本文選題：支架 + 納米纖維��； 參考：《華南理工大學(xué)》2014年博士論文

【摘要】：組織工程（Tissue engineering，TE）的研究旨在構(gòu)建具有生物活性和功能的人工組織/器官以替代體內(nèi)受損、病變或老化的組織/器官。模擬目標(biāo)組織/器官細(xì)胞外基質(zhì)（Extracelluar matrix，ECM）結(jié)構(gòu)的仿生支架在TE研究中起著非常關(guān)鍵的作用。人體周圍神經(jīng)（Peripheral nerve system，PNS）、肌腱等組織的ECM呈縱向排列多通道（Multiple-channeled，MC）結(jié)構(gòu)，通道壁由沿軸向取向的膠原納米纖維（Nanofiber，NF）組成。一直以來(lái)，，制備具有上述結(jié)構(gòu)特征的TE支架面臨諸多困難和挑戰(zhàn)。 為解決該難題，本課題制備了一種由玻璃管、針及間隔物組成的、用來(lái)制備MC支架的模具。利用該模具，本研究將熱致相分離（Thermally-induced phase separation，TIPS）技術(shù)和注射模塑技術(shù)相結(jié)合，制備了聚左旋乳酸（Poly（L-lactic acid），PLLA）MC NF支架。通過(guò)改變模具組件的組合方式、尺寸大小和/或PLLA濃度可以控制支架宏觀（mm及以上）、亞微觀（μm）和微觀（nm）尺度的形貌結(jié)構(gòu)。改變PLLA濃度還能調(diào)控支架的力學(xué)性能。該支架有效解決了當(dāng)前非NF MC支架結(jié)構(gòu)方面存在的壁厚過(guò)大、壁孔結(jié)構(gòu)不合理及力學(xué)性能差等缺陷。 本課題還設(shè)計(jì)了一套以冰水為冷卻介質(zhì)的低溫拉伸裝置，利用該裝置可對(duì)PLLA/四氫呋喃物理凝膠進(jìn)行拉伸，制備取向NF（Aligned-nanofiber，ANF）支架。研究發(fā)現(xiàn)，PLLA ANF支架的取向度、機(jī)械性能隨凝膠拉伸倍率的提高而提高，而NF的形貌結(jié)構(gòu)、熱學(xué)性能幾乎不受影響。該工藝的機(jī)理為凝膠拉伸導(dǎo)致其內(nèi)部聚合物富相（Polymer-rich phase，PR）微區(qū)沿外力方向發(fā)生不可逆滑移，形變的PR微區(qū)在后續(xù)工序中被固定并轉(zhuǎn)變?yōu)锳NF。該工藝解決了TIPS技術(shù)不能控制NF定向排列的不足，為制備MC ANF支架提供了可能性。 本課題考察了上述仿生支架的形貌結(jié)構(gòu)對(duì)蛋白吸附、細(xì)胞黏附、形態(tài)及功能的影響，結(jié)果發(fā)現(xiàn)PLLA MC NF支架能大量且均勻地吸附蛋白質(zhì)，有效促進(jìn)細(xì)胞黏附，為細(xì)胞提供更好的生長(zhǎng)微環(huán)境，PLLA ANF支架可使黏附的細(xì)胞沿著纖維排列方向取向伸展和排列，具有一定的誘導(dǎo)和調(diào)控細(xì)胞行為及功能的能力。 本課題的研究結(jié)果表明所制備的PLLA仿生支架具有促進(jìn)PNS、肌腱等組織修復(fù)和再生的潛力，可應(yīng)用于這些組織的TE研究中。
[Abstract]:Tissue engineering study aims to construct artificial tissues / organs with biological activity and function to replace damaged, diseased or aging tissues / organs in vivo. Biomimetic scaffolds simulating extracellular matrix ECM (ECM) structure of target tissue / organ play a key role in te research. The nerve of peripheral nerve, tendon and other tissues of human peripheral nerve are arranged longitudinally in Multiple-channel (MC) structure, and the channel wall is composed of collagen nanofilament (Nanofiberus NFS) which is oriented along the axis. The preparation of te scaffolds with these structural characteristics has been facing many difficulties and challenges. In order to solve this problem, a mold composed of glass tube, needle and spacer was prepared to fabricate MC scaffold. Using the mould, the thermo-induced phase separation (TIPS) technology and the injection molding technology were used to prepare poly (L-lactic acidactic) PLLAMC NF scaffolds. By changing the combination mode of die assembly, size and / or PLLA concentration, the shape and structure of the support can be controlled on the scale of macroscopes and above, submicroscopic (渭 m) and microcosmic (渭 m). The mechanical properties of the scaffold can also be regulated by changing the concentration of PLLA. The structure of the non-NF MC scaffold has many defects, such as too large wall thickness, unreasonable wall hole structure and poor mechanical properties. A low temperature drawing device with ice water as cooling medium was also designed in this paper. PLLA / tetrahydrofuran physical gel could be stretched by this device and oriented NFA ligned-nanofiberine ANFS scaffold could be prepared. It was found that the orientation degree and mechanical properties of PLLA ANF scaffolds increased with the increase of gel tensile ratio, while the morphology and thermal properties of NF were almost unaffected. The mechanism of this process is that the internal polymer rich phase Polymer-rich phase PRA region is irreversibly slippage along the direction of external force, and the deformed PR microregion is fixed and converted to ANFin in the subsequent process. This process solves the problem that tips technology can not control NF directional arrangement and provides the possibility for the preparation of MC ANF scaffolds. The effects of the morphology and structure of the bionic scaffold on protein adsorption, cell adhesion, morphology and function were investigated. The results showed that PLLA MC NF scaffold could adsorb protein in a large amount and homogeneously, and promote cell adhesion effectively. The PLLA ANF scaffold provides a better growth microenvironment for the cells to extend and arrange along the fiber arrangement direction, and has the ability to induce and regulate the cell behavior and function to a certain extent. The results show that the PLLA biomimetic scaffolds have the potential to promote the repair and regeneration of tissues such as PNSs and tendons, and can be used in the te study of these tissues.
【學(xué)位授予單位】：華南理工大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R318.08

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本文編號(hào)：2015336