(Invited) Electro-Bio-Fabrication of Soft Matter
Authors: Payne Greg F 
Published: February 2024

Vision. Electrochemistry provides unique opportunities to couple top-down with bottom-up fabrication methods for the purpose of creating hydrogels with complex microstructures and bio-relevant functionalities.1 Thus, we envision that the coupling of electrochemistry with modern biological methods could enable a new additive manufacturing approach applicable to large-scale manufacturing yet simple and safe enough to be employed in publicly-available maker spaces.

Electrochemistry as a “Signal-Generator” to Cue the Emergence of Structure and Function. Electrical inputs imposed at an electrode can result in the “transmission” of both electrical and chemical “signals”. The imposed electric field provides cues for charged polymers to migrate (i.e., electrophoresis), and in some cases, to alter their chain conformations (extended vs collapsed) and chain alignments. Electrochemical reactions at the electrode can generate chemical cues (e.g., pH gradients, diffusible oxidants/reductants and metal ions) that can induce polymers to undergo hierarchical assembly through physical, covalent and chelation mechanisms. Together, the electrical and chemical cues provide the opportunity to generate hydrogels with controlled microstructures.

Biology as a Source of Materials and Mechanisms for Electro-assembly. Typically, biology achieves its immense morphological diversity using a small set of polymers (e.g., collagen, cellulose and chitin) that possess internal structural information for assembly. Biology then precisely imposes the contextual cues that control the emergence of higher-order structure from these biopolymers. Numerous studies from various laboratories have shown that several biopolymers can be cued by electrochemical inputs to reversibly self-assemble into organized supramolecular structures (e.g., hydrogels). Examples include proteins (collagen and silk) and polysaccharides (chitosan and alginate) that electro-assemble in response to modest imposed voltages often through pH-based neutralization mechanisms. Also important is that various groups using different biopolymeric systems (e.g., collagen, silk and chitosan) are demonstrating that the imposed electric field can orient and align the polymer chains to form hierarchically organized microstructures (e.g., collagen fibrils).
In addition to using reversible mechanisms for assembly, biology also uses oxidation mechanisms to induce protein matrix crosslinking and functionalization, and these mechanisms are often residue-specific (i.e., different mechanisms are used to induce crosslinking through cysteine thiols, lysine amines and tyrosine phenols). Using biology as a model, we are developing electrochemical approaches to generate diffusible oxidants to induce hydrogel electrodeposition through covalent crosslinking mechanisms. In addition, electrochemically-induced oxidations can be used to directly graft functional moieties to hydrogels, and in some cases to “activate” hydrogels for subsequent functionalization (e.g., for the grafting of enzymes).2,3

Fabrication Examples. The best-studied example is the cathodic electrodeposition of the pH-responsive aminopolysaccharide chitosan through a neutralization mechanism (the high pH adjacent to the cathode induces chitosan’s sol-gel transition). The versatility of electrical signals is illustrated by two studies. First, when the electrical input was provided in an oscillatory fashion, a segmented hydrogel structure emerged with the segment regions controlled by the “ON” signal and the boundary regions controlled by the “OFF” signal.4 Second, when chitosan’s electrodeposition was performed in 2 steps with low salt in the first step and high salt in the second step, a Janus structure emerged with one face being dense and non-porous and the other face being highly porous.5

Conclusion. Biology provides materials and mechanisms for bottom-up assembly, while electrochemistry can provide the precisely controlled top-down cues that guide the emergence of complex structure. The simplicity and safety of electro-bio-fabrication suggests it can be adapted to a wide range of applications. The challenge is to understand the mechanistic details associated with the coupling of top-down and bottom-up “information” to enable flexible design and feedback controlled manufacturing.
Cited Literature

Li et al. 2019. Electrobiofabrication: Electrically-Based Fabrication with Biologically-Derived Materials. Biofabrication. 11 032002

Li, J., E. Kim, K. M. Gray, C. Conrad, C.-Y. Tsao, S. P. Wang, G. Zong, G. Scarcelli, K. M. Stroka, L.-X. Wang, W. E. Bentley, G. F. Payne. 2020. Mediated Electrochemistry to Mimic Biology’s Oxidative Assembly of Functional Matrices. Advanced Functional Materials, 30 (30), 2001776

Li, J., S.P. Wang, G. Zong, C.-Y Tsao, E. VanArsdale, L.-X Wang, W.E. Bentley, G.F. Payne. 2021. Interactive Materials for Bidirectional Redox‐Based Communication. Advanced Materials, 33 (18), 2007758.

Yan et al. 2018. Electrical Programming of Soft Matter: Using Temporally Varying Electrical Inputs to Spatially Control Self Assembly. Biomacromolecules, 19,

Lei et. al. 2019. Programmable Electrofabrication of Porous Janus Films with Tunable Janus Balance for Anisotropic Cell Guidance and Tissue Regeneration. Advanced Functional Materials, 1900065

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