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，可以通过在特定的表面形貌上生长干细胞来控制。这种形貌的使用具有使用患者自身的干细胞在体内靶向生成骨的潜力，从而导致骨折的更快恢复，降低髋关节植入物的失败率以及骨质疏松症和其他骨骼疾病的潜在治疗。初步结果显示，在100纳米至微米的尺寸尺度上的表面形貌的成功，通过光刻制造工艺在毫米尺寸的区域上图案化。然而，这种工艺是昂贵和耗时的，因此，按比例放大到医疗上有用的尺寸，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的功能，在微米级和更小的制造潜力。然而，由于工艺的敏感性，即使是很小的实验噪音水平也会导致制造质量低下，从而阻止将该工艺扩展到所需尺寸的能力。首先，利用机器学习的最新发展，特别是神经网络，开发用于激光加工过程的精确和实时监控系统，以便能够创建大面积，高精度的制造技术，以加工合适的地形基底。其次，推进干细胞在这些制造的基底上的最佳生长和监测的过程，以优化表面形貌的大小、特征和尺寸，从而精确控制干细胞分化和增殖。

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.