{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T15:50:00Z","timestamp":1773330600350,"version":"3.50.1"},"reference-count":77,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Foundation for Science and Technology (FCT)","award":["UIDB\/00276\/2020"],"award-info":[{"award-number":["UIDB\/00276\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)","award":["LA\/P\/0059\/2020"],"award-info":[{"award-number":["LA\/P\/0059\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Wound healing is a complex biological process involving a coordinated sequence of events aimed at restoring tissue integrity and function. Recent advancements in wound care have introduced novel therapies, with topical insulin application emerging as a promising strategy for promoting tissue healing. This study, involving 60 female cats (n = 60) undergoing elective spaying, aimed to evaluate the effects of topical fast-acting insulin on the healing process of surgical wounds. Each surgical suture was divided into two regions: the control zone (Zcr) without insulin application and the study zone (Zst), where insulin was applied topically for 10 min every 24 h over eight consecutive days. Assessment of suture healing was conducted using an adapted scale at two time points post-surgery: T1 (day 2) and T2 (day 8). Statistically significant differences were registered in the final healing scale scores between Zcr and Zst (p &lt; 0.022), as well as for the parameter of regional fluid (p-value = 0.017). Additionally, at T2, all Zst regions exhibited wound closure, whereas Zcr did not, although not in a statistically significant manner. The observed discrepancy at T2 between the Zcr and Zst regions may suggest a potential benefit of utilizing insulin. No side effects resulting from the insulin topical application performed by the tutors were recorded in the Zst suture group. This study represents the first exploration of the benefits of topical insulin application for surgical wound healing in cats.<\/jats:p>","DOI":"10.3390\/ani14091358","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T08:02:22Z","timestamp":1714723342000},"page":"1358","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Use of Fast-Acting Insulin Topical Solution on Skin to Promote Surgical Wound Healing in Cats"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6784-2806","authenticated-orcid":false,"given":"L. Miguel","family":"Carreira","sequence":"first","affiliation":[{"name":"Anjos of Assis Veterinary Medicine Centre\u2014CMVAA, Rua D.\u00aa Francisca da Azambuja N\u00ba9-9A, 2830-077 Barreiro, Portugal"},{"name":"Faculty of Veterinary Medicine, University of Lisbon (FMV\/ULisboa), Av. da Universidade T\u00e9cnica, 1300-477 Lisbon, Portugal"},{"name":"Interdisciplinary Centre for Research in Animal Health (CIISA), University of Lisbon (FMV\/ULisboa), Av. da Universidade T\u00e9cnica, 1300-477 Lisbon, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal"},{"name":"Faculty of American Laser Study Club\u2014ALSC, Altamonte Springs, FL 32714, USA"}]},{"given":"R\u00faben","family":"Silva","sequence":"additional","affiliation":[{"name":"Anjos of Assis Veterinary Medicine Centre\u2014CMVAA, Rua D.\u00aa Francisca da Azambuja N\u00ba9-9A, 2830-077 Barreiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1329-3709","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Alves","sequence":"additional","affiliation":[{"name":"Divis\u00e3o de Medicina Veterin\u00e1ria, Guarda Nacional Republicana (GNR), Rua Presidente Arriaga, 9, 1200-771 Lisbon, Portugal"}]},{"given":"Filipa","family":"In\u00e1cio","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, University of Lisbon (FMV\/ULisboa), Av. da Universidade T\u00e9cnica, 1300-477 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9462-4679","authenticated-orcid":false,"given":"Gra\u00e7a","family":"Pires","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, University of Lisbon (FMV\/ULisboa), Av. da Universidade T\u00e9cnica, 1300-477 Lisbon, Portugal"},{"name":"Interdisciplinary Centre for Research in Animal Health (CIISA), University of Lisbon (FMV\/ULisboa), Av. da Universidade T\u00e9cnica, 1300-477 Lisbon, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal"}]},{"given":"Pedro","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Anjos of Assis Veterinary Medicine Centre\u2014CMVAA, Rua D.\u00aa Francisca da Azambuja N\u00ba9-9A, 2830-077 Barreiro, Portugal"},{"name":"Faculty of American Laser Study Club\u2014ALSC, Altamonte Springs, FL 32714, USA"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1097\/01.ASW.0000416006.55218.d0","article-title":"Acute and impaired wound healing: Pathophysiology and current methods for drug delivery, part 1: Normal and chronic wounds: Biology, causes, and approaches to care","volume":"25","author":"Hamblin","year":"2012","journal-title":"Adv. Skin Wound Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1016\/j.burns.2014.03.020","article-title":"Insulin and wound healing","volume":"40","author":"Hrynyk","year":"2014","journal-title":"Burns"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1136\/bmj.2.4885.437","article-title":"The effect of insulin on nitrogen retention in the hypophysectomized rat","volume":"2","author":"Lawrence","year":"1954","journal-title":"Br. Med. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1210\/jc.2003-031371","article-title":"Insulin-Degrading Activity in Wound Fluid","volume":"89","author":"Duckworth","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1590\/S0102-86502014000200009","article-title":"Use of insulin-like growth factor in the healing of open wounds in diabetic and non-diabetic rats","volume":"29","author":"Achar","year":"2014","journal-title":"Acta Cir. Bras."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1152\/physrev.2003.83.3.835","article-title":"Regulation of wound healing by growth factors and cytokines","volume":"83","author":"Werner","year":"2003","journal-title":"Physiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.cyto.2012.03.019","article-title":"Insulin-like growth factor-1 cytokines cross-talk in type 1 diabetes mellitus: Relationship to microvascular complications and bone mineral density","volume":"59","author":"AboElAsrar","year":"2012","journal-title":"Cytokine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jss.2006.10.034","article-title":"Local Insulin-Zinc Injection Accelerates Skin Donor Site Wound Healing","volume":"142","author":"Zhang","year":"2007","journal-title":"J. Surg. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1002\/jor.22288","article-title":"Effects of local insulin delivery on subperiosteal angiogenesis and mineralized tissue formation during fracture healing","volume":"31","author":"Paglia","year":"2013","journal-title":"J. Orthop. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2121-10-1","article-title":"Cell and molecular mechanisms of keratinocyte function stimulated by insulin during wound healing","volume":"10","author":"Liu","year":"2009","journal-title":"BMC Cell Biol."},{"key":"ref_11","first-page":"22","article-title":"A randomized, double-blind, placebo-controlled trial to determine the effects of topical insulin on wound healing","volume":"55","author":"Rezvani","year":"2009","journal-title":"Ostomy Wound Manag."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"46","DOI":"10.12968\/jowc.2016.25.1.46","article-title":"Biomarkers for wound healing and their evaluation","volume":"25","author":"Patel","year":"2016","journal-title":"J. Wound Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1172\/JCI32169","article-title":"Cellular and molecular basis of wound healing in diabetes","volume":"117","author":"Brem","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1016\/S0002-9440(10)63754-6","article-title":"Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells","volume":"164","author":"Galiano","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1015e","DOI":"10.1097\/PRS.0b013e3182a806f0","article-title":"Local use of insulin in wounds of diabetic patients: Higher temperature, fibrosis, and angiogenesis","volume":"132","author":"Dietsch","year":"2013","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1083\/jcb.107.4.1589","article-title":"Role of laminin and basement membrane in the morphological differentiation of human endothelial cells into capillary-like structures","volume":"107","author":"Kubota","year":"1988","journal-title":"J. Cell Biol."},{"key":"ref_17","first-page":"121","article-title":"Wound healing and diabetes mellitus","volume":"12","author":"Alvarez","year":"1994","journal-title":"Clin. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/S0140-6736(05)67700-8","article-title":"Wound healing and its impairment in the diabetic foot","volume":"366","author":"Falanga","year":"2005","journal-title":"Lancet"},{"key":"ref_19","first-page":"173105","article-title":"Insulin for wound healing","volume":"878","author":"Vetter","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"606","DOI":"10.2337\/diacare.23.5.606","article-title":"Screening techniques to identify people at high risk for diabetic foot ulceration: A prospective multicenter trial","volume":"23","author":"Pham","year":"2000","journal-title":"Diabetes Care"},{"key":"ref_21","unstructured":"V\u00edtor, M.R.d.C., Carreira, L.M.A., and Miguel, E.R.B. (2024, April 06). Proposta de uma Escala para Avalia\u00e7\u00e3o do Processo de Cicatriza\u00e7\u00e3o de Ferida Cir\u00fargica no c\u00e3o e no gato. Disserta\u00e7\u00e3o de Mestrado em Medicina Veterin\u00e1ria. Lisboa: Faculdade de Medicina Veterin\u00e1ria-Universidade de Lisboa. Available online: http:\/\/hdl.handle.net\/10400.5\/14053."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cvsm.2006.02.002","article-title":"Management of Hard-to-Heal Wounds","volume":"36","author":"Amalsadvala","year":"2006","journal-title":"Vet. Clin. N. Am. Small Anim. Pract."},{"key":"ref_23","unstructured":"Fossu, T.W. (2013). Small Animla Surgery, Elsevier. [4th ed.]."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0964-5691(99)00036-8","article-title":"Plastics and South Pacific Island shores: Environmental implications","volume":"42","author":"Gregory","year":"1999","journal-title":"Ocean Coast. Manag."},{"key":"ref_25","unstructured":"Pavletic, M.M. (2010). Atlas of Small Animal Wound Management and Reconstructive Surgery, Wiley\u2014Blackwell. [3rd ed.]."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1097\/SLA.0b013e31820563a8","article-title":"Angiogenesis in wounds treated by microdeformational wound therapy","volume":"253","author":"Erba","year":"2011","journal-title":"Ann. Surg."},{"key":"ref_27","first-page":"379","article-title":"Recent advances in topical wound care","volume":"45","author":"Sarabahi","year":"2012","journal-title":"Indian J. Plast. Surg. Off. Publ. Assoc. Plast. Surg. India"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1590\/1809-2950\/15311923042016","article-title":"Efeito Da estimula\u00e7\u00e3o el\u00e9trica De Alta Voltagem E Insulina t\u00f3pica Em les\u00e3o cut\u00e2nea Experimental","volume":"23","author":"Ferreira","year":"2016","journal-title":"Fisioter. Pesq."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/wrr.12511","article-title":"Efficacy of topical insulin in wound healing: A preliminary systematic review and meta-analysis of randomized controlled trials","volume":"25","author":"Sridharan","year":"2017","journal-title":"Wound Rep. Reg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1056\/NEJM199909023411006","article-title":"Cutaneous wound healing","volume":"341","author":"Singer","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/nature07039","article-title":"Wound repair and regeneration","volume":"453","author":"Werner","year":"2008","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1111\/j.1524-475X.2009.00543.x","article-title":"Human skin wounds: A major and snowballing threat to public health and the economy","volume":"17","author":"Sen","year":"2009","journal-title":"Wound Repair Regen."},{"key":"ref_33","unstructured":"Tobias, K.M., and Johnston, S.A. (2012). Veterinary Surgery: Small Animal, Elsevier."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.1002\/jps.21210","article-title":"Wound healing dressings and drug delivery systems: A review","volume":"97","author":"Boateng","year":"2008","journal-title":"J. Pharm. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1089\/wound.2014.0595","article-title":"Topical collagen-based biomaterials for chronic wounds: Rationale and clinical application","volume":"5","author":"Gould","year":"2016","journal-title":"Adv. Wound Care"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1097\/01.prs.0000225430.42531.c2","article-title":"The basic science of wound healing","volume":"117","author":"Broughton","year":"2006","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.cveq.2018.07.003","article-title":"Wound Management: Wounds with Special Challenges","volume":"34","author":"Eggleston","year":"2018","journal-title":"Vet. Clin. N. Am. Equine Pract."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0002-9440(10)63821-7","article-title":"Cellular dysfunction in the diabetic fibroblast: Impairment in migration, vascular endothelial growth factor production, and response to hypoxia","volume":"162","author":"Lerman","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_39","first-page":"425","article-title":"Topical insulin application improves healing by regulating the wound inflammatory response","volume":"20","author":"Chen","year":"2012","journal-title":"Wound Repair Regen. Publ. Wound Heal. Soc. Eur. Tissue Repair Soc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1038\/jid.2008.230","article-title":"Akt1 controls insulin-driven VEGF biosynthesis from keratinocytes: Implications for normal and diabetes-impaired skin repair in mice","volume":"129","author":"Goren","year":"2009","journal-title":"J. Investig. Dermatol."},{"key":"ref_41","first-page":"48","article-title":"Clinical management of equine wounds with different aspects of hyperglycemia in blood","volume":"43","author":"Rizzo","year":"2016","journal-title":"J. Equine Vet. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/j.joca.2010.07.004","article-title":"Oxygen tension differentially regulates the functional properties of cartilaginous tissues engineered from infrapatellar fat pad-derived MSCs and articular chondrocytes","volume":"18","author":"Buckley","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s11892-018-0970-z","article-title":"Dysfunctional Wound Healing in Diabetic Foot Ulcers: New Crossroads","volume":"18","author":"Davis","year":"2018","journal-title":"Curr. Diabetes Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1046\/j.1464-5491.2002.00692.x","article-title":"Transforming growth factor-beta 1, 2, 3 and receptor type I and II in diabetic foot ulcers","volume":"19","author":"Jude","year":"2002","journal-title":"Diabet. Med."},{"key":"ref_45","first-page":"196","article-title":"Regulation of keratinocyte growth factor gene expression in human skin fibroblasts","volume":"12","author":"Tang","year":"1996","journal-title":"J. Dermatol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1089\/wound.2012.0406","article-title":"Critical role of transforming growth factor beta in different phases of wound healing","volume":"2","author":"Pakyari","year":"2013","journal-title":"Adv. Wound Care"},{"key":"ref_47","first-page":"251","article-title":"The use of topical insulin in the treatment of nonhealing wounds in dogs","volume":"49","author":"Hanson","year":"2013","journal-title":"J. Am. Anim. Hosp. Assoc."},{"key":"ref_48","unstructured":"Gross, T.L., Carr, A.P., and Tranquilli, W.J. (2005). Monitoramento Cl\u00ednico de Doen\u00e7as em C\u00e3es e Gatos, Artmed Editora. [1st ed.]."},{"key":"ref_49","first-page":"127","article-title":"Evaluation of burn wound healing activity of topical regular insulin in non-diabetic and streptozocin-induced diabetic rats","volume":"6","author":"Bairy","year":"2014","journal-title":"Int. J. Pharm. Pharm. Sci."},{"key":"ref_50","first-page":"180","article-title":"Effect of topical insulin on cutaneous wound healing in rats with or without acute diabetes","volume":"35","author":"Izzettin","year":"2009","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_51","first-page":"98","article-title":"Effects of topical application of insulin on the wound healing in scalded rats","volume":"20","author":"Lui","year":"2004","journal-title":"Zhonghua Shao Shang Za Zhi"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1308\/003588408X261816","article-title":"A role for topical insulin in the management of problematic surgical wounds","volume":"90","author":"Wilson","year":"2008","journal-title":"Ann. R. Coll. Surg. Engl."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"H\u00f6gstedtLink\u00f6ping, A. (2021). Microvascular Effects of Insulin in the Skin. [Ph.D. Thesis, Department of Biomedical and Clinical Sciences, Faculty of Health Sciences, University Medical Dissertations]. Thesis No. 1788.","DOI":"10.3384\/diss.diva-180547"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1177\/2292550317740688","article-title":"Effects of Local Use of Insulin on Wound Healing in Non-diabetic Patients","volume":"26","year":"2018","journal-title":"Plast. Surg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1210\/er.2018-00141","article-title":"Insulin Resistance and Atherosclerosis: Implications for Insulin-Sensitizing Agents","volume":"40","author":"DeFronzo","year":"2019","journal-title":"Endocr. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1177\/147323000903700531","article-title":"The wound healing process: An overview of the cellular and molecular mechanisms","volume":"37","author":"Velnar","year":"2009","journal-title":"J. Int. Med. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.tcb.2005.09.002","article-title":"Inflammatory cells during wound repair: The good, the bad and the ugly","volume":"15","author":"Martin","year":"2005","journal-title":"Trends Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1515\/med-2020-0216","article-title":"IGF-1 regulates the growth of fibroblasts and extracellular matrix deposition in pelvic organ prolapse","volume":"15","author":"Yin","year":"2002","journal-title":"Open Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/jcb.240400208","article-title":"Role of growth factors in inflammation and repair","volume":"40","author":"Wahl","year":"1989","journal-title":"J. Cell Biochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4492","DOI":"10.1111\/j.1582-4934.2008.00555.x","article-title":"Cell and molecular mechanism of insulin-induced angiogenesis","volume":"13","author":"Liu","year":"2009","journal-title":"J. Cell Mol. Med."},{"key":"ref_61","first-page":"4682","article-title":"Topical insulin accelerates cutaneous wound healing in insulin-resistant diabetic rats","volume":"9","author":"Yu","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"719","DOI":"10.2147\/DMSO.S237294","article-title":"Effects of Topical Insulin on Wound Healing: A Review of Animal and Human Evidences","volume":"13","author":"Wang","year":"2020","journal-title":"Diabetes Metab. Syndr. Obes. Targets Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1021\/acsptsci.3c00030","article-title":"Chronic Wound Healing Models","volume":"6","author":"Flynn","year":"2023","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"526","DOI":"10.12968\/jowc.1999.8.10.26217","article-title":"Topical insulin in wound healing: A randomized, double-blind, placebo-controlled trial","volume":"8","author":"Greenway","year":"1999","journal-title":"J. Wound Care"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1507\/endocrj.EJ20-0575","article-title":"Effects of topical insulin on wound healing: A meta-analysis of animal and clinical studies","volume":"68","author":"Liu","year":"2021","journal-title":"Endocr. J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1111\/j.1532-950X.2004.04081.x","article-title":"Cutaneous Wound Healing in the Cat: A Macroscopic Description and Comparison with Cutaneous Wound Healing in the Dog","volume":"33","author":"Bohling","year":"2004","journal-title":"Vet. Surg."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jtcme.2015.12.002","article-title":"Evaluation of wound healing, anti-microbial and antioxidant potential of Pongamia pinnata in wistar rats","volume":"7","author":"Dwivedi","year":"2016","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"613","DOI":"10.3389\/fendo.2018.00613","article-title":"The Discovery of Insulin: An Important Milestone in the History of Medicine","volume":"9","author":"Vecchio","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"A259","DOI":"10.1186\/1758-5996-7-S1-A259","article-title":"Insulin topical modulates inflammatory phase and the angiogenesis of the burns wound healing in diabetic-induced rats","volume":"7","author":"Azevedo","year":"2015","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Lima, M.H., Caricilli, A.M., de Abreu, L.L., Ara\u00fajo, E.P., Pelegrinelli, F.F., Thirone, A.C., Tsukumo, D.M., Pessoa, A.F., dos Santos, M.F., and de Moraes, M.A. (2012). Topical insulin accelerates wound healing in diabetes by enhancing the AKT and ERK pathways: A double-blind placebo-controlled clinical trial. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036974"},{"key":"ref_71","first-page":"455","article-title":"The use of insulin in open-wound healing","volume":"65","author":"Belfield","year":"1970","journal-title":"Vet. Med. Small Anim. Clin."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1083\/jcb.201409032","article-title":"FOXO1 differentially regulates both normal and diabetic wound healing","volume":"209","author":"Zhang","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1039\/C5BM00211G","article-title":"Hammond. Three-dimensional multilayered fibrous constructs for wound healing applications","volume":"4","author":"Reis","year":"2016","journal-title":"Biomater. Sci."},{"key":"ref_74","first-page":"125","article-title":"Wound Healing","volume":"Volume 1","author":"Tobias","year":"2012","journal-title":"Veterinary Surgery: Small Animal"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1001\/archsurg.135.11.1265","article-title":"Effects of steroids and retinoids on wound healing","volume":"135","author":"Wicke","year":"2000","journal-title":"Arch. Surg."},{"key":"ref_76","first-page":"e41","article-title":"The use of growth factors and other humoral agents to accelerate and enhance burn wound healing","volume":"11","author":"Ching","year":"2011","journal-title":"Eplasty"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1177\/193229681000400408","article-title":"Novel use of insulin in continuous-instillation negative pressure wound therapy as wound chemotherapy","volume":"4","author":"Scimeca","year":"2010","journal-title":"J. Diabetes Sci. 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