A Comprehensive Review of Advanced Modern Treatments, Strategies, and Techniques for AcceleratingWound Healing

References
[1] Gurtner GC, Werner S, Barrandon Y, Longaker
MT. Wound repair and regeneration. Nature.
2008;453(7193):314-21.
[2] George Broughton I, Janis JE, Attinger CE. The
basic science of wound healing. Plastic and recon-
structive surgery. 2006;117(7S):12S-34S.
[3] Eming SA, Martin P, Tomic-Canic M. Wound
repair and regeneration: mechanisms, signaling,
and translation. Science translational medicine.
2014;6(265):265sr6-sr6.
[4] Landen NX, Li D, Stahle M. Transition from in-
ammation to proliferation: a critical step during
wound healing. Cellular and Molecular Life Sci-
ences. 2016;73:3861-85.
[5] Guo Sa, DiPietro LA. Factors affecting
wound healing. Journal of dental research.
2010;89(3):219-29.
[6] Zangooei MH, Jalili S. Protein fold recognition
with a two-layer method based on SVM-SA, WP-
NN and C4. 5 (TLM-SNC). International Journal
of Data Mining and Bioinformatics. 2013;8(2):203-
23.
[7] Lin Z-Q, Kondo T, Ishida Y, Takayasu T, Mukaida
N. Essential involvement of IL-6 in the skin
wound-healing process as evidenced by delayed
wound healing in IL-6-de cient mice. Journal of
Leucocyte Biology. 2003;73(6):713-21.
[8] Bowden LG, Byrne HM, Maini PK, Moulton DE.
A morphoelastic model for dermal wound closure.
Biomech Model Mechanobiol. 2016;15(3):663-81.
[9] Bedard K, Krause K-H. The NOX family
of ROS-generating NADPH oxidases: physiol-
ogy and pathophysiology. Physiological reviews.
2007;87(1):245-313.
[10] Soneja A, Drews M, Malinski T. Role of nitric ox-
ide, nitroxidative and oxidative stress in wound
healing. Pharmacological reports. 2005;57:108.
[11] Roy S, Khanna S, Nallu K, Hunt TK, Sen CK.
Dermal wound healing is subject to redox control.
Molecular therapy. 2006;13(1):211-20.
[12] Brumberg V, Astrelina T, Malivanova T, Samoilov
A. Modern wound dressings: Hydrogel dressings.
Biomedicines. 2021;9(9):1235.
[13] Hesketh M, Sahin KB, West ZE, Murray RZ.
Macrophage phenotypes regulate scar formation
and chronic wound healing. International journal
of molecular sciences. 2017;18(7):1545.
[14] Krzyszczyk P, Schloss R, Palmer A, Berthiaume
F. The role of macrophages in acute and chronic
wound healing and interventions to promote pro-
wound healing phenotypes. Frontiers in physiol-
ogy. 2018;9:419.
[15] Eming SA, Krieg T, Davidson JM. In amma-
tion in wound repair: molecular and cellular
mechanisms. Journal of Investigative Dermatol-
ogy. 2007;127(3):514-25.
[16] Lauer G, Sollberg S, Cole M, Krieg T, Eming
SA, Flamme I, et al. Expression and proteolysis
of vascular endothelial growth factor is increased
in chronic wounds. Journal of Investigative Der-
matology. 2000;115(1):12-8.
[17] Stojadinovic O, Pastar I, Nusbaum AG, Vukelic S,
Krzyzanowska A, Tomic-Canic M. Deregulation of
epidermal stem cell niche contributes to pathogen-
esis of nonhealing venous ulcers. Wound Repair
and Regeneration. 2014;22(2):220-7.
[18] Stojadinovic O, Brem H, Vouthounis C, Lee B,
Fallon J, Stallcup M, et al. Molecular pathogene-
sis of chronic wounds: the role of  -catenin and
c-myc in the inhibition of epithelialization and
wound healing. The American journal of pathol-
ogy. 2005;167(1):59-69.
[19] Brem H, Stojadinovic O, Diegelmann RF, Entero
H, Lee B, Pastar I, et al. Molecular markers in
patients with chronic wounds to guide surgical de-
bridement. Molecular medicine. 2007;13:30-9.
[20] Pastar I, Stojadinovic O, Krzyzanowska A, Bar-
rientos S, Stuelten C, Zimmerman K, et al. At-
tenuation of the transforming growth factor  -
signaling pathway in chronic venous ulcers. Molec-
ular medicine. 2010;16:92-101.
A Comprehensive Review of Advanced Modern Treatments, Strategies, and Techniques for Accelerating
Wound Healing: 15{32 28
[21] Qian Z, Wang H, Bai Y, Wang Y, Tao L, Wei
Y, et al. Improving chronic diabetic wound heal-
ing through an injectable and self-healing hydro-
gel with platelet-rich plasma release. ACS applied
materials & interfaces. 2020;12(50):55659-74.
[22] Koehler J, Brandl FP, Goepferich AM. Hydrogel
wound dressings for bioactive treatment of acute
and chronic wounds. European Polymer Journal.
2018;100:1-11.
[23] Van Vlierberghe S, Dubruel P, Schacht E.
Biopolymer-based hydrogels as scaffolds for tis-
sue engineering applications: a review. Biomacro-
molecules. 2011;12(5):1387-408.
[24] Bilici C, Can V, No'ochel U, Behl M, Lendlein A,
Okay O. Melt-processable shape-memory hydro-
gels with self-healing ability of high mechanical
strength. Macromolecules. 2016;49(19):7442-9.
[25] Arif MM, Khan SM, Gull N, Tabish TA, Zia S,
Khan RU, et al. Polymer-based biomaterials for
chronic wound management: Promises and chal-
lenges. International Journal of Pharmaceutics.
2021;598:120270.
[26] Kamoun EA, Kenawy E-RS, Chen X. A review on
polymeric hydrogel membranes for wound dress-
ing applications: PVA-based hydrogel dressings.
Journal of advanced research. 2017;8(3):217-33.
[27] Tk H. Oxygen and healing. Am J Surg.
1969;118:207-15.
[28] Dissemond J, Kroger K, Storck M, Risse A,
Engels P. Topical oxygen wound therapies for
chronic wounds: a review. Journal of wound care.
2015;24(2):53-63.
[29] Lee G, Ko Y-G, Bae KH, Kurisawa M, Kwon OK,
Kwon OH. Green tea catechin-grafted silk  broin
hydrogels with reactive oxygen species scavenging
activity for wound healing applications. Biomate-
rials Research. 2022;26(1):62.
[30] Beckman KB, Ames BN. The free radical theory
of aging matures. Physiological reviews. 1998.
[31] Zhu Y, Wang Y, Jia Y, Xu J, Chai Y. Rox-
adustat promotes angiogenesis through HIF-
1 /VEGF/VEGFR2 signaling and accelerates cu-
taneous wound healing in diabetic rats. Wound
repair and regeneration. 2019;27(4):324-34.
[32] Jones RE, Foster DS, Longaker MT. Man-
agement of chronic wounds|2018. Jama.
2018;320(14):1481-2.
[33] Koo M-A, Hong SH, Lee MH, Kwon B-J, Seon
GM, Kim MS, et al. Effective stacking and trans-
plantation of stem cell sheets using exogenous
ROS-producing  lm for accelerated wound heal-
ing. Acta Biomaterialia. 2019;95:418-26.
[34] Hoffmann MH, Griffiths HR. The dual role of Re-
active Oxygen Species in autoimmune and in am-
matory diseases: evidence from preclinical models.
Free radical biology and medicine. 2018;125:62-71.
[35] Xu Z, Han S, Gu Z, Wu J. Advances
and impact of antioxidant hydrogel in chronic
wound healing. Advanced healthcare materials.
2020;9(5):1901502.
[36] He X, Xue J, Shi L, Kong Y, Zhan Q, Sun Y, et al.
Recent antioxidative nanomaterials toward wound
dressing and disease treatment via ROS scaveng-
ing. Materials Today Nano. 2022;17:100149.
[37] Khorsandi K, Hosseinzadeh R, Esfahani H, Zand-
salimi K, Shahidi FK, Abrahamse H. Accelerat-
ing skin regeneration and wound healing by con-
trolled ROS from photodynamic treatment. In-
ammation and regeneration. 2022;42(1):40.
[38] An Y, Liu W, Xue P, Ma Y, Zhang L, Zhu B,
et al. Autophagy promotes MSC-mediated vascu-
larization in cutaneous wound healing via regu-
lation of VEGF secretion. Cell death & disease.
2018;9(2):58.
[39] Asai E, Yamamoto M, Ueda K, Waguri S. Spa-
tiotemporal alterations of autophagy marker LC3
in rat skin  broblasts during wound healing
process. Fukushima Journal of Medical Science.
2018;64(1):15-22.
[40] Koike Y, Yozaki M, Utani A, Murota H. Fibrob-
last growth factor 2 accelerates the epithelial{
mesenchymal transition in keratinocytes dur-
ing wound healing process. Scienti c reports.
2020;10(1):18545.
[41] Cheng C-F, Fan J, Fedesco M, Guan S,
Li Y, Bandyopadhyay B, et al. Transforming
Growth Factor   (TGF )-Stimulated Secretion of
HSP90 : Using the Receptor LRP-1/CD91 To
Promote Human Skin Cell Migration against a
TGF -Rich Environment during Wound Healing.
Molecular and Cellular Biology. 2012;32(1):240.
[42] Lord MS, Ellis AL, Farrugia BL, Whitelock
JM, Grenett H, Li C, et al. Perlecan and vas-
cular endothelial growth factor-encoding DNA-
loaded chitosan scaffolds promote angiogenesis
and wound healing. Journal of Controlled Release.
2017;250:48-61.
Avicenna Veterinary Research/ Vol. 1, No. 3, Summer 2025 29
[43] Seiwerth S, Rucman R, Turkovic B, Sever M,
Klicek R, Radic B, et al. BPC 157 and stan-
dard angiogenic growth factors. Gastrointestinal
tract healing, lessons from tendon, ligament, mus-
cle and bone healing. Current pharmaceutical de-
sign. 2018;24(18)1972-89.
[44] La Monica F, Campora S, Ghersi G. Collagen-
Based Scaffolds for Chronic Skin Wound Treat-
ment. Gels. 2024;10(2):137.
[45] Yao Y, Zhang A, Yuan C, Chen X, Liu Y.
Recent trends on burn wound care: hydro-
gel dressings and scaffolds. Biomaterials science.
2021;9(13):4523-40.
[46] Chong ETJ, Ng JW, Lee P-C. Classi cation and
Medical Applications of Biomaterials-A Mini Re-
view. BIO integration. 2023;4(2):54-61.
[47] Madaghiele M, Demitri C, Sannino A, Ambro-
sio L. Polymeric hydrogels for burn wound care:
Advanced skin wound dressings and regenera-
tive templates. Burns & trauma. 2014;2(4):2321-
3868.143616.
[48] Pan Z, Ye H,Wu D. Recent advances on polymeric
hydrogels as wound dressings. APL bioengineer-
ing. 2021;5(1).
[49] Stoica AE, Chircov C, Grumezescu AM. Hydrogel
dressings for the treatment of burn wounds: an
up-to-date overview. Materials. 2020;13(12):2853.
[50] Yu Y-Q, Yang X, Wu X-F, Fan Y-B. Enhancing
permeation of drug molecules across the skin via
delivery in nanocarriers: novel strategies for ef-
fective transdermal applications. Frontiers in bio-
engineering and biotechnology. 2021;9:646554.
[51] Firlar I, Altunbek M, McCarthy C, Ramalingam
M, Camci-Unal G. Functional hydrogels for treat-
ment of chronic wounds. Gels. 2022;8(2):127.
[52] Rowan MP, Cancio LC, Elster EA, Burmeister
DM, Rose LF, Natesan S, et al. Burn wound
healing and treatment: review and advancements.
Critical care. 2015;19:1-12.
[53] Shu W, Wang Y, Zhang X, Li C, Le H, Chang
F. Functional hydrogel dressings for treatment
of burn wounds. Frontiers in bioengineering and
biotechnology. 2021;9:788461.
[54] Markiewicz-Gospodarek A, Kozio l M, Tobiasz M,
Baj J, Radzikowska-Buchner E, Przekora A. Burn
wound healing: clinical complications, medical
care, treatment, and dressing types: the current
state of knowledge for clinical practice. Interna-
tional journal of environmental research and pub-
lic health. 2022;19(3):1338.
[55] Zaid Alkilani A, McCrudden MT, Donnelly RF.
Transdermal drug delivery: Innovative pharma-
ceutical developments based on disruption of the
barrier properties of the stratum corneum. Phar-
maceutics. 2015;7(4):438-70.
[56] Wang F-Y, Chen Y, Huang Y-Y, Cheng C-M.
Transdermal drug delivery systems for  ghting
common viral infectious diseases. Drug delivery
and translational research. 2021;11(4):1498-508.
[57] Jacob S, Nair AB, Shah J, Sreeharsha N, Gupta S,
Shinu P. Emerging role of hydrogels in drug deliv-
ery systems, tissue engineering and wound man-
agement. Pharmaceutics. 2021;13(3):357.
[58] Kim KH, Kim Y-S, Lee S, An S. The effect of
three-dimensional cultured adipose tissue-derived
mesenchymal stem cell{conditioned medium and
the antiaging effect of cosmetic products con-
taining the medium. Biomedical Dermatology.
2020;4:1-12.
[59] R Johnson N, Wang Y. Drug delivery systems for
wound healing. Current pharmaceutical biotech-
nology. 2015;16(7):621-9.
[60] Zhu L, Chen L. Facile design and development
of nano-clustery graphene-based macromolecular
protein hydrogel loaded with cipro oxacin to an-
tibacterial improvement for the treatment of burn
wound injury. Polymer Bulletin. 2022:1-16.
[61] Saghazadeh S, Rinoldi C, Schot M, Kashaf SS,
Shari  F, Jalilian E, et al. Drug delivery systems
and materials for wound healing applications. Ad-
vanced drug delivery reviews. 2018;127:138-66.
[62] Zhong Y, Xiao H, Seidi F, Jin Y. Natu-
ral polymer-based antimicrobial hydrogels with-
out synthetic antibiotics as wound dressings.
Biomacromolecules. 2020;21(8):2983-3006.
[63] Karande P, Mitragotri S. Enhancement of trans-
dermal drug delivery via synergistic action of
chemicals. Biochimica et Biophysica Acta (BBA)-
Biomembranes. 2009;1788(11):2362-73.
[64] Tiwari V. Burn wound: How it differs from
other wounds? Indian journal of plastic surgery.
2012;45(02):364-73.
[65] Cartotto R. Topical antimicrobial agents for pedi-
atric burns. Burns & trauma. 2017;5.
[66] Souto EB, Ribeiro AF, Ferreira MI, Teixeira MC,
Shimojo AA, Soriano JL, et al. New nanotechnolo-
gies for the treatment and repair of skin burns
infections. International journal of molecular sci-
ences. 2020;21(2):393.
A Comprehensive Review of Advanced Modern Treatments, Strategies, and Techniques for Accelerating
Wound Healing: 15{32 30
[67] Whittam AJ, Maan ZN, Duscher D, Wong VW,
Barrera JA, Januszyk M, Gurtner GC. Challenges
and opportunities in drug delivery for wound heal-
ing. Advances in wound care. 2016;5(2):79-88.
[68] McClements DJ, Jafari SM. General aspects of
nanoemulsions and their formulation. Nanoemul-
sions: Elsevier; 2018. p. 3-20.
[69] Gorain B, Pandey M, Leng NH, Yan CW, Nie
KW, Kaur SJ, et al. Advanced drug delivery sys-
tems containing herbal components for wound
healing. International Journal of Pharmaceutics.
2022;617:121617.
[70] Lo S, Fauzi MB. Current update of colla-
gen nanomaterials|fabrication, characterisation
and its applications: A review. Pharmaceutics.
2021;13(3):316.
[71] Solans C, Sole I. Nano-emulsions: Formation by
low-energy methods. Current opinion in colloid &
interface science. 2012;17(5):246-54.
[72] Obagi Z, Damiani G, Grada A, Falanga V. Prin-
ciples of wound dressings: a review. Surg Technol
Int. 2019;35(5):0-57.
[73] Braza ME, Fahrenkopf MP. Split-thickness skin
grafts. 2019.
[74] Kumar R, Singh AK, Gupta A, Bishayee A,
Pandey AK. Therapeutic potential of Aloe
vera-A miracle gift of nature. Phytomedicine.
2019;60:152996.
[75] Tam JCW, Ko CH, Zhang C, Wang H, Lau CP,
Chan WY, et al. Comprehensive proteomic anal-
ysis of a Chinese 2-herb formula (Astragali Radix
and Rehmanniae Radix) on mature endothelial
cells. Proteomics. 2014;14(17-18):2089-103.
[76] Tam ChorWing [Tam CJ, Ko ChunHay KC,
Lau KitMan LK, To MingHo TM, Kwok Hin-
Fai KH, Siu WingSum SW, Lau ChingPo LC,
Chan WaiYee CW, Leung PingChung LP, Fung
KwokPui FK, Lau BikSan [Lau B. Enumeration
and functional investigation of endothelial progen-
itor cells in neovascularization of diabetic foot ul-
cer rats with a Chinese 2-herb formula. Journal of
Diabetes. 2015;7(5):718-28.
[77] Naji A, Eitoku M, Favier B, Deschaseaux F,
Rouas-Freiss N, Suganuma N. Biological func-
tions of mesenchymal stem cells and clinical im-
plications. Cellular and Molecular Life Sciences.
2019;76:3323-48.
[78] Kumar P, Kandoi S, Misra R, Vijayalakshmi S,
Rajagopal K, Verma RS. The mesenchymal stem
cell secretome: A new paradigm towards cell-free
therapeutic mode in regenerative medicine. Cy-
tokine & growth factor reviews. 2019;46:1-9.
[79] Dominici M, Le Blanc K, Mueller I, Slaper-
Cortenbach I, Marini F, Krause D, et al. Mini-
mal criteria for de ning multipotent mesenchymal
stromal cells. The International Society for Cel-
lular Therapy position statement. Cytotherapy.
2006;8(4):315-7.
[80] Mishra VK, Shih H-H, Parveen F, Lenzen D, Ito
E, Chan T-F, Ke L-Y. Identifying the therapeu-
tic signi cance of mesenchymal stem cells. Cells.
2020;9(5):1145.
[81] Mazini L, Rochette L, Admou B, Amal S, Malka
G. Hopes and limits of adipose-derived stem cells
(ADSCs) and mesenchymal stem cells (MSCs) in
wound healing. International journal of molecular
sciences. 2020;21(4):1306.
[82] Oualla-Bachiri W, Fernandez-Gonzalez A,
Qui~nones-Vico MI, Arias-Santiago S. From grafts
to human bioengineered vascularized skin substi-
tutes. International journal of molecular sciences.
2020;21(21):8197.
[83] Yu J, Lu S, McLaren AM, Perry JA, Cross KM.
Topical oxygen therapy results in complete wound
healing in diabetic foot ulcers. Wound Repair and
Regeneration. 2016;24(6):1066-72.
[84] Driver VR, Yao M, Kantarci A, Gu G, Park N,
Hasturk H. A prospective, randomized clinical
study evaluating the effect of transdermal contin-
uous oxygen therapy on biological processes and
foot ulcer healing in persons with diabetes melli-
tus. Ostomy Wound Manage. 2013;59(11):19-26.
[85] Driver VR, Reyzelman A, Kawalec J, French M.
A Prospective, Randomized, Blinded, Controlled
Trial Comparing Transdermal Continuous Oxygen
Delivery to Moist Wound Therapy for the Treat-
ment of Diabetic Foot Ulcers. Ostomy/wound
management. 2017;63(4):12-28.
[86] Serena TE, Bullock NM, Cole W, Lantis J, Li
L, Moore S, et al. Topical oxygen therapy in the
treatment of diabetic foot ulcers: a multicentre,
open, randomised controlled clinical trial. Journal
of wound care. 2021;30(Sup5): S7-S14.
[87] Al-Jalodi O, Kupcella M, Breisinger K, Serena
TE. A multicenter clinical trial evaluating the
durability of diabetic foot ulcer healing in ulcers
treated with topical oxygen and standard of care
versus standard of care alone 1 year post healing.
International Wound Journal. 2022;19(7):1838-42.
Avicenna Veterinary Research/ Vol. 1, No. 3, Summer 2025 31
[88] Vater C, Bosch L, Mitter A, Gols T, Seiser S, Heiss
E, et al. Lecithin-based nanoemulsions of tradi-
tional herbal wound healing agents and their effect
on human skin cells. European Journal of Pharma-
ceutics and Biopharmaceutics. 2022;170:1-9.
[89] Zain MSC, Edirisinghe SL, Kim C-H, De Zoysa
M, Shaari K. Nanoemulsion of  avonoid-enriched
oil palm (Elaeis guineensis Jacq.) leaf extract en-
hances wound healing in zebra sh. Phytomedicine
Plus. 2021;1(4):100124.
[90] Gharibzahedi SM, Jafari SM. Fabrication of na-
noemulsions by ultrasonication. Nanoemulsions:
Elsevier; 2018. p. 233-85.
[91] Che Marzuki NH, Wahab RA, Abdul Hamid
M. An overview of nanoemulsion: concepts
of development and cosmeceutical applications.
Biotechnology & biotechnological equipment.
2019;33(1):779-97.
[92] Abdellatif MM, Elakkad YE, Elwakeel AA, Al-
lam RM, Mousa MR. Formulation and charac-
terization of propolis and tea tree oil nanoemul-
sion loaded with clindamycin hydrochloride for
wound healing: In-vitro and in-vivo wound heal-
ing assessment. Saudi Pharmaceutical Journal.
2021;29(11):1238-49.
[93] Ahmad N, Alam MA, Ahmad FJ, Sarafroz
M, Ansari K, Sharma S, Amir M. Ultrasoni-
cation techniques used for the preparation of
novel Eugenol-Nanoemulsion in the treatment
of wounds healings and anti-in ammatory. Jour-
nal of drug delivery science and technology.
2018;46:461-73.
[94] Teo SY, Yew MY, Lee SY, Rathbone MJ, Gan
SN, Coombes AG. In vitro evaluation of novel
phenytoin-loaded alkyd nanoemulsions designed
for application in topical wound healing. Journal
of pharmaceutical sciences. 2017;106(1):377-84.
[95] Bonferoni M, Riva F, Invernizzi A, Dellera E, San-
dri G, Rossi S, et al. Alpha tocopherol loaded
chitosan oleate nanoemulsions for wound healing.
Evaluation on cell lines and ex vivo human biop-
sies, and stabilization in spray dried Trojan mi-
croparticles. European Journal of Pharmaceutics
and Biopharmaceutics. 2018;123:31-41.
[96] Sugumar S, Ghosh V, Nirmala MJ, Mukherjee
A, Chandrasekaran N. Ultrasonic emulsi cation
of eucalyptus oil nanoemulsion: antibacterial ac-
tivity against Staphylococcus aureus and wound
healing activity in Wistar rats. Ultrasonics sono-
chemistry. 2014;21(3):1044-9.
[97] Shanmugapriya K, Kim H, Saravana PS, Chun B-
S, Kang HW. Astaxanthin-alpha tocopherol na-
noemulsion formulation by emulsi cation meth-
ods: Investigation on anticancer, wound healing,
and antibacterial effects. Colloids and Surfaces B:
Biointerfaces. 2018;172:170-9.
[98] Albanna M, Binder KW, Murphy SV, Kim J,
Qasem SA, Zhao W, et al. In situ bioprinting of
autologous skin cells accelerates wound healing of
extensive excisional full-thickness wounds. Scien-
ti c reports. 2019;9(1):1856.
[99] Wu Y, Liang T, Hu Y, Jiang S, Luo Y, Liu C, et
al. 3D bioprinting of integral ADSCs-NO hydrogel
scaffolds to promote severe burn wound healing.
Regenerative biomaterials. 2021;8(3): rbab014.
[100] Teoh JH, Tay SM, Fuh J,Wang C-H. Fabricating
scalable, personalized wound dressings with cus-
tomizable drug loadings via 3D printing. Journal
of Controlled Release. 2022;341:80-94.