CAREER: Cell-Instructive Smart Bioinks for Tissue and Organ Printing

职业：用于组织和器官打印的细胞指导智能生物墨水

• 批准号: 2044479
• 负责人: Murat Guvendiren
• 金额: $ 49.98万
• 依托单位: New Jersey Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2044479&HistoricalAwards=false
• 关键词: CAREER; Cell; Instructive; Smart; Bioinks

PART 1: NON-TECHNICAL SUMMARY Developing biomaterials that enable the production of fully functional, human-scale tissues and organs capable of replacing failed organs would be a transformative benefit to society. Bioprinting could potentially be utilized to construct highly complex and patient-specific tissues and organs as well as tissue interfaces. Despite this potential, the lack of diverse bioinks that can mimic the dynamic properties of the native tissue is one of the major bottlenecks that hinders bioprinting of fully functional tissues and organs. This project aims to investigate materials design strategies to create smart bioinks to address this gap, and to apply these bioinks for bioprinting of fully functional osteochondral (OC) tissues. In particular, this project will answer the following fundamental research questions: (i) how to control printability by adjusting macromer properties while ensuring high cell viability; (ii) how to tune printability, stiffness, degradation and bioactivity independent from each other; (iii) how to tailor chemistry to enable cell-mediated manipulation of bioactivity, and (vi) how to instruct stem cells to differentiate spatially within a 3D bioprinted construct towards OC tissue formation. The interdisciplinary nature of the proposed research will provide opportunities for minority undergraduate students and high school students in local schools traditionally underrepresented in STEM education to gain hands-on research experiences towards development of a highly qualified workforce. The proposed outreach program with the New Jersey Commission for the Blind and Visually Impaired will enhance STEM education accessibility for blind and visually impaired students. Research findings will be disseminated broadly to students, families, and educators at all levels. PART 2: TECHNICAL SUMMARYBioprinting technology has expanded dramatically over the past few years, yet there is a significant lack of diverse and smart bioinks which could facilitate reversible and spatiotemporal control of the mechanics, degradation, and bioactivity of the 3D printed constructs independently to mimic dynamic, extracellular matrix (ECM) changes which occur during tissue development and disease. The proposed research will specifically tailor the building blocks of cell-laden hydrogels for bioprintability and for responsiveness to user- and cell-triggered changes in mechanics, degradation, and bioactivity. These smart bioinks will capture dynamic changes happening in the ECM during tissue development, disease, and healing processes. This project will utilize these bioinks to investigate temporal contributions of developmentally relevant cell-matrix and cell-cell interactions to instruct stem cells spatially to regenerate osteochondral (OC) interface. The three objectives of the proposed research are: 1) to synthesize novel functional bioinks with tunable printability, stiffness, and degradation; 2) to tailor pendant-chain chemistry for cell-triggered temporal control of bioactivity to enhance stem cell chondrogenesis; and 3) to investigate the ability of smart bioinks to fabricate heterogenous constructs for regeneration of osteochondral interface. The proposed educational plan includes: 1) developing customized research projects for undergraduate students from NJIT and other universities; 2) engaging high school students, from selected local schools with low income and underrepresented student population, in hands-on research experience and providing long-term mentorship; 3) creating a bioprinting class module with hands-on laboratory component; 4) enhancing accessibility of STEM education for blind and visually impaired students.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.

开发能够生产功能齐全的人体组织和器官的生物材料，能够替代衰竭的器官，将对社会产生变革性的好处。生物打印技术有可能用于构建高度复杂和患者特异性的组织和器官以及组织界面。尽管有这种潜力，但缺乏能够模仿天然组织动态特性的多种生物墨水是阻碍生物打印功能齐全的组织和器官的主要瓶颈之一。本项目旨在研究创造智能生物墨水的材料设计策略，以解决这一空白，并将这些生物墨水应用于全功能骨软骨（OC）组织的生物打印。特别是，该项目将回答以下基本研究问题：(i)如何通过调整大分子特性来控制可打印性，同时确保高细胞活力；（ii）如何独立地调整可打印性、刚度、降解性和生物活性；（iii）如何调整化学以实现细胞介导的生物活性操纵，以及（vi）如何指导干细胞在3D生物打印构建物中向OC组织形成的空间分化。拟议研究的跨学科性质将为传统上在STEM教育中代表性不足的当地学校的少数民族本科生和高中生提供机会，让他们获得实践研究经验，从而培养高素质的劳动力。与新泽西州盲人和视障人士委员会拟议的外展计划将提高盲人和视障学生的STEM教育可及性。研究结果将广泛传播给各级学生、家庭和教育工作者。在过去的几年中，生物打印技术得到了极大的发展，然而，缺乏多样化和智能的生物墨水，这些生物墨水可以促进对3D打印结构的力学、降解和生物活性的可逆和时空控制，以独立地模拟组织发育和疾病期间发生的动态细胞外基质（ECM）变化。拟议的研究将专门定制装载细胞的水凝胶的构建块，以实现生物可打印性，以及对用户和细胞触发的力学、降解和生物活性变化的响应。这些智能生物墨水将捕捉在组织发育、疾病和愈合过程中发生的ECM动态变化。本项目将利用这些生物连接来研究与发育相关的细胞-基质和细胞-细胞相互作用的时间贡献，以指导干细胞在空间上再生骨软骨（OC）界面。提出的研究的三个目标是：1)合成具有可调打印性、刚度和降解性的新型功能性生物墨水；2)为细胞触发的生物活性的时间控制量身定制垂链化学，以增强干细胞软骨形成；3)研究智能生物连接材料制备骨软骨界面再生异质结构的能力。建议的教育计划包括：1)为新泽西理工大学和其他大学的本科生定制研究项目；2)从选定的当地低收入和学生人数不足的学校中招收高中学生，让他们获得实践研究经验，并提供长期指导；3)创建具有动手实验室组件的生物打印类模块；4)提高盲人和视障学生接受STEM教育的机会。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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

4D Printing of Surface Morphing Hydrogels

• DOI: 10.1002/admt.202101118
• 发表时间: 2021-12
• 期刊: Advanced Materials Technologies
• 影响因子: 6.8
• 作者: Chya‐Yan Liaw;J. Pereyra;A. Abaci;Shen Ji;M. Guvendiren

Three-dimensional bioprinting vascularized bone tissue

• DOI: 10.1557/s43577-023-00547-y
• 发表时间: 2023-06
• 期刊: MRS Bulletin
• 影响因子: 5
• 作者: Hadis Gharacheh;M. Guvendiren

Three-dimensional bioprinting for medical applications

• DOI: 10.1557/s43577-023-00546-z
• 发表时间: 2023-06-12
• 期刊: MRS BULLETIN
• 影响因子: 5
• 作者: Abaci, Alperen;Camci-Unal, Gulden;Guvendiren, Murat
• 通讯作者: Guvendiren, Murat

Airbrushed nanofibrous membranes to control stem cell infiltration in 3D ‐printed scaffolds

• DOI: 10.1002/aic.17475
• 发表时间: 2021-10
• 期刊: AIChE Journal
• 影响因子: 3.7
• 作者: Chya‐Yan Liaw;Shawn Huynh;Christina Gedeon;Shen Ji;Caroline D’souza;A. Abaci;M. Guvendiren