Speaker
Description
Self-assembling peptide amphiphiles (PAs) offer a unique combination of biofunctionality, structural tunability, and nanofibre alignment under shear, making them highly promising materials for advanced in vitro tissue models. Despite this potential, their inherent fragility and the lack of scalable structuring strategies have restricted their wider adoption for in vitro modelling. To address these challenges, we present a novel platform that merges molecular self-assembly with top-down processing - integrating peptide nanofibre gelation with continuous fibre-based extrusion. This enables the scalable creation of robust, hierarchically structured hydrogel coatings with controlled nanostructural alignment, organised concentrically around a mechanically supportive core.
Our system employs a custom-designed, modular extrusion platform featuring a stereolithography (SLA)-printed coaxial nozzle. A syringe pump delivers precise control over peptide solution flow, while a motorised drive module advances a central thermally drawn PLA optical fibre (225 µm diameter). During the process, the peptide amphiphile solution - formulated with thermally annealed E3 (C₁₆–V₃A₃E₃) at 2 wt.% - is deposited around the moving fibre and extruded into a calcium chloride bath, where calcium ions rapidly induce gelation. This continuous coaxial setup allows simultaneous alignment of the nanofibre network and solidification of the coating layer.
A key innovation of this approach is the use of power-law rheology in shear-thinning PA solutions to modulate alignment within the gel. By tuning flow rate and fibre velocity, we demonstrate control over shear stress, which directly influences the orientation of nanofibres across the hydrogel thickness. Lower extrusion speeds result in weakly aligned surface layers, while higher speeds generate fully aligned coatings, as confirmed via birefringence imaging (Figure 1). The resulting ~80 µm thick coatings are uniform, reproducible, and stable, with mechanical integrity provided by the inner fibre core.
The suspended fibre geometry supports advanced imaging and characterisation. Using rotationally resolved birefringence microscopy, we map the geometry and internal alignment of the gel layer in 3D. These experimental results are supported by rheological characterisation and will inform computational fluid dynamics (CFD) simulations to establish predictive links between process parameters and structural outcomes.
Preliminary biological validation involved seeding primary mouse cortical neurons onto the coated fibres. Cells exhibited strong attachment and healthy morphology, suggesting excellent compatibility of the aligned peptide hydrogel environment with neuronal culture. This confirms the platform’s potential as a next-generation neural model, capable of supporting further development into electrically or chemically stimulated systems.
By bridging bottom-up self-assembly and top-down processing, this fibre extrusion system represents a major step forward in structuring bioactive, aligned hydrogels for tissue engineering. It offers a robust, scalable solution to the key limitations of fragile peptide hydrogel systems while introducing a new approach for using flow dynamics to guide nanostructural assembly. Our future work will explore how alignment and stimuli from the central fibre can modulate neuronal behaviour, enabling the creation of smart, bioactive models for neuroscience and regenerative medicine.
Attached Figure 1: Birefringence images of PA Gel coated optical fibre at 5mm/s (a), 6mm/s (b), and 8mm/s (c), showing increased aligned domains with extrusion speed.
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