两种壳聚糖膜片的制备、性质及生物学评价

发布时间：2018-03-25 02:33

  本文选题：N-羧甲基壳聚糖　切入点：羟乙基壳聚糖　出处：《中国海洋大学》2012年硕士论文

【摘要】：目的：壳聚糖是一种糖基上带正电荷的天然大分子多糖，通常由甲壳动物外壳提炼出甲壳素，并由甲壳素脱乙酰化而形成，来源十分广泛。虽然壳聚糖相对于甲壳素来说生物性质有所改善，但是由于壳聚糖只能溶解在弱酸溶液中，因此这也大大的限制了它的应用。于是，通过对壳聚糖的分子接枝改性形成壳聚糖衍生物，来对其物化性质和生物性质进行改善。常见的衍生物主要包括羧基化壳聚糖、羟基化壳聚糖，磺基化壳聚糖，聚合改性等，他们各自的结构不同，生物特性也不尽相同。由于壳聚糖及其衍生物良好的溶解性、成膜性、乳化性、生物相容性、降解性和无毒性等特点，被广泛的应用于日常生活生产的各个方面。 生物医用材料是指对生物体进行诊断、治疗和置换有损伤的器官或保护增进其功能的材料，一般来说，优秀的生物功能材料是生物活性较好的功能性材料。之前所选用的医用材料主要是选用惰性物质材料，这些材料多是一些化学合成的高聚物，不具备良好的生物相容性和降解性等，，因此植入体内后常常引起免疫系统的排斥，这也是医学组织工程一直以来的难以解决的问题。近年来，随着临床对功能性生物材料的需求量增大以及相关研究的进行，对新型生物材料的研究逐渐兴起。由于临床上的要求，它们通常需要具备以下的特性：（1）具有良好的生物相容性，植入体内后不会引起严重的炎症反应和免疫反应；（2）具有良好的生物降解性，且降解产物对生物体无不良影响；（3）无毒性；（4）属于生物活性大分子，可以根据某些特定的要求具备特殊的功能：如在寻找用于抗癌药物药物缓释系统的支架材料就要拥有抑制癌症细胞生长的特性等。（5）具有良好的物理化学性质，可以根据要求来制作成恰当的形状或者状态。（6）来源广泛。寻找这样的生物材料一直是研究的热点。 在本实验中，我们对两种重要的壳聚糖衍生物：N-羧甲基壳聚糖和羟乙基壳聚糖进行研究，观察两种衍生物的物化性质并制备出物理性质和生物学性质合适的膜片。接下来证明这两种膜片对成纤维细胞生长的抑制作用及生物相容性、生物降解性等，为它们作为优秀的生物材料的进一步开发提供了理论基础，同时对于拓宽壳聚糖的应用范围也有很重要的意义。 方法： 1、制备羟乙基壳聚糖（HECTS）和N-羧甲基壳聚糖（N-CMCTS）。 2、对得到的两种壳聚糖分别纯化，通过脱乙酰度、取代度、分子量等对其物理化学性质进行表征； 3、两种材料均用丁二醇双缩水甘油醚进行分子间交联，避光条件下制备出不同交联程度的壳聚糖膜片；通过测定膜片的吸水率和溶胀比、通透性；通过进行皮下植入和肌肉植入试验、对成纤维细胞生长影响试验，分别评价膜片的生物相容性、降解性和抑制成纤维细胞生长的性质。 结果：1、制备出N-CMC和HEC，确定了最优的合成方案以及配料比。其中HEC取代位在6位C上，N-CMC取代位在2位C上，取代度为63.7%。两种材料均细胞相容性良好，无细胞毒性。 2、制备了交联比为80:1的两种膜片，具有良好的通透性以及亲水性；大鼠体内埋膜实验表明膜片能够逐步降解，对周围的组织并没有产生炎症反应。这就说明两种材料的可在体内存在一定的时间，随后逐步降解，在降解的过程中生物相容性良好。相比而言，N-CMC膜片的降解时间较长，但是生物相容性比HEC膜片差；而HEC膜片具有较好的生物相容性，同时其在体内降解的时间也较长。 3.细胞实验中：对体外培养的成纤维细胞没有抑制作用；膜片的细胞实验表明：N-CMC膜片对于成纤维细胞的生长有抑制作用，HEC膜片则没有较为明显的影响。 结论：两种壳聚糖衍生物具有良好的特性，由两种材料制备成的膜片均具有良好的柔韧性、通透性、亲水性以及机械强度等；细胞实验中可以看出能两种膜片对成纤维细胞具有一定的抑制生长的作用，动物体内植膜实验证明两种材料具有良好的生物相容性及降解性，为材料的进一步研究和应用提供了理论基础。
[Abstract]:Objective: chitosan is a polysaccharide based on positively charged natural macromolecular polysaccharide extracted from animal usually consists of crustacean shell chitin, and the deacetylation of chitin and the formation of a wide range of sources. Although the biological properties of chitin chitosan to improve, but because chitosan is only soluble in weak acid solution. Therefore, this also greatly limits its application. Then, through molecular grafting of chitosan modified chitosan derivatives to improve its physicochemical properties and biological properties. Common derivatives include carboxylated chitosan, chitosan hydroxyl, sulfonic chitosan, polymerization modification etc. and their different biological characteristics are not the same. The solubility of chitosan and its derivatives with good film-forming properties, emulsifying properties, biocompatibility, biodegradability and non-toxic, is widely used In every aspect of daily life.
Biomedical materials refers to diagnosis and treatment of organism, organ damage or replacement protection enhance the function of the material, in general, bio functional materials is excellent functional materials with better biological activity. Before the medical material is mainly made of inert materials, these materials are synthetic polymers and do not have good biocompatibility and biodegradability, so after implantation, often cause the immune system rejection, which is the medical tissue engineering has been a difficult problem to solve. In recent years, with the clinical of functional biomaterials increased demand and related research, research of new biological materials gradually on the rise. Due to the clinical requirements, they usually need to have the following characteristics: (1) have good biocompatibility, after implantation does not cause serious The inflammatory reaction and immune response; (2) with good biodegradability, and the degradation product of organisms without adverse effects; (3) non-toxic; (4) belongs to the molecular biological activity, can according to some specific requirements have special functions: such as looking for scaffolds used for anti-cancer drug drug delivery system must have the characteristics of inhibiting cancer cell growth. (5) with excellent physical and chemical properties, can according to the requirements to make proper shape or state. (6) find widespread sources. Such biological material has been a hot point of research.
In this experiment, we studied two kinds of important chitosan derivatives: N- carboxymethyl chitosan and hydroxyethyl chitosan were studied. The observation of two kinds of derivatives of physicochemical properties and preparation of membrane physical properties and biological properties of the right. Then prove that two kinds of diaphragm compatibility and biological inhibition of fibroblast the growth of biodegradability, provides a theoretical basis for the further development of them as excellent biological materials, but also has the important significance to broaden the scope of application of chitosan.
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