【作者】 何敏；

【导师】 张立群；

【作者基本信息】 北京化工大学 ， 材料科学与工程， 2015， 硕士

【摘要】 炎症反应是目前导致引导组织再生膜植入手术失败的主要原因之一,通过抗炎药定点持续释放以抑制炎症反应是目前组织工程领域的热点问题。传统的制备引导组织再生膜的方法主要是将药物与高分子基体共混后再通过各种方法制备出引导组织再生膜,但这类膜的主要缺点是前期药物突释严重,药物释放持续性不足。因此,本文采用同轴静电纺丝技术,将药物与一种高分子基体混合,并被另一种高分子包裹在纳米纤维的核层,以实现药物的持续控制释放。合成高分子聚己内酯被用作纳米纤维的核层材料,其具有优良的生物相容性,力学强度高,体内可降解,已经被广泛的用作医疗器械的组成材料,安全性能可靠；天然高分子材料明胶,因为其具有优良的生物相容性和细胞亲和性,能有效促进细胞的增值与粘附,而被用作同轴纤维的壳层材料。甲硝唑被用作抗炎模型药物与聚己内酯共混,其因为对口腔厌氧菌的良好抑制作用被广泛用在口腔临床。具有核壳结构的载药型纳米纤维膜的药物释放规律受多种因素调节,例如药物与高分子基体的相容性,纤维的形貌与结构,载药量,壳层包裹材料的亲水性等。本文就以上因素进行了考察。首先,制备出了以聚己内酯为核,明胶为壳的不同载药量的纳米纤维膜;其次,分别制备出了以聚己内酯为核,玉米醇溶蛋白为壳,不同载药量,不同壳层厚度的纳米纤维膜。SEM和TEM表征证明,多数纤维具有光滑连续的形貌,并且都具有核壳结构；DSC和XRD证明载药量低于20%时,药物呈分子态分散在高分子基体中,当载药量高于20%时,药物开始聚集结晶；体外药物释放结果表明,壳层的包裹能有效抑制药物的前期突释,壳层越厚,药物释放速率越慢；药物释放机理遵循扩散定律,载药量越高,药物释放越快；壳层包裹材料的亲水性对药物释放的影响显著,疏水性的玉米醇溶蛋白比亲水性的明胶能更有效的抑制药物的释放。抑菌实验结果表明,从纳米纤维膜释放出的甲硝唑对厌氧菌具有良好的抑制作用,载药量越大,抑制效果越强,有效抑制时间能长达30天；生物相容性评估表明,明胶和玉米醇溶蛋白都能很好的促进细胞的粘附与增值,甲硝唑的释放对细胞生长无副作用,材料的细胞毒性为零级。研究结果表明,同轴纺丝制备的载甲硝唑的聚己内酯／明胶纳米纤维膜有望成为具有良好抗炎疗效的引导组织再生膜在临床广泛使用。更多还原

【Abstract】 Guided tissue regeneration technology has become a standard procedure for periodontal tissue regeneration therapy. However, infection is the major reason for GTR failure in clinical applications. Although systemic administration of antibiotics is effective, high oral doses are necessary to obtain effective concentrations in the gingival fluid without systemic side effects. Besides, long-term usage of antibiotics may lead to the development of resistant bacterial strains. The drawbacks have led researchers worldwide to focus on the development of drug loaded GTRM with the function of localized delivery of antibiotics directly at the diseased site to realize controlled release in accordance with the therapeutic purpose and the pharmacological or biological properties. with an aim of developing a biologically mimetic guided tissue regeneration (GTR) membrane with an anti-inflammatory function for periodontal disease, the coaxial electrospinning technique was conducted to fabricate anti-inflammatory-loaded core/shell nanofibers coated with a layer of natural polymer for purpose of controlled release.The drug release behavior was affected by many factors, such as drug loading, fibers’morphology, the compatibility between drug and polymer matrix, and the shell material’s hydrophilicity. In this study, synthetic PCL was selected as the core material for its good biocompatibility and mechanical property. MNA was selected as drug model for its ability of inhibit anerobic bacteria colonized during GTR infection. The hydrophilic gelatin and the hydrophobic zein was separately selected as shell material to investigate the effect of hydrophilicity to the drug release behavior.Different types of MNA-loaded nanofibers was fabricated and displayed a uniform bead-free round morphology with core/shell structure by mean of scanning electron microscopy (SEM) and transmission electron microscopy (TEM). X-ray diffraction and differential scanning calorimetry verified that MNA presents an amorphous state in all nanofibers with MNA content below 20 wt%. In vitro drug release results showed that with the encapsulation of shell material, MNA released from the nanofiber membranes with biphasic release profile over a period of 4 days via a diffusion mechanism without initial burst release, and the encapsulation of hydrophobic zein is superior to delay the drug release. The released MNA remained antibacterial activity and inhibited the colonization of anaerobic bacteria. All the membranes showed good biocompatibility, and the surface natural polymer could enhance cell attachment and proliferation. Thus, the MNA loaded core/shell nanofiber membrane can be considered as a promising candidate for anti-inflammatory GTR membrane.更多还原