شده است.

چکیده انگلیسی:

In the last two decades, given the importance of biotechnological drugs and their important role in the treatment of chronic wounds, studies have predicted that the market for advanced wound care targeting surgical wounds and chronic wounds is likely to reach $15-22 billion by 2024. Therefore, in the present study, the recent advances in biotechnology in the field of preparing wound dressings from compounds obtained from plants and animals for people with diabetic foot ulcers have been discussed. In this research, the methods and approaches of delivery of therapeutic agents for the treatment of DFUs and in fact the recent results of in vitro and in vivo studies, emphasizing the unique potential of wound dressings based on natural polymers in the treatment of DFUs, have been collected and analyzed. This expansion is expected to be driven by advances in technology, increased incidence of chronic wounds, and an increasing elderly population. A review of the challenges ahead in the treatment of chronic wounds reveals the inadequacy of the effectiveness of some wound care products, suggesting that families and governments must contend with medical challenges for longer periods. Diabetic foot ulcer (DFIU) is a chronic ulcer that can cause severe infections and even amputation. Biomaterials that are currently used as matrices for wound healing can be classified into natural and synthetic types according to their origin. Natural biomaterials such as chitosan, alginate, cellulose, hyaluronic acid, silk fibroin, and collagen have been widely recommended for diabetic foot wound healing due to their easy degradability, remarkable biocompatibility, reduced inflammatory responses, and non-immunogenic nature. Biotechnology guarantees the possibility of using natural biomaterials to develop advanced wound dressings with appropriate and patient-friendly therapeutic results. 

منابع و مأخذ:

1. Agarwal, Y., Rajinikanth, P., Ranjan, S., Tiwari, U., Balasubramnaiam, J., Pandey, P., Deepak, P. 2021. Curcumin loaded polycaprolactone-/polyvinyl alcohol-silk fibroin based electrospun nanofibrous mat for rapid healing of diabetic wound: An in-vitro and in-vivo studies. International Journal of Biological Macromolecules, 176:376-386.


2. Alhajj, M., Goyal, A. 2021. Physiology, granulation tissue. In StatPearls [Internet]: StatPearls Publishing.


3. Alven, S., Aderibigbe, B.A. 2021. Hyaluronic acid-based scaffolds as potential bioactive wound dressings. Polymers, 13(13):2102.


4. Alven, S., Khwaza, V., Oyedeji, O.O., Aderibigbe, B.A. 2021. Polymer-based scaffolds Loaded with aloe vera extract for the treatment of wounds. Pharmaceutics, 13(7):961.


5. Alven, S., Nqoro, X., Aderibigbe, B.A. 2020. Polymer-based materials loaded with curcumin for wound healing applications. Polymers, 12(10):2286.


6. Barbu, A., Neamtu, B., Zăhan, M., Iancu, G. M., Bacila, C., Mireșan, V. 2021. Current trends in advanced alginate-based wound dressings for chronic wounds. Journal of Personalized Medicine, 11(9):890.


7. Bašić-Kes, V., Zavoreo, I., Rotim, K., Bornstein, N., Rundek, T., Demarin, V. 2011. Recommendations for diabetic polyneuropathy treatment. Acta Clinica Croatica, 50(2):289-302.


8. Blanco-Fernandez, B., Castaño, O., Mateos-Timoneda, M.Á., Engel, E., Pérez-Amodio, S. 2021. Nanotechnology approaches in chronic wound healing. Advances in Wound Care, 10(5):234-256.


9. Bryant, R., Nix, D. 2015. Acute and chronic wounds: current management concepts: Elsevier Health Sciences, 648 p.


10. Buckley, C., Murphy, E.J., Montgomery, T. R., Major, I. 2022. Hyaluronic acid: a review of the drug delivery capabilities of this naturally occurring polysaccharide. Polymers, 14(17): 3442.


11. Cañedo-Dorantes, L., Cañedo-Ayala, M. 2019. Skin acute wound healing: a comprehensive review. International journal of inflammation, 2019:3706315.


12. Catanzano, O., Quaglia, F., Boateng, J. S. 2021. Wound dressings as growth factor delivery platforms for chronic wound healing. Expert Opinion on Drug Delivery, 18(6):737-759.


13. Chittleborough, C., Grant, J., Phillips, P., Taylor, A. 2007. The increasing prevalence of diabetes in South Australia: the relationship with population ageing and obesity. Public Health, 121(2);92-99.


14. Dai, L., Cheng, T., Duan, C., Zhao, W., Zhang, W., Zou, X., Ni, Y. 2019. 3D printing using plant-derived cellulose and its derivatives: A review. Carbohydrate Polymers, 203:71-86.


15. Derakhshan, M.A., Nazeri, N., Khoshnevisan, K., Heshmat, R., Omidfar, K. 2022. Three-layered PCL-collagen nanofibers containing melilotus officinalis extract for diabetic ulcer healing in a rat model. Journal of Diabetes and Metabolic Disorders, 21(1):313-321.


16. Deshmukh, S.N., Dive, A. M., Moharil, R., Munde, P. 2016. Enigmatic insight into collagen. Journal of oral and maxillofacial pathology: JOMFP, 20(2):276.


17. Diaz-Gomez, L., Gonzalez-Prada, I., Millan, R., Da Silva-Candal, A., Bugallo-Casal, A., Campos, F., Alvarez-Lorenzo, C. 2022. 3D printed carboxymethyl cellulose scaffolds for autologous growth factors delivery in wound healing. Carbohydrate polymers, 278:


18. Ding, X., Kakanj, P., Leptin, M., Eming, S. A. 2021. Regulation of the wound healing response during aging. Journal of Investigative Dermatology, 141(4):1063-1070.


19. Eivazzadeh-Keihan, R., Khalili, F., Khosropour, N., Aliabadi, H.A.M., Radinekiyan, F., Sukhtezari, S., Mahdavi, M. 2021. Hybrid bionanocomposite containing magnesium hydroxide nanoparticles embedded in a carboxymethyl cellulose hydrogel plus silk fibroin as a scaffold for wound dressing applications. ACS Applied Materials Interfaces, 13(29):33840-33849.


20. El-Samad, L.M., Hassan, M.A., Basha, A. A., El-Ashram, S., Radwan, E. H., Aziz, K.K. A., El Wakil, A. 2022. Carboxymethyl cellulose/ sericin-based hydrogels with intrinsic antibacterial, antioxidant, and anti-inflammatory properties promote re-epithelization of diabetic wounds in rats. International Journal of Pharmaceutics, 629:


21. Emamzadeh, M., Emamzadeh, M., Pasparakis, G. 2019. Dual controlled delivery of gemcitabine and cisplatin using polymer-modified thermosensitive liposomes for pancreatic cancer. ACS Applied Bio Materials, 2(3):1298-1309.


22. Ferrante, C.J., Leibovich, S.J. 2012. Regulation of macrophage polarization and wound healing. Advances in Wound Care, 1(1), 10-16.


23. FrykbergRobert, G. 2015. Challenges in the treatment of chronic wounds. Advances in Wound Care, 4(9):560-582.


24. Galiano, F., Briceño, K., Marino, T., Molino, A., Christensen, K. V., Figoli, A. 2018. Advances in biopolymer-based membrane preparation and applications. Journal of Membrane Science, 564:562-586.


25. Geng, K., Ma, X., Jiang, Z., Huang, W., Gao, C., Pu, Y., Xu, Y. 2021. Innate immunity in diabetic wound healing: focus on the mastermind hidden in chronic inflammatory. Frontiers in Pharmacology, 12:653940.


26. Ghobadi, M. Z., Emamzadeh, R., Afsaneh, E. 2022. Exploration of mRNAs and miRNA classifiers for various ATLL cancer subtypes using machine learning. BMC Cancer, 22(1):1-8.


27. Gonzalez, A.C.D.O., Costa, T.F., Andrade, Z.d.A., Medrado, A.R.A.P. 2016. Wound healing-A literature review. Anais Brasileiros de Dermatologia, 91:614-620.


28. Greaves, N.S., Ashcroft, K.J., Baguneid, M., Bayat, A. 2013. Current understanding of molecular and cellular mechanisms in fibroplasia and angiogenesis during acute wound healing. Journal of dermatological science, 72(3):206-217.


29. He, X., Liu, X., Yang, J., Du, H., Chai, N., Sha, Z., He, C. 2020. Tannic acid-reinforced methacrylated chitosan/methacrylated silk fibroin hydrogels with multifunctionality for accelerating wound healing. Carbohydrate Polymers, 247:


30. Hussain, Z., Thu, H.E., Shuid, A.N., Katas, H., Hussain, F. 2018. Recent advances in polymer-based wound dressings for the treatment of diabetic foot ulcer: an overview of state-of-the-art. Current Drug Targets, 19(5): 527-550.


31. Jafari, S.S., Emamzadeh, R., Nazari, M., Ganjalikhany, M.R. 2023. Structural studies and cell proliferation activity of human Follistatin-like 1 in reducing and non-reducing conditions. Process Biochemistry, 130:245-255.


32. Jafari, S.S., Jafarian, V., Khalifeh, K., Ghanavatian, P., Shirdel, S.A. 2016. The effect of charge alteration and flexibility on the function and structural stability of sweet-tasting brazzein. RSC advances, 6(64):59834-59841.


33. Kaku, M., Vinik, A., Simpson, D. M. 2015. Pathways in the diagnosis and management of diabetic polyneuropathy. Current Diabetes Reports, 15(6):1-16.


34. Kanikireddy, V., Varaprasad, K., Jayaramudu, T., Karthikeyan, C., Sadiku, R. 2020. Carboxymethyl cellulose-based materials for infection control and wound healing: A review. International Journal of Biological Macromolecules, 164:963-975.


35. Khalid, A., Madni, A., Raza, B., ul Islam, M., Hassan, A., Ahmad, F., Wahid, F. 2022. Multiwalled carbon nanotubes functionalized bacterial cellulose as an efficient healing material for diabetic wounds. International Journal of Biological Macromolecules, 203:256-267.


36. Kim, J., Lee, K.M., Han, S.H., Ko, E.A., Yoon, D.S., Park, I.K., Lee, J.W. 2021. Development of stabilized dual growth factor-loaded hyaluronate collagen dressing matrix. Journal of tissue engineering, 12:


37. Kleine‐Börger, L., Kalies, A., Meyer, R. S., Kerscher, M. 2021. Physicochemical properties of injectable hyaluronic acid: skin quality boosters. Macromolecular Materials and Engineering, 306(8):2100134.


38. Lu, X., Qin, L., Guo, M., Geng, J., Dong, S., Wang, K., Liu, M. 2022. A novel alginate from Sargassum seaweed promotes diabetic wound healing by regulating oxidative stress and angiogenesis. Carbohydrate polymers, 289:


39. Lv, H., Zhao, M., Li, Y., Li, K., Chen, S., Zhao, W., Han, Y. 2022. Electrospun Chitosan–Polyvinyl Alcohol Nanofiber Dressings Loaded with Bioactive Ursolic Acid Promoting Diabetic Wound Healing. Nanomaterials, 12(17):2933.


40. Mahendra, C.K., Tan, L.T.H., Mahendra, C. K., Ser, H.L., Pusparajah, P., Htar, T.T., Ming, L.C. 2021. The Potential of sky fruit as an anti-aging and wound healing cosmeceutical agent. Cosmetics, 8(3):79.


41. Maity, B., Alam, S., Samanta, S., Prakash, R. G., Govindaraju, T. 2022. Antioxidant silk fibroin composite hydrogel for rapid healing of diabetic wound. Macromolecular Bioscience, 22(9):2200097.


42. Malone, M., Bjarnsholt, T., McBain, A. J., James, G. A., Stoodley, P., Leaper, D., Wolcott, R.D. 2017. The prevalence of biofilms in chronic wounds: a systematic review and meta-analysis of published data. Journal of Wound Care, 26(1):20-25.


43. Meng, Q., Sun, Y., Cong, H., Hu, H., Xu, F.J. 2021. An overview of chitosan and its application in infectious diseases. Drug Delivery and Translational Research, 11(4):1340-1351.


44. Mohan, S., Oluwafemi, O. S., Kalarikkal, N., Thomas, S., Songca, S. P. 2016. Biopolymers–application in nanoscience and nanotechnology. Recent Advances in Biopolymers, 1(1):47-66.


45. Monika, P., Chandraprabha, M.N., Rangarajan, A., Waiker, P.V., Chidambara Murthy, K.N. 2022. Challenges in healing wound: role of complementary and alternative medicine. Frontiers in Nutrition, 8:


46. Morgan, A., Hartmanis, S., Tsochatzis, E., Newsome, P.N., Ryder, S.D., Elliott, R., Stanley, G. 2021. Disease burden and economic impact of diagnosed non-alcoholic steatohepatitis (NASH) in the United Kingdom (UK) in 2018. The European Journal of Health Economics, 22(4): 505-518.


47. Mortazavi, M., Hosseinkhani, S., Torkzadeh-Mahani, M., Lotfi, S., Emamzadeh, R., Ghasemi, Y. 2021. In Silico Analysis of Relative Rareness, Codon Usage, and Enzymesubstrate Docking of Lampyroidea Maculata luciferase. Current Proteomics, 18(3): 424-434.


48. Naomi, R., Bahari, H., Ridzuan, P. M., Othman, F. 2021. Natural-based biomaterial for skin wound healing (Gelatin vs. collagen): Expert review. Polymers, 13(14):2319.


49. Nazari, M., Emamzadeh, R., Jahanpanah, M., Yazdani, E., Radmanesh, R. 2022. A recombinant affitoxin derived from a HER3 affibody and diphteria-toxin has potent and selective antitumor activity. International Journal of Biological Macromolecules, 219: 1122-1134.


50. Nazari, M., Zamani Koukhaloo, S., Mousavi, S., Minai‐Tehrani, A., Emamzadeh, R., Cheraghi, R. 2019. Development of a ZHER3‐Affibody‐Targeted Nano‐Vector for Gene Delivery to HER3‐Overexpressed Breast Cancer Cells. Macromolecular Bioscience, 19(11): 1900159.


51. Nori, Z. Z., Bahadori, M., Moghadam, M., Tangestaninejad, S., Mirkhani, V., Mohammadpoor-Baltork, I., Alem, H. 2023. Synthesis and characterization of a new gold-coated magnetic nanoparticle decorated with a thiol-containing dendrimer for targeted drug delivery, hyperthermia treatment and enhancement of MRI contrast agent. Journal of Drug Delivery Science and Technology, 81: 104216.


52. Nourian Dehkordi, A., Mirahmadi Babaheydari, F., Chehelgerdi, M., Raeisi Dehkordi, S. 2019. Skin tissue engineering: wound healing based on stem-cell-based therapeutic strategies. Stem Cell Research and Therapy, 10(1):1-20.


53. Nussbaum, S.R., Carter, M. J., Fife, C.E., DaVanzo, J., Haught, R., Nusgart, M., Cartwright, D. 2018. An economic evaluation of the impact, cost, and medicare policy implications of chronic nonhealing wounds. Value in Health, 21(1):27-32.


54. Nuutila, K., Singh, M., Kruse, C., Philip, J., Caterson, E.J., Eriksson, E. 2016. Titanium wound chambers for wound healing research. Wound Repair and Regeneration, 24(6):1097-1102.


55. Ogurtsova, K., Guariguata, L., Barengo, N. C., Ruiz, P.L.D., Sacre, J.W., Karuranga, S., Magliano, D. J. 2022. IDF diabetes Atlas: Global estimates of undiagnosed diabetes in adults for 2021. Diabetes Research and Clinical Practice, 183:1


56. Pasomboon, P., Chumnanpuen, P.E., Kobon, T. 2021. Modified Genome-Scale Metabolic Model of Escherichia coli by Adding Hyaluronic Acid Biosynthesis-Related Enzymes (GLMU2 and HYAD) from Pasteurella multocida. International Journal of Biotechnology and Bioengineering, 15(5):54-58.


57. Pettifor, J.L. 2012. Book Review of Encyclopedia of Applied Ethics. Canadian Journal of Counselling and Psychotherapy, 46(4):335-343.


58. Powers, J.G., Higham, C., Broussard, K., Phillips, T.J. 2016. Wound healing and treating wounds: Chronic wound care and management. Journal of the American Academy of Dermatology, 74(4):607-625.


59. Qian, B., Li, J., Guo, K., Guo, N., Zhong, A., Yang, J., Xiong, L. 2021. Antioxidant biocompatible composite collagen dressing for diabetic wound healing in rat model. Regenerative Biomaterials, 8(2):rbab003.


60. Reinke, J., Sorg, H. 2012. Wound repair and regeneration. European Surgical Research, 49(1):35-43.


61. Rezaei, F.S., Sharifianjazi, F., Esmaeilkhanian, A., Salehi, E. 2021. Chitosan films and scaffolds for regenerative medicine applications: A review. Carbohydrate Polymers, 273:


62. Schubert-Bast, S., Kay, L., Simon, A., Wyatt, G., Holland, R., Rosenow, F., Strzelczyk, A. 2022. Epidemiology, healthcare resource use, and mortality in patients with probable Dravet syndrome: A population-based study on German health insurance data. Epilepsy and Behavior, 126:108442.


63. Seddiqi, H., Oliaei, E., Honarkar, H., Jin, J., Geonzon, L.C., Bacabac, R.G., Klein-Nulend, J. 2021. Cellulose and its derivatives: Towards biomedical applications. Cellulose, 28(4):1893-1931.


64. Seidi, F., Yazdi, M.K., Jouyandeh, M., Dominic, M., Naeim, H., Nezhad, M.N., Saeb, M.R. 2021. Chitosan-based blends for biomedical applications. International Journal of Biological Macromolecules, 183:1818-1850.


65. Sen, C.K. 2019. Human wounds and its burden: an updated compendium of estimates. In (Vol. 8, pp. 39-48): Mary Ann Liebert, Inc., publishers 140 Huguenot Street, 3rd Floor New.


66. Shah, S.A., Sohail, M., Khan, S.A., Kousar, M. 2021. Improved drug delivery and accelerated diabetic wound healing by chondroitin sulfate grafted alginate-based thermoreversible hydrogels. Materials Science and Engineering: C, 126:112169.


67. Shahverdi, S., Hajimiri, M., Esfandiari, M. A., Larijani, B., Atyabi, F., Rajabiani, A., Dinarvand, R. 2014. Fabrication and structure analysis of poly (lactide-co-glycolic acid)/silk fibroin hybrid scaffold for wound dressing applications. International Journal of Pharmaceutics, 473(1-2):345-355.


68. Shamsi, M., Shirdel, S.A., Jafarian, V., Jafari, S.S., Khalifeh, K., Golestani, A. 2016. Optimization of conformational stability and catalytic efficiency in chondroitinase ABC Ι by protein engineering methods. Engineering in Life Sciences, 16(8):690-696.


69. Sharma, S., Rai, V.K., Narang, R.K., Markandeywar, T.S. 2021. Collagen-based formulations for wound healing: A literature review. Life Sciences, 120096.


70. Shaw, J.E., Sicree, R.A., Zimmet, P.Z. 2010. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Research and Clinical Practice, 87(1), 4-14.


71. Shen, T., Dai, K., Yu, Y., Wang, J., Liu, C. 2020. Sulfated chitosan rescues dysfunctional macrophages and accelerates wound healing in diabetic mice. Acta Biomaterialia, 117:192-203.


72. Su, S., Bedir, T., Kalkandelen, C., Sasmazel, H.T., Basar, A.O., Chen, J., Gunduz, O. 2022. A drug-eluting nanofibrous hyaluronic acid-keratin mat for diabetic wound dressing. Emergent Materials, 5(6):1617-1627.


73. Sun, H., Saeedi, P., Karuranga, S., Pinkepank, M., Ogurtsova, K., Duncan, B. B., Mbanya, J.C. 2022. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Research and Clinical Practice, 183:


74. Sun, H., Yang, Y., Wu, Y., Fu, Z., Zhang, Y., Liu, Y., Mai, B. 2022. Zinc alginate hydrogels with embedded RL-QN15 peptide-loaded hollow polydopamine nanoparticles for diabetic wound healing therapy. Materials and Design, 222:111085.


75. Tan, C., Yuan, Z., Xu, F., Xie, X. 2022. Electrospun cellulose acetate wound dressings loaded with Pramipexole for diabetic wound healing: an in vitro and in vivo study. Cellulose, 29(6):3407-3422.


76. Teixeira, M.A., Paiva, M.C., Amorim, M. T.P., Felgueiras, H.P. 2020. Electrospun nanocomposites containing cellulose and its derivatives modified with specialized biomolecules for an enhanced wound healing. Nanomaterials, 10(3):557.


77. Varaprasad, K., Jayaramudu, T., Kanikireddy, V., Toro, C., Sadiku, E. R. 2020. Alginate-based composite materials for wound dressing application: A mini review. Carbohydrate Polymers, 236:


78. Varnosfaderani, Z.G., Emamzadeh, R., Nazari, M., Zarean, M. 2019. Detection of a prostate cancer cell line using a bioluminescent affiprobe: An attempt to develop a new molecular probe for ex vivo studies. International Journal of Biological Macromolecules, 138:755-763.


79. Verma, G., Ravichandran, S. 2020. Evolution of biotechnology as a million dollar market: The Management and commerce of a biotech start-up. Biotechnology Business-Concept to Delivery, 2020:161-178.


80. Wahid, F., Huang, L.H., Zhao, X.Q., Li, W.C., Wang, Y.Y., Jia, S.R., Zhong, C. 2021. Bacterial cellulose and its potential for biomedical applications. Biotechnology Advances, 53:


81. Wang, T., Zheng, Y., Shi, Y., Zhao, L. 2019. pH-responsive calcium alginate hydrogel laden with protamine nanoparticles and hyaluronan oligosaccharide promotes diabetic wound healing by enhancing angiogenesis and antibacterial activity. Drug Delivery and Translational Research, 9(1):227-239.


82. Xu, X., Wang, X., Qin, C., Zhang, W., Mo, X. 2021. Silk fibroin/poly-(L-lactide-co-caprolactone) nanofiber scaffolds loaded with Huangbai Liniment to accelerate diabetic wound healing. Colloids and Surfaces B: Biointerfaces, 199:111557.


83. Xu, Z., Liu, G., Zheng, L., Wu, J. 2023. A polyphenol-modified chitosan hybrid hydrogel with enhanced antimicrobial and antioxidant activities for rapid healing of diabetic wounds. Nano Research, 16:905-916.


84. Yılmaz, R. 2019. Modern biotechnology breakthroughs to food and agricultural research in developing countries. GM Crops and Food, 10(1):12-16.


85. Zarei Ghobadi, M., Emamzadeh, R. 2022. Integration of gene co-expression analysis and multi-class SVM specifies the functional players involved in determining the fate of HTLV-1 infection toward the development of cancer (ATLL) or neurological disorder (HAM/TSP). Plos One, 17(1):


86. Zhang, Y., Zheng, Y., Shu, F., Zhou, R., Bao, B., Xiao, S., Xia, Z. 2022. In situ-formed adhesive hyaluronic acid hydrogel with prolonged amnion-derived conditioned medium release for diabetic wound repair. Carbohydrate Polymers, 276:


87. Zhu, T., Mao, J., Cheng, Y., Liu, H., Lv, L., Ge, M., Li, H. 2019. Recent progress of polysaccharide‐based hydrogel interfaces for wound healing and tissue engineering. Advanced Materials Interfaces, 6(17):1900761.