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，生物相容性的，纳米粘土添加剂的三维（3D）挤出生物打印过程的研究。材料挤出生物打印是一种基于压缩的添加剂制造过程，其中材料被迫流过喷嘴以产生连续的细丝以逐层沉积。通常用于打印的水凝胶中的纳米粘土将增加印刷生物遵循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（固化），以在打印后立即保持其形状，并支撑以下印刷层。这将可打印的生物材料的选择限制在表现出合适的快速凝胶化机制的人身上，并限制了可行的几何形状，而无需使用辅助材料，必须以后将其除去。水凝胶的纳米粘土添加是一种内部支架材料，在打印后直接保持挤出材料的形状。仅在整个部分完成后才凝胶印刷结构。这具有避免层间粘结问题并增强结构的机械完整性的其他潜在优势。如果成功，这项研究可以通过为骨骼组织工程应用（例如骨骼替代和再生）启用个性化的印刷脚手架来推动美国生物打印的制造能力和国家福利。该奖项还将促进对未来劳动力的培训，因为各个级别的学生将获得生物医学制造业的曝光率和经验。其他教育外展活动包括让高中生参加由佛罗里达州的教育和培训中心组织的STEM浸入周。该项目的研究目标是了解仅触变纳米层和纳米粘土 - 纳米粘土混合胶体混合胶体的特征和基本处理限制。触变的，自支撑的凝胶，尤其是由高浓度的laponite纳米粘土制成的基于硅酸盐的纳米粘土胶体，从静态条件下的粘性转变为压力时粘性较小。在各种纳米粘土混合胶质胶体中也观察到了这种触变的，自支撑的特性，使laponite纳米粘土成为纳米 - 粘土层复合3D直接在空气中的有希望的内部支架材料。为此，假设在某些老化时间和浓度上制备的纳米粘土胶体形成了有吸引力的凝胶状态，并导致具有触变，自支撑特性的分形网络。为了检验假设，将使用散射和显微镜技术来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。将使用基于流体的仿真方法对纳米层挤出过程中的流体动力学进行建模，并使用一组非二维数字来表示细丝的表现性，并与实验观察结果相比。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束理论确定材料特性对可打印几何形状的影响并经过实验验证。印刷的纳米层 - 凝胶支架将根据骨骼组织工程应用的降解，生物学和生物矿化特性进行评估。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的智力和更广泛影响的评估来通过评估来获得支持的。

项目成果

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

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

Realizations of vascularized tissues: From in vitro platforms to in vivo grafts

• DOI: 10.1063/5.0131972
• 发表时间: 2023-03-01
• 期刊: BIOPHYSICS REVIEWS
• 作者: Ren，Bing;Jiang，Zhihua;Huang，Yong
• 通讯作者: Huang，Yong

Nanoclay Suspension-Enabled Extrusion Printing of 3D Soft Structures for Biomedical Applications

用于生物医学应用的 3D 软结构纳米粘土悬浮液挤出打印

• DOI: 10.1115/msec2020-8330
• 发表时间: 2020
• 期刊: ASME 2020 15th International Manufacturing Science and Engineering Conference
• 作者: Jin, Yifei;Antonelli, Patrick J.;Long, Christopher J.;McAleer, Christopher W.;Hickman, James J.;Xiong, Ruitong;Huang, Yong
• 通讯作者: Huang, Yong