含丝蛋白肝脏组织工程支架材料的制备及体外评价
发布时间：2018-10-14 14:31
【摘要】：各类肝病引发的肝功能衰竭已严重影响人类健康。虽然肝脏组织工程技术是当今最具潜力的治疗手段，但是寻找理想的支架材料一直是该领域的技术难题。家蚕丝胶蛋白(silk siricin, SS)是一种宝贵的天然高分子材料，是人类利用很早的动物蛋白质之一，在丝绸工业中，产生的大量丝胶常作为废物随废水直接排放，对其开发利用可节约资源、保护环境。作为天然蛋白，丝胶具备特异性分子识别信号，可促进细胞粘附和增殖，诱导细胞分化及为其提供支架。基于丝胶良好的凝胶化性能、低免疫原性，，特殊的生物相容性和可降解性等，逐渐在组织工程支架等医学领域得到了广泛的重视和研究。但是丝胶在低温冷冻时为凝胶，加热到室温左右即成为溶胶，调控较为困难，对其改性调制必不可少。当前报道较多的壳聚糖/甘油磷酸钠(CS/GP)温敏性复合凝胶材料，具有低温溶胶，体温范围内呈凝胶状态的特点，可作为对丝胶的改性物质之一。同时，玉米淀粉(Maize Starth, MS)是一类可完全生物降解的多糖类天然高分子，来源广泛、价格低廉；聚乙烯醇(PolyvinylAlcohol, PVA)具有优良成膜性、力学性能，以及良好的亲水性、生物相容性和降解性，二者均可作为安全医用生物材料用于对丝胶性质的完善。 本课题分为两个大部分，先后尝试制备了溶胶状态经注射后可在体内成型和直接在体外成型两类可调控型肝脏组织工程支架材料，即SS/CS/GP温敏性复合凝胶和SS/PVA/MS凝胶膜，从结构、性能及应用方面，分析了二者用于肝脏组织工程支架的可行性。首先进行了对SS/CS/GP温敏性复合凝胶的研究，即将废弃蚕茧中提取的丝胶蛋白(SS)，外加高脱乙酰度的壳聚糖(CS)、α、β-甘油磷酸钠(GP)，三者经冰浴下的特定方式混合，得到不同配比SS/CS/GP复合物，该复合物可在20℃以下长时间保持液态，在体温环境(37±5℃)附近、大范围生理pH值(6.9-7.45)下，快速凝胶化；对其结构性能研究显示SS/CS/GP凝胶具备贯通的三维多孔结构、适当的力学强度、良好的生物降解性且降解速率可调控，无细胞毒性且具备一定的促BRL大鼠肝细胞生长性能，并可通过注射实现体内成型。然后进行了SS/PVA/MS凝胶膜材料的研究，即将废弃蚕茧中提取的SS，与MS和PVA经水相共混和反复冻融可实现体外不同配比的SS/PVA/MS凝胶膜材料成型。研究其力学性能和降解机制表明，SS/PVA质量比为3/7，MS添加量为18%时，凝胶膜整体力学性能最优，不同配比SS/PVA/MS凝胶膜均具备降解性，且降解速率可通过SS/PVA比例及MS含量得到调控，该凝胶膜材料通过体外成型且具备可调控的降解性能，有望作为体外肝脏组织工程支架使用。
[Abstract]:Liver failure caused by various liver diseases has seriously affected human health. Although liver tissue engineering technology is the most potential treatment, finding ideal scaffold materials has always been a technical problem in this field. Silk gelatin (silk siricin, SS) is a valuable natural polymer material, which is one of the early animal proteins used by human beings. In the silk industry, a large amount of sericin is often discharged directly with the waste water as waste water. It can save resources and protect environment. As a natural protein sericin has a specific molecular recognition signal which can promote cell adhesion and proliferation induce cell differentiation and provide scaffolds. Sericin with good gelation property, low immunogenicity, special biocompatibility and biodegradability has been paid more and more attention in the field of tissue engineering scaffolds. However, sericin is gel at low temperature and becomes sol when heated to room temperature, which is difficult to control and is necessary for modification and modulation of sericin. At present, more chitosan / sodium glycerophosphate (CS/GP) thermo-sensitive composite gel materials are reported, which have the characteristics of low temperature sol and gel state in the temperature range, and can be used as one of the modified materials for sericin. At the same time, corn starch (Maize Starth, MS) is a kind of completely biodegradable polysaccharides, which has a wide range of sources and low price. (PolyvinylAlcohol, PVA) has good film formation, mechanical properties and good hydrophilicity. Biocompatibility and biodegradability can be used as safe biomaterials for the improvement of sericin properties. This thesis is divided into two parts. Two kinds of controllable scaffold materials for liver tissue engineering, SS/CS/GP thermo-sensitive composite gel and SS/PVA/MS gel membrane, have been prepared after injection of sol-state in vivo and directly in vitro. The feasibility of the two scaffolds for liver tissue engineering was analyzed in terms of performance and application. Firstly, the SS/CS/GP thermo-sensitive composite gel was studied. The sericin protein (SS), extracted from the abandoned cocoon and chitosan (CS), 伪, 尾 -glycerophosphate sodium (GP), with high deacetylation degree were mixed in a special way under ice bath to obtain the SS/CS/GP complex with different proportions. The complex can be rapidly gelatinized under 20 鈩
本文编号：2270758
[Abstract]:Liver failure caused by various liver diseases has seriously affected human health. Although liver tissue engineering technology is the most potential treatment, finding ideal scaffold materials has always been a technical problem in this field. Silk gelatin (silk siricin, SS) is a valuable natural polymer material, which is one of the early animal proteins used by human beings. In the silk industry, a large amount of sericin is often discharged directly with the waste water as waste water. It can save resources and protect environment. As a natural protein sericin has a specific molecular recognition signal which can promote cell adhesion and proliferation induce cell differentiation and provide scaffolds. Sericin with good gelation property, low immunogenicity, special biocompatibility and biodegradability has been paid more and more attention in the field of tissue engineering scaffolds. However, sericin is gel at low temperature and becomes sol when heated to room temperature, which is difficult to control and is necessary for modification and modulation of sericin. At present, more chitosan / sodium glycerophosphate (CS/GP) thermo-sensitive composite gel materials are reported, which have the characteristics of low temperature sol and gel state in the temperature range, and can be used as one of the modified materials for sericin. At the same time, corn starch (Maize Starth, MS) is a kind of completely biodegradable polysaccharides, which has a wide range of sources and low price. (PolyvinylAlcohol, PVA) has good film formation, mechanical properties and good hydrophilicity. Biocompatibility and biodegradability can be used as safe biomaterials for the improvement of sericin properties. This thesis is divided into two parts. Two kinds of controllable scaffold materials for liver tissue engineering, SS/CS/GP thermo-sensitive composite gel and SS/PVA/MS gel membrane, have been prepared after injection of sol-state in vivo and directly in vitro. The feasibility of the two scaffolds for liver tissue engineering was analyzed in terms of performance and application. Firstly, the SS/CS/GP thermo-sensitive composite gel was studied. The sericin protein (SS), extracted from the abandoned cocoon and chitosan (CS), 伪, 尾 -glycerophosphate sodium (GP), with high deacetylation degree were mixed in a special way under ice bath to obtain the SS/CS/GP complex with different proportions. The complex can be rapidly gelatinized under 20 鈩
本文编号：2270758
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