本文選題：可降解輸尿管支架管 + PGLA�。� 參考：《東華大學(xué)》2015年博士論文

【摘要】：輸尿管支架管是置放在患者輸尿管管腔面的特殊設(shè)計的中空管狀支架，是泌尿外科常用的器械之一。它主要起到支撐和引流作用，保證輸尿管的通暢�？山到廨斈蚬苤Ъ芄茉谥萌塍w內(nèi)一段時間后會降解并隨尿液排出體外，避免了二次手術(shù)拔出造成的損傷和相應(yīng)的并發(fā)癥，因而在國內(nèi)外得到了廣泛地開發(fā)和研究，但由于復(fù)雜的制備工藝，降解過程無規(guī)律，降解過程中易堵塞等缺點(diǎn)仍未得到臨床應(yīng)用，因此需要設(shè)計一種新型的輸尿管支架管，在特定時間內(nèi)起到良好引流支撐作用，隨后在體內(nèi)程序性降解，隨尿液順利排出體外，并同時具備臨床可操作性及易加工成型性，以改善現(xiàn)有可降解支架管的不足，推進(jìn)其在臨床上的早日應(yīng)用。 本文針對現(xiàn)有可降解支架管存在的問題，采用微型編織及后處理工藝制備一種“纖-膜”雙組份可降解輸尿管支架管，建立制備工藝與支架管的結(jié)構(gòu)之間的關(guān)系，比較不同結(jié)構(gòu)支架管之間的力學(xué)性能的特點(diǎn)，并多方位評價其體內(nèi)外降解性能及生物相容性。 基于臨床使用要求，從結(jié)構(gòu)設(shè)計、原料選擇、編織工藝、熱處理工藝和涂層處理四個方面，闡述了可降解輸尿管支架管的設(shè)計依據(jù)，系統(tǒng)探討了制備過程及其成型工藝與管壁結(jié)構(gòu)的關(guān)系�；谳斈蚬苤Ъ芄艿男阅芤�，設(shè)計一定規(guī)格、形狀及雙組份結(jié)構(gòu)的支架管，選擇聚乙交酯（PGA）和聚乙交酯-丙交酯（PGLA（910））作為纖維支架管的基本原料。根據(jù)輸尿管支架管的結(jié)構(gòu)及性能特點(diǎn)，選用編織工藝作為支架管原型的制備工藝，并探索編織機(jī)齒輪比、錠子排布與支架管管壁結(jié)構(gòu)參數(shù)之間的關(guān)聯(lián)。其中齒數(shù)比為14:140時可制備出編織密度最大的支架管結(jié)構(gòu)。設(shè)計并通過配置不同紗線組合的錠子來實現(xiàn)兩種纖維材料在管壁上的三種不同分布結(jié)構(gòu)。使用高溫?zé)崽幚矸绞綄崿F(xiàn)管壁結(jié)構(gòu)中膜與纖維均勻相互交織的新型“纖-膜”雙組份結(jié)構(gòu)，探索并選用的最佳熱處理溫度和時間為210℃，46s。相比于商用支架管，熱處理后的“纖-膜”支架管從薄壁和輕質(zhì)上都有明顯的優(yōu)勢。不同支架管間甚至是支架管內(nèi)外表面間的膜相對覆蓋率都大于理論值的50%。不同雙組份排布支架管熱處理后支架管的長度、管壁厚度和質(zhì)量損失及單位面積重量增長不同，雙組份排布更加分散的支架管熱處理后尺寸變化較大�；诰幙椇蜔崽幚砉に嚕剿鞑崿F(xiàn)支架管的環(huán)狀末端結(jié)構(gòu)的制備工藝。為實現(xiàn)可降解支架管的可顯影性，嘗試了兩種顯影材料和涂層方法，探索最佳顯影效果及可能對其他性能造成的影響。硫酸鋇涂層支架管具有良好的顯影效果，材料易得且工藝簡單可行，同時初步嘗試一種新型點(diǎn)狀涂層方法，優(yōu)化了硫酸鋇涂層的不足，但有待繼續(xù)探索。 從軸向拉伸性能和徑向壓縮性能兩個角度對可降解輸尿管支架管進(jìn)行力學(xué)性能評價，系統(tǒng)研究了不同“纖-膜”分布結(jié)構(gòu)對支架管主要力學(xué)性能的構(gòu)效關(guān)系。“纖-膜”支架管中的膜組分的相對覆蓋率直接與支架管的徑向壓縮強(qiáng)力相關(guān)，而支架管中纖維含量則直接影響支架管的軸向拉伸強(qiáng)度，因此膜和纖維組分分別增強(qiáng)支架管的抗壓縮和拉伸性能，可通過調(diào)控雙組份的比例和含量來進(jìn)一步優(yōu)化結(jié)構(gòu)和力學(xué)性能。三種雙組份結(jié)構(gòu)中，支架管C具有較好的抗壓縮和回彈性能以及拉伸性能，屬于最佳結(jié)構(gòu)。相比于商用不可降解支架管，可降解支架管具有更高的壓縮強(qiáng)力和拉伸強(qiáng)度，能夠在體內(nèi)更持久地保持支撐效果，且不易斷裂�？山到庵Ъ芄艿膹椥詾樯逃弥Ъ芄艿�90%。 構(gòu)建不同的降解環(huán)境，研究支架管的“纖-膜”組分，及經(jīng)過不同工藝條件處理后支架管的體外降解行為，全面揭示了“纖-膜”支架管的降解特性�？山到庵Ъ芄茉谌梭w尿液、模擬尿液及三種pH的PBS中的降解有較大差異，在堿性降解液里降解速度更快，人體尿液中的降解明顯最快，在第18天時降解成碎段，21天時呈粉末狀，模擬尿液和人體尿液較大的降解差異不僅受到了降解液pH的影響，還受到人體尿液中其他組分如微量元素和酶的影響；支架管的膜和纖維組分在模擬和人體尿液中的降解分別呈現(xiàn)不同的力學(xué)性能及形態(tài)變化。兩種組分在力學(xué)性能上的不同作用保證了雙組份支架管在降解第10天內(nèi)有足夠的綜合力學(xué)性能。纖維組分在兩種降解液中分別出現(xiàn)環(huán)狀裂紋和整體降解兩種模式，而在雙組份支架管上的膜組分由于被纖維組分分割成小塊，比純膜支架管降解更快，膜組分在降解中出現(xiàn)規(guī)則的裂紋形態(tài)。降解過程中壓縮曲線的變化反映出膜組分的降解程度，膜組分碎裂的程度同樣也能從支架管拉伸曲線的前端的波動程度體現(xiàn)，而曲線的后段則幾乎完全反映了支架管中纖維組分的拉伸狀態(tài)。人體尿液中的純纖維支架管在降解后期表面上出現(xiàn)結(jié)殼現(xiàn)象，主要是由生物膜而形成的鈣鹽；熱處理溫度越高，支架管降解越快，兩種組分的結(jié)晶度值差異越大，因而雙組份具有越大的降解差異；經(jīng)過涂層的支架管降解性能明顯加快，且涂層顯影劑的支架管在降解過程中顯影效果可維持1周時間；設(shè)計的一種體外動態(tài)模擬降解儀為進(jìn)一步的支架管降解性能的優(yōu)化和評價提供一個良好的平臺。 對“纖-膜”可降解輸尿管支架管的生物相容性及體內(nèi)降解行為進(jìn)行研究，證實了本實驗支架管具有優(yōu)良的生物相容性，發(fā)現(xiàn)了體內(nèi)外降解行為的差異及其可能影響因素。通過體外細(xì)胞毒性和大鼠肌肉填埋實驗對硫酸鋇涂層處理后的可降解支架管材料進(jìn)行生物相容性評價，結(jié)果表明支架管材料細(xì)胞及組織相容性良好。后處理和滅菌過程并未對相容性良好的原材料造成影響；體內(nèi)降解實驗中雙側(cè)放置輸尿管支架管的手術(shù)過程安全可行，未對體內(nèi)降解結(jié)果造成影響。病理學(xué)分析得出植入期間可降解與商用支架管具有相近的生物相容性；綜合B超檢測圖像，標(biāo)本內(nèi)支架管樣品的觀測及取出的支架管樣的形態(tài)學(xué)和力學(xué)評價確定可降解支架管在體內(nèi)的降解過程和特點(diǎn)。植入7天后，支架管保持管狀和環(huán)狀彎頭形狀，雙組份中的膜組分碎裂成小塊，仍有良好的力學(xué)性能；植入14天后，，膜組分大多已脫落，由于纖維網(wǎng)狀結(jié)構(gòu)存在仍保持管狀結(jié)構(gòu)及一定的抗壓縮和拉伸強(qiáng)度；植入21天后支架管大多完全降解，剩余少量碎片；植入28天支架管材料降解完全。降解過程中也有出現(xiàn)在第14天時出現(xiàn)折痕、膜結(jié)構(gòu)較快脫落及第21天出現(xiàn)斷裂的現(xiàn)象；體內(nèi)降解環(huán)境有復(fù)雜的力學(xué)作用，在支架管降解前期加速其降解過程，與體外降解有較大差異，針對這些特點(diǎn)改進(jìn)支架管的結(jié)構(gòu)和力學(xué)性能，減少體內(nèi)降解中出現(xiàn)的提前斷裂現(xiàn)象，同時完善體外動態(tài)模擬降解裝置，以便于更準(zhǔn)確地模擬并評價可降解支架管的降解性能。 綜上所述，本文以PGA和PGLA復(fù)絲為原料，采用微型編織及后處理工藝制備一種新型“纖-膜”可降解輸尿管支架管，建立制備工藝與支架管的結(jié)構(gòu)之間的關(guān)系，比較不同結(jié)構(gòu)支架管之間的力學(xué)性能的特點(diǎn)，并多方位評價和驗證了其良好的體內(nèi)外降解性能及生物相容性。改善了已有可降解輸尿管支架管的不足，充實了可降解支架管性能評價體系，為進(jìn)一步支架管的研究及結(jié)構(gòu)性能優(yōu)化甚至是推向臨床試驗奠定基礎(chǔ)。
[Abstract]:The ureteral stent tube is a specially designed hollow tubular stent placed on the patient ' s ureter lumen surface , which is one of the commonly used devices in the urology . It mainly plays the role of supporting and drainage to ensure the smooth smooth of the ureter . The degradable ureteral stent tube can degrade and discharge with the urine after being placed in the body for a certain period of time , thus avoiding the damage caused by the extraction of the secondary operation and the corresponding complication .

In view of the problems existing in the existing degradable stent tubes , a kind of " fiber - membrane " dual - component degradable ureteral stent was prepared by micro - weaving and post - treatment process . The relationship between the preparation process and the structure of scaffold tube was established . The mechanical properties of scaffold tubes with different structures were compared .

Based on the requirements of clinical use , the design basis of degradable ureteral stent was discussed from four aspects : structural design , raw material selection , braiding process , heat treatment process and coating treatment .

The mechanical properties of degradable ureteral stent were evaluated from two angles of axial tension and radial compression . The relative coverage rate of membrane components in " fiber - membrane " stent was directly related to the radial compression strength of stent tube .

The degradable stent tube was degraded in human urine , simulated urine and three kinds of pH in vitro . The degradation rate of degradable scaffold tube in human urine , simulated urine and three pH PBS was faster .
The membrane and fiber components of the scaffold tube exhibited different mechanical properties and morphological changes in the simulated and human urine respectively . The different effects of the two components on the mechanical properties ensured that the two groups of scaffold tubes had sufficient comprehensive mechanical properties in the 10 days of degradation .
The higher the heat treatment temperature , the faster the degradation of the stent tube , the greater the difference between the crystallinity values of the two components , and thus the greater the degradation difference of the two components .
the degradation performance of the coated stent tube is obviously accelerated , and the developing effect of the scaffold tube of the coating developer can be maintained for 1 week in the degradation process ;
An in vitro dynamic simulation degradation instrument is designed to provide a good platform for further optimization and evaluation of degradation performance of stent tube .

The biocompatibility and the in vivo degradation behavior of the " fiber - membrane " degradable ureteral stent were studied . The biocompatibility of the scaffold tube was confirmed . The biocompatibility evaluation of degradable stent tube material after the treatment of barium sulfate coating was carried out through in vitro cytotoxicity and muscle filling experiment .
In vivo degradation experiment , the procedure of bilateral placement of ureteral stent tube was safe and feasible , which did not affect the result of in vivo degradation . The pathological analysis showed that the degradable and commercial stent tube had similar biocompatibility during implantation .
The degradation process and the characteristics of degradable stent tube in vivo were determined by the observation and mechanical evaluation of the stent tube samples . After 7 days of implantation , the stent tube remained tubular and annular , and the membrane components in the two components were fragmented into small pieces , still having good mechanical properties .
After 14 days of implantation , most of the membrane components have fallen off , and because of the existence of the fiber net structure , the tubular structure and certain compressive and tensile strength remain .
Most of the stent tubes were completely degraded after 21 days of implantation , and a small amount of debris remained ;
There were folds on the 14th day in the course of degradation , and the membrane structure was faster and the rupture occurred in 21 days .
In order to improve the structure and the mechanical property of the scaffold tube and reduce the early fracture phenomenon occurring in the in vivo degradation , the in vitro dynamic simulation and degradation device is improved , so that the degradation performance of the degradable stent tube can be simulated and evaluated more accurately .

In conclusion , using PGA and PGLA multifilament as raw materials , a novel " fiber - membrane " degradable ureteral stent was prepared by micro - weaving and post - treatment process . The relationship between the preparation process and the structure of stent was established . The properties and biocompatibility of biodegradable stent were compared .

【學(xué)位授予單位】：東華大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號】：R699

【參考文獻(xiàn)】

相關(guān)博士學(xué)位論文 前1條

1 王曉慶;梯度可降解輸尿管支架管的研制及動物實驗研究[D];吉林大學(xué);2014年

本文編號：1853996