Manufacturing USA: Study of Self-Supporting Nanoclay as Internal Scaffold Material for Printing of Skeletal Tissue Constructs

该奖项支持使用独特的生物相容性纳米粘土添加剂进行三维（3D）挤出生物打印工艺的研究。材料挤出生物打印是一种基于压缩的增材制造工艺，其中材料被迫流过喷嘴以产生用于逐层沉积的连续长丝。将纳米粘土添加到通常用于打印的水凝胶中将增加打印的生物支架结构的几何复杂性和机械完整性。目前，挤出的水凝胶应迅速凝胶化（固化），以在打印后立即保持其形状，并支撑随后的打印层。这将可印刷生物材料的选择限制为表现出合适的快速凝胶化机制的那些，并且限制了在不使用随后必须去除的支撑材料的情况下可行的几何形状。添加到水凝胶中的纳米粘土用作内部支架材料，以在打印后直接保持挤出材料的形状。打印的结构仅在整个部件完成后凝胶化;这具有避免层间粘合问题和增强结构的机械完整性的额外潜在益处。如果成功，这项研究可以通过为骨骼组织工程应用（如骨置换和再生）提供个性化的打印支架来提高美国的生物打印制造能力和国家福利。该奖项还将促进未来劳动力的培训，因为各级学生将获得生物医学制造方面的接触和经验。其他教育推广活动包括让高中生参与由佛罗里达大学前教育和培训中心组织的STEM沉浸周。本项目的研究目标是了解触变性纳米粘土和纳米粘土-水凝胶混合胶体的特性和基本加工限制。触变自支撑凝胶，特别是由高浓度Laponite纳米粘土制成的硅酸盐基纳米粘土胶体，从静态条件下的粘性转变为应力时的较低粘性。在各种纳米粘土-水凝胶混合胶体中也观察到这种触变的自支撑性质，使得Laponite纳米粘土能够作为有前途的内部支架材料用于在空气中直接打印纳米粘土-水凝胶复合物3D。为此，假设在一定的老化时间和浓度下制备的纳米粘土胶体形成有吸引力的凝胶状态，并导致具有触变性、自支撑性质的分形网络。为了验证这一假设，高浓度纳米粘土胶体的微观结构将使用散射和显微镜技术来表征，以揭示其独特的凝胶状态。纳米粘土使能挤出过程中的流体动力学将使用基于流体的模拟方法的体积来建模，并且长丝可成形性将使用一组无量纲数字来表示，并进一步与实验观察结果进行比较。基于高浓度纳米粘土胶体的剪切和拉伸屈服应力，将使用Euler-Bernoulli梁理论确定材料特性对可打印几何形状的影响，并进行实验验证。打印的纳米粘土水凝胶支架将在其降解，生物和生物矿化性能方面进行评估，用于骨骼组织工程应用。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

This award supports research on three-dimensional (3D) extrusion bioprinting processes using a unique, biocompatible, nanoclay additive. Material extrusion bioprinting is a compression-based additive manufacturing process in which material is forced to flow through a nozzle to produce continuous filaments for layer-by-layer deposition. The addition of the nanoclay to hydrogels typically used in printing will increase the geometric complexity and mechanical integrity of the printed bioscaffold structures. Currently the extruded hydrogel should be rapidly gelled (solidified) to hold its shape immediately after printing, and to support the following printed layers. This limits the selection of printable biomaterials to those exhibiting suitable rapid gelation mechanisms, and limits the geometries feasible without the use of supporting materials that must be later removed. The nanoclay addition to the hydrogel functions as an internal scaffold material to hold the shape of the extruded material directly after printing. The printed construct is only gelled after the whole part is finished; this has the additional potential benefit of avoiding interlayer bonding issues and enhancing the structure's mechanical integrity. If successful, this research can advance U.S. bioprinting manufacturing capabilities and national welfare by enabling personalized, printed scaffolds for skeletal tissue engineering applications such as bone replacement and regeneration. The award will also facilitate training of the future workforce as students across all levels will gain exposure and experience in biomedical manufacturing. Additional educational outreach activities include engaging high school students in STEM immersion weeks organized by the Florida Center for Precollegiate Educational and Training.The research objective of this project is to understand the characteristics and fundamental processing limitations of thixotropic nanoclay only and nanoclay-hydrogel mixed colloids. Thixotropic, self-supporting gels, in particular silicate-based nanoclay colloids made from high-concentration Laponite nanoclay, transition from being viscous under static conditions to less viscous when stressed. This thixotropic, self-supporting property is also observed in various nanoclay-hydrogel mixed colloids, enabling Laponite nanoclay as a promising internal scaffold material for nanoclay-hydrogel composite 3D direct printing in air. To this end it is hypothesized that nanoclay colloids prepared at certain aging times and concentrations form an attractive gel state and result in a fractal network with thixotropic, self-supporting property. To test the hypothesis, the microstructure of high-concentration nanoclay colloids will be characterized using scattering and microscopic technologies to reveal their unique gel state. The fluid dynamics during nanoclay-enabled extrusion will be modeled using a volume of fluid-based simulation approach, and the filament formability will be represented using a set of non-dimensional numbers and further compared with experimental observations. Based on the shear and tensile yield stresses of high-concentration nanoclay colloids, the effect of material properties on the printable geometry will be determined using the Euler-Bernoulli beam theory and experimentally validated. Printed nanoclay-hydrogel scaffolds will be evaluated in terms of their degradation, biological, and biomineralization properties for skeletal tissue engineering applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.