本文選題：肩袖損傷 + 腱-骨愈合�。� 參考：《上海交通大學(xué)》2014年博士論文

【摘要】：肩袖損傷是中老年人群中最常見的損傷之一,可引起肩關(guān)節(jié)疼痛、不穩(wěn)定、肌力下降甚至活動(dòng)障礙。盡管手術(shù)技術(shù)不斷進(jìn)步,肩袖修補(bǔ)的失敗率仍達(dá)到20%~90%。骨質(zhì)疏松、肩袖退變、肌肉萎縮以及缺損嚴(yán)重等因素削弱了損傷部位的自我修復(fù)能力,最終影響修補(bǔ)手術(shù)的效果。改變肩袖腱-骨止點(diǎn)損傷后反應(yīng)性瘢痕愈合方式,促進(jìn)腱-骨止點(diǎn)天然多層復(fù)合結(jié)構(gòu)的重建是改善肩袖愈合的關(guān)鍵。目前利用組織工程支架提高患者內(nèi)源性再生修復(fù)潛能以改善肩袖修補(bǔ)效果是當(dāng)前國(guó)內(nèi)外研究的熱點(diǎn)。目的1.評(píng)估聚乳酸乙醇酸(PLGA)電紡纖維支架負(fù)載堿性成纖維細(xì)胞生長(zhǎng)因子(b FGF)誘導(dǎo)肩袖腱-骨止點(diǎn)組織再生的能力;2.評(píng)估硅磷酸鈣(CPS)生物活性陶瓷改變腱-骨界面骨礦含量、誘導(dǎo)腱-骨止點(diǎn)纖維軟骨再生的能力;3.構(gòu)建具有仿生結(jié)構(gòu)的聚己內(nèi)酯-殼聚糖(PCL-CS)混合纖維支架,評(píng)估活性支架誘導(dǎo)腱-骨止點(diǎn)多層結(jié)構(gòu)重建和促進(jìn)肩袖愈合的能力。方法1.利用乳液電紡技術(shù)制備具有芯核結(jié)構(gòu)的PLGA纖維支架并負(fù)載b FGF,觀察材料表征和b FGF釋放,通過體外細(xì)胞培養(yǎng)觀察b FGF-PLGA的細(xì)胞親和力,并利用大鼠慢性肩袖損傷模型從組織形態(tài)學(xué)、生物力學(xué)評(píng)估b FGF-PLGA誘導(dǎo)組織再生的能力。2.利用CPS生物陶瓷加強(qiáng)修復(fù)大鼠的慢性肩袖損傷,從影像學(xué)、組織形態(tài)學(xué)和生物力學(xué)評(píng)估術(shù)后腱-骨界面骨礦含量的變化、組織再生的程度以及生物力學(xué)強(qiáng)度。3.利用雙電紡技術(shù),將CS納米纖維與PCL微纖維結(jié)合,制備具有仿生結(jié)構(gòu)的混合纖維支架PCL-CS(圖1),觀察材料表征及體外培養(yǎng)時(shí)細(xì)胞親和力,并利用大鼠慢性肩袖損傷模型從影像學(xué)、組織形態(tài)學(xué)、生物力學(xué)評(píng)估評(píng)估PCL-CS誘導(dǎo)促進(jìn)腱-骨止點(diǎn)多層結(jié)構(gòu)重建的能力。結(jié)果1.b FGF-PLGA組成纖維細(xì)胞培養(yǎng)5天后與1天后或3天后的增殖差異有統(tǒng)計(jì)學(xué)意義(p0.05)。使用兩種PLGA纖維支架加強(qiáng)修補(bǔ)的實(shí)驗(yàn)組在術(shù)后的各個(gè)時(shí)間點(diǎn)的纖維軟骨量和膠原排布都優(yōu)于對(duì)照組,而且b FGF-PLGA組在各個(gè)時(shí)間點(diǎn)的膠原排列較單純PLGA組有顯著改善(P0.05)。局部使用兩種PLGA纖維支架在術(shù)后第4周顯著提高了肩袖的極限負(fù)荷以及剛度,而在術(shù)后第8周,b FGF-PLGA組在腱-骨止點(diǎn)處的機(jī)械強(qiáng)度較單純PLGA組也有顯著增加(P0.05)。2.在各時(shí)間點(diǎn)CPS和羥基磷灰石(HA)組的骨密度(BMD)、組織骨密度(TMD)以及骨體積分?jǐn)?shù)(BV/TV)均顯著高于對(duì)照組。而且,CPS組的BMD、TMD和BV/TV在各時(shí)間點(diǎn)也都顯著高于HA組。CPS生物陶瓷具有良好的降解能力和組織相容性。實(shí)驗(yàn)組腱-骨界面植入生物陶瓷材料在術(shù)后的各個(gè)時(shí)間點(diǎn)的纖維軟骨面積和膠原結(jié)構(gòu)都優(yōu)于對(duì)照組,而且CPS組在各個(gè)時(shí)間點(diǎn)的新生纖維軟骨面積也顯著高于HA(P0.05)組。從生物力學(xué)檢測(cè)結(jié)果來看,在植入材料術(shù)后4周時(shí),兩個(gè)實(shí)驗(yàn)組的極限負(fù)荷和剛度均優(yōu)于對(duì)照組。此外,在術(shù)后第8周,CPS組在腱-骨止點(diǎn)處的機(jī)械強(qiáng)度顯著高于HA組(P0.05)。3.細(xì)胞在PCL-CS支架表面培養(yǎng)3天和7天后與1天后相比增殖差異有統(tǒng)計(jì)學(xué)意義(P0.05)。在各時(shí)間點(diǎn),PCL-CS組的BMD、TMD和BV/TV值均顯著高于PCL組和對(duì)照組(P0.05),而PCL組和對(duì)照組間的BMD、TMD和BV/TV均無顯著差異。使用PCL纖維支架加強(qiáng)修補(bǔ)的實(shí)驗(yàn)組在術(shù)后的各個(gè)時(shí)間點(diǎn)的纖維軟骨量和膠原排布都優(yōu)于對(duì)照組,而且PCL-CS組在各個(gè)時(shí)間點(diǎn)的番紅異染面積均有顯著優(yōu)勢(shì)(P0.05)。PCL纖維支架在術(shù)后第4周使肩袖的極限負(fù)荷以及剛度均有所增加,在術(shù)后第8周PCL-CS組腱-骨止點(diǎn)復(fù)合體的機(jī)械性能顯著增加P0.05)。結(jié)論1.PLGA芯-殼纖維結(jié)構(gòu)對(duì)b FGF的活性提供了很好的保護(hù)。b FGF-PLGA電紡纖維支架對(duì)成纖維細(xì)胞的增殖有促進(jìn)作用。在大鼠的慢性肩袖損傷模型中,與單純修復(fù)相比,在腱-骨止點(diǎn)處應(yīng)用b FGF-PLGA可以提高腱-骨止點(diǎn)的力學(xué)強(qiáng)度,促進(jìn)纖維軟骨的再生和膠原的成熟。2.在大鼠的慢性肩袖損傷修補(bǔ)術(shù)中,在腱-骨界面植入CPS生物活性陶瓷可以增加界面骨礦含量,促進(jìn)纖維軟骨的再生和膠原的成熟,提高腱-骨止點(diǎn)的力學(xué)強(qiáng)度。3.CS納米纖維與PCL微纖維結(jié)合可改善支架的細(xì)胞親和力,促進(jìn)細(xì)胞的粘附、增殖。在大鼠腱-骨止點(diǎn)處應(yīng)用PCL-CS電紡混合纖維支架可以促進(jìn)新骨形成,提高腱-骨止點(diǎn)的力學(xué)強(qiáng)度,促進(jìn)纖維軟骨的再生和膠原的成熟。
[Abstract]:The rotator cuff injury is one of the most common injuries in the elderly, can cause shoulder pain, instability, decreased muscle strength and activity disorder. Although the surgical techniques and rotator cuff repair failure rate reached 20%~90%. osteoporosis, rotator cuff degeneration, muscle atrophy and defect serious factors such as weakening the ability to repair itself the site of injury, and ultimately affect the repair effect. The change of rotator cuff tendon bone insertion reaction of scar healing after injury, promote tendon bone reconstruction for natural multilayer structure is the key to improve the rotator cuff healing. The use of tissue engineering scaffolds to improve patients with endogenous regeneration potential in order to improve the rotator cuff repair the effect is the focus of research at home and abroad. The 1. objective assessment of poly lactic acid glycolic acid (PLGA) electrospun fiber scaffolds loaded with basic fibroblast growth factor (B FGF) induced rotator cuff tendon bone insertion tissue The capacity of 2.; evaluation of silicon calcium phosphate (CPS) bioactive ceramic change of tendon bone interface bone tendon bone mineral content, induced by the ability to stop the regeneration point of cartilage; 3. built with bionic structure Polycaprolacton chitosan (PCL-CS) hybrid scaffolds, to evaluate the activity of stent induced tendon bone insertion multilayer structure reconstruction and promote the ability of rotator cuff healing. PLGA fiber scaffolds 1. by emulsion electrospinning preparation with core structure and method of load B FGF, observe the material characterization and release of FGF B, B FGF-PLGA cells cultured in vitro by affinity cells, and the use of chronic rotator cuff injury rats from histomorphology biomechanical evaluation of B, FGF-PLGA induced tissue regeneration ability of.2. using CPS bioceramic enhancing chronic rotator cuff repair from rats, imaging, histological changes and biomechanical evaluation of postoperative tendon bone interface bone mineral content, The degree of tissue regeneration and biomechanical strength of.3. using electric double spinning technology, combining the CS and PCL micro nano fiber fiber, preparation of hybrid scaffolds of PCL-CS bionic structure (Figure 1), to observe the training materials characterization and in vitro cell affinity, and the use of chronic rotator cuff injury model of rats from imaging, tissue morphology biomechanical evaluation, PCL-CS induced ability to promote tendon bone insertion of multilayer structure reconstruction. Results the difference was statistically significant proliferation 5 days later and 1 days or 3 days after the culture of 1.b FGF-PLGA fibroblasts (P0.05). Using two PLGA fiber scaffolds to strengthen the repair of experimental group at each time point after operation of the fibrous cartilage the amount and arrangement of collagen were better than the control group, B and FGF-PLGA were significantly improved at each time point of the collagen than PLGA group (P0.05). The local use of two types of PLGA fiber scaffolds after fourth Week to significantly improve the ultimate load and the rigidity of the rotator cuff, and eighth weeks after operation, B group FGF-PLGA in the mechanical strength of tendon bone insertion compared to simple PLGA group were increased significantly (P0.05).2. at each time point CPS and hydroxyapatite (HA) bone density group (BMD), organization bone mineral density (TMD) and bone volume fraction (BV/TV) were significantly higher than the control group. Moreover, the CPS group of BMD, TMD and BV/TV at each time point were significantly higher than those in HA group.CPS bioceramic has good biodegradability and biocompatibility. Experimental group tendon bone interface implanted bioceramic materials in various time points after operation, the area of cartilage and collagen structure are better than the control group, and CPS group in the new area of cartilage at each time point was significantly higher than that in HA (P0.05) group. The biomechanical test results, in 4 weeks after implant surgery, two limit load and stiffness of the experimental group excellent In the control group. In addition, after eighth weeks, CPS group in the mechanical strength of the tendon bone insertion was higher than that in group HA (P0.05).3. cells were cultured in PCL-CS scaffolds for 3 days and 7 days compared with 1 days of proliferation was statistically significant (P0.05). At each time point, PCL-CS group BMD, TMD and BV/TV were significantly higher than that of PCL group and control group (P0.05), and between PCL group and control group BMD, there were no significant differences between TMD and BV/TV. Using PCL fiber scaffolds to strengthen the repair of experimental group at each time point after operation, the amount of cartilage and collagen fiber arrangement are better than those of the control group and PCL-CS group at each time point of the safranin metachromatic area has significant advantage (P0.05) increased.PCL fiber scaffolds after fourth weeks the limit load of the rotator cuff and stiffness were significantly increased in P0.05 mechanical properties after eighth weeks in the PCL-CS group of tendon bone insertion complex). Conclusion 1.PLGA core shell fiber node The B activity of FGF provides good protection of.B FGF-PLGA electrospun fibrous scaffold has a promoting effect on the proliferation of fibroblasts. In chronic rotator cuff injury model in rats, compared with the simple repair, the tendon bone insertion point of the application of B FGF-PLGA can improve tendon bone insertion of Li Xueqiang and promote cartilage regeneration and collagen maturation of.2. in chronic rotator cuff injury repair in rats at the tendon bone interface with CPS bioactive ceramics can increase bone mineral content of the interface, promote cartilage regeneration and collagen maturation, improve the combination of support can improve the cell affinity of tendon bone insertion Li Xueqiang of.3.CS nanofiber and PCL micro fiber, promote cell adhesion, proliferation in rat tendon bone insertion application of electrospun PCL-CS hybrid scaffolds can promote new bone formation, improve the mechanical strength of the tendon bone insertion, promote the regeneration of cartilage And the maturation of collagen.

【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R687;R318.08

【共引文獻(xiàn)】

相關(guān)期刊論文 前10條

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2 王琳;;運(yùn)動(dòng)相關(guān)骨腱結(jié)合部損傷動(dòng)物模型研究進(jìn)展[J];北京體育大學(xué)學(xué)報(bào);2014年07期

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4 王立曼;王妍;段翠密;王海濱;王常勇;;兩種肝臟全器官脫細(xì)胞基質(zhì)制備方法的比較[J];解放軍醫(yī)學(xué)雜志;2014年04期

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10 高曉嶙;白云飛;王若晗;張曉蘭;;肱二頭肌長(zhǎng)頭肌腱過度使用中相關(guān)生長(zhǎng)因子蛋白表達(dá)規(guī)律的研究[J];體育科學(xué);2014年09期

相關(guān)博士學(xué)位論文 前10條

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7 蔣勵(lì);食蟹猴模型中sC-MSCs定向分化修復(fù)軟骨缺損的實(shí)驗(yàn)研究[D];復(fù)旦大學(xué);2012年

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10 應(yīng)志敏;PDGF-bb聯(lián)合BMP-2生長(zhǎng)因子對(duì)骨膜來源干細(xì)胞在二維培養(yǎng)和可注射水凝膠Gelatin-Hpa中增殖及成骨分化能力的影響研究[D];浙江大學(xué);2015年

相關(guān)碩士學(xué)位論文 前10條

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2 郁賢舜;富血小板血漿凝膠對(duì)前交叉韌帶重建術(shù)后腱—骨界面愈合影響的形態(tài)學(xué)觀察[D];安徽醫(yī)科大學(xué);2013年

3 劉俊;血小板衍化生長(zhǎng)因子對(duì)兔膝前交叉韌帶重建術(shù)后早期腱骨愈合影響的實(shí)驗(yàn)研究[D];南華大學(xué);2013年

4 周勝濤;自制肌腱骨吻合裝置修復(fù)肌腱末端損傷的動(dòng)物實(shí)驗(yàn)研究[D];南華大學(xué);2013年

5 周鑫;脫細(xì)胞豬角膜基質(zhì)載體支架的制備及其與人角膜基質(zhì)細(xì)胞的生物相容性研究[D];中國(guó)海洋大學(xué);2013年

6 李萬里;去細(xì)胞犬喉支架的體內(nèi)埋植實(shí)驗(yàn)[D];第四軍醫(yī)大學(xué);2013年

7 陳奇;肩袖岡上肌骨—肌腱結(jié)合部損傷愈合模型的實(shí)驗(yàn)研究[D];第二軍醫(yī)大學(xué);2013年

8 曾子騰;MLRS、SRμCT對(duì)骨腱連接點(diǎn)結(jié)構(gòu)的評(píng)估及LIPUS對(duì)其愈合的影響[D];中南大學(xué);2013年

9 李紹群;磺酸化絲素蛋白/羥基磷灰石多孔支架的制備及評(píng)價(jià)[D];江蘇科技大學(xué);2013年

10 崔亮;雙層骨—臏腱—骨重建前交叉韌帶術(shù)后的兩種康復(fù)方案下移植物組織學(xué)及生物力學(xué)的相關(guān)研究[D];河北醫(yī)科大學(xué);2014年

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