本文關鍵詞： 聚乙烯醇 卡拉膠 生物活性 定向支架 組織工程　出處：《天津大學》2016年博士論文　論文類型：學位論文

【摘要】：組織工程支架的設計應該按照仿生原理,最大限度地模擬目標組織或器官的細胞外基質(zhì)的組成、結(jié)構和功能,以達到修復創(chuàng)傷和重建功能的目的。天然關節(jié)軟骨組織具有獨特的結(jié)構,這與其功能性密切相關,本文結(jié)合組織仿生學理論,優(yōu)化材料組成和性能,并對支架進行仿生設計和研究。具體研究內(nèi)容如下:1.聚乙烯醇(PVA)水凝膠具有與天然關節(jié)軟骨類似多孔結(jié)構和力學性能,適合于關節(jié)軟骨修復的研究。但純PVA水凝膠不僅缺乏細胞粘附性,而且成型過程中容易出現(xiàn)形貌皺縮的現(xiàn)象,嚴重限制了其在組織工程領域中的應用。本文通過加入天然多糖卡拉膠(CAR)組分,利用冰凍-融化循環(huán)技術得到了PVA與CAR的復合水凝膠(CP),結(jié)果表明所制得的CP水凝膠在冷凍干燥過程中具有抗皺縮性能,表現(xiàn)出良好的結(jié)構穩(wěn)定性。同時,由于CAR組分對PVA結(jié)晶性產(chǎn)生影響,得到的復合材料內(nèi)部結(jié)構相對疏松,明顯提高了CP凝膠材料的孔徑;2.對CP復合材料進行生物學評價,體外細胞實驗結(jié)果表明CAR的加入可以顯著提高PVA水凝膠的生物活性,促進細胞在材料上的粘附和增殖,并且能夠維持細胞的良好表型;通過體外溶血實驗以及巨噬細胞激活實驗表明,CP復合材料不會引起溶血,保持很低的巨噬細胞激活率,具有潛在的體內(nèi)應用前景。3.利用定向冰凍-融化循環(huán)技術,得到具有取向結(jié)構的PVA-CAR定向支架,仿生了天然軟骨的組織結(jié)構,具有優(yōu)異的理化性能。體外細胞實驗表明,定向支架相對非定向支架,更有利于細胞的遷移和增殖,有效地提高了細胞在支架內(nèi)部的均勻分布,保證支架結(jié)構的均勻穩(wěn)定。同時,體內(nèi)組織相容性實驗結(jié)果表明支架的取向結(jié)構賦予其良好的滲透性,能夠引導宿主細胞的長入和增殖,為新生組織提供適宜的生存環(huán)境,促進組織與支架之間的相互作用;4.以PVA和CAR為基體,添加無機組分羥基磷灰石(HA),制備了HA-CP復合支架材料,在優(yōu)選支架材料理化性能基礎上對其進行生物學性能評價,結(jié)果表明HA-CP支架表現(xiàn)出良好的細胞與組織相容性;在此基礎上,采用滲透與定向冰凍-融化循環(huán)相結(jié)合的技術,得到OCP/HA-CP雙層復合支架材料,其上層具有取向結(jié)構用于構架軟骨層,下層為多孔結(jié)構用于構建骨層,模擬了關節(jié)軟骨與軟骨下骨的特點。提高滲透時間可以提高雙層支架的界面結(jié)合強度,有效地防止上下層的分離,有希望解決以往因存在明顯的界面而導致軟骨與軟骨下骨難以結(jié)合的問題。
[Abstract]:Tissue engineering scaffolds should be designed to maximize the composition, structure and function of the extracellular matrix of the target tissue or organ in accordance with the bionic principle. Natural articular cartilage has a unique structure, which is closely related to its function. In this paper, the material composition and properties are optimized based on tissue bionics theory. And the biomimetic design and study of the scaffold. The specific research contents are as follows: 1. Polyvinyl alcohol PVA) hydrogel has similar porous structure and mechanical properties to natural articular cartilage. It is suitable for the repair of articular cartilage, but the pure PVA hydrogel is not only lack of cell adhesion, but also prone to the appearance of shrinkage during the molding process. The application of Carrageenan in tissue engineering was severely restricted. In this paper, the natural polysaccharide carrageenan carrageenan (Carrageenan) component was added. The composite hydrogels of PVA and CAR were obtained by freezing and melting cycle technique. The results show that the prepared hydrogels have anti-shrinkage property during freeze-drying process. At the same time, due to the effect of CAR composition on the crystallinity of PVA, the internal structure of the composite is relatively loose, which obviously improves the pore size of CP gel material. 2. The biological evaluation of CP composite material in vitro showed that the addition of CAR could significantly improve the biological activity of PVA hydrogel and promote cell adhesion and proliferation on the material. And can maintain the good phenotype of cells; In vitro hemolysis test and macrophage activation test showed that CP composite did not cause hemolysis and maintained a very low rate of macrophage activation. The PVA-CAR scaffold with oriented structure was obtained by using the technique of directional freeze-thawing cycle, and the tissue structure of natural cartilage was simulated. 3. In vitro cell experiments show that the directional scaffold is more conducive to cell migration and proliferation than the non-directional scaffold and can effectively improve the uniform distribution of cells in the scaffold. At the same time, the results of in vivo histocompatibility experiment showed that the oriented structure of the scaffold has good permeability and can guide the growth and proliferation of host cells. To provide suitable living environment for newborn tissue and promote the interaction between tissue and scaffold. 4. HA-CP composite scaffolds were prepared by adding hydroxyapatite as inorganic component and PVA and CAR as matrix. The biological properties of HA-CP scaffolds were evaluated on the basis of physicochemical properties. The results showed that HA-CP scaffolds showed good cell and histocompatibility. On this basis, the OCP/HA-CP bilayer composite scaffold material was obtained by using the technique of osmosis and directional freeze-melting cycle. The upper layer of the composite scaffold has a oriented structure for the framework cartilage layer. The lower layer is a porous structure to construct the bone layer, which simulates the characteristics of articular cartilage and subchondral bone. Increasing the osmotic time can improve the interface bonding strength of the double-layer scaffold and effectively prevent the separation of the upper and lower layers. It is hopeful to solve the problem that cartilage and subchondral bone are difficult to combine because of obvious interface.
【學位授予單位】：天津大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R318.08

【相似文獻】

相關期刊論文 前10條

1 周棟,黃維坤,高百順;組織工程心臟瓣膜支架材料的應用進展[J];中國臨床康復;2002年18期

2 孫紅;真皮支架材料的研究進展[J];中國美容醫(yī)學;2004年01期

3 崔福齋,孟波,張金山;介入治療中支架材料的研究進展[J];中國介入影像與治療學;2004年01期

4 吳燕,成國祥;可注射可吸收凝膠支架材料的研究進展[J];生物醫(yī)學工程學雜志;2005年01期

5 丁敏;;廈大研制出可將組織器官“種”在體外的醫(yī)用支架材料[J];功能材料信息;2006年04期

6 陳思;董念國;史嘉瑋;;組織工程心臟瓣膜支架材料進展[J];心血管病學進展;2008年06期

7 王雪力;侯理;譚競;湯克勤;夏和生;劉霆;;生物相容性聚氨酯支架材料的研究[J];高分子材料科學與工程;2008年02期

8 鄒明暉;董念國;;組織工程心臟瓣膜支架材料的研究與進展[J];中國組織工程研究與臨床康復;2010年29期

9 哈里木·克里木;王磊;齊海;;組織工程心臟瓣膜支架材料的選擇與應用[J];中國組織工程研究與臨床康復;2011年34期

10 郭各樸;馬青玉;王f ;趙波;章東;;聚乳酸微孔支架材料熱分解動力學特性[J];科學通報;2011年34期

相關會議論文 前10條

1 張亞;王曉東;;細胞復合型絲素支架材料修復兔橈骨骨缺損[A];蘇州市自然科學優(yōu)秀學術論文匯編(2008-2009)[C];2010年

2 楊光輝;王英杰;張世昌;劉濤;;聚氨酯支架材料內(nèi)肝細胞培養(yǎng)的初步研究[A];第一屆全國疑難重型肝病大會、第四屆全國人工肝及血液凈化學術年會論文集[C];2008年

3 趙斌;馬信龍;孫曉雷;李秀蘭;馬劍雄;徐康;張楊;郭躍;;低滲聯(lián)合凍干改良制備脫細胞神經(jīng)支架材料的研究[A];第十九屆全國中西醫(yī)結(jié)合骨傷科學術研討會論文匯編[C];2012年

4 儕y，

本文編號：1468949