Black phosphorus boosts wet-tissue adhesion of composite patches by enhancing water absorption and mechanical properties

Tissue adhesives are valuable in biomedical applications for hemostasis, device fixation, reduced trauma, and pain relief, but maintaining strong adhesion on wet tissues is challenging due to hydration films that block direct contact and form hydrogen bonds with adhesive functional groups, weakening interfacial binding. Strategies inspired by mussels and barnacles include hydrophilic and hydrophobic water-removal approaches, dry-crosslinking tapes, and repellent pastes, as well as leveraging mechanical robustness and diverse surface interactions (hydrogen bonding, dynamic covalent bonding, bioinspired and topological adhesion) to target functional groups (e.g., NH2) on tissue surfaces. Black phosphorus (BP) nanosheets are biodegradable and can degrade under oxygen and water to phosphate anions (PO2−, PO3−, PO43−). Because swelling in polymers arises from interactions of hydrophilic chains with water and many networks contain zwitterionic cationic and anionic groups, introducing phosphate anions can disrupt inter- and intrachain electrostatic attractions, promoting chain dissociation and enhanced swelling. BP also provides near-infrared photothermal conversion and electrical conductivity useful for photothermal therapy and conductive hydrogels. This work proposes a composite patch with BP nanosheets (CPB) to enhance water absorption and mechanical properties for immediate, robust wet-tissue adhesion and to enable applications such as rapid hemostasis, biosensing, and postsurgical tumour-recurrence prevention.

The study builds on extensive research into wet-tissue adhesives and bioinspired adhesion strategies. Prior work has addressed the hydration barrier on wet tissues using hydrophilic and hydrophobic water-removal designs, including dry double-sided tapes and barnacle-inspired pastes, and by enhancing mechanical strength in tape-type adhesives. Molecular strategies have included hydrogen bonding, dynamic covalent bonding, and bioinspired/topological adhesion to interact with tissue surface groups. Nature-inspired systems (mussels, barnacles, spider glue) demonstrate mechanisms to mitigate hydration layers. Additionally, black phosphorus has been studied for biomedical applications due to biodegradability, photothermal properties for NIR-driven therapy, and electrical conductivity for conductive hydrogels. These literatures underpin the CPB design that combines a robust, multi-network polymer with BP nanosheets to increase water absorption and functional performance under wet conditions.

Materials: Patches composed of methacrylate anhydride-modified hyaluronic acid (HAMA), gelatin (Gel), and poly(vinyl alcohol) (PVA), with BP nanosheets integrated; surface treatment with dopamine-modified polyacrylic acid (PAA-DA) to form a third crosslinked network via topological entanglement. Patches without BP (CP) served as controls. BP nanosheets (~100 nm–1 µm lateral, 10–100 nm thickness) were commercially sourced. Preparation: Solutions of HAMA (6 wt%), PVA (30 wt%), BP (1 mg ml−1), EDC/NHS linker, and photoinitiator (12959) were mixed, then Gel (30 wt%) added. EDC/NHS-mediated intercrosslinking formed between HAMA and Gel; UV irradiation (365 nm, ~68 mW cm−2, 5 min) induced HAMA self-crosslinking. Films were dried overnight. PAA-DA (5 wt%, 0.5 µl mm−2) was drop-cast for 1 min to permeate and create a surface network. Characterization: SEM/EDS for morphology; Raman and FTIR for BP incorporation; XPS for chemical states (N 1s speciation; P 2p showing P–P and P–O indicating phosphate formation from BP degradation). Swelling degree measured in water over 60 min; water vapor sorption at 90–95% RH over 60 min; contact angle over 10 min; confocal fluorescence with calcein dye to visualize absorption; IR thermal imaging in hot steam; pore morphology post-lyophilization. Computational: DFT (Gaussian 16, M06-2X-D3(0)/6-311+G(d)) to compute binding energies among HAMA/Gel segment pairs and phosphate–Gel interactions, assessing disruption of electrostatic associations by PO43−. Mechanical/electrical/thermal: Young’s modulus, tensile strength, elongation at break; electrical resistivity; photothermal heating under NIR in wet state. Adhesion testing: Lap-shear (ASTM F2256) and modified 180° peel (ASTM F2255) on wet porcine tissues (skin, heart, stomach, liver) and nude mouse skin, with and without PAA-DA; commercial cyanoacrylate adhesives as controls. Adhesion assessed at 0, 12, 48 h. Ex vivo model: Rabbit stomach perforation sealing test with water-filled organ to evaluate leakage sealing. In vivo studies: SD rat liver and heart perforation models for hemostasis; nude mouse EMG sensing using CPB as electrode; tumour recurrence prevention in MCF-7 RFP xenograft model with groups: surgery only (S), NIR only, S+CP, S+CPB, S+CPB+NIR (808 nm, 1 W cm−2, 5 min). Body weight, tumour volume recorded bi-daily; IVIS fluorescence weekly. Histology (H&E) of major organs at 4 weeks for toxicity. In vivo degradation with/without NIR monitored up to 8 weeks. Statistics: two-tailed Student’s t-test; n typically = 3 independent samples.

- BP nanosheets enhance water absorption: After 60 min immersion, swelling degree increased with BP content: CPB-1.2 ~272%, CPB ~250% vs CP ~184%; CPB-0.2 ~220%. - Water vapor uptake at 90–95% RH (60 min): CPB ~0.48 g g−1 vs CP ~0.37 g g−1. - Wetting/absorption: Lower contact angles for CPB; after 10 min CP ~34° while CPB absorbed most droplet. Confocal imaging showed multiple absorption clouds for CPB vs one for CP; IR thermal imaging confirmed faster uptake. Lyophilized pore size increased with BP content. - Mechanism supported by DFT: In absence of PO43−, HAMA–Gel electrostatic interactions had binding energies ~−60 to −90 kcal mol−1; presence of PO43− increased affinity to cationic sites (Ebind PO43−–Gel up to −111 kcal mol−1), disrupting zwitterionic self-association and promoting chain expansion and water uptake. - Mechanical properties: CPB Young’s modulus ~102 MPa and tensile strength ~11 MPa vs CP ~45 MPa and ~6 MPa; elongation at break ~30% for CPB. - Electrical/thermal: CPB resistivity ~0.35 Ω·cm (vs CP ~0.70 Ω·cm; Cu foil ~0.33 Ω·cm). Photothermal heating in wet state reached ~54 °C in 5 min; in vivo surface heating to ~55 °C under 808 nm (1 W cm−2) within 5 min. - Adhesion (wet porcine tissues): Without PAA-DA, CPB shear stress ~119 kPa and interfacial toughness ~422 N m−1 on skin vs CP ~66 kPa and ~378 N m−1. With PAA-DA, CPB reached ~171 kPa and ~638 N m−1 (vs CP ~134 kPa and ~457 N m−1). Commercial cyanoacrylates showed ~74–105 kPa and ~73–88 N m−1 on wet skin, lower than CPB. - Adhesion (nude mouse skin): With PAA-DA, CPB shear stress ~252 kPa and interfacial toughness ~251 N m−1 vs CP ~203 kPa and ~144 N m−1. Adhesion strength increased over 48 h; CPB at 0 h ~42 kPa and ~34 N m−1, increasing >4× by 48 h. - Functional demonstrations: Instant adhesion to wet organs and blood-covered bone; sealed ex vivo perforated rabbit stomach rapidly. - Hemostasis (rat liver perforation): CPB achieved hemostasis within ~1–2 s with minimal bloodstain; total blood loss ~0.07 g vs blank ~0.4 g and commercial controls ~0.11–0.13 g. Heart model also showed rapid sealing. - Biosensing: CPB adhered as EMG electrode on nude mouse, showing sensing performance comparable to Cu foil and superior to CP. - Tumour recurrence prevention: In S+CPB+NIR group, no tumour reemergence within 4 weeks; other groups (S, NIR only, S+CP, S+CPB) showed varying recurrence. In vivo thermal imaging confirmed effective photothermal heating. Body weights showed no significant differences among treated groups; H&E of major organs showed no notable toxicity. - Degradation: In PBS at 37 °C, CPB lost >50% weight in 1 week and >75% in 2 months. In vivo residual mass ~40–42% at 8 weeks; NIR did not significantly affect biodegradation.

The study addresses the core challenge of wet-tissue adhesion—the interfacial hydration layer—by integrating BP nanosheets that degrade to phosphate anions. These anions preferentially bind cationic sites, disrupt inter- and intrachain electrostatic associations in the zwitterionic polymer network, and promote chain expansion and rapid water absorption. This mechanism reduces or removes interfacial water, enabling formation of hydrogen bonds and enhanced interfacial interactions with tissues. Combined with a robust triple-network architecture and catechol-containing PAA-DA surface treatment, CPB achieves immediate and strong adhesion on diverse wet tissues with superior shear strength and interfacial toughness compared to BP-free controls and commercial cyanoacrylates. The improved mechanics and flexibility maintain adhesion under dynamic conditions. Multifunctionality from BP provides low resistivity for biosensing and potent photothermal conversion for postsurgical tumour ablation, which, together with strong adhesion, enables precise local therapy that prevented tumour recurrence in vivo over 4 weeks. Biodegradation and histocompatibility results support short-term in vivo use.

This work introduces a BP-integrated composite patch (CPB) with a triple-network design and catechol surface treatment that enhances water absorption, mechanics, and wet-tissue adhesion. Mechanistically, phosphate anions from BP disrupt zwitterionic electrostatic associations, accelerating water uptake and eliminating hydration barriers. CPB exhibits superior wet adhesion (up to ~171 kPa on wet porcine skin and ~252 kPa on nude mouse skin), robust mechanical properties, conductivity for biosensing, and effective photothermal performance. Demonstrations include rapid hemostasis within ~1–2 s, reliable physical-activity monitoring, and complete prevention of postsurgical tumour recurrence in a mouse model with NIR irradiation, with good biodegradability and histocompatibility. Potential future directions include optimizing BP content and degradation kinetics for tailored absorption and adhesion profiles, expanding testing to larger animal models and longer-term implantation, evaluating sterilization and storage stability, and integrating drug delivery or antimicrobial functions for advanced clinical applications.

The study focuses on short-term animal models with relatively small sample sizes (commonly n=3), which may limit statistical power and generalizability. Long-term safety, immune responses, and performance in larger animals or under clinically relevant mechanical loads were not comprehensively assessed. Adhesion metrics were primarily measured ex vivo or in small animals; translation to human-scale tissues may require further validation. Environmental factors (e.g., variable biofluid compositions) and potential variability in BP degradation rates in vivo were not deeply explored.