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兩種殼聚糖膜片的制備、性質(zhì)及生物學(xué)評價(jià)

發(fā)布時(shí)間:2018-03-25 02:33

  本文選題:N-羧甲基殼聚糖 切入點(diǎn):羥乙基殼聚糖 出處:《中國海洋大學(xué)》2012年碩士論文


【摘要】:目的:殼聚糖是一種糖基上帶正電荷的天然大分子多糖,通常由甲殼動物外殼提煉出甲殼素,并由甲殼素脫乙;纬,來源十分廣泛。雖然殼聚糖相對于甲殼素來說生物性質(zhì)有所改善,但是由于殼聚糖只能溶解在弱酸溶液中,因此這也大大的限制了它的應(yīng)用。于是,通過對殼聚糖的分子接枝改性形成殼聚糖衍生物,來對其物化性質(zhì)和生物性質(zhì)進(jìn)行改善。常見的衍生物主要包括羧基化殼聚糖、羥基化殼聚糖,磺基化殼聚糖,聚合改性等,他們各自的結(jié)構(gòu)不同,生物特性也不盡相同。由于殼聚糖及其衍生物良好的溶解性、成膜性、乳化性、生物相容性、降解性和無毒性等特點(diǎn),被廣泛的應(yīng)用于日常生活生產(chǎn)的各個(gè)方面。 生物醫(yī)用材料是指對生物體進(jìn)行診斷、治療和置換有損傷的器官或保護(hù)增進(jìn)其功能的材料,一般來說,優(yōu)秀的生物功能材料是生物活性較好的功能性材料。之前所選用的醫(yī)用材料主要是選用惰性物質(zhì)材料,這些材料多是一些化學(xué)合成的高聚物,不具備良好的生物相容性和降解性等,,因此植入體內(nèi)后常常引起免疫系統(tǒng)的排斥,這也是醫(yī)學(xué)組織工程一直以來的難以解決的問題。近年來,隨著臨床對功能性生物材料的需求量增大以及相關(guān)研究的進(jìn)行,對新型生物材料的研究逐漸興起。由于臨床上的要求,它們通常需要具備以下的特性:(1)具有良好的生物相容性,植入體內(nèi)后不會引起嚴(yán)重的炎癥反應(yīng)和免疫反應(yīng);(2)具有良好的生物降解性,且降解產(chǎn)物對生物體無不良影響;(3)無毒性;(4)屬于生物活性大分子,可以根據(jù)某些特定的要求具備特殊的功能:如在尋找用于抗癌藥物藥物緩釋系統(tǒng)的支架材料就要擁有抑制癌癥細(xì)胞生長的特性等。(5)具有良好的物理化學(xué)性質(zhì),可以根據(jù)要求來制作成恰當(dāng)?shù)男螤罨蛘郀顟B(tài)。(6)來源廣泛。尋找這樣的生物材料一直是研究的熱點(diǎn)。 在本實(shí)驗(yàn)中,我們對兩種重要的殼聚糖衍生物:N-羧甲基殼聚糖和羥乙基殼聚糖進(jìn)行研究,觀察兩種衍生物的物化性質(zhì)并制備出物理性質(zhì)和生物學(xué)性質(zhì)合適的膜片。接下來證明這兩種膜片對成纖維細(xì)胞生長的抑制作用及生物相容性、生物降解性等,為它們作為優(yōu)秀的生物材料的進(jìn)一步開發(fā)提供了理論基礎(chǔ),同時(shí)對于拓寬殼聚糖的應(yīng)用范圍也有很重要的意義。 方法: 1、制備羥乙基殼聚糖(HECTS)和N-羧甲基殼聚糖(N-CMCTS)。 2、對得到的兩種殼聚糖分別純化,通過脫乙酰度、取代度、分子量等對其物理化學(xué)性質(zhì)進(jìn)行表征; 3、兩種材料均用丁二醇雙縮水甘油醚進(jìn)行分子間交聯(lián),避光條件下制備出不同交聯(lián)程度的殼聚糖膜片;通過測定膜片的吸水率和溶脹比、通透性;通過進(jìn)行皮下植入和肌肉植入試驗(yàn)、對成纖維細(xì)胞生長影響試驗(yàn),分別評價(jià)膜片的生物相容性、降解性和抑制成纖維細(xì)胞生長的性質(zhì)。 結(jié)果:1、制備出N-CMC和HEC,確定了最優(yōu)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,取代度為63.7%。兩種材料均細(xì)胞相容性良好,無細(xì)胞毒性。 2、制備了交聯(lián)比為80:1的兩種膜片,具有良好的通透性以及親水性;大鼠體內(nèi)埋膜實(shí)驗(yàn)表明膜片能夠逐步降解,對周圍的組織并沒有產(chǎn)生炎癥反應(yīng)。這就說明兩種材料的可在體內(nèi)存在一定的時(shí)間,隨后逐步降解,在降解的過程中生物相容性良好。相比而言,N-CMC膜片的降解時(shí)間較長,但是生物相容性比HEC膜片差;而HEC膜片具有較好的生物相容性,同時(shí)其在體內(nèi)降解的時(shí)間也較長。 3.細(xì)胞實(shí)驗(yàn)中:對體外培養(yǎng)的成纖維細(xì)胞沒有抑制作用;膜片的細(xì)胞實(shí)驗(yàn)表明:N-CMC膜片對于成纖維細(xì)胞的生長有抑制作用,HEC膜片則沒有較為明顯的影響。 結(jié)論:兩種殼聚糖衍生物具有良好的特性,由兩種材料制備成的膜片均具有良好的柔韌性、通透性、親水性以及機(jī)械強(qiáng)度等;細(xì)胞實(shí)驗(yàn)中可以看出能兩種膜片對成纖維細(xì)胞具有一定的抑制生長的作用,動物體內(nèi)植膜實(shí)驗(yàn)證明兩種材料具有良好的生物相容性及降解性,為材料的進(jìn)一步研究和應(yīng)用提供了理論基礎(chǔ)。
[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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