Towards 4D Bioprinting: Encoding Stimuli-Triggered Shape-Morphing Behavior in Printable Hydrogels

In tissue engineering, a major challenge is the development of materials for 4D bioprinting, i.e. materials that not only serve as scaffolds for living cells and are printable but also dynamically change shape in response to external stimuli. Our team has recently engineered a hyaluronic acid-based hydrogel crosslinked via dynamic covalent bonds, which is compatible with extrusion printing and shows promise as a cellular scaffold. The goal of this PhD project is to transform this 3D-printable hydrogel into a stimuli-responsive, shape-morphing material for 4D bioprinting.

To achieve this, we will focus on precisely controlling the hydrogel’s swelling behavior post-printing. Our approach combines two complementary strategies. First, we will graft thermoresponsive polymers onto the hyaluronic acid chains, rendering the hydrogel temperature-sensitive. Above the polymer’s phase transition temperature, the gel will deswell, enabling controlled swelling after printing. Second, we will incorporate biocompatible microfibers into the hydrogel. During extrusion printing, these fibers can be aligned, which influence the direction of the swelling/deswelling phenomenon. By printing constructs with varying fiber orientations, we can create domains that swell in different directions, generating mechanical stresses that induce shape changes.

By combining these approaches, we aim to develop advanced hydrogel systems for 4D bioprinting. As a proof of concept, we will design synthetic vascular tissues for the reinforcement or replacement of damaged vessels. Endothelial cell-laden hydrogels will be printed into designs that can adopt the targeted shape in situ upon integration into the body at 37°C.

This project will give the student practical experience in the chemical modification of polymers, the design and characterization of soft biomaterials as well as an experience with cell manipulation. The experimental work will cover the synthesis of components, the preparation and characterization of complex hydrogel systems, the 3D printing and analysis of their shape-morphing behavior and the evaluation of the cytocompatibility.

The internship will take place in the CERMAV Laboratory in Grenoble, France. The CERMAV is a leading research center in the field of natural polymer. More specifically, the candidate will work in the team “Structure and Modification of Polysaccharides” which employs modified polysaccharide molecules to design innovative materials for biomedical applications.

The candidate should have strong knowledge in polymer chemistry and physical chemistry. They should be curious, proactive in facing technical challenges, and interested in “smart materials.” Good writing skills and work organization are also essential for the successful completion of this project.