Micro-fabrication of Tissue Engineering Scaffolds by photon and self-organization

通过多学科的努力，用由活细胞和生物相容的图案化支架组合而成的人造组织来替换受损或患病的器官正在成为现实。与使用自组织的光或电子束光刻和自下而上的技术相比，双光子聚合作为制造微器件的工具的优点在于它的三维能力，它已经在特征尺寸接近衍射极限的光子器件和微型机械中得到应用。本文介绍了利用双光子聚合制备生物相容图案化表面的方法。新合成的具有生物相容性和光交联基的聚(2-甲氧基丙烯酸乙酯)^4共聚物，以及光引发剂：反式-4-(P-(N-乙基-N-hydroxylethylamino)styryl)-N-methylpyridium-tetraphenyl)硼酸酯，对钛宝石锁模激光(750-800 nm，80 MHz，100fs)的超短脉冲光束透明并允许其深度穿透。该聚合物可以通过双光子吸附进行光聚反应。图案完成后，未反应的聚合物用甲乙酮洗涤。研究了制备工艺参数对空间分辨率的影响。通过改变激光脉冲能量(激光功率)、曝光时间、聚合物类型、激发波长和扫描速度，可以将分辨率控制在亚μm到5-μm的范围内。这种生物相容的微图案化表面可以用于各种医疗设备，如植入物、生物传感器芯片和细胞支架。

The possibility to replace damaged or diseased organs with artificial tissues engineered from a combination of living cells and biocompatible patterned-scaffolds is becoming a reality through multidisciplinary efforts^1. Compared with light or electron beam lithography and bottom-up technologies using the self organization^2, the virtue of two-photon polymerization^3 as a tool for making microdevices lies in its three dimensional capability, which has found application in photonic devices and micromachines with feature sizes close to diffraction limit. The present studies describe the preparation of biocompatible patterned surfaces by two photon polymerization. Newly synthesized poly(2-methoxyethyl acrylate)^4 copolymers, which have biocompatibility and potocrosslinking moiety, as well as photo-initiators:trans-4-(P-(N-ethyl-N hydroxylethylamino)styryl)-N-methylpyridium-tetraphenyl borate, is transparent to an ultrashort-pulsed beam from a Ti:sapphire mode-locked laser (750-800nm, 8OMHz, 100fs) and allows it to penetrate deeply. The polymer can be poto-polymerized by using two-photon adsorption. After the pattern is completed, unreacted polymer is washed away with an metylethylketone. The fabrication parameters affecting the spatial resolution are investigated. The resolution can be controlled in the range from sub-μm to 5-μm by changing the laser-pulse energy (laser power), exposure time, polymer type, excitation wavelength, and scanning speeds. The biocompatible micro-patterned surfaces could be used for various medical devices, eg, implants, biosensor chip and cell-supported scaffolds.