Role of Honey in Advanced Wound Care

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Role of Honey in Advanced Wound Care molecules Review Role of Honey in Advanced Wound Care Hana Scepankova 1,†, Patricia Combarros-Fuertes 2,† , José María Fresno 2 , María Eugenia Tornadijo 2, Miguel Sousa Dias 3, Carlos A. Pinto 1 , Jorge A. Saraiva 1 and Letícia M. Estevinho 3,* 1 LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal; [email protected] (H.S.); [email protected] (C.A.P.); [email protected] (J.A.S.) 2 Department of Food Hygiene and Technology, Faculty of Veterinary Science, Campus de Vegazana, University of León, 24071 León, Spain; [email protected] (P.C.-F.); [email protected] (J.M.F.); [email protected] (M.E.T.) 3 CIMO, Mountain Research Center, Polytechnic Institute of Bragança, Campus Santa Apolónia, 5301-855 Bragança, Portugal; [email protected] * Correspondence: [email protected]; Tel.: +351-273303342 † These authors contributed equally to this work. Abstract: Honey is a natural product rich in several phenolic compounds, enzymes, and sugars with antioxidant, anticarcinogenic, anti-inflammatory, and antimicrobial potential. Indeed, the develop- ment of honey-based adhesives for wound care and other biomedical applications are topics being widely investigated over the years. Some of the advantages of the use of honey for wound-healing solutions are the acceleration of dermal repair and epithelialization, angiogenesis promotion, immune response promotion and the reduction in healing-related infections with pathogenic microorganisms. This paper reviews the main role of honey on the development of wound-healing-based applications, the main compounds responsible for the healing capacity, how the honey origin can influence the Citation: Scepankova, H.; healing properties, also highlighting promising results in in vitro and in vivo trials. The challenges in Combarros-Fuertes, P.; Fresno, J.M.; the use of honey for wound healing are also covered and discussed. The delivery methodology (direct Tornadijo, M.E.; Dias, M.S.; Pinto, application, incorporated in fibrous membranes and hydrogels) is also presented and discussed. C.A.; Saraiva, J.A.; Estevinho, L.M. Role of Honey in Advanced Wound Keywords: honey; wound-healing; antioxidant; antimicrobial; hydrogels; dermal repair; hydrogel Care. Molecules 2021, 26, 4784. https://doi.org/10.3390/ molecules26164784 1. Introduction Academic Editor: Juraj Majtan The skin is composed of three layers (epidermis, dermis, and hypodermis), and is considered the first physical barrier against external infectious agents. Wounds are defined Received: 13 July 2021 as the disruption in the continuity of the skin, induced by mechanical, chemical, or thermal Accepted: 29 July 2021 harms, and resulting in the loss of the defensive functions of this tissue [1]. Published: 7 August 2021 The wound-healing process has the purpose of recovering the integrity of the damaged tissue and the regeneration of the epithelium that was lost, and it is a dynamic and complex Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in process that globally occurs in four overlapping steps: hemostasis, inflammation, tissue published maps and institutional affil- proliferation, and regeneration [1,2] (Figure1). iations. The cascade of initial vasoconstriction of blood vessels and platelet aggregation play a key role in stopping the loss of blood. The initial vasoconstriction is followed by a vasodilation, which allows an influx of a variety of inflammatory cells which release several types of mediators and cytokines to promote thrombosis, angiogenesis, and re- epithelialization. In addition, the fibroblasts release extracellular components which initiate Copyright: © 2021 by the authors. the formation of collagen fibers that will serve as scaffolding [1,3]. During the inflammatory Licensee MDPI, Basel, Switzerland. This article is an open access article phase the hemostasis, chemotaxis, and the increased vascular permeability limit further distributed under the terms and damage, close the wound, remove cellular debris and bacteria, and promote cellular conditions of the Creative Commons migration [3]. Afterwards, the proliferative phase implicates the formation of granulation Attribution (CC BY) license (https:// tissue, re-epithelialization, and neovascularization, a process that can last from several creativecommons.org/licenses/by/ weeks until some months, or even more time in the case of the existence of some co- 4.0/). morbidities or particular patient situations [4]. In the end, during the maturation period, Molecules 2021, 26, 4784. https://doi.org/10.3390/molecules26164784 https://www.mdpi.com/journal/molecules Molecules 2021, 26, 4784 2 of 19 Molecules 2021, 26, x FOR PEER REVIEW 2 of 22 the new tissues are remodeled, the excess of collagen is reduced, and the wound contracts and reaches the maximum tensile strength [1]. Figure 1. Stages of wound-healingFigure process. 1. Stages of wound-healing process. Acute wounds derived from unexpected accidents or surgical injury commonly heal The cascade of initial vasoconstriction of blood vessels and platelet aggregation play within a predictable period depending on the size, depth, and extent of damage. Nev- a key role in stoppingertheless, the loss deficiencies of blood. in The the wound-healing initial vasoconstriction process cause is more followed than 38 by million a vaso- patients dilation, which allowswith an chronic influx wounds of a worldwide,variety of whichinflammatory reaches epidemic cells which proportions release and causesseveral a large types of mediators andeconomic cytokines weight to on promote healthcare thrombosis, systems [5]. angiogenesis, and re-epitheliali- zation. In addition, the fibroblastsProlonged chronicity release ofextracellular wounds is normally components related to which a bacterial initiate injured-tissue the for- colo- nization, which can progress into a bacterial resistance to topical and systemic antimicrobial mation of collagen agents,fibers orthat into will biofilm serve development, as scaffolding which complicates, [1,3]. During in both the cases, inflammatory their treatment [6]. phase the hemostasis,In the chemotaxis, end, this type and of wound the increased can cause vascular sepsis and permea inflammationbility in limit organs further and lead to damage, close the wound,increased remove morbidity cellular and mortality. debris and bacteria, and promote cellular mi- gration [3]. Afterwards,The the clinical proliferative considerations phase in wound-healingimplicates the management formation include of granulation preventing and controlling the infection and/or contamination, maintaining the adequate moisture en- tissue, re-epithelialization,vironment, and treating neovascularization, edema, and preventing a proce furtherss injury.that can Conventional last from chronic several wound weeks until some monthscare involves, or even debridement more time to remove in the non-viablecase of the tissue existence and bacterial of some biofilms, co-mor- followed bidities or particularby patient wound dressing.situations The [4] common. In the wound end, dressingsduring the consist maturation of a standard period, cotton the bandage new tissues are remodeled,or highly absorbent the excess dressings, of collag suchen as is collagen reduced, and alginate,and the or wound hydrocolloids; contracts however, and reaches the maximumthis procedure tensile of woundstrength care [1] is. often ineffective. Due to this need for new, efficient, and improved therapies, there has been a revived interest in alternative treatment approaches, Acute woundssuch derived as honey. from Theunexpected management accidents of wound or healingsurgical has injury become commonly the primary heal field of within a predictabletherapeutic period depending application ofon this the natural size, productdepth, [7and,8]. extent of damage. Never- theless, deficiencies in Honeythe wound has been-healing used for process wound healing cause since more ancient than times, 38 million mainly due patients to its antimi- with chronic woundscrobial worldwide, activity. In which addition reach to thees broad epidemic spectrum proportions of antibacterial and activity cause againsts a large common wound-infecting microorganisms, honey has been demonstrated to be effective against economic weight onantibiotic-resistant healthcare systems bacteria [5] and. was able to restore the efficacy of some antibiotics against Prolonged chronicitybacteria withof wounds previously is acquirednormally resistance related [8 –to10 a]. Furthermore,bacterial injured due to- itstissue several col- antimi- onization, which cancrobial progress components into a and bacterial its different resistance antibacterial to topical action mechanisms,and systemic the antimi- development crobial agents, or intoof bacterial biofilm resistance development, to honey which is unlikely complicates [8,11,12]. Moreover,, in both thecases, wound-healing their treat- ability ment [6]. In the end,of this honey type is alsoof wound related tocan its cause anti-inflammatory sepsis and andinflammation antioxidant activity,in organs as welland as its capacity to promote re-epithelialization and angiogenesis and stimulate skin and immune lead to increased morbiditycells [13,14 and]. All mortality. these mechanisms act together favoring the regeneration process of the The clinical considerationsdamaged tissue. in wound-healing management include preventing and controlling the infectionSeveral and/or case contamination, studies and randomized maintain controlleding the trials adequate provide
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