發(fā)布時間：2018-07-06 19:10

  本文選題：靜電紡絲 + 聚氨酯�。� 參考：《天津大學》2012年博士論文

【摘要】：隨著組織工程發(fā)展，通過靜電紡絲技術構建既具有生物相容性又有合適機械性能的小口徑血管成為研究熱點。本論文通過共混和復合靜電紡絲技術構建了聚氨酯(PU)基的具有良好生物相容性的小口徑血管支架。其研究成果概括如下： 1.通過共混的方式將親水性的聚乙二醇(PEG)引入PU纖維支架內部，，混合PU/PEG纖維支架的纖維直徑隨著PEG的加入降低，孔隙率增大；支架表面的親水性隨著PEG含量的增加而顯著增加。PEG結晶導致混合纖維支架的力學強度提高；通過血小板黏附實驗和溶血率結果證明，混合PU/PEG纖維支架比空白PU支架具有更好的血液相容性。臍靜脈內皮細胞(HUVECs)黏附實驗表明，當PEG含量為20%和30%時，最利于細胞的黏附和增殖。 2.通過乳液電紡技術將抗凝血的肝素鈉引入電紡PU/PEG纖維支架中，結果表明肝素鈉在體內最初24小時呈現(xiàn)突釋的現(xiàn)象，緊接著是一個穩(wěn)定的釋放期，隨著藥物含量的增加，藥物釋放量減少，其釋放符合Fickian擴散釋放機理。血小板黏附實驗和溶血率實驗結果表明，肝素鈉的加入可以明顯提高支架表面長時間血液接觸的抗凝血性能。肝素鈉能夠支持HUVECs在纖維支架上更好的黏附與生長，同時抑制小鼠的平滑肌細胞(VCMCs)生長及增殖。 3.通過原位光聚合靜電紡絲技術將聚乙二醇單丙烯酸酯(PEGMA)交聯(lián)固定在PU纖維支架上，當PU/PEGMA的質量比為90/10和80/20時，纖維的平均直徑分別為622±110nm和547±77nm，較少的PEGMA的加入就能顯著提高混合支架的力學強度，同時纖維的形貌能夠得到較好保持�；旌侠w維支架的親水性可以通過改變PU/PEGMA的比率進行調節(jié)，合適的親水性表面（接觸角在55-75o）能夠支持HUVECs更好的生長及增殖。 4.采用分層復合靜電紡絲技術構建了PU/明膠-肝素鈉復合小口徑血管，復合管狀支架內層為負載肝素鈉的明膠納米纖維組成，內層纖維支架的孔隙率可以達到70%,明膠內層通過戊二醛蒸汽交聯(lián)，可以使支架的質量損失率大大降低，保證支架在應用時的性能的穩(wěn)定。PU外層由平均直徑784±312nm的纖維組成，平均孔徑為1.6μm。力學性能測試證明彈性PU外層能夠提高支架的柔韌性同時降低明膠基內層的剛性。明膠基的納米纖維支架能夠支持HUVECs的黏附與增殖，血小板黏附實驗和溶血實驗證明支架具有很好的血液相容性。
[Abstract]:With the development of tissue engineering, it has become a research focus to construct small diameter vessels with biocompatibility and suitable mechanical properties by electrostatic spinning technology. In this paper, polyurethane (pu) based small diameter vascular stent with good biocompatibility was constructed by blending and composite electrospinning technology. The research results are summarized as follows: 1. The hydrophilic polyethylene glycol (PEG) was introduced into the pu fiber scaffold by blending. The fiber diameter of the mixed pu / PEG fiber scaffold decreased with the addition of PEG and the porosity increased. The hydrophilicity of the scaffold surface increased significantly with the increase of PEG content. The mechanical strength of the scaffold increased with the increase of PEG content, and the results of platelet adhesion test and hemolysis rate showed that the hydrophilicity of the scaffold increased with the increase of PEG content. The mixed pu / PEG fiber scaffold has better blood compatibility than the blank pu scaffold. Umbilical vein endothelial cells (HUVECs) adhesion assay showed that when PEG content was 20% and 30%, the adhesion and proliferation of HUVECs were the best. 2. The anticoagulant sodium heparin was introduced into the electrospun PUP / PEG fiber scaffold by emulsion electrospinning technology. The results showed that heparin sodium showed sudden release in the first 24 hours of the body, followed by a stable release period, with the increase of drug content. The drug release was reduced, and the release was consistent with the Fickian diffusion release mechanism. The results of platelet adhesion test and hemolysis rate test showed that heparin sodium could significantly improve the anticoagulant performance of long-term blood contact on the stent surface. Heparin sodium can support better adhesion and growth of HUVECs on fiber scaffolds and inhibit the growth and proliferation of mouse smooth muscle cells (VCMCs). Polyethylene glycol monoacrylate (PEGMA) was crosslinked and fixed on pu fiber scaffold by in situ photopolymerization electrospinning. When the mass ratio of pu / PEGMA was 90 / 10 and 80 / 20, The average diameters of the fibers were 622 鹵110nm and 547 鹵77nmrespectively. The mechanical strength of the mixed scaffolds could be significantly improved by adding less PEGMA, and the morphology of the fibers could be maintained. The hydrophilicity of mixed fiber scaffold can be adjusted by changing the ratio of PU- / PEGMA. The suitable hydrophilic surface (contact angle is 55-75o) can support the better growth and proliferation of HUVECs. The small diameter blood vessels of PU- / gelatin-heparin sodium composite were constructed by stratified composite electrostatic spinning technique. The inner layer of the composite stent was composed of gelatin nanofibers loaded with heparin sodium. The porosity of the inner fiber scaffold can reach 70%, the gelatin inner layer can be crosslinked by glutaraldehyde steam, the mass loss rate of the scaffold can be greatly reduced, and the stability of the performance of the scaffold can be ensured. The outer layer of pu is composed of fibers with an average diameter of 784 鹵312nm. The average pore size is 1.6 渭 m. The mechanical properties test showed that the elastic pu outer layer could improve the flexibility of the scaffold and reduce the rigidity of the inner layer of gelatin base. Gelatin based nanofiber scaffolds can support the adhesion and proliferation of HUVECs. Platelet adhesion and hemolysis experiments show that the scaffolds have good blood compatibility.
【學位授予單位】：天津大學
【學位級別】：博士
【學位授予年份】：2012
【分類號】：R318.08

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本文編號：2103818