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bioRxiv · 10.64898/2026.10.20.760419

Fibronectin Tethering as a Shear-thinning Bio-Annealing Strategy for Granular Hydrogels

Nicklow, E. J.·Ernst, O. D.·Highley, C. B.·Griffin, D. R.
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Abstract

Granular hydrogel scaffolds (GHS) are injectable, integrative biomaterials built from hydrogel microparticles that permit rapid cell infiltration independent of scaffold degradation. Microporous annealed particle (MAP) scaffolds, a sub-class of GHS, use inter-microparticle crosslinks to anneal adjacent particles, providing greater mechanical stability than purely jammed assemblies. A growing range of inter-particle crosslinking strategies, including covalent photo-initiated radical polymerization and reversible guest-host chemistries, some intended to mimic extracellular matrix (ECM) viscoelasticity, focus on mechanical stabilization, while surface bioactivity is typically added separately via orthogonally tethered cell-adhesion ligands such as RGD, a peptide derived from fibronectin (FN), a key mediator of cell-ECM and ECM-ECM interactions. Here, we present an alternative that unifies these functions: coating MAP microparticle building blocks with covalently bound fibronectin to create fibronectin-modified MAP (FN-MAP). FN-MAP exhibits shear-thinning annealing with complete recovery of scaffold mechanics after physical mixing. Human lung fibroblasts respond favorably, adopting spread morphologies with high viability. Translationally, FN-MAP shows proof-of-principle promise for 3D bioprinting (greater stability and higher print resolution) and wound healing (increased epidermal closure in a diabetic mouse model). FN-MAP thus delivers both increased scaffold strength and bioactivity without exogenous soluble linkers or mixed particle populations.

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Nicklow, E. J., Ernst, O. D., Highley, C. B., Griffin, D. R.. 2026-10-21. Fibronectin Tethering as a Shear-thinning Bio-Annealing Strategy for Granular Hydrogels. https://doi.org/10.64898/2026.10.20.760419

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