Designing nanohesives for rapid, universal, and robust hydrogel adhesion

Wet adhesion is ubiquitous in living systems (cells to ECM, tendon-to-bone, mussel threads to rocks) and inspires biomedical engineering applications such as hydrogel machines. Numerous strategies for robust wet adhesion between hydrogels and diverse solids have been developed, including bioinspired chemistries (mussel, sandcastle worm, slugs, barnacles), surface-initiated or ultrasound-mediated techniques, enabling advances in devices and tissue repair. Nanoparticles have been explored as interfacial interlinks to bond hydrogels and tissues, with diverse nanoparticle chemistries (e.g., mesoporous silica, ceria-decorated silica, metal oxides) offering added functionalities. However, existing nanoparticle-based glues often have adhesion energies mostly below 100 J/m², limited adherend ranges, and slow formation (minutes), and often require substrate pre-treatments, which hinder practical applications. The authors hypothesize that tuning nanoparticle surface chemistry and hydrogel properties (mechanics, water absorption) can markedly improve adhesion performance. They propose "nanohesives" that combine surface-activated nanoparticles (ANP) with a dissipative hydrogel to enable rapid, robust, and universal hydrogel adhesion.

Prior work spans bioinspired wet adhesives (mussel, sandcastle worm, slugs, barnacles) and physical/chemical bonding methods (surface-initiated, ultrasound-mediated). Hydrogel adhesion has enabled anticoagulant coatings, fault-tolerant hydrogel tapes, and scarless wound repair platforms. Nanoparticle-based glues have served as interfacial interlinks with added functions: mesoporous silica to activate benign inflammation, ceria-decorated silica for ROS scavenging, silica nanoparticle coatings to promote coagulation, and metal oxide nanoparticles for imaging or antimicrobial effects. Adhesion enhancement strategies included increasing nanoparticle surface area, assembly forms, and exploiting nanoparticle shape effects. Despite these advances, reported adhesion energies typically remain below 100 J/m² and adhesion spectrum is narrow, with formation times of minutes and frequent need for substrate pre-treatments. These limitations motivate the current design focusing on nanoparticle surface activation and hydrogel mechanics/water absorption to improve performance.

Design and materials:

• Nanohesives comprise surface-activated nanoparticles (ANP) and a matched dissipative hydrogel. ANP are silica nanoparticles modified to present carboxylic groups via silanization (APTES) followed by succinic anhydride chemistry in DMF with DMAP, yielding abundant adhesive sites without changing particle size.
• Dissipative hydrogel consists of two networks: (i) a covalently crosslinked long-chain polyacrylamide network incorporating positively charged quaternary ammonium monomer (MOTAC, 10–50 mol%) to promote electrostatic interactions, and (ii) a physically crosslinked agarose network providing sacrificial bonds for energy dissipation.
• The hydrogel can be fabricated as single- or double-sided tapes. ANP glue is applied as a 20 wt% aqueous dispersion to wet interfaces, using dipping, brushing, or spraying; the hydrogel tape is then attached to form adhesion within seconds.

Preparation details (from Methods):

• Hydrogels: Hybrid agarose–polyacrylamide hydrogels prepared by dissolving agarose at 97 °C, casting to gel agarose, then UV-curing acrylamide/MOTAC networks (Irgacure 1173 photoinitiator, MBAA crosslinker). Control hydrogels (agarose–PAM without MOTAC; PDMA) synthesized similarly. Composition examples provided (e.g., agarose 250 mg; AAm ~2.18–3.03 g; MOTAC solution 3.635 g; MBAA and Irgacure specified; water ~11.49 g).
• Silica nanoparticles: Stöber synthesis in ethanol/water/ammonium hydroxide with TEOS at 30 °C for 6 h. Particle sizes varied by adjusting water/TEOS amounts (e.g., 50 nm typical synthesis). Particles washed and dispersed in ethanol.
• ANP surface activation: Disperse silica in ethanol; add DMF solution containing APTES (1 M), succinic anhydride (1 M), DMAP (0.01 M); react at 60 °C for 12 h; wash by ethanol.

Adhesion testing and mechanics:

• Adhesion to rigid substrates: 90° peel tests (ASTM D3330) on Instron 5565A with 500 N load cell and 90° peel fixture. Rigid substrates 150×50×20 mm³; hydrogel strips 100×25×2 mm³ laminated with 180 µm PC stiff backing via ethyl cyanoacrylate to localize energy at crack tip. Adhesion energy taken as plateau force/width. PTFE comparisons included Scotch tape and cyanoacrylate bonding.
• Adhesion to soft substrates: 180° peel tests (ASTM F2256); adhesion energy = 2× plateau force/width.
• Hydrogel fracture toughness: Pure shear tests on notched/unnotched specimens (50×5×2 mm³; 20 mm edge crack), computing energy from stress–stretch curves.

Parametric studies:

• Nanoparticle size vs hydrogel mesh size: Varied hydrogel crosslinker to adjust mesh size; evaluated adhesion energy vs ANP size, observing non-monotonic trends and peak shifts with mesh size.
• Interface chemistry: Compared adhesion without ANP, with poly(acrylic acid) solution as glue, with pristine silica (silanol) vs ANP (carboxyl) and with/without MOTAC in hydrogel network to probe electrostatics.
• Dissipative capacity: Varied agarose content to tune hysteresis/fracture toughness and studied correlation with adhesion energy.

Biocompatibility and antibacterial tests:

• Conditioned medium cytocompatibility: Human gingival fibroblasts cultured with nanohesives-conditioned medium for 24–48 h; viability via CCK-8 assay at 450 nm.
• Antibacterial activity: S. aureus (10^6 CFU/mL) cultured with material discs (6 mm) for 24 h; OD600 measured to assess growth inhibition.

Application demonstrations:

• In vitro vessel model: Strain sensor (Au serpentine gauges on PI) conformally fixed around a silicon rubber tube (4 mm diameter) using nanohesives; pulsatile expansion driven by syringe pump; force gauge and electrical resistance recorded; frequency and amplitude varied.
• In vivo canine femoral artery monitoring: Anesthetized labrador dog; sterilized materials; ANP brushed on vessel/sensor; sensor fixed via nanohesives around femoral artery; resistance-based pulse signals recorded and compared with ECG over 30 min.

Stability/tolerance assessments:

• Adhesion after PBS soaking (24 h) and under load (6 kPa, 24 h); tolerance to surface foulants (PBS, blood, fat) on porcine skin surfaces.

Characterization: Zeta potential/size (Malvern Nano-ZS90), SEM (Zeiss Merlin), contact angles (OCA-25), electrical resistance (Keithley DMM7510).

• Rapid formation: Nanohesion forms within seconds via an absorption–interaction mechanism where the dissipative hydrogel absorbs interfacial water, concentrates ANP at the interface, and promotes intimate contact and bonding.
• Interface chemistry critical: Without ANP or using poly(acrylic acid) solution as glue, adhesion energy ~10 J/m² on impermeable substrates. Pristine PAM hydrogel (without MOTAC) shows limited adhesion even with ANP. Electrostatic carboxylate–quaternary ammonium interactions (ANP carboxyl with hydrogel MOTAC) strongly enhance adhesion.
• Surface activation benefit: Carboxyl-functionalized ANP increase adhesion energy from ~250 J/m² (pristine silica, silanol) to ~1500 J/m² under comparable conditions.
• Dissipative mechanics govern toughness: Increasing agarose content raises hydrogel fracture energy and linearly correlates with higher nanohesion energy, indicating improved resistance to interfacial damage. Overall adhesion varies non-monotonically with MOTAC content due to trade-off between bonding sites and mechanical performance.
• Size/mesh-size effects: Adhesion energy vs ANP size is non-monotonic; adjusting hydrogel mesh size (via crosslinker) shifts the peak adhesion for different ANP sizes, evidencing dependence on interfacial interaction strength.
• Universal adhesion to engineering materials without pre-treatment: Metals and ceramics up to ~1400 J/m²; plastics and rubbers ~500–1400 J/m². On PTFE, adhesion ~500 J/m², outperforming Scotch tape and cyanoacrylate in tests.
• Tolerance to surface roughness: Robust adhesion on rough PLA surfaces comparable to smooth surfaces due to fine ANP size and good wetting.
• Adhesion to biological tissues ex vivo: Skin ~1200 J/m²; bone ~1200 J/m²; kidney ~600 J/m²; liver ~350 J/m². Lower values on fragile tissues due to tissue rupture prior to interfacial failure. Nanohesives can exclude fluid foulants (PBS, blood, fat) and rapidly form protective adhesion; adhesion on PBS-covered skin ~1100 J/m².
• Stability: Slight decline after 24 h PBS soak (e.g., ~1200 J/m² on glass; ~1000 J/m² on porcine skin). Sustains 6 kPa load in PBS for at least 24 h.
• Biocompatibility and antibacterial activity: Human gingival fibroblasts maintain full viability after 24 h in conditioned medium. Nanohesives show significant S. aureus growth inhibition compared to controls, attributed to quaternary ammonium components.
• Device integration and sensing accuracy: In vitro artificial artery tests show strain sensor fixed by nanohesives tracks pulsation frequencies from ~47 to 225 b.p.m with <5% frequency error versus force gauge. In vivo canine tests show pulse signals closely match ECG; over 30 min, rate difference <2 b.p.m in >90% of time, with stable conformal fixation enabling accurate monitoring.

The study addresses key limitations of nanoparticle-based hydrogel adhesives—low adhesion energy, limited adhesion spectrum, and slow formation—by combining chemically active nanoparticles with a dissipative hydrogel network. The absorption–interaction mechanism, enhanced by hydrogel water uptake and electrostatic interactions between ANP carboxyl groups and hydrogel quaternary ammonium groups, enables rapid interfacial assembly and bonding in wet environments. Concurrently, the agarose-based dissipative network toughens the interface by resisting crack propagation, translating hydrogel fracture toughness into higher interfacial adhesion energy. The nanohesives demonstrate broad-spectrum, robust adhesion to untreated engineering materials and biological tissues, with tolerance to interfacial foulants (PBS, blood, fat) and surface roughness, enabling practical deployment where pre-treatment is not feasible. The substantial increase in adhesion energy (up to ~1500 J/m²) and rapid formation expands design flexibility and utility over prior nanoparticle glues. The successful integration of flexible sensors for in vitro and in vivo blood flow monitoring underscores the capacity of nanohesives to create stable, conformal human–machine interfaces, supporting accurate biomechanical signal acquisition. These findings validate the hypothesis that tuning nanoparticle surface chemistry and hydrogel mechanics synergistically improves adhesion performance. The work also highlights how nanoparticle functionalities (e.g., antimicrobial) can be co-delivered at interfaces, suggesting routes to multifunctional adhesive systems.

This work introduces nanohesives that synergize carboxyl-functionalized silica nanoparticles with a dissipative, cationic hydrogel to achieve rapid, universal, and tough wet adhesion across engineering solids and biological tissues without surface pre-treatment. The system leverages an absorption–interaction mechanism and hydrogel energy dissipation to reach adhesion energies up to ~1500 J/m², while maintaining biocompatibility and inherent antibacterial activity. Demonstrations of robust, conformal fixation of strain sensors enable accurate blood flow monitoring in vitro and in vivo, illustrating translational potential for biomedical devices and human–machine interfaces. Future research directions include: optimizing nanoparticle shapes (e.g., plates) to enhance interfacial stacking at lower concentrations; incorporating covalent bonding chemistries to stabilize long-term adhesion in challenging physiological environments; further tuning hydrogel dissipative mechanics and charge density; and expanding in vivo validations and application scenarios.

• Measured adhesion on fragile tissues (e.g., liver, kidney) is limited by tissue rupture before interfacial failure, potentially underestimating intrinsic interfacial toughness.
• Slight reduction in adhesion strength after 24 h PBS soaking; long-term stability in physiological environments requires further study.
• Current bonding relies primarily on physical and electrostatic interactions; additional covalent mechanisms may be needed for prolonged stability in body fluids.
• Parametric optimization (nanoparticle shape, size, concentration; hydrogel charge and mesh size) can further improve performance; only selected conditions were explored.
• In vivo demonstrations are limited in scope (single animal model and short monitoring duration); broader preclinical studies are needed to generalize findings.