3D Bioprinting of Complex Tissue Structures Using Nanoengineered Ionic-Covalent Entanglement (NICE) Bioinks

使用纳米工程离子共价纠缠 (NICE) 生物墨水对复杂组织结构进行 3D 生物打印

• 批准号: 1705852
• 负责人: Akhilesh Gaharwar
• 金额: $ 30万
• 依托单位: Texas A&M Engineering Experiment Station
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1705852&HistoricalAwards=false
• 关键词: 3D; Bioprinting; Complex; Tissue; Structures

PI: Gaharwar, Akhilesh K.Proposal: 1705852Engineering complex tissues that can mimic, augment, or replace native tissue functions holds enormous potential for treating organ failures resulting from injuries, aging, and diseases. 3D bioprinting is an emerging approach for rapid fabrication of complex tissue structures using cell-loaded hydrogels, called bioinks. However, 3D bioprinting has hit a bottleneck in progress due to the lack of suitable bioinks that are printable and can guide cell functions. This project focuses on designing a novel family of nanoengineered ionic-covalent entanglement (NICE) bioinks for 3D-printing. The NICE bioink combines two approaches - nanocomposites using 2D nanosilicates and ICE networks formed from gelatin methacrylate (a collagen based bioink often used in bioprinting) and k-carrageenan (a polysaccharide based gel often used for thickening and stabiliazation) - to achieve mechanical properties superior to either approach alone. This work will lead to a novel platform technology to selectively control and pattern cell behavior that will have broad scientific impact on human health; specifically, regenerative engineering and therapeutic delivery. The development of a new family of bioinks will also spur growth in biofabrication, leading to positive impacts on society and the national economy. The integrated multidisciplinary research platform will provide a unique environment to attract, motivate, and retain students, particularly underrepresented groups, in science and engineering education. The project will provide educational and outreach opportunities through a diverse array of K-12 activities, including: development of educational screencasts; training teachers; engaging local schools in after-school programs; and hosting high school students for research. Specifically, a range of educational and research screencasts will be developed to engage and promote awareness about nanomaterials, and bioprinting. Outreach will be extended by sharing and distributing the screencasts via popular social media sites (including blogs, Facebook, Flickr, Pinterest, SlideShare, Twitter, Vimeo, and YouTube) and by interacting with online K-12 video portals such as Khan Academy.This project addresses a key challenge in biomedical engineering - how to engineering three-dimensional complex structures consisting of biomolecules, cells, and scaffolds - by designing a novel family of nanoengineered ionic-covalent entanglement (NICE) bioinks for 3D-printing to control and pattern cell behavior. The approach taken will elucidate key fundamental properties of ionic covalent entanglement (ICE) networks loaded with unique, two-dimensional (2D) nanosilicates. The research will reveal the interactions among nanomaterials, growth factors, and human cells, paving the way for novel nanoengineered approaches to harness and augment these interactions. Intellectual contributions include: 1) introducing a novel material design (NICE) to form shear-thinning bioinks, using 2D nanomaterials and ionic-covalent entanglement (ICE), will enable deposition of cells in complex 3D structures which in turn will advance understanding and knowledge of cell-biomaterial interactions in complex microenvironments; 2) Elucidating interactions between 2D nanosilicates and the ICE network will advance fundamental understanding for leveraging non-covalent interactions to mechanically reinforce hydrogel networks; 3) establishing 2D nanosilicates as a modular approach for plug-and-play types of therapeutics delivery will be facilitated by eliminating complex chemical modification of labile therapeutics. Understanding the interactions between 2D nanomaterials and biomolecules will provide insight into retaining bioactivity of labile therapeutics for prolonged durations and will lead to discovery of new phenomena; and 4) establishing a new paradigm for sustained and effective delivery of therapeutics to modulate the cellular function will ultimately lead to development of more effective delivery systems.

主要研究者：Gaharwar，Akhilesh K.提案：1705852可以模拟、增强或替代天然组织功能的工程化复杂组织具有治疗由损伤、衰老和疾病引起的器官衰竭的巨大潜力。3D生物打印是一种新兴的方法，用于使用负载细胞的水凝胶（称为生物墨水）快速制造复杂的组织结构。然而，由于缺乏合适的可打印且可以引导细胞功能的生物墨水，3D生物打印遇到了瓶颈。该项目的重点是设计一种用于3D打印的新型纳米工程离子-共价纠缠（NICE）生物墨水。NICE bioink结合了两种方法-使用2D纳米硅酸盐的纳米复合材料和由明胶甲基丙烯酸酯（通常用于生物打印的胶原蛋白生物墨水）和k-角叉菜胶（通常用于增稠和稳定的多糖凝胶）形成的ICE网络-以实现上级单独使用任何一种方法的机械性能。这项工作将导致一种新的平台技术，以选择性地控制和模式化细胞行为，这将对人类健康产生广泛的科学影响;特别是再生工程和治疗交付。新的生物墨水家族的开发也将刺激生物制造业的增长，对社会和国民经济产生积极影响。综合多学科研究平台将提供一个独特的环境，以吸引，激励和留住学生，特别是代表性不足的群体，在科学和工程教育。该项目将通过各种K-12活动提供教育和推广机会，包括：开发教育视频;培训教师;让当地学校参与课后计划;以及接待高中生进行研究。具体而言，将开发一系列教育和研究屏幕播放，以参与和促进对纳米材料和生物打印的认识。将通过流行的社交媒体网站分享和分发屏幕播放来扩大宣传范围（包括博客，Facebook，Flickr，Pinterest，SlideShare，Twitter，Vimeo和YouTube），并与在线K-12视频门户网站（如Khan Academy）互动。该项目解决了生物医学工程中的一个关键挑战-如何设计由生物分子，细胞，和支架-通过设计一种新型的纳米工程离子-共价纠缠（NICE）生物墨水家族，用于3D打印以控制和图案化细胞行为。所采取的方法将阐明离子共价纠缠（ICE）网络加载独特的，二维（2D）纳米硅酸盐的关键基本特性。这项研究将揭示纳米材料，生长因子和人类细胞之间的相互作用，为利用和增强这些相互作用的新型纳米工程方法铺平道路。智力贡献包括：1）引入新型材料设计（NICE）以使用2D纳米材料和离子-共价缠结（ICE）形成剪切稀化生物墨水，将使得细胞能够沉积在复杂的3D结构中，这反过来将促进对复杂微环境中细胞-生物材料相互作用的理解和知识; 2）阐明2D纳米硅酸盐和ICE网络之间的相互作用将促进对利用非生物学的基本理解。共价相互作用以机械地增强水凝胶网络; 3）通过消除不稳定治疗剂的复杂化学修饰，将促进建立2D纳米硅酸盐作为即插即用型治疗剂递送的模块化方法。理解2D纳米材料和生物分子之间的相互作用将提供对长时间保持不稳定治疗剂的生物活性的洞察，并将导致发现新现象;以及4）建立持续有效递送治疗剂以调节细胞功能的新范例将最终导致开发更有效的递送系统。

项目成果

3D-printed bioactive scaffolds from nanosilicates and PEOT/PBT for bone tissue engineering

• DOI: 10.1093/rb/rby024
• 发表时间: 2019-02-01
• 期刊: REGENERATIVE BIOMATERIALS
• 影响因子: 6.7
• 作者: Carrow, James K.;Di Luca, Andrea;Gaharwar, Akhilesh K.
• 通讯作者: Gaharwar, Akhilesh K.

Printing Therapeutic Proteins in 3D using Nanoengineered Bioink to Control and Direct Cell Migration

• DOI: 10.1002/adhm.201801553
• 发表时间: 2019-06-01
• 期刊: ADVANCED HEALTHCARE MATERIALS
• 影响因子: 10
• 作者: Peak, Charles W.;Singh, Kanwar Abhay;Gaharwar, Akhilesh K.
• 通讯作者: Gaharwar, Akhilesh K.

Sustained and Prolonged Delivery of Protein Therapeutics from Two-Dimensional Nanosilicates

• DOI: 10.1021/acsami.8b17733
• 发表时间: 2019-02-20
• 期刊: ACS APPLIED MATERIALS & INTERFACES
• 影响因子: 9.5
• 作者: Cross, Lauren M.;Carrow, James K.;Gaharwar, Akhilesh K.
• 通讯作者: Gaharwar, Akhilesh K.

Shear-Thinning and Thermo-Reversible Nanoengineered Inks for 3D Bioprinting

• DOI: 10.1021/acsami.7b13602
• 发表时间: 2017-12-20
• 期刊: ACS APPLIED MATERIALS & INTERFACES
• 影响因子: 9.5
• 作者: Wilson, Scott A.;Cross, Lauren M.;Gaharwar, Akhilesh K.
• 通讯作者: Gaharwar, Akhilesh K.

2D Nanosilicate for additive manufacturing: Rheological modifier, sacrificial ink and support bath

• DOI: 10.1016/j.bprint.2021.e00187
• 发表时间: 2022-01
• 期刊: Bioprinting
• 作者: Satyam Rajput;Kaivalya A. Deo;Tanmay Mathur;Giriraj Lokhande;Kanwar Abhay Singh;Yuxiang Sun;D. Alge;A. Jain;T. R. Sarkar;A. Gaharwar