Rapidly damping hydrogels engineered through molecular friction

Hydrogels are increasingly used in applications requiring robustness under dynamic loading, such as wearable sensors, soft robotics, and tissue engineering. Conventional approaches to energy dissipation and toughening rely on viscoelastic mechanisms that use sacrificial bonds or secondary networks (hydrophobic interactions, ionic pairing, hydrogen bonding, coordination interactions, host-guest interactions, microcrystals). Breaking these interactions dissipates energy but often reforms slowly and non-specifically, impairing rapid recovery of dissipation capacity over cycles. This creates a challenge to simultaneously achieve efficient damping and fast recovery. The authors propose leveraging molecular-level friction as an alternative energy dissipation mechanism. Internal or intermolecular friction dissipates energy via sliding under normal forces and is tunable by force and velocity. They hypothesize that embedding controlled molecular friction into a hydrogel network can deliver high damping during deformation while enabling rapid recovery immediately after unloading, since the network structure remains minimally altered.

Prior work on hydrogel toughening emphasizes viscoelastic dissipation via sacrificial interactions and double-network architectures, which enhance hysteresis but suffer from slow bond reformation and recovery over multiple cycles. Slide-ring hydrogels use cyclodextrin (CD) rings threaded on PEG as slidable crosslinks, enabling tension equalization and toughness; however, after initial deformation, CDs relocate to balanced positions and subsequent long-range sliding is limited, leading to minimal hysteresis in later cycles. Friction as a dissipation mechanism at atomic/molecular scales is well-established, with energy loss controlled by normal forces and sliding velocity. Quasi-static recovery in conventional networks is limited by rebinding kinetics, whereas frictional dissipation is only active during motion and ceases upon load removal, suggesting a path to rapid recovery if integrated into an appropriate network design.

• Molecular design: Introduce chain walkers composed of cyclodextrin dimers (α- or β-CD) tethered by a short PEG linker (2 kDa), denoted PEG-α-CD and PEG-β-CD. These chain walkers slide along longer PEG strands (“railways”) within a covalently crosslinked tetra-arm PEG network (20 kDa arms), enabling molecular friction during deformation and allowing rapid diffusion-based repositioning after unloading.
• Single-molecule force spectroscopy (SMFS): AFM-based SMFS in PBS at ~25 °C measured sliding friction between a PEG chain (10 kDa) attached to a cantilever and surface-immobilized α-CD-NH2 or β-CD-NH2. Successful threading events (~1.65% pickup rate) yielded force plateaus; dynamic force spectroscopy probed pulling speeds from 200 to 3200 nm s−1. Control experiments with unmodified substrates confirmed specificity.
• Molecular dynamics (MD) simulations: GAFF/Antechamber force fields for PEG (n=34), α-CD, β-CD in TIP3P water. Steered pulling of PEG through CD, then in water, to quantify work and frictional force as a function of pulling speed (1–14 m s−1). Hydrogen bond analysis assessed interaction dynamics.
• Hydrogel synthesis: Maleimide-terminated 4-arm PEG (PEG-Mal, 20 kDa) and thiol-terminated 4-arm PEG (PEG-SH, 20 kDa) crosslinked via Michael addition. PEG-CD chain walkers were pre-mixed with PEG-SH (PEG-SH:PEG-CD molar ratios 1:1 or 1:2) to allow threading before adding PEG-Mal. Controls lacked PEG-CD; additional controls used unlinked CD monomers. Integration and threading efficiencies were assessed by NMR/UV and uptake analyses (>95% network integration; ~90% rings filled). Hydrogels with longer PEG-CD linkers (5 kDa) and lower solid content (2 mM precursors) were also prepared.
• Mechanical testing: Compressive stress–strain, compression–relaxation, and cyclic tests (Instron-5944) in air. Typical deformation rates: 0.2%–200% min−1; strains 30%–70%. Toughness from area under compression curves; dissipated energy from hysteresis loop; relative dissipation E/E0.
• Recovery assessment: Consecutive compression–relaxation cycles (e.g., 20 cycles) without waiting, including high-rate cycles (200% min−1), to quantify retention of maximum stress and dissipated energy.
• Cell protection studies: hMSCs encapsulated (5×10^5 mL−1) in hydrogels, cultured 24 h, then subjected to cyclic compression–relaxation at 0.5 Hz for 2000 cycles at 30% or 60% strain in culture medium. Viability assessed by calcein-AM/PI staining via LCFM; stemness assessed by immunostaining for Oct4 and Sox2 with DAPI nuclear counterstain. Additional controls included no-compression and varying solid contents.

• Molecular friction (SMFS): Distinct constant-force plateaus observed when pulling PEG through CD rings. At 200 nm s−1, mean frictional forces were 26 ± 10 pN (α-CD, n=107) and 19 ± 9 pN (β-CD, n=122). Friction increased with pulling speed from 200 to 3200 nm s−1 for both CDs. Extrapolated diffusion speeds at zero pulling force were 23 nm s−1 (α-CD) and 26 nm s−1 (β-CD), indicating rapid diffusion in the absence of load.
• MD simulations: Friction forces during PEG traversal through CD exceeded those in water and increased with pulling speed (1–14 m s−1), approximately doubling over this range; α-CD showed slightly higher friction than β-CD. Hydrogen bond formation/rupture events correlated with sliding, supporting a hydrogen-bond-mediated friction mechanism.
• Macroscale damping (compression-relaxation): Hydrogels with PEG-α-CD showed energy dissipation ~4.2× (1:1) and ~6.2× (1:2) greater than controls at ~50% strain; relative dissipations 42.0% and 49.2%. PEG-β-CD hydrogels showed ~1.6× (1:1) and ~3.3× (1:2) increases; relative dissipations 28.2% and 37.0%.
• Strain dependence: Increasing strain from 50% to 70% raised dissipated energy by 3.1× (α-CD) and 3.5× (β-CD). At 70% strain, relative dissipations reached 49.2% (α-CD) and 40.0% (β-CD), exceeding control (26.7%).
• Rate dependence: Energy dissipation increased with deformation rate. PEG-α-CD hydrogels showed a ~400% increase when rate rose from 0.2% to 200% min−1; PEG-β-CD showed ~340% increase. Controls were largely rate-insensitive.
• Linker length effect: Extending PEG-CD linker from 2 kDa to 5 kDa substantially reduced energy dissipation, approaching control levels, indicating walker legs must be shorter than network strands for effective friction.
• Recovery and durability: Under consecutive cycles without waiting, both α- and β-CD hydrogels retained >94% of maximum stress and dissipated energy after 20 cycles at 20% min−1, evidencing rapid recovery within seconds. At higher rate (200% min−1), dissipated energy after 20 cycles decreased to ~89%, attributed to incomplete walker restoration at very high rates.
• Controls with CD monomers: Adding unlinked CD monomers did not enhance energy dissipation or strength relative to controls, underscoring the necessity of dimeric chain walkers.
• Cell protection: After 2000 compression cycles at ~60% strain and 0.5 Hz, cell viability in PEG-CD hydrogels generally exceeded 50%, at least double that in control hydrogels; PEG-α-CD provided slightly higher protection than PEG-β-CD. Protective effect scaled with strain (lower strain yielded smaller enhancements). Hydrogels without compression maintained similar viabilities, indicating protection arises from damping, not CD addition.
• Stemness maintenance: hMSCs in PEG-CD hydrogels showed markedly higher Oct4 and Sox2 expression than controls after cyclic loading, indicating preservation of stemness under dynamic mechanical stress.
• Rheology and stability: Permanent deformations were <5% after 2000 cycles; loss moduli were significantly smaller than storage moduli; negligible stress relaxation observed, indicating responses dominated by the covalently crosslinked network while friction provided additional rate-dependent damping.

The study demonstrates that integrating molecular friction via CD-based chain walkers into a covalently crosslinked PEG network enables hydrogels to dissipate substantial mechanical energy during deformation and to recover their damping capacity rapidly after unloading. Unlike sacrificial bond-based viscoelastic mechanisms that require slow bond reformation and can degrade over repeated loading, frictional dissipation occurs only during motion and ceases upon load removal, leaving the network largely unaltered. The covalent network constrains the track length, allowing chain walkers to diffuse back quickly to their original positions once normal forces vanish. The observed strain and rate dependences at the macroscale closely mirror single-molecule friction behaviors, validating the molecular origin of damping. The design decouples toughness (enhanced via frictional energy loss) from network strength (set by crosslinking and polymer concentration), addressing a longstanding trade-off in hydrogel engineering. Compared to traditional slide-ring hydrogels where rings move to tension-balanced positions and offer little hysteresis in subsequent cycles, these chain walkers repeatedly slide and dissipate energy with rapid recovery, maintaining performance over cycles. The hydrogels effectively protect encapsulated stem cells from cyclic mechanical insult and preserve stemness markers under dynamic loading, highlighting relevance to biomechanical environments where repeated stresses occur.

This work introduces a hydrogel architecture that harnesses molecular friction through CD dimer chain walkers on covalently crosslinked PEG tracks to achieve high, rate-tunable energy dissipation with rapid recovery. Single-molecule and MD results establish hydrogen-bond-mediated PEG–CD friction that scales with pulling speed; macroscale tests show large, strain- and rate-dependent hysteresis, fast recovery (>94% retention after 20 cycles), and robust cell protection with maintained stemness under cyclic loading. The design principles—short walker legs relative to network strands and end-fixed tracks defined by covalent crosslinks—enable repeated sliding and rapid repositioning, overcoming the limitations of sacrificial-bond damping. Potential future work includes optimizing walker chemistry and length scales, exploring alternative host–guest pairs and polymer backbones, and integrating these rapidly recovering damping hydrogels into biomedical devices, tissue scaffolds, and soft robotic components operating under dynamic loads.

• At very high deformation rates (e.g., 200% min−1), energy dissipation retention decreased to ~89% after 20 cycles, suggesting incomplete restoration of chain walker positions between rapid cycles.
• Effective damping requires chain walker legs shorter than network strands; increasing linker length (from 2 kDa to 5 kDa) substantially diminished frictional dissipation, constraining design space.
• During gelation, both CD rings in a dimer may thread the same PEG chain (intra-chain slide-ring linkage), which does not contribute to friction-based dissipation, potentially reducing effective walker population.
• Protective effects for cells scaled with applied strain; lower strains yielded smaller improvements in viability consistent with reduced dissipation, indicating performance depends on loading conditions.