4D Bioprinting: The Next Generation of Living Biosystem Manufacturing

4D printing is a new and exciting manufacturing process that creates structures designed to change shape or function over time when exposed to specific stimuli. Compared to traditional 3D bioprinting, incorporating a time dimension in bioprinting is intriguing, as the dynamic 4D effect can more accurately mimic natural tissue development and better regulate cell behaviors.

However, the fundamental knowledge of the relationship between living biosystems and dynamic manufacturing is still lacking and needs to be explored to uncover its full potential. This project aims to use this innovative 4D printing technology to develop soft robotic systems and establish the foundational knowledge for targeted stem cell delivery. For this purpose, a versatile 4D bioprinting approach will be created to produce custom living biosystems, expanding therapeutic options and meeting the complex demands of various medical fields.

In addition, the project outlines convergent research, educational, and outreach activities, which will address the critical challenges in advanced biomanufacturing for biomedical studies.

This project will investigate the manufacturing science underlying the design of reprogrammable soft robotic systems for targeted stem cell delivery within a biomimetic environment. These 4D printed soft robots will be capable of reshaping in response to stimuli, enabling cargo loading and release. Additionally, their magnetic controllability will allow precise guidance to the intended delivery site.

To achieve this goal, the project will pursue two aims: Aim 1 focuses on synthesizing a multi-responsive and magnetically controllable 4D ink material for bioprinting structures. Various ink formulations will be explored to optimize printability and achieve desired properties such as stimuli-responsiveness and mechanical strength. Aim 2 involves fabricating soft robots and evaluating their performance in loading, docking, and delivering neural stem cell spheroids (neurospheres) on demand.

Furthermore, the ability of these spheroids to integrate into neural networks will be assessed in vitro. The successful completion of this project will build the foundation to enable a novel biomanufacturing platform and push the boundaries of living biosystem manufacturing.

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.