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

美国制造：自支撑纳米粘土作为骨骼组织结构打印内部支架材料的研究

• 批准号: 1762941
• 负责人: Yong Huang
• 金额: $ 33.95万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-15 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1762941&HistoricalAwards=false
• 关键词: Manufacturing; USA; Study; Self; Supporting

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.

该奖项支持使用独特的、生物兼容的纳米粘土添加剂进行三维(3D)挤压生物打印工艺的研究。材料挤压生物印花是一种基于压缩的添加剂制造工艺，在该过程中，材料被迫流过喷嘴，以生产用于逐层沉积的连续长丝。将纳米粘土添加到通常用于印刷的水凝胶中将增加印刷生物支架结构的几何复杂性和机械完整性。目前，挤出的水凝胶应快速凝胶(固化)，以在印刷后立即保持其形状，并支持以下印刷层。这将可打印生物材料的选择限制在那些表现出合适的快速凝胶机制的生物材料上，并限制了在不使用必须稍后移除的支持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起到内部支架材料的作用，以在打印后直接保持挤压材料的形状。打印的构造只有在整个部分完成后才会被凝胶；这还有一个额外的潜在好处，即避免了层间粘合问题，并增强了结构的机械完整性。如果成功，这项研究可以通过为骨骼组织工程应用(如骨替代和再生)提供个性化的打印支架，从而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，因为所有级别的学生都将获得在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加由佛罗里达大学前教育和培训中心组织的STEM浸泡周。该项目的研究目标是了解仅限触变纳米粘土和纳米粘土-水凝胶混合胶体的特征和基本工艺限制。触变性、自持性凝胶，特别是由高浓度膨润土纳米粘土制成的硅酸盐纳米粘土胶体，在静态条件下是粘性的，在压力下是较低的粘性。这种触变性、自支撑性在各种纳米粘土-水凝胶混合胶体中也可以观察到，这使得滑石型纳米粘土成为一种有望在空气中直接打印纳米粘土-水凝胶复合材料的内部支架材料。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吸引人的凝胶状态，并导致具有触变性、自支撑性的分形网络。为了验证这一假设，将使用散射和显微技术表征高浓度纳米粘土胶体的微观结构，以揭示其独特的凝胶状态。纳米粘土挤出过程中的流体动力学将使用基于流体的体积模拟方法来建模，并将用一组无量纲数字来表示纤维的成形性，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，将使用欧拉-伯努利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。印刷纳米粘土-水凝胶支架将根据其降解、生物和生物矿化特性进行评估，用于骨骼组织工程应用。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Fabrication of Stand-Alone Cell-Laden Collagen Vascular Network Scaffolds Using Fugitive Pattern-Based Printing-Then-Casting Approach

• DOI: 10.1021/acsami.8b09177
• 发表时间: 2018-08-29
• 期刊: ACS APPLIED MATERIALS & INTERFACES
• 影响因子: 9.5
• 作者: Jin, Yifei;Chai, Wenxuan;Huang, Yong
• 通讯作者: Huang, Yong

Printing of Hydrophobic Materials in Fumed Silica Nanoparticle Suspension

• DOI: 10.1021/acsami.9b07433
• 发表时间: 2019-08-14
• 期刊: ACS APPLIED MATERIALS & INTERFACES
• 影响因子: 9.5
• 作者: Jin, Yifei;Song, Kaidong;Huang, Yong
• 通讯作者: Huang, Yong

Effects of transglutaminase cross-linking process on printability of gelatin microgel-gelatin solution composite bioink

• DOI: 10.1088/1758-5090/ac3d75
• 发表时间: 2021-11
• 期刊: Biofabrication
• 影响因子: 9
• 作者: Kaidong Song;B. Ren;Yingnan Zhai;Wenxuan Chai;Yong Huang

Evaluation of bioink printability for bioprinting applications

评估生物打印应用中的生物墨水可打印性

• DOI: 10.1063/1.5053979
• 发表时间: 2018-12
• 期刊: Applied Physics Reviews
• 影响因子: 15
• 作者: Zhengyi Zhang;Yifei Jin;Jun Yin;Changxue Xu;Ruitong Xiong;Kyle Christensen;Bradley R Ringeisen;Douglas B Chrisey;Yong Huang
• 通讯作者: Yong Huang

Computational study of extrusion bioprinting with jammed gelatin microgel-based composite ink

• DOI: 10.1016/j.addma.2021.101963
• 发表时间: 2021-05-01
• 期刊: ADDITIVE MANUFACTURING
• 影响因子: 11
• 作者: Song, Kaidong;Zhang, Deming;Huang, Yong
• 通讯作者: Huang, Yong