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组织在人类患者中仅具有有限的用途（例如，人造皮肤或软骨）。这些挑战包括创新具有成本效益的工具工程，创造具有合适的生物化学和物理化学因素的材料，以及提供原位诊断以指导疾病治疗策略的可持续平台。这个未来制造种子基金（FMSG）-生物制造项目支持基础研究，以开发新的3D打印技术，克服其中的一些困难。例如，新开发的打印机可以以高吞吐量和分辨率打印多功能植入物和支架，避免繁琐的工具工程。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，如组织再生，神经创伤治疗和癌症治疗。该项目汇集了具有不同专业知识的研究人员，包括3D打印，聚合物科学，纳米粒子工程和生物医学工程。这些调查人员还将在各级开展STEM推广活动，从K-12公共教育到研究生课程开发。值得注意的是，研究人员将开发面向教育的TikTok/YouTube内容，向当地和全国的K-12学生展示最新的打印技术。尽管3D打印已被用于分别打印压电或铁磁复合材料，但仍存在一些瓶颈。例如，用于生物医学用途的常规3D打印的多铁性磁电（ME）复合材料在制造精细特征方面具有差的可打印性和有限的效率。该FMSG项目旨在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），通过集成扫描投影和微流体流动控制策略。MM-CLIP技术可以实现具有越来越小的特征和多种材料的功能设备的可扩展制造，这一直是3D打印领域的主要挑战。利用MM-CLIP，多铁性ME复合材料可以被打印成混合压电和磁致伸缩平台，即，多功能植入物或组织支架，其可以从外部控制的磁场产生电信号，该磁场在生物系统中很少衰减。一个额外的推力是多物理场建模框架，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，该项目将系统地探索ME诱导的电刺激对细胞增殖的影响，并将其与细胞分化和生长因子相关联。概念验证研究中的迭代将导致最佳的支架性能，生物医学应用是多铁性ME平台的最终目标。该研究成果将促进新型复合材料在再生医学和多材料生物打印中的应用研究，以直接实现功能性植入物。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进行评估，被认为值得支持的搜索.

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.