Ultra‐Tough Hybrid Supramolecular Gelatin Hydrogels
- 1Program of Macromolecular Chemistry Department of Chemistry – Ångström Laboratory Uppsala University Uppsala Sweden
- 2Translational Chemical Biology Group Science For Life Laboratory Division of Macromolecular Chemistry Department of Chemistry‐Ångstrom Laboratory Uppsala University Uppsala Sweden
Abstract
Natural load‐bearing tissues derive mechanical performance from sequential self‐assembly, in which collagen fibrils first compact and are then stabilized by enzymatic covalent crosslinking. Replicating this design in synthetic hydrogels while limiting swelling and preserving toughness and viscoelasticity remains challenging. Here, we report a gelatin‐based hybrid hydrogel in which tannic acid‐mediated coacervation creates a compact acidic microenvironment that triggers in situ covalent crosslinking. Tannic acid induces rapid phase separation, lowers the local pH to ∼2.7, and promotes proton‐catalyzed ring opening of the preloaded bis‐oxazoline crosslinker, resulting in diester‐linked covalent stabilization of the compacted gelatin network. This decouples physical compaction from covalent stabilization and avoids the metastability of supramolecular tannic acid‐gelatin networks. The optimized formulation showed a ∼60‐fold increase in storage modulus (G′ ∼54 kPa) relative to acid‐swollen controls and combined high extensibility (elongation at break ∼900%), tensile strength (∼2.0 MPa), and toughness (5.46 MJ m−3). It also retained cyclic dissipation (4.21 MJ m−3 in the first cycle) and long‐term structural stability in water. In vitro, the hydrogels supported adhesion, spreading, and proliferation of human dermal fibroblasts over 3 days. Together, these results show that tannic acid‐mediated compaction coupled with acid‐triggered covalent crosslinking provides an effective route to strong, extensible, and dissipative gelatin hydrogels.
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BibTeX
@article{shakari2026ultratough,
title = {{Ultra‐Tough Hybrid Supramolecular Gelatin Hydrogels}},
author = {Patrick Shakari and Christos Leliopoulos and Hamidreza Mokhtari and Rohith Pavan Parvathaneni and Afroditi Kontse and Jöns Hilborn and Oommen P. Varghese},
journal = {Small (Weinheim an Der Bergstrasse, Germany)},
year = {2026},
month = sep,
doi = {10.1002/smll.75441},
url = {https://doi.org/10.1002/smll.75441},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Ultra‐Tough Hybrid Supramolecular Gelatin Hydrogels
AU - Patrick Shakari
AU - Christos Leliopoulos
AU - Hamidreza Mokhtari
AU - Rohith Pavan Parvathaneni
AU - Afroditi Kontse
AU - Jöns Hilborn
AU - Oommen P. Varghese
PY - 2026
DA - 2026/09/02
JO - Small (Weinheim an Der Bergstrasse, Germany)
DO - 10.1002/smll.75441
UR - https://doi.org/10.1002/smll.75441
AB - Natural load‐bearing tissues derive mechanical performance from sequential self‐assembly, in which collagen fibrils first compact and are then stabilized by enzymatic covalent crosslinking. Replicating this design in synthetic hydrogels while limiting swelling and preserving toughness and viscoelasticity remains challenging. Here, we report a gelatin‐based hybrid hydrogel in which tannic acid‐mediated coacervation creates a compact acidic microenvironment that triggers in situ covalent crosslinking. Tannic acid induces rapid phase separation, lowers the local pH to ∼2.7, and promotes proton‐catalyzed ring opening of the preloaded bis‐oxazoline crosslinker, resulting in diester‐linked covalent stabilization of the compacted gelatin network. This decouples physical compaction from covalent stabilization and avoids the metastability of supramolecular tannic acid‐gelatin networks. The optimized formulation showed a ∼60‐fold increase in storage modulus (G′ ∼54 kPa) relative to acid‐swollen controls and combined high extensibility (elongation at break ∼900%), tensile strength (∼2.0 MPa), and toughness (5.46 MJ m−3). It also retained cyclic dissipation (4.21 MJ m−3 in the first cycle) and long‐term structural stability in water. In vitro, the hydrogels supported adhesion, spreading, and proliferation of human dermal fibroblasts over 3 days. Together, these results show that tannic acid‐mediated compaction coupled with acid‐triggered covalent crosslinking provides an effective route to strong, extensible, and dissipative gelatin hydrogels.
SN - 1613-6810
SN - 1613-6829
ER -