Hydrogel-tissue adhesion by particle bridging: sensitivity to interfacial wetting and tissue composition.

Solid particles placed at the interface between hydrogels and biological tissues can create an adhesive joint through the adsorption of macromolecules onto their surfaces. Here, we investigated how this adhesion by particle bridging depends on the wetting of tissue surfaces and on the heterogeneities in tissue composition. Ex vivo peeling experiments were performed using poly(ethylene glycol) films coated with aggregates of silica nanoparticles deposited on the internal tissues of porcine liver. We show that the adhesion produced by particle bridging is altered by the presence of fluid wetting the tissue-hydrogel interface. For both uncoated and coated films, a transition from lubricated to adhesive contact was observed when all the interfacial fluid was drained. The presence of a silica nanoparticle coating shifted the transition towards more hydrated conditions and significantly enhanced adhesion in the adhesive regime. After 5 min of contact, the adhesion energy achieved on liver parenchyma with the coated films (7.7 ± 1.9 J m-2) was more than twice that of the uncoated films (3.2 ± 0.3 J m-2) or with a surgical cyanoacrylate glue (2.9 ± 1.9 J m-2). Microscopic observations during and after peeling revealed different detachment processes through either particle detachment or cohesive fracture in the tissue. These mechanisms could be directly related to the microanatomy of the liver parenchyma. The effects of both interfacial wetting and tissue composition on adhesion may provide guidelines to tailor the design of tissue adhesives using particle bridging.

Silicone Bioadhesive with Shear-Stiffening Effect: Rate-Responsive Adhesion Behavior and Wound Dressing Application.

Stimuli-responsive adhesives with on-demand adhesion capabilities are highly advantageous for facilitating wound healing. However, the triggering conditions of stimuli-responsive adhesives are cumbersome, even though some of them are detrimental to the adhesive and adjacent natural tissues. Herein, a novel stimuli-responsive adhesive called shear-stiffening adhesive (SSA) has been created by constructing a poly(diborosiloxane)-based silicone network for the first time, and SSA exhibits a rate-responsive adhesion behavior. Furthermore, we introduced bactericidal factors (PVP-I) into SSA and applied it as a wound dressing to promote the healing of infected wounds. Impressively, the wound dressing not only has excellent biocompatibility and long-term antibacterial properties but also performs well in accelerating wound healing. Therefore, this study provides a new strategy for the synthesis of intelligent adhesives with force rate response, which simplifies the triggering conditions by the force rate. Thus, SSA has great potential to be applied in wound management as an intelligent bioadhesive with on-demand adhesion performance.

Functionalized chitosan based antibacterial hydrogel sealant for simultaneous infection eradication and tissue closure in ocular injuries.

Management of infections at ocular injury often requires prolonged and high dose of antibiotic, which is associated with challenges of antibiotic resistance and bacterial biofilm formation. Tissue glues are commonly used for repairing ocular tissue defects and tissue regeneration, but they are ineffective in curing infection. There is a critical need for antibacterial ocular bio-adhesives capable of both curing infection and aiding wound closure. Herein, we present the development of an imine crosslinked N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC)­silver chloride nanocomposites (QAm1-Agx) and poly-dextran aldehyde (PDA) based bactericidal sealant (BacSeal). BacSeal exhibited potent bactericidal activity against a broad spectrum of bacteria including their planktonic and stationary phase within a short duration of 4 h. BacSeal effectively reduced biofilm-embedded MRSA and Pseudomonas aeruginosa by ∼99.99 %. In ex-vivo human cornea infection model, BacSeal displayed ∼99 % reduction of ocular infection. Furthermore, the hydrogel exhibited excellent sealing properties by maintaining ocular pressure up to 75 mm-Hg when applied to human corneal trauma. Cytotoxicity assessment and hydrogel-treated human cornea with a retained tissue structure, indicate its non-toxic nature. Collectively, BacSeal represents a promising candidate for the development of an ocular sealant that can effectively mitigate infections and may assist in tissue regeneration by sealing ocular wounds.

Hybrid Double-Sided Tape with Asymmetrical Adhesion and Burst Pressure Tolerance for Abdominal Injury Treatment.

Patients with open abdominal (OA) wounds have a mortality risk of up to 30%, and the resulting disabilities would have profound effects on patients. Here, we present a novel double-sided adhesive tape developed for the management of OA wounds. The tape features an asymmetrical structure and employs an acellular dermal matrix (ADM) with asymmetric wettability as a scaffold. It is constructed by integrating a tissue-adhesive hydrogel composed of polydopamine (pDA), quaternary ammonium chitosan (QCS), and acrylic acid cross-linking onto the bottom side of the ADM. Following surface modification with pDA, the ADM would exhibit characteristics resistant to bacterial adhesion. Furthermore, the presence of a developed hydrogel ensures that the tape not only possesses tissue adhesiveness and noninvasive peelability but also effectively mitigates damage caused by oxidative stress. Besides, the ADM inherits the strength of the skin, imparting high burst pressure tolerance to the tape. Based on these remarkable attributes, we demonstrate that this double-sided (D-S) tape facilitates the repair of OA wounds, mitigates damage to exposed intestinal tubes, and reduces the risk of intestinal fistulae and complications. Additionally, the D-S tape is equally applicable to treating other abdominal injuries, such as gastric perforations. It effectively seals the perforation, promotes injury repair, and prevents the formation of postoperative adhesions. These notable features indicate that the presented double-sided tape holds significant potential value in the biomedical field.

Cellulose fibres enhance the function of hemostatic composite medical sealants.

Tissue adhesives and sealants offer promising alternatives to traditional wound closure methods, but the existing trade-off between biocompatibility and strength is still a challenge. The current study explores the potential of a gelatin-alginate-based hydrogel, cross-linked with a carbodiimide, and loaded with two functional fillers, the hemostatic agent kaolin and cellulose fibres, to improve the hydrogel's mechanical strength and hemostatic properties for use as a sealant. The effect of the formulation parameters on the mechanical and physical properties was studied, as well as the biocompatibility and microstructure. The incorporation of the two functional fillers resulted in a dual micro-composite structure, with uniform dispersion of both fillers within the hydrogel, and excellent adhesion between the fillers and the hydrogel matrix. This enabled to strongly increase the sealing ability and the tensile strength and modulus of the hydrogel. The fibres' contribution to the enhanced mechanical properties is more dominant than that of kaolin. A combined synergistic effect of both fillers resulted in enhanced sealing ability (247%), tensile strength (400%), and Young's modulus (437%), compared to the unloaded hydrogel formulation. While the incorporation of kaolin almost did not affect the physical properties of the hydrogel, the incorporation of the fibres strongly increased the viscosity and decreased the gelation time and swelling degree. The cytotoxicity tests indicated that all studied formulations exhibited high cell viability. Hence, the studied new dual micro-composite hydrogels may be suitable for medical sealing applications, especially when it is needed to get a high sealing effect within a short time. The desired hemostatic effect is obtained due to kaolin incorporation without affecting the physical properties of the sealant. Understanding the effects of the formulation parameters on the hydrogel's properties enables the fitting of optimal formulations for various medical sealing applications.

Adhesive anti-fibrotic interfaces on diverse organs.

Implanted biomaterials and devices face compromised functionality and efficacy in the long term owing to foreign body reactions and subsequent formation of fibrous capsules at the implant-tissue interfaces1-4. Here we demonstrate that an adhesive implant-tissue interface can mitigate fibrous capsule formation in diverse animal models, including rats, mice, humanized mice and pigs, by reducing the level of infiltration of inflammatory cells into the adhesive implant-tissue interface compared to the non-adhesive implant-tissue interface. Histological analysis shows that the adhesive implant-tissue interface does not form observable fibrous capsules on diverse organs, including the abdominal wall, colon, stomach, lung and heart, over 12 weeks in vivo. In vitro protein adsorption, multiplex Luminex assays, quantitative PCR, immunofluorescence analysis and RNA sequencing are additionally carried out to validate the hypothesis. We further demonstrate long-term bidirectional electrical communication enabled by implantable electrodes with an adhesive interface over 12 weeks in a rat model in vivo. These findings may offer a promising strategy for long-term anti-fibrotic implant-tissue interfaces.

Moldable Tissue-Sealant Hydrogels Composed of In Situ Cross-Linkable Polyethylene Glycol via Thiol-Michael Addition and Carbomers.

Moldable tissue-sealant hydrogels were developed herein by combining the yield stress fluidity of a Carbomer and in situ cross-linking of 3-arm PEG-thiol (PEG-SH) and 4-arm PEG-acrylate (PEG-AC). The Carbomer was mixed with each PEG oligomer to form two aqueous precursors: Carbomer/PEG-SH and Carbomer/PEG-AC. The two hydrogel precursors exhibited sufficient yield stress (>100 Pa) to prevent dripping from their placement on the tissue surface. Moreover, these hydrogel precursors exhibited rapid restructuring when the shear strain was repeatedly changed. These rheological properties contribute to the moldability of these hydrogel precursors. After mixing these two precursors, they were converted from yield-stress fluids to chemically cross-linked hydrogels, Carbomer/PEG hydrogel, via thiol-Michael addition. The gelation time was 5.0 and 11.2 min at 37 and 25 °C, respectively. In addition, the Carbomer/PEG hydrogels exhibited higher cellular viability than the pure Carbomer. They also showed stable adhesiveness and burst pressure resistance to various tissues, such as the skin, stomach, colon, and cecum of pigs. The hydrogels showed excellent tissue sealing in a cecum ligation and puncture model in mice and improved the survival rate due to their tissue adhesiveness and biocompatibility. The Carbomer/PEG hydrogel is a potential biocompatible tissue sealant that surgeons can mold. It was revealed that the combination of in situ cross-linkable PEG oligomers and yield stress fluid such as Carbomer is effective for developing the moldable tissue sealant without dripping of its hydrogel precursors.

Facile Solvent-Free Fabrication of All-Small-Molecule Supramolecular Photothermal Bioadhesive for Sutureless Wound Closure.

Achieving underwater adhesion possesses a significant challenge, primarily due to the presence of interfacial water, which restricts the potential applications of adhesives. In this study, we present a straightforward and environmentally friendly one-pot approach for synthesizing a solvent-free supramolecular TPFe bioadhesive composed of thioctic acid, proanthocyanidins, and FeCl3. The bioadhesive exhibits excellent biocompatibility and photothermal antibacterial properties and demonstrates effective adhesion on various substrates in both wet and dry environments. Importantly, the adhesive strength of this bioadhesive on steel exceeds 1.2 MPa and that on porcine skin exceeds 100 kPa, which is greater than the adhesive strength of most reported bioadhesives. In addition, the bioadhesive exhibits the ability to effectively halt bleeding, close wounds promptly, and promote wound healing in the rat skin wound model. Therefore, the TPFe bioadhesive has potential as a medical bioadhesive for halting bleeding quickly and promoting wound healing in the biomedical field. This study provides a new idea for the development of bioadhesives with firm wet adhesion.

Tracheal regeneration and mesenchymal stem cell augmenting potential of natural polyphenol-loaded gelatinmethacryloyl bioadhesive.

Hydrogels incorporating natural biopolymer and adhesive substances have extensively been used to develop bioactive drugs and to design cells encapsulating sturdy structure for biomedical applications. However, the conjugation of the adhesive in most hydrogels is insufficient to maintain long-lasting biocompatibility inadequate to accelerate internal organ tissue repair in the essential native cellular microenvironment. The current work elaborates the synthesis of charged choline-catechol ionic liquid (BIL) adhesive and a hydrogel with an electronegative atom rich polyphenol (PU)-laden gelatinmethacryloyl (GelMA) to improve the structural bioactivities for in vivo tracheal repair by inducing swift crosslinking along with durable mechanical and tissue adhesive properties. It was observed that bioactive BIL and PU exhibited potent antioxidant (IC 50 % of 7.91 µg/mL and 24.55 µg/mL) and antibacterial activity against E. coli, P. aeruginosa and S. aureus. The novel integration of photocurable GelMA-BIL-PU revealed outstanding mechanical strength, biodegradability and sustained drug release. The in vitro study showed exceptional cell migration and proliferation in HBECs, while in vivo investigation of the GelMA-BIL-PU hydrogel on a rat's tracheal model revealed remarkable tracheal reconstruction, concurrently reducing tissue inflammation. Furthermore, the optimized GelMA-BIL-PU injectable adhesive bioink blend demonstrated superior MSCs migration and proliferation, which could be a strong candidate for developing stem cell-rich biomaterials to address multiple organ defects.

Mussel-inspired tissue adhesive composite hydrogel with photothermal and antioxidant properties prepared from pectin for burn wound healing.

Biodegradable self-healing hydrogels with antibacterial property attracted growing attentions in biomedication as wound dressings since they can prevent bacterial infection and promote wound healing process. In this research, a biodegradable self-healing hydrogel with ROS scavenging performance and enhanced tissue adhesion was fabricated from dopamine grafted oxidized pectin (OPD) and naphthoate hydrazide terminated PEO (PEO NH). At the same time, Fe3+ ions were incorporated to endow the hydrogel with near-infrared (NIR) triggered photothermal property to obtain antibacterial activity. The composite hydrogel showed good hemostasis performance based on mussel inspired tissue adhesion with biocompatibility well preserved. As expected, the composition of FeCl3 improved conductivity and endowed photothermal property to the hydrogel. The in vivo wound repairing experiment revealed the 808 nm NIR light triggered photothermal behavior of the hydrogel reduced the inflammation response and promoted wound repairing rate. As a result, this composite FeCl3/hydrogel shows great potential to be an excellent wound dressing for the treatment of infection prong wounds with NIR triggers.

Injectable ChitHCl-DDA tissue adhesive with high adhesive strength and biocompatibility for torn meniscus repair and regeneration.

Suture pull-through is a clinical problem in meniscus repair surgery due to the sharp leading edge of sutures. Several tissue adhesives have been developed as an alternative to traditional suturing; however, there is still no suitable tissue adhesive specific for meniscus repair treatment due to unsatisfactory biosafety, biodegradable, sterilizable, and tissue-bonding characteristics. In this study, we used a tissue adhesive composed of chitosan hydrochloride reacted with oxidative periodate-oxidized dextran (ChitHCl-DDA) combined with a chitosan-based hydrogel and oxidative dextran to attach to the meniscus. We conducted viscoelastic tests, viscosity tests, lap shear stress tests, Fourier transform infrared (FTIR) spectroscopy, swelling ratio tests, and degradation behavior tests to characterize these materials. An MTT assay, alcian blue staining, migration assay, cell behavior observations, and protein expression tests were used to understand cell viability and responses. Moreover, ex vivo and in vivo tests were used to analyze tissue regeneration and biocompatibility of the ChitHCl-DDA tissue adhesive. Our results revealed that the ChitHCl-DDA tissue adhesive provided excellent tissue adhesive strength, cell viability, and cell responses. This tissue adhesive has great potential for torn meniscus tissue repair and regeneration.

Recent Advances in the Degradability and Applications of Tissue Adhesives Based on Biodegradable Polymers.

In clinical practice, tissue adhesives have emerged as an alternative tool for wound treatments due to their advantages in ease of use, rapid application, less pain, and minimal tissue damage. Since most tissue adhesives are designed for internal use or wound treatments, the biodegradation of adhesives is important. To endow tissue adhesives with biodegradability, in the past few decades, various biodegradable polymers, either natural polymers (such as chitosan, hyaluronic acid, gelatin, chondroitin sulfate, starch, sodium alginate, glucans, pectin, functional proteins, and peptides) or synthetic polymers (such as poly(lactic acid), polyurethanes, polycaprolactone, and poly(lactic-co-glycolic acid)), have been utilized to develop novel biodegradable tissue adhesives. Incorporated biodegradable polymers are degraded in vivo with time under specific conditions, leading to the destruction of the structure and the further degradation of tissue adhesives. In this review, we first summarize the strategies of utilizing biodegradable polymers to develop tissue adhesives. Furthermore, we provide a symmetric overview of the biodegradable polymers used for tissue adhesives, with a specific focus on the degradability and applications of these tissue adhesives. Additionally, the challenges and perspectives of biodegradable polymer-based tissue adhesives are discussed. We expect that this review can provide new inspirations for the design of novel biodegradable tissue adhesives for biomedical applications.

Dynamic injectable tissue adhesives with strong adhesion and rapid self-healing for regeneration of large muscle injury.

Wounds often necessitate the use of instructive biomaterials to facilitate effective healing. Yet, consistently filling the wound and retaining the material in place presents notable challenges. Here, we develop a new class of injectable tissue adhesives by leveraging the dynamic crosslinking chemistry of Schiff base reactions. These adhesives demonstrate outstanding mechanical properties, especially in regard to stretchability and self-healing capacity, and biodegradability. Furthermore, they also form robust adhesion to biological tissues. Their therapeutic potential was evaluated in a rodent model of volumetric muscle loss (VML). Ultrasound imaging confirmed that the adhesives remained within the wound site, effectively filled the void, and degraded at a rate comparable to the healing process. Histological analysis indicated that the adhesives facilitated muscle fiber and blood vessel formation, and induced anti-inflammatory macrophages. Notably, the injured muscles of mice treated with the adhesives displayed increased weight and higher force generation than the control groups. This approach to adhesive design paves the way for the next generation of medical adhesives in tissue repair.

pH-responsive bioadhesive with robust and stable wet adhesion for gastric ulcer healing.

Development of bioadhesives that can be facilely delivered by endoscope and exhibit instant and robust adhesion with gastric tissues to promote gastric ulcer healing remains challenging. In this study, an advanced bioadhesive is prepared through free radical polymerization of ionized N-acryloyl phenylalanine (iAPA) and N-[tris (hydroxymethyl) methyl] acrylamide (THMA). The precursory polymer solution exhibits low viscosity with the capability for endoscope delivery, and the hydrophilic-hydrophobic transition of iAPA upon exposure to gastric acid can trigger gelation through phenyl groups assisted multiple hydrogen bonds formation and repel water molecules on tissue surface to establish favorable environment for interfacial interactions between THMA and functional groups on tissues. The in-situ formed hydrogel features excellent stability in acid environment (14 days) and exhibits firm wet adhesion to gastric tissue (33.4 kPa), which can efficiently protect the wound from the stimulation of gastric acid and pepsin. In vivo studies reveal that the bioadhesive can accelerate the healing of ulcers by inhibiting inflammation and promoting capillary formation in the acetic acid-induced gastric ulcer model in rats. Our work may provide an effective solution for the treatment of gastric ulcers clinically.

An artificial liquid-liquid phase separation-driven silk fibroin-based adhesive for rapid hemostasis and wound sealing.

The powerful adhesion systems of marine organisms have inspired the development of artificial protein-based bioadhesives. However, achieving robust wet adhesion using artificial bioadhesives remains technically challenging because the key element of liquid-liquid phase separation (LLPS)-driven complex coacervation in natural adhesion systems is often ignored. In this study, mimicking the complex coacervation phenomenon of marine organisms, an artificial protein-based adhesive hydrogel (SFG hydrogel) was developed by adopting the LLPS-mediated coacervation of the natural protein silk fibroin (SF) and the anionic surfactant sodium dodecylbenzene sulfonate (SDBS). The assembled SF/SDBS complex coacervate enabled precise spatial positioning and easy self-adjustable deposition on irregular substrate surfaces, allowing for tight contact. Spontaneous liquid-to-solid maturation promoted the phase transition of the SF/SDBS complex coacervate to form the SFG hydrogel in situ, enhancing its bulk cohesiveness and interfacial adhesion. The formed SFG hydrogel exhibited intrinsic advantages as a new type of artificial protein-based adhesive, including good biocompatibility, robust wet adhesion, rapid blood-clotting capacity, and easy operation. In vitro and in vivo experiments demonstrated that the SFG hydrogel not only achieved instant and effective hemostatic sealing of tissue injuries but also promoted wound healing and tissue regeneration, thus advancing its clinical applications. STATEMENT OF SIGNIFICANCE: Marine mussels utilize the liquid-liquid phase separation (LLPS) strategy to induce the supramolecular assembly of mussel foot proteins, which plays a critical role in strong underwater adhesion of mussel foot proteins. Herein, an artificial protein-based adhesive hydrogel (named SFG hydrogel) was reported by adopting the LLPS-mediated coacervation of natural protein silk fibroin (SF) and anionic surfactant sodium dodecylbenzene sulfonate (SDBS). The assembled SFG hydrogel enabled the precise spatial positioning and easy self-adjustable deposition on substrate surfaces with irregularities, allowing tight interfacial adhesion and cohesiveness. The SFG hydrogel not only achieved instant and effective hemostatic sealing of tissue injuries but also promoted wound healing and tissue regeneration, exhibiting intrinsic advantages as a new type of artificial protein-based bioadhesives.

A thermally reversible injectable adhesive for intestinal tissue repair and anti-postoperative adhesion.

Intestine damage is an acute abdominal disease that usually requires emergency sealing. However, traditional surgical suture not only causes secondary damage to the injured tissue, but also results in adhesion with other tissues in the abdominal cavity. To this end, a thermally reversible injectable gelatin-based hydrogel adhesive (GTPC) is constructed by introducing transglutaminase (TGase) and proanthocyanidins (PCs) into a gelatin system. By reducing the catalytic activity of TGase, the density of covalent and hydrogen bond crosslinking in the hydrogel can be regulated to tune the sol-gel transition temperature of gelatin-based hydrogels above the physiological temperature (42 °C) without introducing any synthetic small molecules. The GTPC hydrogel exhibits good tissue adhesion, antioxidant, and antibacterial properties, which can effectively seal damaged intestinal tissues and regulate the microenvironment of the damaged site, promoting tissue repair and regeneration. Intriguingly, temperature-induced hydrogen bond disruption and reformation confer the hydrogel with asymmetric adhesion properties, preventing tissue adhesion when applied in vivo. Animal experiment outcomes reveal that the GTPC hydrogel can seal the damaged intestinal tissue firmly, accelerate tissue healing, and efficiently prevent postoperative adhesion.

A strong, silk protein-inspired tissue adhesive with an enhanced drug release mechanism for transdermal drug delivery.

In transdermal drug delivery system (TDDS) patches, achieving prolonged adhesion, high drug loading, and rapid drug release simultaneously presented a significant challenge. In this study, a PHT-SP-Cu2+ adhesive was synthesized using polyethylene glycol (PEG), hexamethylene diisocyanate (HDI), trimethylolpropane (TMP), and silk protein (SP) as functional monomers which were combined with Cu2+ to improve the adhesion, drug loading, and drug release of the patch. The structure of the adhesion chains and the formation of Cu2+-p-π conjugated network in PHT-SP-Cu2+ were characterized and elucidated using different characterization methods including FT-IR, 13C NMR, XPS, SEM imaging and thermodynamic evaluation. The formulation of pressure-sensitive adhesive (PSA) was optimized through comprehensive research on adhesion, mechanics, rheology, and surface energy. The formulation of 3 wt.% SP and 3 wt.% Cu2+ provided superior adhesion properties compared to commercial standards. Subsequently, the peel strength of PHT-SP-Cu2+ was 7.6 times higher than that of the commercially available adhesive DURO-TAK® 87-4098 in the porcine skin peel test. The adhesion test on human skin confirmed that PHT-SP-Cu2+ could adhere to the human body for more than six days. Moreover, the drug loading, in vitro release test and skin permeation test were investigated using ketoprofen as a model drug, and the results showed that PHT-SP-Cu2+ had the efficacy of improving drug compatibility, promoting drug release and enhancing skin permeation as a TDDS. Among them, the drug loading of PHT-SP-Cu2+ was increased by 6.25-fold compared with PHT, and in the in vivo pharmacokinetic analysis, the AUC was similarly increased by 19.22-fold. The mechanism of α-helix facilitated drug release was demonstrated by Flori-Hawkins interaction parameters, molecular dynamics simulations and FT-IR. Biosafety evaluations highlighted the superior skin cytocompatibility and safety of PHT-SP-Cu2+ for transdermal applications. These results would contribute to the development of TDDS patch adhesives with outstanding adhesion, drug loading and release efficiency. STATEMENT OF SIGNIFICANCE: A new adhesive, PHT-SP-Cu2+, was created for transdermal drug delivery patches. Polyethylene glycol, hexamethylene diisocyanate, trimethylolpropane, silk protein, and Cu2+ were used in synthesis. Characterization techniques confirmed the structure and Cu2+-p-π conjugated networks. Optimal formulation included 3 wt.% SP and 3 wt.% Cu2+, exhibiting superior adhesion. PHT-SP-Cu2+ showed 7.6 times higher peel strength than DURO-TAK® 87-4098 on porcine skin and adhered to human skin for over six days. It demonstrated a 6.25-fold increase in drug loading compared to PHT, with 19.22-fold higher AUC in vivo studies. α-helix facilitated drug release, proven by various analyses. PHT-SP-Cu2+ showed excellent cytocompatibility and safety for transdermal applications. This study contributes to developing efficient TDDS patches.

Protamine-grafted carboxymethyl chitosan based hydrogel with adhesive and long-term antibacterial properties for hemostasis and skin wound healing.

In this study, we developed a tissue-adhesive and long-term antibacterial hydrogel consisting of protamine (PRTM) grafted carboxymethyl chitosan (CMC) (PCMC), catechol groups modified CMC (DCMC), and oxidized hyaluronic acid (OHA), named DCMC-OHA-PCMC. According to the antibacterial experiments, the PCMC-treated groups showed obvious and long-lasting inhibition zones against E. coli (and S. aureus), and the corresponding diameters varied from 10.1 mm (and 15.3 mm) on day 1 to 9.8 mm (and 15.3 mm) on day 7. The DCMC-OHA-PCMC hydrogel treated groups also exhibited durable antibacterial ability against E. coli (and S. aureus), and the antibacterial rates changed from 99.3 ± 0.21 % (and 99.6 ± 0.36 %) on day 1 to 76.2 ± 1.74 % (and 84.2 ± 1.11 %) on day 5. Apart from good mechanical and tissue adhesion properties, the hydrogel had excellent hemostatic ability mainly because of the grafted positive-charged PRTM. As the animal assay results showed, the hydrogel was conducive to promoting the deposition of new collagen (0.84 ± 0.03), the regeneration of epidermis (98.91 ± 6.99 µm) and wound closure in the process of wound repairing. In conclusion, the presented outcomes underline the prospective potential of the multifunctional CMC-based hydrogel for applications in wound dressings.

Multifunctional Self-Healing Carbon Dot-Gelatin Bioadhesive: Improved Tissue Adhesion with Simultaneous Drug Delivery, Optical Tracking, and Photoactivated Sterilization.

Bioadhesives with all-inclusive properties for simultaneous strong and robust adhesion, cohesion, tracking, drug delivery, self-sterilization, and nontoxicity are still farfetched. Herein, a carbon dot (CD) is made to infuse each of the above-desired aspects with gelatin, an inexpensive edible protein. The CD derived through controlled hydrothermal pyrolysis of dopamine and terephthaldehyde retained -NH2, -OH, -COOH, and, most importantly, -CHO functionality on the CD surface for efficient skin adhesion and cross-linking. Facile fabrication of CD-gelatin bioadhesive through covalent conjugation of -CHO of the CD with -NH2 of gelatin through Schiff base formation was accomplished. This imparts remarkable self-healing attributes as well as excellent adhesion and cohesion evident from physicomechanical analysis in a porcine skin model. Improved porosity of the bioadhesive allows loading hemin as a model drug whose disembarkment is tracked with intrinsic CD photoluminescence. In a significant achievement, antibiotic-free self-sterilization of bioadhesive is demonstrated through visible light (white LED, 23 W)-irradiated photosensitization of the CD to produce reactive oxygen species for annihilation of both Gram-positive and Gram-negative bacteria with exceptional efficacy (99.9%). Thus, a comprehensive CD-gelatin bioadhesive for superficial and localized wound management is reported as a promising step for the transformation of the bioadhesive domain through controlled nanotization for futuristic clinical translations.

Multifunctional polypeptide-based hydrogel bio-adhesives with pro-healing activities and their working principles.

Wound healing is a complex physiological process involving hemostasis, inflammation, proliferation, and tissue remodeling. Therefore, there is an urgent need for suitable wound dressings for effective and systematical wound management. Polypeptide-based hydrogel bio-adhesives offer unique advantages and are ideal candidates. However, comprehensive reviews on polypeptide-based hydrogel bio-adhesives for wound healing are still lacking. In this review, the physiological mechanisms and evaluation parameters of wound healing were first described in detail. Then, the working principles of hydrogel bio-adhesives were summarized. Recent advances made in multifunctional polypeptide-based hydrogel bio-adhesives involving gelatin, silk fibroin, fibrin, keratin, poly-γ-glutamic acid, ɛ-poly-lysine, serum albumin, and elastin with pro-healing activities in wound healing and tissue repair were reviewed. Finally, the current status, challenges, developments, and future trends of polypeptide-based hydrogel bio-adhesives were discussed, hoping that further developments would be stimulated to meet the growing needs of their clinical applications.