Title : Channel fidelity limits in in-wound hydrogel printing for cartilage regeneration
Abstract:
Damages to tissues with limited self-regenerative capacity, such as cartilage, require advanced regenerative strategies. One promising approach is in situ photopolymerization (direct in-wound printing) of hydrogel scaffolds, designed to guide the migration of autologous stem cells from surrounding tissue. In this context, embedded channel architectures act as migration pathways and are therefore critical design features. However, most projection-based fabrication approaches rely on layer-by-layer printing of thin films, which is impractical for clinical in situ applications where millimeter-scale constructs must be generated rapidly and directly at the defect site. While channel geometry is known to influence cell migration, the fidelity limits of channel formation in thick, single-step printed hydrogels remain poorly understood, particularly under clinically relevant conditions such as optical scattering from underlying tissue. Here, we investigate thickness-dependent channel fidelity in projection photopolymerized PEG hydrogels and identify fundamental constraints relevant for in-wound fabrication. By systematically varying hydrogel thickness and feature size, we demonstrate that channel distortion increases exponentially with depth, consistent with optical attenuation and beam divergence. Below a critical feature size, channels fail to remain permeable across millimeter-scale thicknesses, defining a geometry-dependent fabrication threshold. Furthermore, substrate-induced scattering, mimicking bone, significantly reduces feature dimensions, while post-curing swelling introduces additional geometry-dependent changes.
Together, these effects establish a predictive framework for estimating achievable channel geometry in thick hydrogel constructs. The results highlight that channel fidelity and not lateral resolution becomes the limiting factor in in situ hydrogel printing. These findings provide practical design constraints for scaffold architecture and support the translation of projection-based photopolymerization toward clinical tissue engineering applications.

