CAREER: 3D Printing High Lipid Content Cultivated Meat to Minimize Livestock Environmental Impacts

目前的农业供应链将无法持续满足世界对动物蛋白日益增长的需求。目前，大多数牲畜都是在集中的动物饲养场饲养的，这引起了环境、公共卫生和粮食安全方面的关切。一种新兴的选择是用实验室中生长的类肉组织（即，培养肉）。养殖肉类可以帮助减少商业化养殖带来的环境、公共卫生和食品安全问题。然而，必须克服与消费者接受有关的主要科学、技术和教育障碍。开发养殖肉类产品（即，具有常规肉制品的质地、风味和熟悉度的碎肉和/或牛排）对于消费者的接受度将是至关重要的。目前的培养肉技术是昂贵的，并且集中在不重建动物牛排的三维（3D）组织结构的碎肉产品上，特别是关于脂肪在这些组织中的分布。因此，这个CAREER项目的目标是建立对肌肉中脂肪积累的生物动力学的基本理解，并开发3D生物打印技术和参数，以创建与传统肉类的特性和结构相匹配的培养肉制品。 3D生物打印将增加最小的生产成本，同时显著提高最终培养产品的价格，提高该行业的财务可行性。与此同时，该提案旨在开展教育和公共宣传活动，以提高消费者对当前动物蛋白供应链关键弱点的认识，以及缓解这些弱点的生物医学工程解决方案，推动消费者接受，并发展细胞农业研究社区。 研究人员的长期研究目标涉及生物组织的3D打印，疾病过程的机制研究和再生医学。 为了实现这一目标，这个CAREER项目旨在通过准确再现传统肉制品的质地，特性和成本来提高消费者对养殖肉类的接受度和适口性。 该研究计划有两个目标：（1）获得肌内脂肪积累的基本理解和（2）打印可行的，脂质负载的脂肪细胞单独进入肌内空间。 这些目标将为养殖肉类行业以及未来在人类疾病建模、再生医学和重建医学方面的工作提供开源基础。拟议的研究将（1）开发尚未实现或报告的成熟脂肪细胞和骨骼肌细胞共培养的条件，（2）为创建肌内脂肪积累生物机制的新模型做出重大贡献，以及（3）建立包含脂质的脂肪细胞和骨骼肌细胞的组织的3D生物打印参数。这些3D打印组织在机械和成分上应与生物组织相似，并将显著提高细胞农业和生物医学工程技术人员的基础研究和应用驱动能力。该奖项反映了NSF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。

The current agricultural supply chain will be unable to sustainably meet the world’s increasing demand for animal proteins. Currently, the majority of livestock are reared in concentrated animal feeding operations causing environmental, public health, and food security concerns. An emerging option is to replace conventionally produced meat with meat-like tissues grown in the lab (i.e., cultured meat). Cultured meat can help to reduce the environmental, public health, and food security issues posed by commercial farming. However, major scientific, technological, and educational barriers related to consumer acceptance must be overcome. Developing cultured meat products (i.e., ground meat and/or steaks) that have the texture, flavor, and familiarity of conventional meat products will be critical to consumer acceptance. Current cultured meat technologies are expensive and have focused on ground meat products that do not re-create the three-dimensional (3D) tissue structures of animal steaks, especially with regards to the distribution of fat in these tissues. Therefore, the goal of this CAREER project is to establish a fundamental understanding of the biological dynamics of fat accumulation in muscle and develop 3D bioprinting techniques and parameters to create cultured meat products that match the properties and structures of conventional meats. 3D bioprinting would add minimal production costs while significantly increasing the price point of the final cultured product, improving the financial viability of the industry. In parallel, this proposal seeks to engage in educational and public outreach activities to increase consumer awareness of the current animal protein supply chain’s critical weaknesses and the biomedical engineering solutions to relieve these, drive consumer acceptance, and grow the cellular agriculture research community. The investigator’s long-term research goals involve 3D printing of biological tissues, mechanistic studies of disease processes, and regenerative medicine. Towards this goal, this CAREER project seeks to enhance consumer acceptance and palatability of cultured meats by accurately reproducing the texture, properties, and costs associated with conventional meat products. The Research Plan is organized under two objectives: (1) Obtain a fundamental understanding of intramuscular fat accumulation and (2) Print viable, lipid-laden adipocytes alone and into the intramuscular space. These objectives will provide an open-source foundation for the cultured meat industry and future work in human disease modelling, regenerative medicine, and reconstructive medicine. The proposed studies will (1) develop conditions for co-culturing mature adipocytes and skeletal muscle cells that have not been achieved or reported, (2) make significant contributions to creating new models of biological mechanisms for intramuscular fat accumulation, and (3) establish parameters for the 3D bioprinting of tissues that contain both lipid-laden adipocytes and skeletal muscle cells. These 3D printed tissues should be mechanically and compositionally similar to their biological counterparts and will significantly improve the fundamental research and application-driven capabilities of technical personnel in cellular agriculture and biomedical engineering.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.