北京生物醫(yī)學(xué)工程

３Ｄ打印多孔 β－ＴＣＰ負(fù)載ＶＡＮ／ＰＬＧＡ緩釋微球復(fù)合支架的表征評(píng)價(jià)

Characterization and evaluation of 3D printed porous β-TCP scaffolds loaded with VAN/PLGA microsphere scaffold

作者：王建范江偉陳洪濤

單位：新疆醫(yī)科大學(xué)第六附屬醫(yī)院創(chuàng)傷骨科（烏魯木齊 830092）<br />通信作者：陳洪濤。E-mail：[email protected]

關(guān)鍵詞： 3D打印；β-磷酸三鈣；VAN/PLGA緩釋微球；復(fù)合支架；表征評(píng)價(jià)

分類號(hào)：R318.08 

出版年·卷·期（頁(yè)碼）：2022·41·5（471-476）

摘要：

目的通過(guò)對(duì)多孔β-磷酸三鈣（tricalcium phosphate，TCP）負(fù)載萬(wàn)古霉素/聚乳酸-羥基乙酸（vancomycin/poly lactic co glycolic acid， VAN/PLGA）緩釋微球復(fù)合支架進(jìn)行表征評(píng)價(jià)，初步判斷其能否能作為修復(fù)骨缺損的材料。方法利用CAD軟件繪制多孔β-TCP支架，由3D打印機(jī)打印制作，再經(jīng)馬弗爐干燥制成β-TCP骨組織支架。采用W/O/W法制備VAN/PLGA緩釋微球，將β-TCP骨支架與VAN/PLGA微球懸液震蕩混勻，使微球吸附到支架的微孔內(nèi)，離心凍干后即得β-TCP負(fù)載VAN/PLGA緩釋微球復(fù)合支架。從支架外觀形態(tài)、孔隙率、藥物緩釋率、力學(xué)性能和體外降解實(shí)驗(yàn)等多方面進(jìn)行表征評(píng)價(jià)。結(jié)果β-TCP負(fù)載VAN/PLGA緩釋微球復(fù)合支架呈白色立方體狀，表面附著有一層大小均勻的圓形顆粒，在光鏡下能清楚地看到內(nèi)部結(jié)構(gòu)；通過(guò)液體置換法測(cè)量得β-TCP負(fù)載VAN/PLGA復(fù)合支架的平均孔隙率為（59.21±1.55）%，小于3D打印β-TCP空白支架的65.27±2.37（t=2.552，P=0.032）；根據(jù)VAN 標(biāo)準(zhǔn)曲線測(cè)得VAN/PLGA微球?qū)AN的藥物負(fù)載率為（17.42±1.85）%，包封率為（35.13±3.59）%；體外藥物釋放實(shí)驗(yàn)表明，β-TCP負(fù)載VAN/PLGA復(fù)合支架在24 d時(shí)釋放率可達(dá)50%，還可以進(jìn)一步釋放，在體內(nèi)能保持長(zhǎng)時(shí)間的抑菌抗感染效果；力學(xué)性能結(jié)果顯示，復(fù)合支架最大負(fù)荷為（174.50±7.80）N，最大強(qiáng)度為（4.83±0.25）MPa；體外降解實(shí)驗(yàn)說(shuō)明，與β-TCP空白支架相比，負(fù)載VAN/PLGA的復(fù)合β-TCP支架在體內(nèi)降解時(shí)間更長(zhǎng)，在20 W時(shí)才能降解完全，對(duì)骨缺損能起到長(zhǎng)久的修復(fù)作用。結(jié)論3D打印多孔β-TCP負(fù)載VAN/PLGA緩釋微球復(fù)合支架具有良好的緩釋性能、力學(xué)性能和抗感染修復(fù)功能，可作為修復(fù)骨缺損的優(yōu)良材料。

Objective Through the characterization evaluation of porous β-（tricalcium phosphate）TCP loaded vancomycin/poly lactic co glycolic acid （VAN/PLGA） sustained-release microspheres composite scaffold designed and manufactured, it is preliminatively determined whether it can be used as a material for repairing bone defects. Methods The porous β-TCP scaffold was drawn by CAD software, printed by 3D printer, and then dried in muff furnace to form β-TCP bone tissue scaffold. VAN/PLGA sustained-release microspheres were prepared by W/O/W method. The β-TCP bone scaffold and VAN/PLGA microspheres suspension were mixed by shaking, and the microspheres were adsorbed into the micropores of the scaffold. After centrifugation and lyophilization, the β-TCP loaded VAN/PLGA sustained-release microspheres composite scaffold was obtained. The scaffolds were characterized by morphology, porosity, sustained drug release rate, mechanical properties and in vitro degradation experiments. Results β-TCP loaded VAN/PLGA sustained-release microspheres composite scaffold was white cube shape, with a layer of uniform size of circular particles attached to the surface, and the internal structure could be clearly seen under the light microscope. The average porosity of β-TCP loaded VAN/PLGA composite scaffold measured by liquid replacement method was （59.21±1.55）%, which was smaller than 65.27±2.37 (t=2.552, P=0.032) of β-TCP blank scaffold. According to VAN standard curve, VAN loading rate and encapsulation rate of VAN/PLGA microspheres were (17.42±1.85) % and (35.13±3.59) % respectively. In vitro drug release experiments showed that the release rate of β-TCP loaded VAN/ PLGA composite scaffold could reach 50% after 24 days, and it could be further released, which could maintain the antibacterial and anti infective effect for a long time. The mechanical performance results show that the maximum load of the composite bracket was (174.50±7.80)N, and the maximum strength was (4.83±0.25)MPa. In vitro degradation experiment showed that compared with β-TCP blank scaffold, the degradation time of compound β-TCP scaffold loaded with VAN/PLGA was longer in vivo, and the degradation was complete at 20W, which could play a long-term role in the repair of bone defects. Conclusions The 3D printed porous β-TCP loaded VAN/PLGA sustained-release microsphere composite scaffold has good sustained-release performance, mechanical properties and anti-infective repair function, which can be used as an excellent material to repair bone defects.

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