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性模式支架结合而成的人工组织来替代受损或患病器官的可能性正在成为现实。与光刻或电子束光刻和自组织自底向上技术相比，双光子聚合技术作为一种制作微器件的工具，其优点在于其三维能力，在特征尺寸接近衍射极限的光子器件和微机械中得到了应用。本研究描述了用双光子聚合法制备生物相容性图案表面。新合成的聚（2-甲氧基乙基丙烯酸酯）^4共聚物具有生物相容性和光交联部分，以及光引发剂：反式4-（P-（n -乙基- n -羟乙胺）苯基）- n -甲基吡啶-四苯基硼酸盐，对来自Ti：蓝宝石锁模激光器（750-800nm, 8OMHz, 100fs）的超短脉冲光束是透明的，并允许其深入穿透。该聚合物可通过双光子吸附进行光聚合。图案完成后，未反应的聚合物用甲乙基酮冲洗掉。研究了制作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 ~ 5 μm之间。生物相容性微图案表面可用于各种医疗设备，如植入物、生物传感器芯片和细胞支撑支架。

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.