Laser Machining Surface Topographies for Stem Cell Control

最近的研究表明，干细胞分化，特别是干细胞向骨细胞的转化，可以通过在特定表面生长的干细胞来控制。使用这种结构有可能利用患者自己的干细胞在体内定向生成骨骼，从而更快地从骨折中恢复，降低髋关节植入物的失败率，并有可能治疗骨质疏松症和其他骨骼疾病。初步结果表明，通过光刻制造工艺在100纳米到微米大小的表面结构上取得了成功。然而，这一过程昂贵且耗时，因此，为了扩大到医学上可用的尺寸，必须开发新的制造工艺。飞秒脉冲激光加工提供了高速和精确制造微米级和更小的特征的潜力。然而，由于该工艺的敏感度很高，即使是很小的实验噪声水平也可能导致制造质量变差，从而无法将该工艺扩大到所需的尺寸。首先，利用机器学习的最新发展，特别是神经网络，开发一种精确和实时的激光加工过程监控系统，以便能够创造大面积、高精度的制造技术来加工合适的地形衬底。其次，推进干细胞在这些制成的基质上最佳生长和监测的工艺，以优化表面形貌的大小、特征和尺寸，从而准确控制干细胞的分化和增殖。

Recent work has shown that stem-cell differentiation, specifically the transformation of stem cells into bone cells, can be controlled by growing stem cells on specific surface topographies. The use of such topographies holds the potential for using a patient's own stem cells for targeted generation of bone within the body, leading to faster recovery from bone fractures, reduced failure rates for hip implants and potential therapies for Osteoporosis and other bone diseases.Preliminary results have shown success with surface topographies on the size scale of 100 nanometers to microns, patterned over millimeter sized areas via a lithographic fabrication process. However, this process is expensive and time-consuming and hence, to scale-up to medically useful dimensions, new fabrication processes must be developed.Femtosecond pulse laser machining offers the potential for high speed and precise fabrication of features that are on the micron-scale and smaller. However, due to the acute sensitivity of the process, even small levels of experimental noise can result in inferior fabrication quality, preventing the ability to scale this process up to the required dimensions.The proposed project has two objectives. Firstly, the development of an accurate and real-time monitoring system for the laser machining process, taking advantage of recent developments in machine learning, specifically neural networks, in order to enable creation of large-area, high precision fabrication techniques to machine suitable topographic substrates. Secondly, advancing the processes for optimal growth and monitoring of stem cells on these fabricated substrates in order to optimize the size, features, and dimensions of the surface topography for accurate control of stem cell differentiation and proliferation.