¿Cuáles son los usos del ácido hialurónico en el tejido óseo?

Los defectos en el tejido óseo causados por traumatismos, tumores, malformaciones congén, infecciones y otros factores patológicos seluno de los problemasque enfrentunlunortopediunclínica, siendo el injeraóseo el principal método parunresolver este problemun[1]. El injerto óseo se divide principalmente en injerto óseo autógeno, injerto óseo alogénico o injerto óseo aloplástico, pero el injerto óseo autólogo se enfrentuna muchos problemas, como la cantidad insuficiente de hueso autólogo, fácil de infectar y volver a traumatial paciente, etc. El injerto óseo alogénico es caro. El injerto óseo alogénico es caro y tiene rechazo inmunitario. El hueso como sustituto de los materiales de reparación ósea puede evitar los defectos de los materiales de reparación biogénicos [2].

Ideal Tejido tejido tejido tejido tejido tejido tejido tejido tejido tejido tejido tejido tejido tejidoscaffolds should have some properties: good biocompatibility; appropriate biodegradability yeventual disappearance; good cell-célulainterface deelmaterial to allow cell adhesion, promote cell growth, yretaencell differentiation; three-dimensional porous structure ygood porosity to allow cell infiltratielyvascularisation; ya certaendegree demechanical strength, which is easy to fabricate [3]. Hyaluronic Ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácidois a new hot spot enelresearch debonebiomaterials. Hyaluronic Ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácidohasa high degree deviscoelasticity, plasticity, excellent water absorption, permeability ygood bioabsorbability, and is non-immuno-antigenic. Modified Ácido hialurónico not only maintains eloriginal superior properties, but also mejoraits properties and makes it more adaptable to the humanaenvironment [4]. Therefore, hialurónicaÁcido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácidois now the hot spot debioengineering boneTejido tejido tejido tejido tejido tejido tejido tejido tejido tejido tejido tejido tejido tejidomaterials.

1aplicación de ácido hialurónico en el tratamiento de la osteoartritis

Osteoarthritis is one dethe most common knee injuries and joint diseases, and injection dehialurónicaÁcido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido(sodium vitrate) hasbecome a common treatment paraosteoarthritis. According to the literature, Manicourt etal[5] reported that the content of hialurónicaÁcido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácidoincreased when the physiological stress enthe joint increased, which suggests that hialurónicaacid, as an important component of proteoglycan polymers, may have a buffering effect on stress. Hyaluronic Ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácido ácidoin synovial fluid has a grandeamount of negative charge when combined conproteins, and it has strong water absorption and high viscosity. Proteoglycan polymers increase the lubricity and viscoelasticity of the synovial fluid and provide a high affinity between the lubricant and the articular cartilage. Hyaluronic acid and proteoglycans adhere tightly to the joint surfaces and act as lubricants, thus reducing the resistance to joint movimiento and protecting the articular carcarcarcarcarcarcarcarcarcarcarcarcardesdeexcessive mechanical wear.

Kawasaki et al.[6] reported that hialurónicaacid increased the Síntesis síntesis síntesisof chondroitin sulphate porchondrocytes cultivadain collagen gels, and Stove et al.[7] found that hyaluronic acid decreased the production of proteoglycans by chondrocytes in osteoarthritic patients, but hyaluronic acid inhibited the reduction of proteoglycans induced by IL-1, and Kikuchi et al.[8] reported that exogenous hyaluronic acid increased the production of chondroitin in seaweed beads. Kikuchi et al.[8] reported that exogenous hyaluronic acid caused the movement of newly synthesised proteoglycans from pericellular to distal Matriz matrizof chondrocytes in algal bead medium and carcarcarcarcarcarcarcarcarcarcarcarcartissues, suggesting that hyaluronic acid may have an effect on the Distribución distribución distribuciónand movement of proteoglycans, and may have a protective effect on the cartilaginous extracellular matrix. In addition, hyaluronic acid is a scavenger of free radical cellular debris, embedding itself in the polymer meshwork formed by hyaluronic acid and metabolising it rapidly within the joint, thus contributing to the elimination of cellular debris and assisting in the elimination of cartilage cellular metabolites.

2 la combinación de ácido hialurónico y biofactores en la reparación de cartílagos y defectos óseos

2.1 promover la proliferación de condrocitos

Después del daño del cartílago, su propia capacidad de reparación es limitada, y el uso del trasplante de condrocitos es el punto caliente actual. Los estudios han demostrado que el El factorde crecimiento similar a la insulina 1 juega un papel importante en la reparación del cartílago. El ácido hialurónico es uno de los principales componentes de la matriz del cartílago. De acuerdo con la literatura, el El factorde crecimiento insulino-1 es el primer El factorde crecimiento que se ha identificado que tiene un efecto regulador sobre los condrocitos articulares. Sin embargo, tiene una vida media corta, se degrada fácilmente y es susceptible a la interferencia de factores internos, limitando así sus efectos [9-10].

Hyaluronic acid is negatively charged, has strong hydrophilicity and high adhesion, and has strong affinity conchondrocytes. In addition, hyaluronic acid has the function of chondroinduction, which can provide nutrition paraarticular chondrocytes, participate in the synthesis of proteoglycan polymers, act as a building block on the surface of chondrocytes through glycoproteoglycans, and promote the Proliferación proliferaciónof superficial joints, maintain the thickness of uncalcified cartilage, and promote the repair of articular cartilage condegenerative changes to a certain extent [11-12]. It has been reported in the literature that the combination of hyaluronic acid and insulin-like crecimientofactor-1 in the in vitro culture of humanaarticular chondrocytes can help to maintain the stability of the phenotipoof hyaluronic acid chondrocytes and promote the proliferation of the cells, thus providing a new method to obtain high-density autologous chondrocytes in vitro that have normal functions, and also providing experimentalbases parathe study of autologous chondrocyte transplantation or cartilage Tejido tejido tejido tejido tejido tejido tejido tejido tejido tejido tejido tejido tejido tejidoengineering [13].

2.2 aloinjerto compuesto

The commonly used material parathe repair of segmentboneLos defectosis allogeneic freeze-dried bone, but due to the weak induced activity of allogeneic freeze-dried boneand its poor osteogénesisability, it only serves as a andamioparaosteoconduction in the process of repair. The development of modern molecularbiology technology has led to a deeper understanding of the osteogenic and osteoinductive activities of bonecrecimientofactors, and bonegrafts containingbonecrecimientofactors combined consuitable carriers have become a new trend in the treatment of bone defects. It has been reported in the literature that implantation of básicoUn blablade de fibroblacrecimientoEl factorfused conhyaluronic acid gel and composite freeze-dried bone into the bone defect area has a good effect on repairing bone defects [14-15]. BFGF can stimulate the proliferation of mesenchymal cells, chondrocytes and osteoblasts, and induce the differentiation of mesenchymal Células célulasto bone and chondrocytes; stimulate the proliferation of vascular endothelial cells, and promote the formation of neovascularisation [16].

Based on the above biological properties of basic Un blablade de fibroblagrowth factor, it was compounded conhyaluronic acid and freeze-dried bone to promote the growth of osteoblasts by taking advantage of their respective strengths. The histological sections of this experiment showed that: in the early stage, a large number of mesenchymal Células célulascould be seen in the bone defect area of the complex containingbasic fibroblasts, hyaluronic acid and lyophilized bone, bridging the bone fracture in the form of cords, and showing a tendency of differentiation to osteoblasts and chondroblasts, conthe appearance of new bone and cartilage islands; in the mid-stage, the neovascularisation grew into the area, and the cartilage tissues matured in the process of ossification, conthe islands fused together into a piece to form a braided bone. The amount of new bone and cartilage in the hyaluronic acid and lyophilised bone group was significantly lower than that in the basic fibroblast, hyaluronic acid and lyophilised bone complex group, and the distribution was uneven [17].

Se ha reportado en la literatura que el papel del factor básico de crecimiento fibroblástico es estimular la proliferación de células mesenquimales al inicio de la reparación ósea, y estas últimas forman costras de cartílago y actúan como factor de crecimiento y otros factores osteoinductivos para estimular a los osteoblastos a diferenciarse en osteoblastos o condrocitos, iniciando el proceso de reparación del defecto. Con el crecimiento de la neovascularización, el suministro de sangre al injerto se restable, promoviendo la osificación endocondral, acelerando el reemplazo del injerto y la maduración del nuevo hueso, y acortando el tiempo de curación. Como matriz, el ácido hialurónico puede proporcionar nutrientes y espacio tridimensional para el crecimiento celular, lo cual es propicio para la reparación del tejido óseo [18].

3 aplicación de complejos de ácido hialurónico modificado en tejido óseo biológico

Hyaluronic acid is easily degraded and its degradation time is closely related to its molecularweight. Therefore, in order to prolong the degradation time of hyaluronic acid molecules in the organism, it is necessary to prepare a derivative with a much higher molecular pesothan that of natural sodium hyaluronate molecules, i.e., cross-vinculadasodium hyaluronate derivatives, through chemical modification. The principle of preparation of cross-linked sodium hyaluronate is to use one or more combinations of chemical cross-linking agents, using the cross-linking agent (oxidation, reduction, esterification, aldolisation, etc.) to make the hyaluronic acid molecules undergo a chemical reaction, so that the hyaluronic acid molecules or hyaluronic acid and the cross-linking agent cross-linking together [19].

The cross-linking reaction lengthens the hyaluronic acid molecules, increases or decreases their solubility properties, and improves their mechanical strength or resistance to degradation by the body. Therefore, various chemical modifications of hyaluronic acid have been carried out and applied to the study of bone Tejido tejido tejido tejido tejido tejido tejido tejido tejido tejido tejido tejido tejido tejidoengineering. Martinez-Sanz et al. used aminopropanetriol as a cross-linking agent to form perylene-HA matrix by amidation, and this hyaluronic acid derivative complexed with bone-forming protein-2was proved to be non-cytotoxic and histocompatible in in vitro tests. When the Compuestos compuestos compuestos compuestos compuestoswas injected into the cranial surface of rats, histological examination showed that there was new bone formation on the cranial surface after 8 weeks, and the expression of osteocalcin and bone Médula óseaangiogenesis was also high, which means that perylenic-hyaluronic acid can act as a carrier of osteoblast-2and can promote bone expansion. This finding has been confirmed by subsequent studies [18-19].

Bae et al.[20] observed the effects of photocured hyaluronic acid in combination with simvastatinaon bone regeneration. The results showed that the viscoelasticity of the 2-aminoethyl methacrylate-hyaluronic acid matrix was significantly improved compared with that of hyaluronic acid, and that it could regulate the stable and slow release of simvastatin, which promoted the increase of MC3T3-E1 cell proliferation. MC3T3-E1 cells proliferated and differentiated, thus inducing new bone formation, i.e., photo-hyaluronic acid combined with simvastatinacould be a good scaffold paratissue-engineered bone.

Lisignoli et al.[21] investigated the osteogenesis of hyaluronic acid derived from its esterification, benzyl ester of hyaluronic acid, in combination with bone marrow estromalcells in a murine model of large bone defects, where the cells were treated with alkaline fibroblast growth factor supplemented or not with supplemented mineralisation medium, and the results showed a significant increase in the viscosity of the matrix. Cells were cultured in mineralisation medium with or without alkaline fibroblast growth factor supplementation, and defect healing was evaluated after 40, 60, 80 and 200 d. In vivo studies have demonstrated that benzyl hyaluronate is a suitable vehicle parabone defect repair and significantly accelerates bone mineralisation when combined with bone marrow stromal cells and alkaline fibroblast growth factor.4 Hyaluronic acid complexes with growth factors are also suitable parabone repair.

4 complejos de ácido hialurónico combinados con factores de crecimiento en el tejido óseo

Hyaluronic acid is a good carrier of growth factors in bone repair, but its main drawback as a scaffold is its low cell Adhesión a la adhesiónproperties, whereas integrins are a major family of cell surface receptors that mediate the adhesion of cells to the extracellular matrix.23 Kisie et al. [24] covalently bonded hyaluronic acid with specific ligandoson integrins to form a hyaluronic acid-integrin matrix and investigated the effects of hyaluronic acid-integrin complexes in large bone defects in a murine model.

Compared with the control group, the hyaluronic acid-integrin hidrogelshowed a significant increase in cell adhesion and bone growth factor delivery, which further mejoradothe osteogenic potencialof recombinant human osteoblast-2. Therefore, the hyaluronic acid-integrin matrix can be used as a growth factor entregavehicle, and has a potential value for clinical application. The study of hyaluronic acid complex is the hot spot of biomaterials research nowadays, this kind of complex combines the advantages of its own material and makes up for its own shortcomings, which has the incomparable advantages of other materials, but there is no in-depth study on the histocompatibility, inflammation and degradability of this kind of composite, which may be the hot spot of future research.

5 problemas y perspectivas

Hyaluronic acid is a biodegradable biomaterial with good biocompatibility, and its hydrophilicity plays an important role in cell adsorption, growth and differentiation. It can be used as a temporary skeleton to support and stimulate the growth of new bone tissues, and then it will be gradually degraded to be replaced by new bone tissues after completing the mechanical support function for a certain period of time. A large number of experimental studies have proved that hidrog«based on hyaluronic acid and compounded with insulin-like factor, growth factor and BMP-2can provide a growth environment for chondrocytes, osteoblasts and myeloid cells, and their three-dimensional structure, good water solubility, no immune reaction and good degradability are the advantages of hyaluronic acid [28-29], but there are still a lot of difficulties that need to be overcome if they are applied in clinical practice. Hyaluronic acid has been discovered for more than 80 years. Hyaluronic acid has been discovered for more than 80 years, and has been used in ophthalmology, joint surgery and other research fields [30-33], and it is a new development to use it as the basis of biomaterials for biological tissues. In recent years, there have been many experimental researches on biomaterials using hyaluronic acid as scaffolds, and it is hoped that it can be really used in the clinic in the near future.

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