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

目前的农业供应链将无法可持续地满足世界对动物蛋白日益增长的需求。目前，大多数牲畜是在集中的动物饲养作业中饲养的，这造成了环境、公共卫生和食品安全方面的担忧。一种新的选择是用实验室培养的类似肉类的组织来取代传统生产的肉类(即培养的肉类)。养殖肉类有助于减少商业养殖带来的环境、公共健康和食品安全问题。然而，必须克服与消费者接受相关的重大科学、技术和教育障碍。开发具有传统肉类产品的质地、风味和熟悉度的培养肉制品(即绞肉和/或牛排)将对消费者的接受度至关重要。目前的养殖肉类技术价格昂贵，主要集中在不能重建动物牛排的三维(3D)组织结构的绞肉制品上，特别是在脂肪在这些组织中的分布方面。因此，这个职业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了解，并开发3D生物打印技术和参数，以创造出与传统肉类的特性和结构相匹配的培养肉制品。3D生物打印将增加最低的生产成本，同时显著提高最终培养产品的价格点，提高该行业的财务可行性。同时，该提案旨在开展教育和公共推广活动，以提高消费者对当前动物蛋白供应链的关键弱点和生物医学工程解决方案的认识，以缓解这些弱点，推动消费者的接受，并发展细胞农业研究社区。研究人员的长期研究目标包括生物组织的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，这个职业项目寻求通过准确地复制与传统肉类产品相关的质地、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)对肌肉内脂肪的积累有一个基本的了解；(2)将可存活的、富含脂肪的脂肪细胞单独打印到肌肉间隙中。这些目标将为养殖肉类行业和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一个开源基础。拟议的研究将(1)开发尚未实现或报道的成熟脂肪细胞和骨骼肌细胞共培养的条件，(2)为创建肌肉内脂肪积累的生物机制的新模型做出重大贡献，以及(3)为同时包含高脂脂肪细胞和骨骼肌细胞的组织的3D生物打印建立参数。这些3D打印组织应该在机械和成分上与生物组织相似，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。

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.