뼈 조직에서 히알루론산의 용도는 무엇인가요?

외상, 종양, 선천성 기형, 감염 및 기타 병리적 요인으로 인한 골조직 결함은 임상 정형외과에서 직면하는 문제 중 하나이며, [1]이 문제를 해결하기 위한 주요 방법이 골이식이다.골이식은 주로 자가골이식, 동종골이식 또는 동종성형골이식으로 나뉘지만 자가골이식은 자가골의 양이 부족하고, 감염되기 쉽고 환자에게 재충격을 주는 등 많은 문제에 직면한다.동종 뼈 이식은 비싸다.동종 뼈 이식은 비싸고 면역 거부 반응이 있다.뼈 회복재를 대신하는 조직공학 생체재료골은 생물성 회복재 [2]의 결함을 피할 수 있다.

Ideal 조직scaffolds should have some properties: good biocompatibility; appropriate biodegradability 그리고eventual disappearance; good cell-셀interface 의이material 을allow cell adhesion, promote cell growth, 그리고reta에서cell differentiation; three-dimensional porous structure 그리고good porosity to allow cell infiltrati에그리고vascularisation; 그리고한certa에서degree 의mechanical strength, which is easy to fabricate [3]. Hyaluronic 산is 한new hot spot 에서이research 의뼈biomaterials. Hyaluronic 산h로한high degree 의viscoelasticity, plasticity, excellent water absorption, permeability 그리고good bioabsorbability, and is non-immuno-antigenic. Modified 루 론 산 not only maintains 이original superior properties, but also 개선its properties and makes it more adaptable to the 인간environment [4]. Therefore, 루 론산is now the hot spot 의bioengineering 뼈조직materials.

골관절염 치료에 히알루론산 적용 1

Osteoarthritis is one 의the most comm에knee injuries and joint diseases, and injection 의루 론산(sodium vitrate) h로become 한common treatment 을osteoarthritis. According to the literature, Manicourt etal[5] reported that the content of 루 론산increased when the physiological stress 에서the joint increased, which suggests that 루 론acid, 로an important component of proteoglycan polymers, may have 한buffering effect on stress. Hyaluronic 산in synovial fluid has 한큰amount of negative charge when combined 와proteins, 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 운동 and protecting the articular 연골에서excessive mechanical wear.

Kawasaki et al.[6] reported that 루 론acid increased the 합성of chondroitin sulphate 에 의해chondrocytes 교양in 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 행렬of chondrocytes in algal bead medium and 연골tissues, suggesting that hyaluronic acid may have an effect on the 분포and 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.

연골 및 골결손 회복에 히알루론산과 생체인자의 결합 2

2.1조골세포 증식 촉진

연골 손상 후에는 자체 회복 능력에 한계가 있어 연골세포 이식을 이용하는 것이 현재 각광받는 분야다.연구에 따르면 insulin-like 성장factor-1이 연골 회복에 중요한 역할을 하는 것으로 나타났다.히알루론산은 연골 행렬의 주요 성분 중 하나입니다.문헌에 따르면, insulin-like 성장factor-1은 관절연골세포에 조절효과가 있음이 확인된 최초의 성장인자이다.그러나 반감기가 짧고, 쉽게 분해되며, 내부요인에 의한 간섭을 받기 쉬워 [9-10] 그 영향에 한계가 있다.

Hyaluronic acid is negatively charged, has strong hydrophilicity and high adhesion, and has strong affinity 와chondrocytes. In addition, hyaluronic acid has the function of chondroinduction, which can provide nutrition 을articular chondrocytes, participate in the synthesis of proteoglycan polymers, act as a building block on the surface of chondrocytes through glycoproteoglycans, and promote the 확산of superficial joints, maintain the thickness of uncalcified cartilage, and promote the repair of articular cartilage 와degenerative changes to a certain extent [11-12]. It has been reported in the literature that the combination of hyaluronic acid and insulin-like 성장factor-1in the in vitro culture of 인간articular chondrocytes can help to maintain the stability of the pheno유형of 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 실험적bases 을the study of autologous chondrocyte transplantation or cartilage 조직engineering [13].

2.2 복합 동종 이식

The commonly used material 을the repair of 세그먼트뼈결점is allogeneic freeze-dried bone, but due to the weak induced activity of allogeneic freeze-dried 뼈and its poor osteogenicability, it only serves as a 비계을osteoconduction in the process of repair. The development of modern 분자biology technology has led to a deeper understanding of the osteogenic and osteoinductive activities of 뼈성장factors, and 뼈grafts 포함하는뼈growth factors combined 와suitable carriers have become a new trend in the treatment of bone defects. It has been reported in the literature that implantation of 기본적인섬유 아세 포growth 요인fused 와hyaluronic 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 세포to 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 섬유 아세 포growth factor, it was compounded 와hyaluronic 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 세포could be seen in the bone defect area of the complex 포함하는basic 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, 와the 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, 와the 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].

기본적인 섬유아세포 성장인자의 역할은 골 회복 초기에 중간엽세포의 증식을 자극하고, 후자는 연골깍지를 형성하며 성장인자와 다른 골유도인자로 작용하여 조골세포를 자극하여 조골세포나 연골세포로 분화하여 결손 회복 과정을 시작하는 것으로 문헌에서 보고되었다.신생세포의 성장과 함께 이식편에 공급되는 혈액공급이 재확립되어 내연골 골화를 촉진하고 이식편 교체 및 새로운 뼈의 성숙을 가속화하며 치유시간을 단축시킨다.히알루론산은 매트릭스로서 세포 성장을 위한 영양분과 3차원 공간을 제공할 수 있으며, 이는 뼈 조직의 회복에 도움이 된다 [18].

변형된 히알루론산 복합체를 생물학적 뼈 조직에 적용 3

Hyaluronic acid is easily degraded and its degradation time is closely related to its 분자weight. 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 무게than that of natural sodium hyaluronate molecules, i.e., cross-연결sodium 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 조직engineering. 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 화합물was 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 골수angiogenesis 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 simvastatinon 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 simvastatincould be a good scaffold 을tissue-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 기질cells in a murine model of large bone defects, where the cells were treated with alkaline fibroblast growth 요인supplemented 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 요인supplementation, and defect healing was evaluated after 40, 60, 80 and 200 d. In vivo studies have demonstrated that benzyl hyaluronate is a suitable vehicle 을bone 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 을bone repair.

4 히알루론산 복합체가 뼈 조직의 성장 인자와 결합

Hyaluronic acid is a good carrier of growth factors in bone repair, but its main drawback as a scaffold is its low cell 접착properties, 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 습니까showed a significant increase in cell adhesion and bone growth 요인delivery, which further 향상 된the osteogenic 잠재적인of recombinant human osteoblast-2. Therefore, the hyaluronic acid-integrin matrix can be used as a growth factor 배달vehicle, 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.

문제점 및 전망 5

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 겔based 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.

참조

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[25]Bae MS,Yang DH,Lee JB 외, photo-cure hyaluronic acid 기반  hydrogels    containing     simvastatin    as    a    bone    tissue  [J] 비계 재생 합니다.Biomaterials,2011,32 (32):8161-  8171다.

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