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  4. Spatial Control of Electrical and Mechanical Functionalities in Hydrogels through Additive Manufacturing
 
doctoral thesis

Spatial Control of Electrical and Mechanical Functionalities in Hydrogels through Additive Manufacturing

Lucherini, Lorenzo  
2025

Hydrogels are widely used in cell biology and tissue engineering because of their high water content, biocompatibility, and adjustable mechanical properties. These qualities make them ideal for mimicking the extracellular matrix and creating soft devices that interact with biological tissues. However, their lack of electronic conductivity and low mechanical stiffness limit their application in bioelectronics and load-bearing uses such as bone tissue engineering. Efforts to overcome these limitations by adding conductive fillers or biominerals often reduce processability, especially through additive manufacturing techniques like direct laser writing (DLW) or extrusion-based 3D printing. To address these issues, I explore two strategies centered on the bottom-up, in-situ formation of functional fillers within hydrogels. By spatially localizing these fillers, the hydrogel gains electrical or mechanical functions not present in the original material, without losing compatibility with advanced manufacturing methods. In the first strategy, I use two-photon DLW to create high-resolution silver microstructures inside optically clear, soft hydrogel matrices. This technique reduces silver salts within the hydrogel through photoreduction, resulting in conductive features with resolutions as small as 5 µm and conductivities up to 1505 S/cm, without pre-mixing conductive fillers. This separates hydrogel formulation from filler addition and enables the creation of embedded or surface-exposed conductive pathways, opening new possibilities for soft, hydrogel-based bioelectronic devices. The second strategy uses a nature-inspired approach to 3D print biomineralized hydrogel scaffolds. Ureolytic bacteria are encapsulated in printable microgels to create a bioactive ink capable of inducing calcium carbonate mineralization in situ. This mineralization happens after printing, allowing independent optimization of the ink's rheological properties for printability. Spatial and temporal control over biomineralization results in scaffolds with mineral content up to 93% by weight. The microgels act as sacrificial templates, guiding the development of a 3D porous network that mimics trabecular bone architecture and achieves compressive strengths up to 3.5 MPa. This process uses only mild, biocompatible reagents and avoids high-temperature sintering. I demonstrate proof-of-concept applications in bone tissue engineering by printing complex porous structures and suggest potential use in art restoration. Together, these methods demonstrate that in-situ formation of functional fillers allows the spatial integration of conductivity and stiffness into hydrogels without compromising optical or rheological properties essential for additive manufacturing. I also outline future directions to enhance and expand these approaches, including using DLW to create 3D interconnects inspired by microfabrication techniques and developing hybrid scaffolds that combine electronic and mechanical functionalities for advanced tissue engineering. These innovations establish bottom-up hydrogel functionalization as a versatile platform for next-generation cell culture materials, bioelectronic devices, and engineered tissue scaffolds.

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EPFL_TH11445.pdf

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