Estudio sobre el uso del ácido hialurónico para vendajes de heridas

La piel, como el cuerpo ', desempeña un papel muy importante en la resistencia a la invasión de agentes patógenos. Sin embargo, en la vida diaria, la piel es vulnerable a lesiones y formación de heridas. La cicatride heridas es un proceso complejo y dinámico que involucra hemostasis, inflamación, proliferación y remodelación. El proceso de cicatride la herida puede ser prevenido o retrassi la herida se infecta o si otras complicaciones tales como inflamación excesiva ocurrir. Además, algunas quemaduras y heridas quirúrgicas a menudo resultan en cicatrices de la piel, también conocida como dermatofibrosis, que es perjudicial para la función normal de la piel. La cicatriexcesiva del tejido de la piel puede llevar a una disminución de la flexibilidad, función anormal e incluso comezón y dolor. Para superar las limitaciones del proceso de cicatride heridas, los investigadores han desarrollado diferentes biomateriales para producir apócicatri. Dependiendo de su morfo, los vendajes de heridas pueden ser clasificados como seda hilada electrostáticamente, hidrogel, membrana o espon. A pesar de las diferentes formas, la mayoría de los vendajes no son tóxicos, antimicrobianos, biocompatibles y biodegradables, y tienen propiedades de cicatrirápida [1].

Ácido hialurónico is an anionic mucopolysaccharide composed of D-glucuronic acid alternately linked with N-acetylaminoglucosamine, which is found in the extracellular matrix of vertebrates, skin, vitreous body of the eye, cartilage, and joint fluid. The physicochemical properties of hyaluronic acid include hydrophilicity, antioxidant properties, fluidity, and viscoelasticity. The biological functions of hyaluronic acid are related to its molecular weight, e.g., high molecular weight hyaluronic acid inhibits inflammation, anti-angiogenesis, and scarring, whereas low molecular weight hyaluronic acid promotes angiogenesis, inflammation, and scarring. Due to the limited role of endogenous hyaluronic acid, it is important to use exogenous hyaluronic acid to prepare different types of wound dressings for wound repair. The molecular structure of hyaluronic acid is shown in Figure 1.

1 propiedades fisicoquímicas del ácido hialurónico

Hyaluronic acid belongs to a group of glycosaminoglycans that, unlike other glycosaminoglycans, are not sulfated and are usually not covalently attached to any core protein. The unique physicochemical properties of hyaluronic acid, such as hydrophilicity, fluidity, viscoelasticity, and antioxidant properties, have led to its widespread use in the production of various forms of wound dressings.

1.1 hidrofilia

Hyaluronic acid is one of the important components of the extracellular matrix. Due to the presence of a large number of hydroxyl and carboxyl groups in its structure, hyaluronic acid is highly hydrophilic. This property also makes hyaluronic acid with a large number of negative charges, so as to attract more cations and water molecules. Hyaluronic acid has the properties of water absorption, water retention, etc., and also has a strong ability to complex water molecules, which is known as ‘nature's factor hidratante ', y puede ser utilizado para la lubricación de los ojos, hidratante, y el tratamiento del ojo seco.

1.2 propiedades de Fluidising

Hyaluronic acid is also an important component of joint fluid, which can lubricate joints and reduce vibration, which is inseparable from its fluidity. In medical treatment, tracheal intubation is a key step in mechanical ventilation and respiratory support, and is used in cardiopulmonary resuscitation and respiratory diseases, etc. However, prolonged friction between the trachea and human tissues leads to damage of the mucous membrane of the laryngeal trachea, which results in inflammation, difficulty in articulation, and other symptoms, and in serious cases, it may endanger the lives of the patients. Clinical lubricants, including benzydamine hydrochloride gel, lidocaine 5% gel/cream, and corticosteroid creams, are commonly used to relieve these symptoms. The most commonly used lubricant is lidocaine cream, but it contains additives that can cause hypersensitivity reactions or trigger atopic dermatitis, so lubricating, non-toxic agents are constantly being investigated, and hyaluronic acid is a good candidate.

viscoelasticidad

A temperatura ambiente,El ácido hialurónico es un sólido blanco en polvo secoSin olor, soluble en disolventes inorgánicos e insoluble en disolventes orgánicos. Cuando el ácido hialurónico se disuelve en agua, su solución acuosa tiene buena viscoelasy presión de permeabilidad, y también tiene propiedades de fluido no newtoniano. Debido a que el ácido hialurónico puede ser fácilmente modificado químicamente, se pueden formar estructuras de alto peso molecular. Las soluciones viscoelásticas de ácido hialurónico de alto peso molecular son muy adecuadas para imitar el líquido sinovial en las articulaciones, pero no tienen una integridad mecánica duradera [2].

1.4 propiedades antioxidantes

Hyaluronic acid also has antioxidant properties and can act as an antioxidant due to the formation of a viscous pericellular meshwork around the cell that limits the movement of ROS in the vicinity of the cell or other biomolecules, where excess reactive oxygen species can damage proteins, lipids, and DNA. Some of the antioxidant properties of hyaluronic acid are able to reduce the risk of apoptosis induced by UV light and the risk of acid-induced DNA damage.

2 propiedades biológicas del ácido hialurónico

Los estudios han demostrado que elbiological functions of hyaluronic acid (HA) are closely related to its molecular weight [3-4] . Hyaluronic acid can be classified into five categories according to its molecular weight (MW), i.e., HA oligosaccharides (O-HA, MW < 1×104 Da), which can promote angiogenesis, anti-tumour, wound healing, osteogenesis, immune and metabolic regulation, and ageing; and low-molecular-weight HA (LMW-HA, MW < 25×104 Da), which is more easily absorbed by the human body and can promote wound healing. Low molecular weight HA (LMW-HA, 1×104 Da < MW < 25×104 Da), more easily absorbed by the human body, can promote wound healing, vascularity, scarring, and plays an important role in chronic wound healing; medium molecular weight HA (MMW-HA, 25×104 Da < MW < 100×104 Da), moisturising, lubricating, and slow release of medicines, etc.; high molecular weight HA (HMW-HA, MW ≥ 1×106 Da), has good moisturising, lubricating, and adhesion properties. High molecular weight HA (HMW-HA, MW ≥ 1×106 Da) has good moisturising, lubrication, viscoelasticity, and can inhibit inflammation, anti-angiogenesis, and inhibit scarring; Ultra-high molecular weight HA (vHMW-HA, MW ＞ 6×106 Da) has lubrication, viscoelasticity, and so on.

2.1 biodegradabilidad

Hyaluronic acid is a kind of unsulfated glycosaminoglycan, which is the main component of the extracellular matrix of proliferating and migrating cells, and is especially abundant in early embryos. Exogenous hyaluronic acid can be degraded by physical (gamma radiation, ultrasound), chemical (acid hydrolysis, alkaline hydrolysis, oxygenation degradation), and enzymatic methods, and is commonly used in biomedical, cosmetic, and drug delivery applications. Endogenous hyaluronic acid is usually degraded by hyaluronidase and free radicals to low molecular weight hyaluronic acid and glucosamine.

2.2 propiedades bacteriostáticas

Comparison of the antimicrobial effect of hyaluronic acid with other natural polymers shows that chitosan is structurally similar to hyaluronic acid and has antimicrobial properties. Bacteria can avoid the inhibitory effect of hyaluronic acid in two ways, either when they contain the ability to produce hyaluronic acid as a mucus capsule, or when they can produce hyaluronan lytic enzymes to lyse it. Therefore, infections can occur in some hyaluronic acid applications, such as contact lenses and wound dressings. Low molecular weight hyaluronic acid has no inhibitory effect on Staphylococcus aureus, and high molecular weight hyaluronic acid has only a minimal inhibitory effect on Staphylococcus aureus.

2.3 promover la cicatrización de heridas

In the human body, hyaluronic acid binds to CD44, a receptor for keratinocytes in wounds, and stimulates cell proliferation and migration. The affinity of CD44 for hyaluronic acid is related to its molecular weight, i.e. the higher the molecular weight, the higher the affinity for the receptor.

3 diferentes formas de ácido hialurónico en apósitos de heridas

The unique physicochemical and biological properties of hyaluronic acid have led to its use in a wide range of different forms of medical wound dressings such as electrostatically spun silk, membranes, hydrogels and sponges.

3.1 hialuronic acid based electrostatic spinning (en inglés)

El spinning electrostático es una técnica efectiva para la producción de filamentos poliméricos cargados con diámetros que van desde el microna la escala de nanómetros bajo un campo electrostático. Los apósitos de herida de fibra preparados por ESP tienen una alta porosidad, excelente ductilidad y buena capacidad de transporte de fármacos, que no solo permiten que las células de la herida respiren, sino que también inhiel crecimiento bacteriano. Los vendajes electrostáticos también pueden cubrir áreas que son difíciles de cubrir con vendajes convencionales. Estas excelentes propiedades han llevado al uso de la tecnología de hilado electrostático en una amplia gama de aplicaciones biomédicas.

Su Sena et al. [5] extrajeron ácido hialurónico y queratina de animales y los cargaron como agentes bioen estructuras de fibras electrohiladas coaxipara el tratamiento de heridas, y Sun Juan-feng et al. [6] preparcon éxito nanofibras electrohiladas a partir de una solución cohecompuesta de quitosano y ácido hialurónico.

Abbas Zakeri Bazmandeh et al [7] prepared hyaluronic acid crosslinked chitosan and gelatin electrostatically spun membrane (Cs-Gel-HA) by electrostatic spinning, and the results showed that the Cs-Gel-HA membrane is more suitable for cell adhesion and can better promote skin regeneration. Hyaluronic acid is soluble in water, but its ionic nature leads to long-range electrostatic interactions, and the presence of counterions leads to a dramatic increase in the viscosity of the aqueous solution of hyaluronic acid but does not ensure sufficient chain entanglement for stable and efficient electrospinning.Morgane Séon-Lutz et al. [8] prepared insoluble hyaluronan-based nanofibres in pure water by using an electrostatic spinning technique. Polyvinyl alcohol (PVA) was added as a carrier polymer and the addition of hydroxypropylcyclodextrin (HPBCD) was found to promote the effective formation of nanofibre scaffolds and to make the electrostatic spinning process more stable.Yasmein Hussein et al [9] prepared enhanced polyvinyl alcohol/hyaluronic acid nanofibres using cellulose nanocrystallites (CNCs) as nanofillers and L-arginine as a wound healing promoter. Polyvinyl alcohol/hyaluronic acid nanofibres (PVA/HA-NFs) were prepared. The results showed that the PVA/HA/CNC/L-arginine NFs had good haemocompatibility, high protein adsorption, proliferation and adhesion ability.

3.2 membrana a base de ácido hialurónico

Membrane is a soft and flexible material. Yin Chuan-Jin et al [10] covalently attached hyaluronic acid (HA) to the surface of bovine serum albumin/silver (BSA/Ag) porous membranes to prepare BSA/Ag/HA films, which can be used as contact lenses, and showed good clarity, high water content, haematocompatibility, non-cytotoxicity, and antimicrobial properties. Josef Chmelař et al [11] used a solution flow-through method to produce water-insoluble freestanding films of lauroyl-modified hyaluronic acid as a novel biomaterial, which were homogeneous in texture, mechanically strong, and pliable.Abou-Okeil et al [12] prepared hyaluronic acid/sodium alginate films for use as a topical bioactive wound dressing.Rocha Neto J.B.B. [13] used BSA/Ag/HA films as contact lenses. Rocha Neto J.B.M et al [13] also developed hyaluronic acid (HA)/chitosan (Chi) based films and showed that platelet adhesion was significantly reduced in the sulphated modified functional films, providing new insights into the development of novel antithrombotic biomaterials.Fernanda Zamboni et al [14] used the cross-linking agent, bis- (β-ethyl isocyanate) disulphide (BIED), as a cross-linker. Fernanda Zamboni et al [14] used the cross-linker bis-(β-ethyl isocyanate) disulfide (BIED) to heterogeneously cross-link HA and then doped it with carbon nanofibres to optimise the mechanical and antimicrobial properties of the resulting film, which showed excellent mechanical and antimicrobial properties of the film-type wound dressing.

3.3 hidrogeles a base de ácido hialurónico

El hidrogel es un tipo de vendaje húmedo con alto contenido de agua, que es suave y ligeramente elástico. Las quemaduras son una de las lesiones más devastadoras, y a pesar de los tratamientos modernos, los pacientes todavía se enfrentan a muchas complicaciones y cicatrices post-quem. En este sentido, Dong Yi-Xiao et al [15] diseñuna plataforma de entrega de células madre a base de ácido hialurónico para la rápida gelación In situ en contacto con la herida, que mejora la neovascularización en el sitio de la herida y promueve la cicatride quemy reduce la cicatri. Zhang Shao-Han et al [16] introdujeron un nuevo material antioxidante, los derivados de argin(da), en el ácido hialurónico (HA) funcionalizado por dopamina, que HA demostrado ser una buena opción para el tratamiento de quemaduras. Zhang Shao-Han et al. [16] introdujeron un nuevo material antioxidante, derivado de argin(da), en el ácido hialurónico funcionalizado por dopamina (HA-DA) para preparar un nuevo hidrogel con actividad antioxidante. La tasa de absorción de radicales DPPH y -OH fue mayor que la de hidrogel HA-DA. Además, el hidrogel proporcionó una mejor protección celular contra el estrés oxidativo externo (reducción de los niveles de ROS y MDA, aumento de las actividades de las enzimas SOD y GPx) y una mejor cicatride heridas (mayor expresión de VEGF y CD31, mayor remodelación de tejidos).

Inspirado por la obstrucción espontánea de las células sanguíneas durante la hemostasis, Liu Yi-Hao et al. [17] prepararon un 5'-adenosine diphosphate-modified haemagglutinating hyaluronic acid (HA-ADP) hydrogel by physically cross-linking and freeze-drying, and the prepared hydrogel could promote the adhesion of platelets and erythrocytes and could induce significant procoagulant ability by activating platelets, which could complete hemostasis in vitro in a relatively short period of time. The hydrogel can promote the adhesion of blood platelets and erythrocytes. In addition, materials with antioxidant properties have attracted much attention in wound healing.

3,4 espona base de ácido hialurónico

Los apósitos de esponson materiales altamente porosos que permiten el intercambio de gas entre las células en la herida para acelerar la cicatride la herida y tienen una buena absorción de agua para mantener la herida húmeda. Sin embargo, los apósitos de esponordinarios tienen una resistencia mecánica débil y necesitan ser cruzados con otros polímeros para utilizar plenamente sus características.

Meng Xin et al [18] prepared a chitosan/alginate/hyaluronic acid composite sponge crosslinked with genipin, which has high mechanical strength, good biocompatibility and accelerated blood coagulation.Sanda-Maria Bucatariu et al [19] obtained a new type of sponge dressing by solvent-free thermal cross-linking of hyaluronic acid and poly(vinylmethyl ether-alt-maleic acid). Sanda-Maria Bucatariu et al. [19] obtained a novel sponge hydrogel (HA3P50) by solvent-free thermal cross-linking of hyaluronic acid and poly (methyl vinyl ether -alt-maleic acid), which is a biocompatible material to support the growth of tumour cells and provides a 3D platform to mimic tumour function for screening of anti-tumour drugs.20 Mathie Najberg et al. [20] prepared aerogel sponges with filipin, hyaluronic acid and heparin for soft tissue engineering. The aerogel sponge has high expansion, high porosity, high connectivity and soft texture close to the brain.

Rania Abdel-Basset Sanad et al [21] exitosamente preparado chitosan-hyaluronic acid/andrographolide nanocomposite scaffolds for wound healing and Annapoorna Mohandas et al [22] prepared composite sponge dressings made of chitosan and hyaluronic acid and loaded with vascular endothelial growth factor (VEGF). The results showed that the sponge dressing has the potential to induce angiogenesis in wound healing. Effective haemostasis is particularly important in the treatment of wounds, and Liu Jia-Ying et al [23] used a simple self-foaming method to produce a polysaccharide-based haemostatic porous sponge composed of hyaluronic acid and cationised dextran, which showed excellent in vivo haemostatic properties in a mouse model of hepatic haemorrhage.

4 conclusión y perspectivas

Hyaluronic acid stands out as one of the most attractive biomaterials among many others due to its excellent physicochemical and biological properties. Due to its high molecular weight and excellent water absorption capacity, it contributes to the maintenance of mechanical integrity, homeostasis, viscoelasticity and lubricity of tissues. In addition, it actively participates in important biological processes such as cell adhesion, migration, proliferation, differentiation and angiogenesis, and plays a crucial role in inflammation regulation, wound healing, tissue repair, morphogenesis, tumour proliferation and metastasis.

The excellent biodegradability and biocompatibility of hyaluronic acid-based biomaterials have also contributed to their wide application in the biomedical field. The use of hyaluronic acid and its substrates is increasing with the growing demand for products. For this reason, researchers in different countries have developed new smart dressings with different efficacies using hyaluronic acid as a base material. This article systematically describes the use of hyaluronic acid in different types of wound dressings, such as electrostatic spinning, membranes, hydrogels, sponges, etc., with the aim of providing ideas for the development of new biomaterials. In the future, hyaluronic acid-based wound dressings will be of great value in clinical wound repair.

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