本文選題：骨誘導(dǎo)　切入點(diǎn)：多孔支架　出處：《西南交通大學(xué)》2012年碩士論文

【摘要】：隨著社會(huì)進(jìn)步、人民生活水平的不斷提高,人民對(duì)生物醫(yī)用材料尤其是植入性生物醫(yī)用材料的需求越來(lái)越高,單一組分和結(jié)構(gòu)的植入材料已不能滿足復(fù)雜多變的臨床需求。一方面,在骨組織領(lǐng)域中,多孔貫通的陶瓷支架有利于組織長(zhǎng)入、細(xì)胞遷移、營(yíng)養(yǎng)物質(zhì)的交換以及血管化過(guò)程進(jìn)行,多孔貫通結(jié)構(gòu)被確認(rèn)是影響多孔支架修復(fù)材料在體內(nèi)組織工程化的、發(fā)揮其骨傳導(dǎo)、骨誘導(dǎo)性能的重要因素。雖然多孔貫通支架的宏觀孔隙結(jié)構(gòu)與其異位骨誘導(dǎo)特性之間的關(guān)系獲得了廣泛關(guān)注,但是這種關(guān)系還遠(yuǎn)未完全揭示。另一方面,對(duì)于藥物洗脫支架(drag eluting stent, DES),為避免高分子支架不能有效控制藥物緩釋以及鈷鉻合金(Co-Cr)表面性能單一且不具備生物活性等弊端,對(duì)鈷鉻合金表面生物功能化以形成具有生物活性載藥涂層的需要日益迫切。為此,本研究擬通過(guò)構(gòu)建結(jié)構(gòu)互補(bǔ)的多孔貫通孔隙結(jié)構(gòu),進(jìn)一步研究支架多孔結(jié)構(gòu)與異位成骨的關(guān)系；同時(shí),通過(guò)對(duì)鈷鉻合金表面進(jìn)行載藥修飾改善其表面性能。 在研究過(guò)程中,通過(guò)球粒堆積和顆粒造孔的方法制備了宏觀孔隙互補(bǔ)的兩種羥基磷灰石(Hydroxyapatite, HA)多孔支架。將兩種支架同時(shí)植入成年狗的背部肌肉以揭示孔隙互補(bǔ)結(jié)構(gòu)對(duì)HA支架異位骨誘導(dǎo)性能的影響。兩種支架的高貫通性均利于組織的長(zhǎng)入,在支架植入早期(1個(gè)月),顆粒造孔支架組織學(xué)觀察到更明顯的鈣質(zhì)沉積層,說(shuō)明其在植入早期具有更好的組織-材料界面活性；在植入3個(gè)月后,球粒堆積支架內(nèi)發(fā)現(xiàn)有新骨生成,而在顆粒造孔支架內(nèi)并未發(fā)現(xiàn)有新骨生成；同時(shí),球粒堆積支架力學(xué)性能亦優(yōu)于顆粒造孔支架。由于球粒堆積支架的外凸弧形孔結(jié)構(gòu)更有利于體液的流動(dòng),故有利于蛋白和細(xì)胞遷移粘附,導(dǎo)致球粒堆積支架的體內(nèi)組織工程改建效果優(yōu)于顆粒造孔支架。實(shí)驗(yàn)結(jié)果再次表明,支架的孔隙結(jié)構(gòu)對(duì)其異位成骨性能有重要影響。 論文另一部分研究采用堿熱處理和生物模擬礦化在鈷鉻合金表面形成具有生物活性的鈣磷涂層,并作為載體固定西羅莫司,得到一種新的鈷鉻合金生物功能化的表面涂層,達(dá)到藥物洗脫系統(tǒng)緩釋、控釋的目的。首先利用酸蝕處理和堿熱處理在合金基體上獲得了均勻且利于磷灰石晶體形核、生長(zhǎng)的表面。再采用生物模擬的方法,在基體表面形成結(jié)合牢固的鈣磷涂層,通過(guò)滴注法在鈣磷涂層表面固定西羅莫司。采用以上工藝固定的藥物可在模擬體液中的緩慢釋放至少90天,改善了藥物洗脫支架的性能。
[Abstract]:With the progress of society and the improvement of people's living standard, the demand for biomedical materials, especially implantable biomedical materials, is getting higher and higher. The single component and structure implant materials can not meet the complex and changeable clinical needs.On the one hand, in the field of bone tissue, porous ceramic scaffolds facilitate tissue growth, cell migration, nutrient exchange, and vascularization.The perforated structure is confirmed to be an important factor affecting the tissue engineering of the porous scaffold in vivo and exerting its bone conduction and osteoinductive properties.Although the relationship between macroporous structure and ectopic osteoinductive characteristics of porous perforated scaffolds has been widely concerned, this relationship is far from fully revealed.On the other hand, for the drug-eluting stents drag eluting stents, in order to avoid the polymer stents can not effectively control the drug release and Cobalt-Chromium alloy Co-Cr surface properties are single and do not have biological activities and so on.The need for biofunctionalization of cobalt-chromium alloy to form bioactive drug-loading coating is becoming more and more urgent.Therefore, the relationship between porous structure and heterotopic osteogenesis of the scaffold was further studied by constructing porous and perforated pore structure with complementary structure, and the surface properties of cobalt-chromium alloy were improved by drug loading modification.During the study, two kinds of hydroxyapatite (HA) porous scaffolds with complementary macroporous pores were prepared by the methods of spherulite accumulation and particle pore-forming.Two scaffolds were simultaneously implanted into the back muscles of adult dogs to reveal the effect of porous complementary structure on the heterotopic bone induction of HA scaffolds.The high permeability of the two scaffolds was beneficial to the growth of the tissue. At the early stage of stent implantation (1 month after implantation, a more obvious calcium deposit layer was observed in the grained scaffold, which indicated that the scaffold had better tissue-material interface activity at the early stage of implantation.After 3 months of implantation, new bone formation was found in the spherical scaffold, but no new bone formation was found in the granular scaffold. At the same time, the mechanical properties of the spherical scaffold were better than those of the granular scaffold.Because the protruding arc-shaped pore structure is more favorable to the flow of body fluid, it is advantageous to the migration and adhesion of protein and cells, which leads to the effect of tissue engineering reconstruction of spherulite stacking scaffold is better than that of granular scaffold.The experimental results show that the pore structure of the scaffold has an important effect on the heterotopic osteogenesis.To achieve the drug elution system slow release, the purpose of controlled release.At first, the homogeneous and suitable apatite crystal nucleation and growth surface were obtained by acid etching and alkali heat treatment on the base of the alloy.Then a solid calcium phosphorus coating was formed on the substrate surface by biological simulation. Sirolimus was immobilized on the surface of calcium phosphorus coating by drip method.The drugs fixed by the above process can be released slowly in simulated body fluid for at least 90 days, which improves the performance of drug-eluting stents.
【學(xué)位授予單位】：西南交通大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R318.08

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