【摘要】：開放性骨折是創(chuàng)傷骨科的常見病,隨著現(xiàn)代化交通工具的普及和人們生活節(jié)奏的加快,病例逐年遞增,并且治療困難。嚴(yán)重的骨折必須通過手術(shù)復(fù)位并植入內(nèi)固定支架進(jìn)行治療。而由于傷口污染及引入內(nèi)固定支架所導(dǎo)致的創(chuàng)口感染幾乎是不可避免的,嚴(yán)重時(shí)可導(dǎo)致骨髓炎,必須通過抗生素給藥進(jìn)行治療。然而,傳統(tǒng)口服及注射抗生素藥物容易對(duì)人體重要器官造成不可逆的損傷,長期不間斷抗生素給藥也存在產(chǎn)生超級(jí)細(xì)菌的風(fēng)險(xiǎn),從而對(duì)人體健康甚至生命產(chǎn)生嚴(yán)重的威脅。在植入物表面構(gòu)筑載藥涂層局部遞送抗生素,是解決上述問題的有效策略。鑒于此,本文利用靜電噴涂技術(shù),在骨折支架表面構(gòu)筑具有高載藥容量的聚合物膜,然后利用電紡絲技術(shù)將聚合物多孔纖維覆蓋到載藥膜表面,通過調(diào)整纖維孔徑的密度及尺寸控制抗生素的釋放速度。主要研究工作總結(jié)為以下兩方面:1.靜電噴涂聚乙烯醇微凝膠制備聚合物膜以硼砂作為交聯(lián)劑,在水溶液中制備聚乙烯醇-硼砂(PVA-B)微凝膠。利用靜電噴涂方法,以PVA-B為基元,制備PVA-B微凝膠膜。研究結(jié)果表明,當(dāng)PVA和硼砂濃度分別為25 mg·mL-1和3.0 mM時(shí),得到粒徑為712.4 nm均勻分散的微凝膠。PVA-B膜的質(zhì)量與沉積時(shí)間為線性關(guān)系,沉積速率為0.187mg·cm-2·h-1。噴涂時(shí)間為1 h時(shí),得到厚度為1.35μm微凝膠膜。通過傅里葉紅外(FTIR)、熱重分析(TGA)對(duì)微凝膠膜進(jìn)行表征;通過應(yīng)力應(yīng)變曲線研究了微凝膠膜的力學(xué)性能。以槲皮素作為藥物模型,研究了PVA-B微凝膠膜的藥物負(fù)載能力,結(jié)果表明PVA-B微凝膠膜具有高藥物負(fù)載能力,在藥物遞送領(lǐng)域有潛在的應(yīng)用價(jià)值。2.雙層結(jié)構(gòu)聚合物膜控釋鹽酸萬古霉素將鹽酸萬古霉素(VH)與PVA-B微凝膠以1:1的質(zhì)量比混合,利用靜電噴涂技術(shù)制備VH@PVA-B膜,VH@PVA-B膜浸泡于生理鹽水中,5 min內(nèi)VH完全釋放。為減慢VH的釋放速度,利用電紡絲技術(shù)在VH@PVA-B膜表面覆蓋聚乙烯醇縮丁醛(PVB)纖維氈,結(jié)果表明當(dāng)PVB纖維氈的質(zhì)量為1.036 mg·cm-2時(shí),VH的釋放可以持續(xù)4 d。為了進(jìn)一步減緩VH的釋放速率,利用乙醇蒸汽處理PVB纖維氈,隨著處理時(shí)間的延長,PVB纖維氈的接觸角降低,孔密度減少,孔尺寸縮小,逐漸轉(zhuǎn)變?yōu)槎嗫啄ぁ．?dāng)PVB纖維氈(0.842 mg·cm-2)用乙醇蒸汽處理12 min時(shí),VH的釋放時(shí)間可以持續(xù)35 d(滿足臨床給藥需求),利用Weibull模型擬合VH釋放行為,相關(guān)系數(shù)R2高達(dá)0.982,證明VH從復(fù)合膜中的釋放屬于Fickian擴(kuò)散。此外,經(jīng)過乙醇蒸汽處理12 min的VH@PVA-B/PVB膜,其在生理鹽水中釋放VH 0.5、1和2 d時(shí)均可以有效殺滅金黃色葡萄球菌。這種聚合物膜和多孔纖維復(fù)合結(jié)構(gòu)有望成為普適性的藥物控釋載體用于植入物表面。
[Abstract]:Open fracture is a common disease in orthopedic trauma. With the popularization of modern transportation and the acceleration of people's life rhythm, the number of cases increases year by year and the treatment is difficult. Severe fractures must be treated by surgical reduction and internal fixation. The wound infection caused by wound contamination and the introduction of internal fixation stent is almost inevitable, and can lead to osteomyelitis in severe cases, which must be treated with antibiotics. However, traditional oral and injecting antibiotic drugs are prone to irreversibly damage to important organs of human body, and long-term continuous antibiotic administration also has the risk of producing super bacteria, which is a serious threat to human health and even life. It is an effective strategy to solve the above problem by constructing a drug-loaded coating to deliver antibiotics locally on the implant surface. In view of this, a polymer film with high drug loading capacity was constructed on the surface of fracture scaffold by electrostatic spraying technology, and then the porous polymer fiber was covered on the surface of drug-loaded film by electrospinning technology. The release rate of antibiotics is controlled by adjusting the density and size of fiber aperture. The main research work is summarized as follows: 1. Poly (vinyl alcohol) borax (PVA-B) microgel was prepared by electrostatically sprayed polyvinyl alcohol (PVA) microgel with borax as crosslinking agent in aqueous solution. PVA-B microgel films were prepared by electrostatic spraying with PVA-B as the basic element. The results showed that when the concentration of PVA and borax were 25 mg mL-1 and 3.0 mM, the microgels with particle size of 712.4 nm were obtained. The quality of PVA-B film was linearly related to the deposition time. The deposition rate is 0.187mg cm-2 h-1. When spraying time is 1 h, the thickness of microgel film is 1.35 渭 m. The microgel films were characterized by FTIR (FTIR), thermogravimetric analysis (TGA) and the mechanical properties of microgel films were studied by stress-strain curves. Quercetin was used as a drug model to study the drug loading capacity of PVA-B microgel membrane. The results showed that PVA-B microgel membrane had high drug loading ability and had potential application value in drug delivery field. 2. Controlled release Vancomycin Hydrochloride (vancomycin Hydrochloride) was used to prepare (VH) / PVA-B microgel at 1:1 mass ratio. VH@PVA-B film was prepared by electrostatic spraying. VH@PVA-B film was immersed in normal saline. 5 VH was completely released within min. In order to slow down the release rate of VH, polyvinyl butyral (PVB) fiber felt was coated on the surface of VH@PVA-B membrane by electrospinning technique. The results showed that when the mass of PVB fiber felt was 1.036 mg cm-2, the release of VH could last 4 days. In order to further slow down the release rate of VH, PVB fiber felt was treated with ethanol vapor. With the extension of treatment time, the contact angle, pore density and pore size of PVB fiber felt decreased and gradually changed into porous membrane. When PVB fiber felt (0.842 mg cm-2) was treated with ethanol vapor for 12 min, the release time of VH could last 35 days (to meet the requirement of clinical administration). The Weibull model was used to fit the release behavior of VH. The correlation coefficient (R2) was as high as 0.982. It is proved that the release of VH from the composite membrane belongs to Fickian diffusion. In addition, when the VH@PVA-B/PVB membrane was treated with ethanol vapor for 12 min, it could effectively kill Staphylococcus aureus when VH was released in normal saline for 1 and 2 days. The composite structure of polymer membrane and porous fiber is expected to become a universal drug controlled release carrier for the surface of implants.
【學(xué)位授予單位】：西北農(nóng)林科技大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R683;TQ465

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