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Degradation is regulated by extracellular and intracellular pathways. The rst involves membrane- bound and secreted proteolytic enzymes. The second involves internalization of intact and fragmented collagen brils (through phagocytosis, macropinocytosis, or endocytosis), followed by enzymatic degradation [10, 11]. Proteolytic enzymes include two important groups: matrix metalloproteinases (MMPs) and serine proteases. The production and secretion of these enzymes are tightly regulated and are associated with specic cellular subtypes. Among the MMPs, collagenases and gelatinases, which degrade intact and damaged brillar collagen, respectively, are the most important for collagen turnover during wound healing. Collagens I and III are cleaved preferentially by MMP-1 (also called collagenase-1) and MMP-8 (collagenase-

2), while collagen IV is degraded by gelatinase MMP-9. Extensive research has determined that collagenolytic enzymes are able to recognize, bind, unwind, and cut individual strands of the triple helix (Fig.23.2).

The bioactive peptides resulting from their action play a key role in “remodeling” the blood vessels developed as a result of neoangiogenesis and the tissue being formed.

Among serine proteases, neutrophil elastase has actions overlapping with those described.

23.3.3 Collagen & Tissue Repair

23.3.3.1 Anti-Inammatory Action

As a result of tissue damage, collagen bers in the extracellular matrix induce platelet activation, their aggregation to the point of platelet plug formation. Collagen I and IV represent the true mediators of anti-inammatory activity as they exert chemotactic action for neutrophils, stimulate phagocytosis, immune response, and modulate gene expression [5].

Collagen matrix is able to accelerate the inammatory response leading to a more rapid restitutio adintegrum. Reduction, in fact, of collagen levels in chronic wounds underlies delayed healing.

MMPs

Integrin

Cell membrane

Fig. 23.2 Onursal C, Dick E, Angelidis I, Schiller HB, Staab-Weijnitz CA. Collagen Biosynthesis, Processing, and Maturation in Lung Ageing. Front Med (Lausanne).

Phagosome

Phagolysosome

MMPs

Extracellular cathepsins

Receptors for endosomal collagen uptake

Lysosomal cathepsins

Lysosome

2021 May 20;8:593874. doi: 10.3389/fmed.2021.593874. PMID: 34095157; PMCID: PMC8172798 [7]

new epithelium formation (days to weeks)

M: Maturation – Remodeling of ECM and increase in tensile strength of wound (weeks-months/years)

promote recruitment of fibroblasts, epithelial and endothelial cells, infection surveillance and response (hours to days)

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23.3.3.2 Neoangiogenic Action

Collagen exhibits both pro-angiogenic and antiangiogenic character: The stimulation of neoangiogenesis is provided by type I collagen, which, through the release of peptide C, attracts endothelial cells both invivo and invitro; type IV and XVIII (non-brillar) collagen exhibit antiangiogenic action because their proteolytic fragments inhibit the migration and proliferation of endothelial cells and induce their apoptosis.

23.3.3.3 Role inECM Remodeling

The process of forming a denitive scar is a long process that takes years. It is due to the changes to which the extracellular matrix at the scar level is subjected. The degradation and neo-apposition of collagen bers related to their orientation are the basis for the formation of a normo-conformed scar as opposed to a pathological scar.

Keloid scars are characterized by thick bundles of disorganized collagen bers with a reduced number of crosslinked bonds located in the deep dermis. In contrast, hypertrophic scars consist of thin bundles of collagen bers (Fig.23.3).

23.3.3.4 Dressings

Collagen has been widely used in the manufacture of wound dressings because of its biological characteristics [12]: hemostaticity, biocompatibility, low antigenicity, controlled biodegradability, and ability to stimulate cell attachment and growth [13].

In addition, collagen dressings are exible and can absorb high amounts of exudate, acting as a competitive substrate for collagenase, which can reduce enzymatic tissue degradation [14].

Collagen dressings consist of type I collagen and can be classied as follows:

• according to the conformation of the collagen,

i.e., hydrolyzed, denatured, and triple helical,

• according to the characteristics of the dress-

ing, i.e., spray, powder, lm, pad, gel, scaf-

fold, and mesh,

• according to the components of the dressing

itself, i.e., 100% collagen or collagen com-

bined with other molecules,

• according to origin in equine, bovine, and

porcine.

collagen

platelet activation & aggregation

leading to fibrin dot formation

Collagen Photo by Unknown Author & formed under CC BY-SA

fibroblast proliferation &

fibroblasts, epithelial and

endothelial cells recruited

growth factor synthesis

tissue remodeling and

development oftensile strength

Hemostasis – crosslinked fibrin together with aggregated platelets help stop the bleeding (seconds to hours)

Inflammation – immune cell activation and recruitment driving the secretion of proinflammatory cytokines that

Proliferation – Fibroblast proliferation and collagen deposition, angiogenesis, granulation tissue formation,

Fig. 23.3 Collagen and wound healing [6]

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Dressings with 100% of non-hydrolyzed collagen are used for the treatment of both burns and acute and chronic wounds [15]. These dressings are typically nonporous and chemically superimposed on the collagen extracellular matrix. They are used in noninfected wounds with mild to intermediate exudation. The need to apply it to wounds with limited exudation is due to the rapidity with which it would disintegrate and the ease of over-infection and maceration damage if adopted in hyper-exuding wounds. Collagen pads, moreover, act as a veritable scaffold for broblasts, macrophages, and neutrophils by speeding up wound healing.

The role of collagen on MMP activity has not been demonstrated. In some cases, the pads are composed of a combination of collagen and Manuka Honey, which, by causing a reduction in wound PH, exhibit inhibitory action on MMPs and antimicrobial action through the formation of H2O2 and NO.Honey will facilitate the maintenance of a cleansed wound, thereby facilitating the healing process and having a synergistic effect with collagen thus reducing wound depth, increasing granulation tissue formation, reducing wound extension, and facilitating reepithelialization [16].

Another commercially available formulation is triple helix collagen combined with hyaluronic acid. In addition to the characteristics of collagen, this dressing takes advantage of the HA’s ability to moisturize the wound, promote cell proliferation and migration, and promote angiogenesis. This dressing is strongly discouraged in infected wounds. Please refer to the specic section on HA for further discussion.

Hydrolyzed and denatured collagen formulations have been introduced into clinical practice in order to promote greater cytokine release, attract more neutrophils, and overcome the limitations of triple helical collagen such as:

• Poor solubility.

• Long solubility in an aqueous environment

[17].

Some products in addition to unhydrolyzed bovine collagen are combined with polypeptides

and glycerin or oxidized and regenerated cellulose (ORC), typically formulated in pads that have a greater absorptive capacity than 100% unhydrolyzed bovine collagen pads [18].

It would appear that formulations with ORC

are able to:

• reduce enzyme activity at the wound bed by conversely promoting the apposition of new tissue,

• promote the release of PDGF,

A more recently introduced formulation com-

bines the capabilities of denatured collagen, the absorptive properties of carboxymethylcellulose, and sodium alginate with the abilities of EDTA to bind calcium so as to regulate MMPs and collagenases [19] (Table23.2).

23.3.3.5 Hyaluronic Acid

Hyaluronic acid (HA) is a natural polymer that belongs to a heterogeneous group of polysaccharides, the glycosaminoglycans (GAGs). In humans, it is found mainly in the vitreous humor, joints, umbilical cord, skin, and connective tissue. For many years, it was extracted from animals, mainly from the cockscomb, the tissue with the highest concentration of it (~7500 μg/mL). Currently, it is mainly obtained by bacterial fermentation.

It is composed of the repetition of disaccha-

ride units of β-D-glucuronic acid and N-acetyl-Dglucosamine linked, alternately, by β-1,3 and β-1,4 glycosidic bonds. It has a semiexible structure [21], with variable molecular weight (Table23.3).

Its formula is characterized by a high number

of carboxyl (-COOH) and hydroxyl (-OH) groups responsible for the pronounced hydrophilicity. At physiological pH, the carboxyl groups and acetoamide groups on the surface of the molecule establish hydrogen bridges with water, resulting in the stabilization of the secondary structure of the biopolymer. HMW-HA exhibits greater stability, viscosity, and viscoelasticity than smaller molecules. In any case, it is crucial to remember that the rheological properties of HA depend not only on molecular weight but also on the ionic

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Table 23.2

Form of dressing Composition

Gel Collagen Cellera RX Maintain

Gel Collagen polypeptides Stimulen Provide

Pad Collagen eece, gentamicin

Pad Collagen,

Pad Collagen and ca alginate Fibracol

Pad Bovine collagen and

Pad Type I equine collagen Boiopad Free from

Pad Bovine collagen and

Some of the formulations currently on the market are listed in the following table [20]

Product Name Advantage Limitations Wounds Suitable for

moisture for wound bed

salts

Carboxymethylcellulose, sodium alginate, AgCl

Manuka honey

oxidized cellulose

Septocoll EActivate

ColActive plus ag

plus

Puracol No extra

Promogran Hemostatic

platelets

Hinders the function of MMPs

Maintain moisture for wound bed

debridement required

collagen degradation products

activity

Bovine sources and require secondary wound dressing

Skin responses Partial and

Bovine sources and require secondary wound dressing

Require secondary wound dressing

Bovine sources and expensive

Equine source, timeconsuming and expensive

Bovine source, not to be utilized on third-degree burns

Partial and full-thickness injuries including traumatic wounds, surgical wounds, diabetic ulcers and burns

Full and partial thickness wounds including pressure ulcers, partial thickness burns, abrasions

full-thickness injuries including infected wounds and bleeding lesions

Full and partial thickness wounds including burns, dehisced surgical incisions, abrasions, diabetic venous or pressure ulcers

(continued)

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Table 23.2

Form of dressing Composition

Pad Collagen Catrix Decrease

Pad Porcine dermal collagen,

Powder Collagen, polycarbonate

Membrane Type I collagen Orcel Full resorbable Not suitable

Table 23.3

oligosaccharide O-HA <1×104 Da Low molecular weight HA LMW-HA 1–25×10 Medium molecular weight HA MMW-HA 25×104–1×106Da High molecular weight HA HMW-HA >1×10 Very high molecular weight HA vHMW-HA >6×10

(continued)

Product Name Advantage Limitations Wounds Suitable for

bleeding, biodegradable

Biobrane Flexibility Bovine

nylon, silicon

Apligraf Resorbable Not suitable

membrane

Classication of HA according to molecular weight

Bovine sources and require secondary wound dressing

sources and require secondary wound dressing

for infected injuries, bovine source, expensive

Full and partial thickness wounds including cuts, abrasions, irritations, pressure and diabetic ulcers, radiation dermatitis

Partial thickness burn wounds

Full and partial thickness wounds including VLU, DFU

Full-thickness injuries including burns

charge of the solution in which it is contained (solution ionic strength) pH and temperature. In case of skin damage, for example, the pH in the wound bed is about 8 and reaches a value of 5 at the end of the healing process.

Under normal conditions, HA is generally synthesized as a high molecular weight polymer (HMW-HA). When ECM homeostasis is disrupted by pathological conditions, such as cancer, inammation, oxidative stress, and tissue remodeling, endogenous HMW-HA can be degraded more rapidly by hyaluronidases (HYALs) and ROS, thus unbalancing the balance toward a higher concentration of low molecular weight HA (LMW) that can be further fragmented into shorter oligomers (o-HA) (Table23.4). These changes underlie its multiple actions in the wound-healing process (Table23.4):

Table 23.4

the Tissue Level

O-HA Creati in condizioni patologiche (es:

LMW-HA Proprietà angiogeniche

HMW-HA

HA Polymers and Activities Carried Out at

brosi, inammazione e cancro) agiscono come segnali di allarme cellulare stimolano angiogenesi, proliferazione cellulare, invasione e inammazione

Stimola la produzione citochine pro-inammatorie e fattori di crescita coinvolti nel rimodellamento della matrice Modula le funzioni chiave delle cellule tumorali attraverso l’interazione con CD44 e RHAMM [22, 23]

Promuove formazione del tappo di brina Ruolo chiave nell’omeostasi Dei tessuti, Protegge l’integrità del tessuto epiteliale Promuove effetti antinammatori, antiproliferativi e antiangiogenici [24]

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• promotes brin plug formation,

• promotes the production and release of inter-

leukins and pro-inammatory cytokines,

• stimulates, together with bronectin, the inva-

sion, and proliferation of broblasts and induces

their transformation into myobroblasts essen-

tial in the process of wound contraction,

• stimulates the migration and proliferation of

keratinocytes,

biocompatibility, biodegradability, and ease to chemical modication, makes it an excellent object of research in the eld of wound healing. Numerous dressings containing hyaluronic acid that are already on the market (Table23.5) and others being studied in order to improve its stability in water mechanical properties and biological performance.

In general, HA dressings should be used on

acute and chronic, cleansed, low- to medium-

The hydrophilic nature that allows exudate absorption and cell adhesion, combined with its

Table 23.5 HA Dressings—A Selection [25]

Commercially available product Characteristics References

Bionect

Connettivina Cream containing 10mg/ml of hyaluronate sodium used for the

Hyaloll Cream-colored non-adherent produced of a derived-HA (HYAFF).

Hyalomatrix

Hyalosafe This transparent lm is designed to cover supercial wounds and

Hylase Wound gel It is a gel composed of a combination of emollients and sodium

HylaSponge

Topical solution composed of LMW-HA sodium salt (0.2%), that is used to prevent abrasion, removal of harmful agents, and skin integrity restoration.

treatment of skin irritations. It assures a hydrated environment that promotes cell migration and skin regeneration.

It is applied for the management of chronic wounds, including diabetic foot ulcers. It is available either as a at sheet (Hyaloll-F) or as a rope (Hyaloll-R). When applied at wound site, it interacts with wound exudate and a hydrophilic gel is produced. The gel creates an HA-rich tissue interface, providing a moist wound environment that promotes cell activity and the healing process.

It is a transparent membrane composed of HYAFF that allows cellular invasion and capillary growth, processes that are fundamental for encouraging skin re-epithelialization. It is indicated for the management of partial- and full- thickness wounds, second-degree burns, pressure ulcers, venous ulcers, chronic vascular ulcers, as well as surgical and trauma wounds.

create a moist healing environment. It is composed of HYAFF (a total benzyl ester of HA) and is applied directly at wound site, since its transparency allows the continuous monitoring of healing process. It is indicated for the management of supercial moderately exuding wounds, such as post-laser surgery wounds, supercial surgical wounds, and rst- and second- degree burns.

hyaluronate (2.5%), that avoids tissue dehydration and support the healing process. It is suitable to treat different types of wounds namely: Leg, pressure, and diabetic ulcers as well as for the management of wounds that are prone to bleeding.

It is a sponge that possesses a network of large hyaluronan molecular chain assemblies. It can absorb and release large volumes of water, assuring the skin hydration along the healing process. It acts as an equilibrium barrier or elastic “second skin.”

exuding wounds. They require a secondary dressing.

Vasir, Tambwekar, and Garg (2003)

Paghetti, Bellingeri, Pomponio, Sansoni, and Paladino (2009)

Colletta, Dioguardi, Di Lonardo, Maggio, and Torasso (2003)

Longinotti (2014)

Khel (2018)

Mahedia etal. (2016)

(continued)

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Table 23.5

Commercially available product Characteristics References

Laserskin

(continued)

It is a HYAFF- biopolymer- based scaffold, which possesses a microperforated HA membrane allowing the growth and migration of autologous keratinocytes and broblasts to the wound bed. It is used in the management of acute and chronic wounds.

We can schematically divide them into:

Price, Berry, and Navsaria (2007)

tive therapeutic approaches such as honey, which has been used since ancient times for wound

• simple dressings: gauze, creams, sprays.

Sometimes enriched with sulfadiazine, silver,

collagenase,

• Vials for local inltration or topical treatment

(e.g., Nucliaskin with polynucleotides).

• Granules and powders.

• Esters- HYAFF®.

• Sponges with hyaluronic acid and native

equine collagen type 1.

healing, also taking into account its high biocompatibility. The management of wound healing has become the main eld of therapeutic application of this natural product [27, 28].

What has most piqued the interest of researchers is, in addition to the broad spectrum of antibacterial activity against common wound-infecting microorganisms, the evidence that honey is not only effective against antibioticresistant bacteria but is able to restore the effec-

Simple dressings require as per the data sheets to be renewed several times a day; other types of dressings require more spaced out changes. Granules and powders can aid autolytic wound debridement and in exudate management.

HYAFF® [26]family of semisynthetic biopolymers that make possible the production of various biomaterials through esterication of the carboxyl groups of the hyaluronic acid molecule with benzyl alcohol. Esterication protects the molecule from rapid enzymatic degradation, allowing a longer-lasting in situ presence of the device 11. Upon contact with serum or wound exudate, HYAFF

turns into a hydrophilic gel that coats the wound, creating a hyaluronic acidrich interface that provides the ideal moist environment for granulation and healing.

tiveness of some antibiotics to which the microorganisms had developed resistance [29]. In addition, due to its many antimicrobial components and diverse antibacterial mechanisms of action, the development of bacterial resistance to honey is unlikely [30].

Studies conducted have shown that honey is able to interfere in multiple modalities in the process of restitutio adintegrum: it reduces the inammatory process, accelerates dermal repair and re-epithelialization, promotes angiogenesis and immune response, reduces healing time, and limits infection by pathogenic microorganisms.

The bioactivity of honey, and consequently its potential for wound healing, is inuenced by many variables, primarily its composition, which varies according to the oral source from which

23.3.3.6 Honey

Honey is a natural product rich in various phenolic compounds, enzymes, and sugars with antioxidant, anticarcinogenic, anti-inammatory, and antimicrobial potential. It is composed of water, sucrose, glucose, fructose, amino acids, beeswax, pollen, pigments, minerals, and glucose oxidase.

The difculties in the management of hard-to-

heal wounds have awakened interest in alterna-

it is derived. Other factors that determine its activities are as follows: certain intrinsic characteristics (acidity and osmotic pressure), seasonality, environment, processing, handling, packaging, and storage conditions [31, 32].

Literature suggests good results in the management of acute and chronic wounds, including amputation stump dehiscences, diabetic foot ulcers, and burns. However, the use of honey per se may have some limitations, which

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are being overcome with the development of different honey formulations and honey wound dressings.

23.4 Honey andits Properties

23.4.1 Antibacterial Activity

Honey has effective antimicrobial property against a broad spectrum of bacteria, including those that commonly cause wound infections such as Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis, Acinetobacter baumannii [33–35].

Honey acts directly on bacterial growth and survival due to its high osmolarity and acidity and its antimicrobial components (hydrogen peroxide, produced by the enzyme glucose oxidase contained in honey; phenolic compounds, methylglyoxal, and bee peptic defensin-1) and indirectly by promoting the production of lymphocytes, antibodies, cytokines, and nitric oxide. It has been shown both invivo and invitro that honey acts against antibiotic-resistant bacteria and blocks bacterial biolm formation by reducing the expression of genes related to biolm development and reducing the metabolic activity of the already formed biolm [36, 37].

In addition, studies have shown that manuka honey acts synergistically with several antibiotics, reducing the doses required to inhibit bacterial growth or reversing previously acquired antibiotic resistance [38]. These results suggest a potential application of combination therapy of honey and antibiotics.

nents, which allows it to hinder tissue necrosis,

• blocks the activity of cyclooxygenase 1 and 2(COX 1, COX 2), reducing the synthesis of prostaglandins responsible for vasodilatation, increased vascular permeability that allows the passage of leukocytes, antiplatelet action, and pain symptoms. Reduction of prostaglandins reduces edema, pain, and inammation.

• Inhibits the expression of tumor necrosis factor (TNF-α) and reduces the levels of proinammatory cytokines through the reduction of nuclear factor kappa b (NF-kB) levels. NF-kb is involved in the synthesis of the enzyme nitric oxide synthetase. During the inammatory process, the enzyme (iNO) induced by cytokines, TNF-α, interleukins stimulates nitric oxide production, which under physiological conditions contributes to the progression of healing. Excess nitric acid production causes the development of an altered inammatory process.

• Reduces edema by improving microcirculation and thus tissue oxygenation, limiting exudate production and promoting tissue repair and tissue growth.

The anti-inammatory activity of honey has

been attributed mainly to phenolic compounds.

However, no correlation has been found so far

between the level of anti-inammatory activity of different honey samples and phenolic compounds. This could be due to the synergistic interaction of multiple substances in it.

23.4.3 Antioxidant Activity

23.4.2 Anti-Inammatory Activity

The inammatory phase is critical for wound healing. When the inammatory response is inadequate there may be a delay in healing. The anti-inammatory activity of honey occurs through several mechanisms [39]:

• it reduces the production of free radicals due to the synergistic action of antioxidant compo-

The antioxidant activity of honey contributes to improving the inammatory response. Various components of honey are responsible for this: avonoids, phenolic acids, ascorbic acid, tocophenols, and certain enzymes such as superoxide dismutase and catalase. To these should be added melanoidins, substances produced by the Maillard reaction [40], which are capable of reducing the negative effects of reactive oxygen species (ROS) and nitrogen species (RNS) and

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inhibiting the enzymes responsible for the production of superoxide anions, act as metal chelators and interfere in free radical chain reactions and can play a preventive role in the process of their formation.

23.4.4 Promoter ofWound

Debridement

Honey induces debridement of the lesions to which it is applied by autolytic and enzymatic processes. Autolytic debridement is brought about by its high osmotic power. This, by inducing a recall of uids from the wound, causes the formation of a thin liquid stratum between the dressing and the wound bed that facilitates the removal of brin, necrotic or infected tissue, prevents the wound from drying out and, at the same time, avoids pain in the removal of the dressing and damage to the underlying tissue. [41] Enzymatic debridement is expressed in two ways:

• activation of proteases contained in the lymphatic uid operated by H2O2 generated by glucose oxidase contained in honey,

• Inhibition of PAI (plasminogen activation inhibitor) production by macrophages. This allows the activation of plasminogen into plasmin, an enzyme that can specically degrade brin attached to the wound surface without damaging the collagen matrix.

23.4.5 Neoangiogenesis Promoter

Angiogenesis is a dynamic process strongly regulated by signals from the serum and the surrounding extracellular matrix environment.

Honey has been shown, both in vivo and

invitro, to stimulate neoangiogenesis and endothelial proliferation. Hydrogen peroxide, which is produced by the enzyme glucose oxidase contained in raw honey, induces leukocyte recruitment by a concentration gradient mechanism and VEGF production by macrophages stimulating new vessel formation. In addition, the high

amount of sugars, amino acids, vitamins, and trace elements it contains in honey ensure an additional local source of nutrition [41, 42]. Contrary to the above, Eteraf-Oskouei has shown that honey has anti-angiogenic activity. This disparity between the studies could be explained by the concentration of honey tested, since the highest pro-angiogenic effect was found in a low concentration of honey, while higher concentrations demonstrated an anti-angiogenic effect.

23.4.6 Promoter ofImmune System Response

Studies have demonstrated an action of honey on mediators of the immune system:

• stimulating B and T lymphocytes and activat-

ing neutrophil phagocytosis in cell culture [34, 43],

• induce monocytes to secrete cytokines, tumor

necrosis factor α (TNF-α), interleukin-1 (IL-

1), and interleukin-2,

• stimulate antibody production during primary

and secondary immune responses against thymus- dependent and thymus-independent antigens,

• increase humoral immunity,

23.4.6.1 Healing Promoter

Honey determines the progression of the reparative process because of its acidic pH, nutrient richness, and stimulation of monocytes.

The acidic pH:

promotes macrophage action, limits bacterial

growth, and neutralizes ammonia produced by bacterial metabolism that could damage tissues;

also limits the activity of proteases that could

inactivate tissue growth factors and destroy plasma bronectin and collagen matrix;

makes more oxygen available from hemoglobin

in the blood.

Local nutrient concentration is a booster to

induce tissue reconstruction.

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Activation of monocytes to secrete TNF-α, IL-1, and IL-6 responsible for collagen synthesis from broblasts and proliferation and migration of keratinocytes.

23.4.6.2 Limits toUse andSide

Eects

Honey, although a natural product, has limitations to its use. Their composition is highly variable, mainly dependent, on the botanical origin, geographical and not all the elements that compose it are known biological activities. The methods of harvesting, processing, processing can also change their characteristics.

Such changes alter bioactivity proles and, consequently, therapeutic efcacy.

Medical honeys are sterilized by gamma irradiation for the purpose of killing Clostridium spores, produced under strict hygienic standards, without pollutants or contaminating pesticides in its composition, and standardized according to several dened criteria. They have potent.

in vitro bactericidal activity against antibioticresistant bacteria and are approved for application in wound management.

Manuka honey is one of the most widely used honeys in the medical eld. It is a monooral honey of New Zealand and Australian origin. To produce it, bees mainly collect nectar and pollen from Leptospermum scoparium (called manuka in the local language).

In addition to manuka, tualang, kanuka, and capilan honeys also show high antibacterial action, but this is reduced by heat treatments at high temperatures [44, 45].

Considering the presence of multiple substances with antibacterial action (such as methylglyoxal, leptosperine, or methyl syringate), the concept of UMF (unique manuka factor), also called “non-hydrogen peroxide-dependent activity” (NPA), was developed.

The UMF value quanties antibacterial activity through a relationship to the corresponding activity of a phenol solution: for example, a honey labeled UMF 5 has the same antibacterial activity as a 5% phenol solution. The number can range from UMF 5+ to UMF 20+; the higher the score, the higher the antibacterial activity of the product.

23.4.6.3 The Dressings

Honey dressings can be used on acute and chronic wounds, limited in burns.

Useful in cases of critical colonization or bac-

terial strains no responder to antibiotic therapy.

They can be used mainly on mild to moderate exuding wounds to prevent the honey from being too diluted by the exudate. Molan in his 2015 work [46] suggests use even in heavily exuding wounds in cases of infection because, despite even when honey is heavily diluted by wound exudate, it still has sufciently potent antibacterial activity to inhibit bacterial growth (MIC values were found to be less than 11%).

They are on the market as:

• simple dressings: creams, ointments, impreg-

nated gauzes,

• advanced dressings: hydrogels, alginates, col-

lagen pads.

They always require a secondary dressing. They can go under compression bandaging.

Dressing change time should be evaluated according to exudate management (Table23.6).

23.4.7 Eects onDierent Types

ofWounds

23.4.7.1 Chronic Ulcers

Honey can be used to treat different chronic ulcers, such as diabetic foot ulcers, venous ulcers, and arterial ulcers. Combined with various products already used for the treatment of wounds, it has been shown to enhance their effect. Association with hydrogel in venous ulcers has been shown to bring a reduction in healing time.

Manuka honey dressings have shown greater antibacterial action than regular saline and improved wound healing, reduced need for antibiotic use, and reduced hospitalization.

In the treatment of diabetic foot, honey dressings have shown a reduced risk of amputation compared with patients treated with iodopovidone.

Still debated, however, is the superiority of honey-based dressings over silver-based dressings in terms of bacterial colonization and wound

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29.08.202648 Мб0@xirurgi_2025 - 371 - файл.pdf
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29.08.202648 Мб0@xirurgi_2025 - 372 - файл.pdf
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29.08.202648 Мб0@xirurgi_2025 - 373 - файл.pdf
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29.08.202647 Мб0@xirurgi_2025 - 376 - файл.pdf
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29.08.202647 Мб0@xirurgi_2025 - 378 - файл.pdf
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29.08.202647 Мб0@xirurgi_2025 - 380 - файл.pdf
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29.08.202647 Мб0@xirurgi_2025 - 381 - файл.pdf
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29.08.202647 Мб0@xirurgi_2025 - 384 - файл.pdf
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29.08.202647 Мб0@xirurgi_2025 - 386 - файл.pdf
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29.08.202645 Мб0@xirurgi_2025 - 391 - файл.pdf
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29.08.202645 Мб0@xirurgi_2025 - 392 - файл.pdf