FMSG: Bio: Rapid Bio-Printing of Hybrid Piezoelectric and Magnetostrictive Platforms for Tissue Engineering

组织工程是一种生物医学工程过程，通常涉及结合细胞、生物分子、支架和生物相互作用材料来维持、恢复或改善组织或器官。然而，这些人工制造的功能性组织在人类患者中的应用有限（例如，人造皮肤或软骨）。挑战包括创新具有成本效益的工具工程，创造具有合适生化和物理化学因素的材料，以及为指导疾病治疗策略提供原位诊断的可持续平台。这项未来制造种子基金(FMSG)-生物制造项目支持开发新的3D打印技术的基础研究，以克服这些困难。例如，新开发的打印机可以打印多功能植入物和支架，具有高通量和分辨率，避免了繁琐的工具工程。此外，新发明的生物相容性复合材料也将为各种生物医学应用带来机会，例如组织再生，神经创伤治疗和癌症治疗。该项目联合了具有不同专业知识的研究人员，包括3D打印、聚合物科学、纳米颗粒工程和生物医学工程。这些调查人员还将在从K-12公共教育到研究生课程开发的各个层面开展STEM外展活动。重要的是，调查人员将开发以教育为导向的TikTok/YouTube内容，向当地和全国K-12学生展示最新的印刷技术。虽然3D打印已经被用于分别打印压电或铁磁复合材料，但仍然存在一些瓶颈。例如，用于生物医学用途的传统3D打印多铁磁电（ME）复合材料具有较差的可打印性，并且在制造精细特征方面效率有限。FMSG项目旨在通过集成扫描投影和微流体流动控制策略，开发一种新的打印技术，称为多尺度和多材料连续液体界面打印（MM-CLIP）。MM-CLIP技术可以实现功能器件的可扩展制造，这些器件具有越来越小的特征和多种材料，这一直是3D打印领域的主要挑战。利用MM-CLIP，多铁ME复合材料可以打印成压电和磁致伸缩的混合平台，即多功能植入物或组织支架，这些平台可以从外部控制的磁场中产生电信号，在生物系统中很少衰减。多物理场建模框架是一个额外的推力，用于阐明可打印复合材料的ME耦合效率，从而预测和精确控制电刺激。同时，本项目将系统探讨me诱导的电刺激对细胞增殖的影响及其与细胞分化和生长因子的关系。概念验证研究中的迭代将导致最佳支架性能，生物医学应用是多铁ME平台的最终目标。该研究成果将为再生医学和多材料生物打印领域新型复合材料的研究提供参考，直接实现功能性植入物的实现。这个未来制造奖是由民用、机械和制造创新部门支持的。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。

Tissue engineering is a biomedical engineering process that usually involves combining cells, biomolecules, scaffolds, and biologically interactive materials to maintain, restore, or improve tissues or organs. However, these manually made functional tissues have only limited use in human patients (e.g., artificial skin or cartilage). The challenges include innovating cost-efficient tooling engineering, creating materials with suitable biochemical and physicochemical factors, and sustainable platforms delivering in-situ diagnosis for directing the disease healing strategies. This Future Manufacturing Seed Grant (FMSG)-BioManufacturing project supports fundamental research for developing a new 3D printing technology to overcome some of these difficulties. For example, the newly developed printer can print multifunctional implants and scaffolds with high throughput and resolution, avoiding tedious tooling engineering. In addition, the newly invented biocompatible composites will also bring opportunities for various biomedical applications, such as tissue regeneration, neurotrauma treatment, and cancer curing. This project unites researchers with diverse expertise, including 3D printing, polymer science, nanoparticle engineering, and biomedical engineering. These investigators will also conduct STEM outreach at all levels, from K-12 public education to graduate course development. Significantly, the investigators will develop education-oriented TikTok/YouTube content to expose the most updated printing techniques to local and national K-12 students.Though 3D printing has been utilized to print piezoelectric or ferromagnetic composites separately, some bottlenecks remain. For example, conventionally 3D printed multiferroic magnetoelectric (ME) composites for biomedical uses have poor printability and limited efficiency in manufacturing fine features. This FMSG project aims to develop a new printing technology, named Multi-Scale and Multi-Material Continuous Liquid Interface Printing (MM-CLIP), by integrating scanning-projection and microfluidic flow control strategies. The MM-CLIP technology can enable scalable manufacturing of functional devices with increasingly small features and multiple materials, which have been the main challenge for the 3D printing field. With the MM-CLIP, multiferroic ME composites can be printed into hybrid piezoelectric and magnetostrictive platforms, i.e., multifunctional implants or tissue scaffolds, which can generate electrical signals from externally controlled magnetic fields that rarely attenuate in biosystems. An additional thrust is the multiphysics modeling framework for elucidating the ME coupling efficiencies of the printable composites and, thus, predicting and precisely controlling the electrical stimulation. In parallel, the project will systematically explore ME-induced electrical stimulation's effects on cell proliferation and correlates it to cell differentiation and growth factors. The iteration within the proof-of-concept studies will lead to optimal scaffold performance, and biomedical application is the ultimate goal of the multiferroic ME platforms. The research outcomes will facilitate the research on novel composites for application in regenerative medicine and multi-material bioprinting for the direct realization of functional implants.This Future Manufacturing award was supported by the Division of Civil, Mechanical, and Manufacturing Innovation.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.