Quelles sont les utilisations de l’acide hyaluronique dans le tissu osseux?

Les anomalies du tissu osseux causées par un traumatisme, une tumeur, une malformatiSur lecongénitale, une infectiSur leEt etd’autres facteurs pathologiques sont l’un des problèmes auxquels fait face l’orthopédie clinique, et lA agreffe osseuse est lA aprincipale méthode pour résoudre ce problème [1]. LA agreffe osseuse est principalement divisée en greffe osseuse autologue, greffe osseuse allogénique ou greffe osseuse alloplastique, mais lA agreffe osseuse autologue fait face à de nombreux problèmes, tels que lA aquantité insuffisante d’os autologue, lA afacilité à être infecté et de nouveau traumatiser le patient, etc. La greffe osseuse allogénique est coûteuse. La greffe osseuse allogénique est coûteuse et entraîne un rejet immunitaire. L’os biomatérial issu du génie tissulaire comme substitut des matériaux de réparation osseuse peut éviter les défauts des matériaux de réparation biogéniques [2].

Ideal tissusscaffolds should have some properties: good biocompatibility; appropriate biodegradability Et en pluseventual disappearance; good cell-celluleinterface De laLe conseil des ministresmaterial À propos deallow cell adhesion, promote cell growth, Et en plusretadanscell differentiation; three-dimensional porous structure Et en plusgood porosity to allow cell infiltration Et en plusvascularisation; Et en plusa certadansdegree De lamechanical strength, which is easy to fabricate [3]. Hyaluronic acideis a new hot spot dansLe conseil des ministresresearch De laosbiomaterials. Hyaluronic acidehEn tant quea high degree De laviscoelasticity, plasticity, excellent water absorption, permeability Et en plusgood bioabsorbability, and is non-immuno-antigenic. Modified Acide hyaluronique not only maintains Le conseil des ministresoriginal superior properties, but also amélioreits properties and makes it more adaptable to the humainenvironment [4]. Therefore, hyaluroniqueacideis now the hot spot De labioengineering ostissusmaterials.

1Application d’acide hyaluronique dans le traitement de l’arthrose

Osteoarthritis is one De lathe most common knee injuries and joint diseases, and injection De lahyaluroniqueacide(sodium vitrate) hEn tant quebecome a common treatment pourosteoarthritis. According to the literature, Manicourt et al[5] reported that the content of hyaluroniqueacideincreased when the physiological stress dansthe joint increased, which suggests that hyaluroniqueacid, En tant quean important component of proteoglycan polymers, may have a buffering effect on stress. Hyaluronic acidein synovial fluid has a Grande tailleamount of negative charge when combined avecproteins, 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 Le mouvement and protecting the articular Le cartilageÀ partir deexcessive mechanical wear.

Kawasaki et al.[6] reported that hyaluroniqueacid increased the synthèseof chondroitin sulphate Par:chondrocytes En culturein 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 matriceof chondrocytes in algal bead medium and Le cartilagetissues, suggesting that hyaluronic acid may have an effect on the distributionand 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 combinaison d’acide hyaluronique et de biofacteurs dans la réparation des défauts du cartilage et des os

2.1 favoriser la prolifération des chondrocytes

Après une lésion du cartilage, sa propre capacité de réparation est limitée, et l’utilisation de la transplantation de chondrocytes est le point chaud actuel. Des études ont montré que le facteur de croissance de Type de produitinsuline-1 joue un rôle important dans la réparation du cartilage. L’acide hyaluronique est l’un des principaux composants de la matrice du cartilage. Selon la littérature, le facteur de croissance de type insuline-1 est le premier facteur de croissance qui a été identifié pour avoir un effet régulateur sur les chondrocytes articulaires. Cependant, il a une demi-vie courte, est facilement dégradé, et est sensible à l’interférence par des facteurs internes, limitant ainsi ses effets [9-10].

Hyaluronic acid is negatively charged, has strong hydrophilicity and high adhesion, and has strong affinity avecchondrocytes. In addition, hyaluronic acid has the function of chondroinduction, which can provide nutrition pourarticular chondrocytes, participate in the synthesis of proteoglycan polymers, act as a building block on the surface of chondrocytes through glycoproteoglycans, and promote the La proliférationof superficial joints, maintain the thickness of uncalcified cartilage, and promote the repair of articular cartilage avecdegenerative changes to a certain extent [11-12]. It has been reported in the literature that the combination of hyaluronic acid and insulin-like La croissancefactor-1 in the in vitro culture of humainarticular chondrocytes can help to maintain the stability of the phenotype of 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 expérimentalbases pourthe study of autologous chondrocyte transplantation or cartilage tissusengineering [13].

2.2 allogreffe Composite

The commonly used material pourthe repair of segmentéosdéfautsis allogeneic freeze-dried bone, but due to the weak induced activity of allogeneic freeze-dried osand its poor ostéogéniqueability, it only serves as a échafaudagepourosteoconduction in the process of repair. The development of modern moléculairebiology technology has led to a deeper understanding of the osteogenic and osteoinductive activities of osLa croissancefactors, and osgrafts Contenant:osLa croissancefactors combined avecsuitable carriers have become a new trend in the treatment of bone defects. It has been reported in the literature that implantation of De basefibroblasteLa croissanceLe facteurfused avechyaluronic 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 cellulesto 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 fibroblastegrowth factor, it was compounded avechyaluronic 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 cellulescould be seen in the bone defect area of the complex Contenant:basic 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, avecthe 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, avecthe 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].

Il a été signalé dans la littérature que le rôle du facteur de croissance de base des fibroblastes est de stimuler la prolifération des cellules mésenchymateuses au début de la réparation osseuse, et ces dernières forment des crottes cartilagènes et agissent comme un facteur de croissance et d’autres facteurs ostéoinductifs pour stimuler les ostéoblastes à se différencier en ostéoblastes ou chondrocytes, initiant le processus de réparation de défaut. Avec la croissance de la néovascularisation, l’apport sanguin à la greffe est rétablie, favorisant l’ossification endochondrique, accélérant le remplacement de la greffe et la maturation du nouvel os, et raccourcissant le temps de guérison. En tant que matrice, l’acide hyaluronique peut fournir des nutriments et de l’espace tridimensionnel pour la croissance cellulaire, ce qui est propice à la réparation du tissu osseux [18].

3 Application de complexes d’acide hyaluronique modifiés dans le tissu osseux biologique

Hyaluronic acid is easily degraded and its degradation time is closely related to its moléculaireweight. 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 Poids poidsthan that of natural sodium hyaluronate molecules, i.e., cross-liéssodium 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 tissusengineering. 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-2 -2-2was proved to be non-cytotoxic and histocompatible in in vitro tests. When the composéwas 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 moelleangiogenesis was also high, which means that perylenic-hyaluronic acid can act as a carrier of osteoblast-2 and 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 La simvastatineon 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 La simvastatinecould be a good scaffold pourtissue-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 stromalcells in a murine model of large bone defects, where the cells were treated with alkaline fibroblast growth Le facteursupplemented 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 Le facteursupplementation, and defect healing was evaluated after 40, 60, 80 and 200 d. In vivo studies have demonstrated that benzyl hyaluronate is a suitable vehicle pourbone 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 pourbone repair.

4 complexes d’acide hyaluronique combinés à des facteurs de croissance dans les tissus osseux

Hyaluronic acid is a good carrier of growth factors in bone repair, but its main drawback as a scaffold is its low cell adhérenceproperties, 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 ligandson 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 hydrogelshowed a significant increase in cell adhesion and bone growth Le facteurdelivery, which further amélioréthe osteogenic potentielof recombinant human osteoblast-2. Therefore, the hyaluronic acid-integrin matrix can be used as a growth factor livraisonvehicle, 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 problèmes et perspectives

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 hydrogelsbased 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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