2.1 Mechanism of catechol-based underwater adhesion

Ability of mussels to adhere to various surfaces under wet conditions has attracted considerable attention because these abilities originate from the catecholic amino acid of DOPA secreted by the feet of mussels [16]. Catechol groups in polydopamine (PDA) play critical roles in adhesion because of the penetrating water boundary layers. Nevertheless, PDA formation from DA and its derivatives, as shown in Fig. 1, [17] still needs to be elucidated [18]. Catechol groups are reduced and converted to O-quinone groups under alkaline conditions, followed by reaction with the thiol and amino groups of the substrates [19]. Furthermore, they react with metal ions, including Fe3+, Cu2+, and Zn2+, contributing to PDA adhesion [20]. Consequently, the catechol moieties of DOPA have been investigated as an important inspiration for the design of underwater adhesives [21]. Moreover, mussel foot proteins comprise several functional groups, which can exhibit various interactions such as H-bonding, hydrophobic interaction, metal coordination bonding, and cation/anion/π-π interaction [10]. Therefore, mussels simultaneously demonstrate high interfacial adhesion (Fig. 2) and cohesion (Fig. 3) based on the interaction between proteins and between proteins and substrates.

Fig. 1

Chemical structure of DA and common DA derivatives. [Adapted from Barros NR et al. (2021) with permission from the Royal Society of Chemistry]

Fig. 2

Adhesion mechanisms of the mussel foot proteins interfacial adhesion. [Adapted from Yanfei M et al. (2021) with permission from John Wiley and Sons.]

Fig. 3

Adhesion mechanisms of the mussel foot proteins cohesion. [Adapted from Yanfei M et al. (2021) with permission from John Wiley and Sons.]

2.2 Classification of current underwater adhesives

Generally, underwater adhesives can be classified into two major categories according to the bonding methods: glue-type adhesives (GTAs) and tape-type adhesives (TTAs) (Fig. 4) [22]. GTAs prepared from liquid precursor solutions, including monomer solutions, polymer solutions, polymer melts, and coacervates, are polymerized and/or cross-linked to generate solids via molecular-level interfacial interactions [22]. Typically, the bonding strengths of GTAs are higher than the cohesion strengths; however, the curing times are long and bonding is irreversible. GTAs usually utilize chemical structures for solidification and curing to obtain strong cohesion [22]. In contrast, TTAs, as soft solids, directly adhere to wet surfaces via molecular interactions and/or physical suction; nevertheless, their bonding strengths are weak, and they exhibit instant and reversible adhesion due to inadequate interfacial contact resulting from inefficient dehydration and roughness of the substrate surface. TTAs generally focus on dehydration and formation of strong interfacial bridging; however, they involve different length scales [22].

Fig. 4

Current underwater adhesives. A Glue-type underwater adhesives, which are in liquid form and require a curing process to solidify. The liquid can be monomer solutions, polymer solutions, polymer melts, coacervates, or their mixtures. B Tape-type underwater adhesives, which are soft viscoelastic elastomers or gels. Glue-type adhesives form full molecular bonding with the substrate, thus demonstrating strong and irreversible adhesion, whereas tape-type adhesives usually have very weak but reversible adhesion due to the difficulty of forming molecular bonding in water. [Adapted from Fan H et al. (2021) with permission from John Wiley and Sons.]

2.3 DA-modified biomaterials and their applications

Typically, DA-modified biomaterials can be prepared by conjugating DA via its active groups, such as amino and phenolic hydroxyl groups, with biomaterials using N-(3-dimethylaminopropyl)-N”-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide as coupling agents. In this section, we discuss several biomaterials conjugated with the catechol groups of DA.

2.3.1 DA-modified poly(ethylene glycol) (PEG)-based TAs2.3.1.1 Characteristics of PEG

PEG has been widely used as biomaterials in drug delivery systems and tissue engineering because of its numerous advantages, for instance, hydrophilicity, biocompatibility, easy chemical modification, and non-immunogenicity [23].

2.3.1.2 Applications

Wound dressing

Mehdizadeh et al. synthesized citrate-based mussel-inspired PEG-based TAs by reacting PEG, DA, and citric acid to fabricate a prepolymer via polycondensation followed by crosslinking of the prepolymer by mixing it with sodium periodate, as depicted in Fig. 5.[24] Citric acid formed polyesters with PEG and provided pendant carboxyl groups to conjugate DA. These bioadhesives demonstrated 2.5–eightfold higher wet adhesion to porcine small intestine than that of fibrin glue. Additionally, these bioadhesives were applied to close wounds produced on the backs of rats, instantly stopping bleeding and exhibiting excellent tissue compatibility. Moreover, the same group prepared magnesium oxide (MgO)-based mussel-inspired PEG-poly(propylene glycol) (PPG)-PEG-based bioadhesives by reacting PEG-PPG-PEG, DA, and citric acid to generate a prepolymer via polycondensation followed by crosslinking of the prepolymer by mixing it with MgO as both a crosslinking agent and composite filler [25]; PEG-PPG-PEG reduced the swelling of bioadhesives owing to its hydrophobic property, and MgO enhanced the adhesion. Bioadhesives cross-linked by MgO in the presence of sodium periodate as an oxidizing agent demonstrated eightfold higher wet adhesion to porcine intestinal submucosa than that of fibrin glue with high mechanical strength. Furthermore, these bioadhesives were applied to close wounds created on rat skin incisions, exhibiting outstanding biocompatibility in vitro and in vivo.

Fig. 5

Schematic representation of iCMBA pre-polymers synthesis through polycondensation reaction. [Adapted from Mehdizadeh M et al. (2012) with permission from Elsevier]

Bone tissue engineering

Yan et al. prepared mussel-inspired conducting copolymers using aniline tetramer intelligent TAs for bone tissue engineering [26]; conductive TA copolymers obtained by the copolymerization of aniline tetramer methacrylamide, DA methacrylamide, and PEG methyl ether methacrylate were expected to demonstrate multifunctional properties such as conductivity arising from the aniline groups, adhesiveness stemming from the DA groups, and biocompatibility afforded by the PEG groups. Adhesion strengths of these copolymers were 1.28 MPa at 6 mol% aniline due to H-bonding, π-π interactions, and polymer long-chain entanglement. Additionally, osteogenic differentiation, alkaline phosphatase activity, Ca deposition, and relative expression levels of osteogenic genes were significantly enhanced by electrical stimulation, indicating that these TAs are promising for orthopedic and dental applications; nevertheless, their in vivo application was not examined.

Electronic devices

Song et al. fabricated hydrogel strain sensors composed of genipin-cross-linked gelatin (GE) and DA-modified PEG for in vivo monitoring of cardiac function [27]; the two hydrogel compositions exhibited hysteresis-free and highly sensitive strain sensing of ionically conductive property, and the resulting sensors demonstrated implantability, biocompatibility, and adhesiveness. These hydrogel sensors exhibited little to no hysteresis with 30–50 × higher gauge factors. Moreover, the implantable electronic devices demonstrated impedance-based strain sensing of cardiac output in a porcine model, indicative of the applicability of the abovementioned hydrogel sensors in various implantable electronics. Characteristics of DA-modified PEG-based TAs are presented in Table 1.

Table 1 The characteristics of DA-modified PEG-based TAs2.3.1.3 Advantages and disadvantages

PEG-based TAs exhibit advantages, for example, biocompatibility and facile chemical modifications of their functionalities. However, inferior mechanical properties, low cohesive strengths with brittleness, high swelling property owing to their hydrophilic natures, and multiple preparation steps for application are the major disadvantages of PEG-based TAs.

2.3.2 DA-modified GE-based TAs2.3.2.1 Characteristics of GE

GE acquired by thermal treatment of collagen has been applied in biomedical applications, such as tissue engineering, cell culture, and pharmaceutical formulations [28], due to its biodegradability, biocompatibility, low immunogenicity, easy modification by chemical crosslinking with other materials, and low cost.

2.3.2.2 Applications

Hemostasis

Han et al. fabricated a GE-based TA hydrogel comprising DA-grafted GE and a mixture of phenylboronic acid (PBA) and graphene oxide (GO) by oxidative cross-linking between catechol groups and PBA for self-healing hemostasis and electrical conductivity [29]; DA in DA-grafted GE improved adhesion, and the addition of GO enhanced the mechanical properties and electrical conductivity of the hydrogel. This hydrogel demonstrated hemostatic property in a rat hepatic hemorrhage model. Furthermore, the electromyography signals of finger movement were monitored by an adhesive electrode hydrogel monitor, implying the potential applications of TA wearable devices.

Hu et al. prepared an injectable and viscoelastic TA hydrogel composed of DA-grafted GE and PBA-grafted hyaluronic acid (PBA-HA) by cross-linking DA-grafted GE and PBA-HA via boronated ester bonds for the treatment of brain lesions [30]; this self-healing hydrogel mimics the composition, stiffness, and viscoelasticity of native brain parenchyma. It exhibited rapid hemostasis, high tissue adhesion, and efficient self-healing in the right cortex of rats when injected into an artificial cavity. Additionally, the hydrogel supported neural cell infiltration, decreased astrogliosis and glial scarring, and closed lesions in a mouse model of brain lesions, suggesting the ability of self-healing hydrogels to tune cellular mechanical microenvironment in brain lesion treatment.

Wound dressings

Montazerian et al. synthesized a stretchable GE-based TA hydrogel comprising cross-linked GE methacrylate (GEMA) and PDA for wound dressings and wearable devices [31]; this hydrogel demonstrated outstanding mechanical and adhesive properties, attributed to PDA. Its stretchability and adhesion force in tensile modes on porcine skin were 5.7 and 4 times those of GEMA, respectively, owing to the existence of reactive oxidized quinone species, indicating potential application of this skin-attachable TA hydrogel.

Cheng et al. prepared sprayable TA hydrogels composed of DA-conjugated cross-linked GEMA, cerium oxide (CO) nanoparticles (NPs), and antimicrobial peptide (AMP) for wound dressing [32]; DA-conjugated cross-linked GEMA improved the binding affinity of the hydrogels to the wet skin surface, release of AMP from the hydrogels provided contact ablation against bacteria, and CO NPs exhibited reactive oxygen species (ROS)-scavenging properties. These hydrogels demonstrated sprayability, adhesiveness, antibacterial activity, and ROS-scavenging ability in vitro. Moreover, they facilitated the most rapid healing and promoted skin restoration in a rat skin defect model, implying their promising application in wound dressing.

An et al. fabricated a drug-loaded Janus mucosal dressing comprising PDA, GE, and nanoclay by forming a stable network structure between GE and PDA via Michael addition and Schiff base reaction for healing oral ulcers [33]; GE/PDA/nanoclay controlled adhesion and toughness of this dressing via synergistic physical and chemical interactions among GE, DA, and nanoclay. This dressing exhibited a strong wet adhesion force of 53 kPa and high toughness of 10,261 ± 00 J m−1 with high cell adhesion and proliferation in vitro. Additionally, dressing facilitated the healing of oral ulcers in Sprague–Dawley (SD) rats due to its strong mucosal adhesive property and therapeutic effect of the loaded drug, indicating potential applicability of this mucosal dressing in drug delivery systems.

Liu et al. prepared stretchable and breathable TA nanofibrous hydrogels composed of DA and GEMA by in situ hybrid photo-cross-linking of electrospun nanofibers for wound dressing [34]; the balance of adhesion and cohesion based on photo-cross-linking of methacrylate anhydride (MA) groups in GEMA and physical/chemical reaction between DA and GEMA are very important. These hydrogels demonstrated 2 times higher tensile strengths and 2.3 times higher adhesive strengths on porcine skin than those of the GE nanofibrous hydrogels. Furthermore, they accelerated healing of skin defects on the backs of mice and exhibited stretchability and breathability, implying their promising applicability in wound dressings.

Li et al. synthesized self-adhesive sponges comprising DA-grafted GEMA, quaternized chitosan (QCS), and glycerin for wound dressing [35]; DA-grafted GEMA offered excellent self-adhesive ability to the sponges, QCS endowed the sponges with outstanding blood coagulation and antibacterial activities, and glycerin was used as a plasticizer for rendering the sponges more flexible. These sponges demonstrated better antibacterial activity than that of a commercial GE hemostatic sponge. Moreover, hemostasis times of the sponges were 33.3 ± 6.7 s, which are better than that of the commercial GE hemostatic sponge, indicating outstanding potentials of these sponges for hemostatic wound dressings.

Wang et al. prepared a mesenchymal stem cell (MSC)-derived extracellular vesicle (EV)-loaded TA hydrogel composed of DA-grafted GEMA and EV by in situ photo-cross-linking for diabetic wound healing [36]; DA-grafted GEMA provided tissue adhesiveness to this hydrogel under wet conditions, and MSC-EVs afforded high retention rates at wound sites. This hydrogel exhibited high adhesiveness and biocompatibility and promoted cell migration and angiogenesis in vitro. Additionally, it demonstrated prominent wound-healing ability with collagen deposition, skin appendage regeneration, and interleukin-6 expression in a skin wound model of diabetic rats, offering a potential approach for the treatment of diabetic wounds.

Lin et al. fabricated durable TA hydrogels comprising GE, silica, and DA by introducing DA into a GE-silica hybrid dressing created via a sol–gel method using 3-glycidoxypropyltrimethoxysilane as a coupling agent for wound dressing [37]; DA boosted adhesiveness, and coupling established covalent bonds between GE and silica, thereby enhancing structural stability. These hydrogels exhibited approximately 2.5 times higher adhesion to porcine skin under wet conditions than that of GE. Furthermore, they significantly increased wound healing rates on the back skins of SD rats, indicating their promise as moist wound dressings.

Bone defect repair

Sun et al. prepared a three-dimensional (3D) bioprinted bone marrow-derived MSC (BMSC)-laden TA composed of DA-grafted GE, GEMA, methacrylated silk fibroin (SF), and GO nanosheet for artificial periosteum [38]; GEMA provided excellent adhesive property, and the BMSC-laden SF/GO nanosheet promoted bone defect repair in the 3D bioprinted knitted system [38]. Developed bioink demonstrated adequate printability and satisfactory cell viability. Additionally, 3D bioprinted artificial periosteum constructed using the calvarial areas of SD rats effectively enhanced osteogenesis, affording an outstanding strategy for bone defect repair.

Ma et al. prepared an osteoconductive TA hydrogel comprising DA-grafted GE and PDA-conjugated hydroxyapatite (HY) NPs for bone regeneration [39]; DA-grafted GE offered very high adhesive property under wet conditions, and PDA-coated HY NPs created a highly biomimetic native bone tissue microenvironment owing to their high compatibility. The hydrogel exhibited very high compressive strength without any effect on the microstructure due to high crosslinking density between DA-grafted GE and PDA-coated HY NPs. Moreover, the hydrogel accelerated bone repair efficiency in a rat model of femoral defects, suggesting that it is a potential bone repair biomaterial.

Moazami et al. synthesized multifunctional TA hydrogels composed of PDA, bredigite NPs, and Fe3+ for bone fracture healing [40]; PDA-bredigite demonstrated a strong adhesion ability under a wet condition, and BR NPs accelerated the mineralization of calcined tissues. These hydrogels exhibited strong adhesion (45.9 kPa) to cow skin via reversible non-covalent and irreversible covalent crosslinking and antibacterial properties ex vivo. Characteristics of DA-modified GE-based TAs are presented in Table 2.

Table 2 The characteristics of DA-modified GE-based TAs2.3.2.3 Advantages and disadvantages

GE-based TAs offer several advantages such as biocompatibility, biodegradability, anti-inflammatory activity, and induction of cell adhesion. Nevertheless, the molecular weight of GE covers a broad range according to collagen denaturation [74], GE-based TAs are prepared using porcine-derived GE and require heat treatment before being used in surgery [75], and porcine-derived GE is gel-like at room temperature because of its high imino acid content.

2.3.3 DA-modified chitosan (CS)-based TAs2.3.3.1 Characteristics of CS

CS fabricated by the deacetylation of chitin, mainly found in the exoskeletons of animals and cell walls of fungi, has been extensively applied in drug delivery carriers [41], wound dressings [42], and tissue engineering [43, 44] owing to its biodegradability, biocompatibility, antibacterial property, adjustable formulations, and facile chemical modification [45]. Due to these properties, CS has attracted attention for application in TAs.

2.3.3.2 Applications

Hemostasis

Yang et al. prepared multifunctional TA CS hydrogels comprising methacrylate anhydride DA (DAMA), Zn-doped whitlockite NPs, and MA quantized CS (QCSMA) via photopolymerization and coordination of Zn with DA for liver hemostasis and infected wound healing [46]; double bond covalent crosslinking of QCSMA and MADA acted as the first crosslinking network of the hydrogels, and coordination of Zn ions with DA group, stacking of DAMA benzene rings, and H bonding served as the second non-covalent crosslinking network. These hydrogels demonstrated appropriate adhesions (31.0 kPa) with hemostasis, disinfection, and low hemolysis ratios in vitro. Furthermore, they exhibited excellent hemostatic effects (129 ± 22 s) in the hemorrhaging liver of SD rat and the fastest wound closure ratio throughout the treatment period in a rat model of full-thickness skin defect owing to the inherent antibacterial property of QCS and Zn ions released as coagulation factors from Zn-doped whitlockite [47].

Wound dressing

Zhang et al. prepared flexible bilayer TA hydrogels comprising poly (vinyl alcohol) (PVA), DA-CS, and poly(acryl amide) (PAAm) for strain sensors [48]; PVA as the upper hydrogel layer effectively enhanced the mechanical properties of the hydrogels, and DA-CS exhibited adhesive property with outstanding antibacterial effects. PAAm also appropriately adhered to the skin surface. These hydrogels demonstrated excellent adhesions (0.6 kPa) to human skin, tensile strains of 218.0%, antibacterial property, and conductivity of 1.65 S m−1in vitro. Furthermore, they enhanced wound healing in a whole skin defect mouse model due to the synergistic influence of DA and CS in inhibiting the inflammatory response and promoting angiogenesis [49], implying significant potentials of these hydrogels for application in wearable electronic wound dressings.

Cai et al. synthesized platelet-derived growth factor (PDGF)-loaded TA hydrogels composed of methacrylamide CS and DA-conjugated four-arm PEG acrylate via photo-cross-linking for wound dressing [50]; PDGF released from the hydrogels efficiently promoted wound healing owing to the stimulation of cell proliferation and migration, and cross-linked CS and DA-conjugated four-arm PEG hydrogels exhibited excellent mechanical, adhesive, and hemostatic properties. These hydrogels demonstrated superior mechanical and hemostatic properties in in vitro blood clotting and rat liver hemorrhage assays. Additionally, they exhibited faster wound closure and collagen maturation in full-thickness skin excisions of SD rats, demonstrating considerable potential for wound dressing applications.

Song et al. prepared a multifunctional TA hydrogel comprising DA, MA-QCS, and poly(vinyl pyrrolidone) (PVP) via UV irradiation for wound dressing [51]; QCS not only exhibited hemostatic property and prevented infection, but also created a favorable moist condition; DA contributed to the outstanding adhesive property of the hydrogel, and PVP afforded H bonds and demonstrated hydrophobic interactions with the tissue surface. This hydrogel exhibited antioxidant property with adequate adhesion in vitro due to DA. Moreover, it demonstrated fast hemostasis in SD rat tail amputation and liver bleeding models with excellent and reversible adhesive properties (12.23–24.31 kPa), exhibiting potential for application in the rapid and efficient hemostasis of inflammatory wounds.

Skin regeneration

Panwar et al. fabricated conductive and injectable TA hydrogels composed of CS, cellulose, and PDA for bioelectronics and tissue regeneration applications [52]; the combination of PDA-conjugated aldehyde cellulose and carboxyl methyl CS (MCS) formed hydrogels with tunable, conductive, injectable, and adhesive properties via ionic, imine, H, and π-π bondings. These hydrogels demonstrated conductivity of 0.01–3.4 × 10–3 S cm−1 owing to ionic conductivity without a conductive material. Furthermore, complete regeneration of injured rat skin was achieved with extensive collagen deposition when the hydrogels were implanted into SD rats, indicating a promising application of these hydrogels in bioelectronics for tissue regeneration.

Spinal cord injury treatment

Liu et al. prepared DA-modified CS TA hydrogels with outstanding cell compatibility and antioxidant properties comprising DA, CS, and citric acid by crosslinking DA-CS with citric acid for spinal cord injury treatment [53]; inferior mechanical properties of DA-CS were enhanced by crosslinking it with citric acid. DA-CS improved cell survival and adhesion in vitro as compared to the case of CS. Moreover, after being implanted into the injured spinal cord of rat, the hydrogels modulated immunity and promoted macrophage polarization to the M2 phenotype and axonal regeneration, suggesting a new strategy for treating spinal cord injury.

Bone regeneration

Wu et al. synthesized BML-284-loaded sandwich-like hybrid TA scaffolds composed of beta-tricalcium phosphate (β-TCP), PDA, BML-284, and CMCS for bone regeneration [54]; β-TCP provided a biomimetic 3D porous microenvironment, released BML as the Wnt signaling activator facilitated the adhesions, migrations, proliferations, and osteogenic differentiations of MC3T3-E1 cells, PDA promoted high-efficiency drug loading into the scaffolds, and negatively charged CMCS exhibited electrostatic interaction with positively charged drugs [55]. These hybrid scaffolds enhanced the angiogenic activity of human umbilical vein endothelial cells and suppressed osteoclastic activity with osteogenesis and angiogenesis in vitro. Additionally, they stimulated the polarization of M2 macrophages and recruited endogenous stem cells at the injury site to accelerate bone ingrowth and angiogenesis in a critical-sized cranial defect rat model, demonstrating strong potentials for clinical application in orthopedic implants.

Characteristics of DA-modified CS-based TAs are presented in Table 3.

Table 3 The characteristics of DA-modified CS-based TAs2.3.3.3 Advantages and disadvantages

CS-based TAs exhibit numerous advantages such as biodegradability, biocompatibility, antibacterial activity, applicability in various formulations with sponges, bandages, and hydrogels, and many chemical modifications with hydrophilic/hydrophobic groups. However, the physicochemical and biological properties of CS cannot be precisely controlled because they depend on the biological sources, molecular weight, and degree of acetylation of CS.

2.3.4 DA-modified alginate (AL)-based TAs2.3.4.1 Characteristics of AL

AL obtained from brown seaweeds consisting of α-L-guluronic acid (G-blocks) and β-(1–4)-D-mannuronic acid (M-blocks) has been widely applied in tissue engineering, wound dressing, cell therapy, and drug delivery [56] because it is non-toxic, biostable, and biocompatible with facile formulation into gels, films, gauzes, fibers, and wafers [57].

2.3.4.2 Applications

Hemostasis

Zhang et al. prepared nanocomposite TA hydrogels comprising DA, OAL, ε-polylysine (ε-PL), and AM for infected wound repair [58]; DA-grafted OAL improved adhesive and hemostatic properties, ε-PL with antibacterial property formed a nanocomposite with DA-grafted OAL via ionic bonding, and AM cross-linked the nanocomposite via radical polymerization, thereby increasing the mechanical strengths of hydrogels. These hydrogels adhered to the bleeding surface in a rat hemorrhaging liver model, leading to an arrest of bleeding in 30 s. Moreover, they accelerated the healing of infected full-thickness rat wounds when compared with the case of a commercial AL sponge, demonstrating potential as multifunctional dressings for promoting the healing of infected wounds.

Quyang et al. synthesized rapidly degrading TA hydrogels composed of DA-OAL, CMSC, amino-modified montmorillonite (AMM), and PVP for wound hemostasis [59]; DA-OAL provided photothermal and adhesion effects [60], CMCS exhibited outstanding antibacterial property with adequate water solubility, PVP endowed the hydrogels with superior mechanical properties by forming numerous H bonds with other substances, and AMM demonstrated excellent hemostatic property. These hydrogels exhibited outstanding tissue adhesion to pig skin under dynamic stretching, twisting, and bending. Furthermore, they promoted hemostatic property in the femoral artery of a SD rat model when compared with the case of Surgiflo™ as a control, demonstrating promising potentials for emergency hemostasis.

Wound dressing

Qiao et al. prepared antibacterial conductive self-healing TA hydrogels comprising DA-OAL, CMCS, Fe3+, and poly(thiophene-3-acetic acid) (PTA) for infected wound healing [61]; these hydrogels initially produced a cross-linked network via the formation of Schiff bases between DA-OAL and CMCS, and then, the mechanical properties of the hydrogels were further enhanced by adding Fe3+; PTA endowed the hydrogels with conductivity, tissue adhesion, and photothermal properties. These hydrogels exhibited suitable mechanical, antioxidant, tissue adhesive, and hemostatic properties and excellent conductivity in vitro after near-infrared (NIR) irradiation. Moreover, the sizes of the infected full-thickness defect skin wounds in mice were substantially smaller than those in the case of the Tegaderm™ film after 14 days of treatment, rendering these hydrogels promising candidates for wound healing dressing.

Chen et al. fabricated injectable universal dual-network TA hydrogels composed of polyethyleneimine (PEI), poly(acrylic acid) (PAA), DA, and AL for bioadhesive wound dressing [62]; PEI-PAA complexes offered mechanically reinforced cohesion strengths to these hydrogels, and dual-network hydrogels of PEI-PAA with DA-AL/Ca2+ coordination demonstrated synergistic effects of mechanical properties and better instant adhesion to wet surfaces. These hydrogels exhibited superior adhesions, high injectability, stability, and biocompatibility. Additionally, they promoted closure, epidermal regeneration, and tissue functionalization in a full-thickness rat wound-healing model, demonstrating potentials for application in wound dressing.

Ouyang et al. prepared a multifunctional TA hydrogel patch comprising DA-OAL, CMCS, and PVP for wound healing [63], grafting of DA with OAL enhanced tissue adhesion and facilitated excellent photothermal conversion to promote local temperature elevation, and the resulting patch exhibited antioxidant activity; CMCS provided superior antibacterial ability to this patch, and PVP enhanced the mechanical properties of the patch by developing numerous H bonds. The proposed patch demonstrated outstanding tissue adhesion ability, significant scavenging ability against N- and O-free radicals, and antibacterial activity under NIR laser irradiation. Moreover, it enhanced wound healing rates of the infected full-thickness skin defects in mice, indicating its potential for application in wound healing.

Guo et al. synthesized periodontium-mimicking multifunctional TA hydrogels composed of QMACS and DA-OAL for socket healing [64]; QMACS and DA-OAL were cross-linked by dual-cross-linking via blue light irradiation to achieve a tight connection similar to that of gingiva with tissue adhesiveness, antibacterial property, and angiogenesis ability. These hydrogels exhibited superior hemostatic ability and inhibited oral pathogenic microorganisms in vitro. Additionally, they demonstrated superior performances in promoting socket healing in a tooth extraction SD rat model when compared with the case of the control group, exhibiting considerable potentials as clinical tooth extraction wound dressings.

Cartilage regeneration

Zhang et al. prepared cross-linked exosome-loaded injectable TA hydrogels comprising DA-AL, chondroitin sulfate (CDS), regenerated SF (RSF), and exosome for cartilage regeneration [65]; DA-AL demonstrated high adhesion under wet conditions, CDS relieved pain and promoted cartilage regeneration [