Commercial Fibrin Glue Research Articles

A biguanide chitosan-based hydrogel adhesive accelerates the healing of bacterial-infected wounds

The development of tissue adhesives with good biocompatibility and potent antimicrobial properties is crucial for addressing the high incidence of surgical site infections in emergency and clinical settings. Herein, an injectable hydrogel adhesive composed of chitosan biguanidine (CSG), oxidized dextran (ODex) and tannin (TA) was synthesized primarily through Schiff-base reactions, hydrogen bonding, and electrostatic interactions. TA was introduced into the CSG/ODex hydrogel to prepare a physicochemically double cross-linked hydrogel. The hydrogel formulation incorporating 2 wt% TA (CSG/ODex-TA2) exhibited rapid gelation, moderate mechanical properties, good tissue adhesion, and sustained release behavior of TA. Both in vitro and in vivo studies demonstrated that CSG/ODex-TA2 showed significantly enhanced adhesion and antibacterial effectiveness compared to the CSG/ODex hydrogel and commercial fibrin glue. Leveraging the positive charge of CSG, the CSG/ODex-TA2 hydrogel demonstrated a strong contact antibacterial effect, while the sustained release of TA provided diffusion antibacterial capabilities. By integrating contact and diffusion antibacterial mechanisms into the hydrogel, a promising approach was developed to boost antibacterial efficiency and accelerate the healing of wounds infected with methicillin-resistant Staphylococcus aureus (MRSA). The CSG/ODex-TA2 hydrogel has excellent biocompatibility, hemostatic properties, and antibacterial capabilities, making it a promising candidate for improving in vivo wound care and combating bacterial infections.

Injectable, Shear-Thinning, Self-Healing, and Self-Cross-Linkable Benzaldehyde-Conjugated Chitosan Hydrogels as a Tissue Adhesive.

Benzaldehyde-conjugated chitosan (CH-CBA) was synthesized by a coupling reaction between chitosan (CH) and carboxybenzaldehyde (CBA). The pH-sensitive self-cross-linking can be achieved through the Schiff base reaction. The degree of substitution (DS) of CH-CBA was controlled at 1.4-12.7% by optimizing the pH and reagent stoichiometry. The dynamic Schiff base linkages conferred strong shear-thinning and self-healing properties to the hydrogels. The viscosity of the 2 wt/v % CH-CBA hydrogel decreased from 5.3 × 107 mPa·s at a shear rate of 10-2 s-1 to 2.0 × 103 mPa·s at 102 s-1 at pH 7.4. The CH-CBA hydrogel exhibited excellent biocompatibility in vitro and in vivo. Moreover, the hydrogel adhered strongly to porcine small intestine, colon, and cecum samples, comparable to commercial fibrin glue, and exhibited effective in vivo tissue sealing in a mouse cecal ligation and puncture model, highlighting its potential as a biomaterial for application in tissue adhesives, tissue engineering scaffolds, etc.

Bioinspired adhesive hydrogel based on serotonin-modified gelatin and oxidized hyaluronic acid for rapid hemostasis and wound healing

A hybrid hydrogel system (GSOHA) consisting of serotonin-grafted gelatin and oxidized hyaluronic acid (OHA) was developed in this study to efficiently control bleeding and prevent bacterial infections during surgery and trauma. The study results showed that the incorporation of serotonin successfully produced hydrogels with rapid hemostatic, antibacterial, and antioxidant properties. The GSOHA hydrogel exhibited considerably stronger tissue adhesion (15.55 ± 0.36 kPa) to porcine skin than the commercial fibrin glue (1.09 ± 0.04 kPa). In addition, the hydrogel could rapidly absorb blood cells and stimulate cell conjugation with serotonin addition. In vitro experiments using endothelial cells and erythrocytes demonstrated the excellent biocompatibility and hemocompatibility of the hydrogel. Most importantly, the GSOHA hydrogel accelerated the wound healing process in a full-thickness skin defect mice model, and the histological staining results demonstrated that GSOHA significantly promoted collagen deposition and vascularization. In conclusion, this study demonstrated the significant potential of the GSOHA hydrogel as an adhesive dressing for rapid hemostasis and wound healing.

Transplantation of Stem Cell Spheroid-Laden 3-Dimensional Patches with Bioadhesives for the Treatment of Myocardial Infarction.

Myocardial infarction (MI) is treated with stem cell transplantation using various biomaterials and methods, such as stem cell/spheroid injections, cell sheets, and cardiac patches. However, current treatment methods have some limitations, including low stem cell engraftment and poor therapeutic effects. Furthermore, these methods cause secondary damage to heart due to injection and suturing to immobilize them in the heart, inducing side effects. In this study, we developed stem cell spheroid-laden 3-dimensional (3D) patches (S_3DP) with biosealant to treat MI. This 3D patch has dual modules, such as open pockets to directly deliver the spheroids with their paracrine effects and closed pockets to improve the engraft rate by protecting the spheroid from harsh microenvironments. The spheroids formed within S_3DP showed increased viability and expression of angiogenic factors compared to 2-dimensional cultured cells. We also fabricated gelatin-based tissue adhesive biosealants via a thiol-ene reaction and disulfide bond formation. This biosealant showed stronger tissue adhesiveness than commercial fibrin glue. Furthermore, we successfully applied S_3DP using a biosealant in a rat MI model without suturing invivo, thereby improving cardiac function and reducing heart fibrosis. In summary, S_3DP and biosealant have excellent potential as advanced stem cell therapies with a sutureless approach to MI treatment.

Evaluation and comparison of the efficacy of autologous fibrin glue with 4-0 silk sutures in periodontal flap closure and wound healing - A split mouth randomized controlled trial.

Fibrin glue has shown to be a pioneering remedy to overcome the inconvenience of suturing. Autologous products reduce the risk of contamination and immunological responses compared to commercial fibrin glue. Hence using autologous fibrin glue (AFG) as a tissue sealant in periodontal flap closure would be of added value for a predictable outcome. To evaluate and compare the efficacy of AFG with 4-0 silk sutures in periodontal flap closure and healing. Total of 17 patients diagnosed with generalized periodontitis in the age group of 18 to 60years with probing pocket depth of ≥ 6mm and clinical attachment level of ≥5mm in at least two quadrants were categorized into test group (AFG) and control group (4-0 silk sutures). Primary outcome measures [modified gingival index (MGI), early wound index (EHI) and interleukin 1 beta (IL-1ß) and secondary outcome measures (oral hygiene index, plaque index and visual analog scale (VAS) were recorded at baseline, 1, 2, 3 and 4 weeks. A statistically significant reduction of IL-1ß value (p =.005); MGI (p = .02); EHI (p = .004), VAS scores (p < .001) and a positive Spearman's correlation (rho = 0.15) was seen between EHI scores & IL-1ß levels in test group at 1week period in comparison to control group. AFG showed promising results as an alternative to sutures. The use of AFG significantly improved clinical parameters and reduced the levels of pro-inflammatory cytokines making it an effective adhesive with healing properties in the era of suture-less periodontal flap surgery.

Gelable and Adhesive Powder for Lethal Non‐Compressible Hemorrhage Control

AbstractHemostatic powders are widely used in clinical and emergency situations but often exhibit low wet adhesion, cytotoxicity concerns, and do not work well for lethal non‐compressible hemorrhage. Here a new kind of gelable and adhesive powder (GAP) is developed, which integrates chitosan microspheres (CM), tetra‐armed poly(ethylene glycol) amine (Tetra‐PEG‐NH2), and tetra‐armed poly(ethylene glycol) succinimidyl succinate (Tetra‐PEG‐SS). Upon application to the wound site, the macroporous CM can rapidly absorb the interfacial liquids, and meanwhile, the hydrated GAP turns into hydrogel (crosslinking between Tetra‐PEG‐SS and CM/Tetra‐PEG‐NH2) with stable and robust adhesion to the wet tissue though covalent bonding. The in vitro and in vivo results suggest that the GAP with optimized formulation exhibits strong tissue adhesive, high burst pressure, and enhanced blood clotting ability, as well as excellent biocompatibility and on‐demand removal properties. A significantly improved hemostatic efficacy is demonstrated in the rat liver, spleen, and femoral artery injury models compared to that of the CM, commercial fibrin glue, and Yunnan Baiyao (YB). The GAP can also halt the severe bleeding from pig visceral organs. Overall, the proposed GAP has many advantages including good biocompatibility, rapid and effective hemostasis, low cost, and ease of use, making it as a promising hemostat for lethal non‐compressible hemorrhage control.

Hydrophobically modified hydrogel with enhanced tissue adhesion and antibacterial capacity for wound healing

The increasing emergence of drug-resistant bacteria and bacteria-infected wounds highlights the urgent need for new kinds of antibacterial wound dressing. Herein, we reported a novel bio-adhesive and antibacterial hydrogel consisting of hydrophobically modified gelatin, oxidized konjac glucomannan, and dopamine. This kind of functional hydrogel was endowed with developed stability in a liquid environment and strong tissue adhesion, even much higher than the commercial fibrin glue to wounds. The excellent bacteria-killing efficiency of hydrophobically modified hydrogel against S. aureus and E. coli was verified, as well as the low hemolysis ratio against erythrocytes in vitro. The hydrogel also exhibited good cytocompatibility in terms of supporting cell proliferation. Most importantly, these abovementioned properties could be customized by altering the substitution degree of hydrophobic groups during manufacturing, demonstrating its great potential in biomedical fields such as tissue adhesive and wound dressing.

Suture and glue-free autologous graft for pterygium surgery

Of various techniques of pteryium surgeries to prevent recurrence, conjunctival limbal auto graft has been the most successful adjuvant since the studies have shown the role of limbal stem cell deficiency (LSCD) as pathology of pterygium. The most common method of auto-graft fixation post pterygium excision is suturing; with drawbacks of prolonged operating time and postoperative discomfort. Replacing sutures with tissue adhesives may shorten the operating time, improve postoperative comfort; however, the major concern of the commercial fibrin glue is the cost and the potential risk of transmission of infection.To study, 1. The efficacy and complications of suture free and glue free conjunctival-limbal auto-graft for the management of pterygia, 2. The outcome of surgeries by two different qualified surgeons Prospective, interventional case study of 108 consecutive cases of pterygia that had excision with conjunctival-limbal auto-grafting without using glue or sutures. The operated eye patched for a day and followed up on day 1, 3 and 7, 6 weeks and 6 months; watched for hemorrhage beneath the graft, graft retraction, chemosis, recurrence or any other complication. The mean age of the patients was 40.7 years (range, 25 – 68 years) with female preponderance (60.2%) and nasal pterygia in 65.7 %. Not a single graft was dislodged and none had recurrence in the follow up period of 9-20 months. Graft retraction occurred in 7 cases (6.5%) and one patient had sub-graft hemorrhage which lasted for nine days. 76.9% had no discomfort even in immediate post-operative period. The results were comparable among patients of both the surgeons.Suture- and glue-freelimbal conjunctival auto-grafting following pterygium excision is a safe, effective and economical option for the management of both primary and recurrent pterygium. Learning curve is short and consistently similar results possible in different hands.

The use of commercial fibrin glue in dermal replacement material reduces angiogenic and lymphangiogenic gene and protein expression in vitro.

Commercial fibrin glue is increasingly finding its way into clinical practice in surgeries to seal anastomosis, and initiate hemostasis or tissue repair. Human biological glue is also being discussed as a possible cell carrier. To date, there are only a few studies addressing the effects of fibrin glue on the cell-molecular level. This study examines the effects of fibrin glue on angiogenesis and lymphangiogenesis, as well as adipose-derived stem cells (ASCs) with a focus on gene and protein expression in scaffolds regularly used for tissue engineering approaches. Collagen-based dermal regeneration matrices (DRM) were seeded with human umbilical vein endothelial cells (HUVEC), human dermal lymphatic endothelial cells (LECs), or adipose-derived stem cells (ASC) and fixed with or without fibrin glue according to the experimental group. Cultures were maintained for 1 and 7days. Finally, angiogenic and lymphangiogenic gene and protein expression were measured with special regard to subtypes of vascular endothelial growth factor (VEGF) and corresponding receptors using Multiplex-qPCR and ELISA assays. In addition, the hypoxia-induced factor 1-alpha (HIF1a) mediated intracellular signaling pathways were included in assessments to analyze a hypoxic encapsulating effect of fibrin polymers. All cell types reacted to fibrin glue application with an alteration of gene and protein expression. In particular, vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor B (VEGFB), vascular endothelial growth factor C (VEGFC), vascular endothelial growth receptor 1 (VEGFR1/FLT1), vascular endothelial growth receptor 2 (VEGFR2/KDR), vascular endothelial growth receptor 3 (VEGFR3/FLT4) and Prospero Homeobox 1 (PROX1) were depressed significantly depending on fibrin glue. Especially short-term fibrin effect led to a continuous downregulation of respective gene and protein expression in HUVECs, LECs, and ASCs. Our findings demonstrate the impact of fibrin glue application in dermal regeneration with special regard to angiogenesis and lymphangiogenesis. In particular, a short fibrin treatment of 24hours led to a decrease in gene and protein levels of LECS, HUVECs, and ASCs. In contrast, the long-term application showed less effect on gene and protein expressions. Therefore, this work demonstrated the negative effects of fibrin-treated cells in tissue engineering approaches and could affect wound healing during dermal regeneration.

Dynamic Crosslinked Injectable Mussel-Inspired Hydrogels with Adhesive, Self-Healing, and Biodegradation Properties.

The non-invasive tissue adhesives with strong tissue adhesion and good biocompatibility are ideal for replacing traditional wound treatment methods such as sutures and needles. The self-healing hydrogels based on dynamic reversible crosslinking can recover their structure and function after damage, which is suitable for the application scenario of tissue adhesives. Herein, inspired by mussel adhesive proteins, we propose a facile strategy to achieve an injectable hydrogel (DACS hydrogel) by grafting dopamine (DOPA) onto hyaluronic acid (HA) and mixing it with carboxymethyl chitosan (CMCS) solution. The gelation time and rheological and swelling properties of the hydrogel can be controlled conveniently by adjusting the substitution degree of the catechol group and the concentration of raw materials. More importantly, the hydrogel exhibited rapid and highly efficient self-healing ability and excellent biodegradation and biocompatibility in vitro. Meanwhile, the hydrogel exhibited ~4-fold enhanced wet tissue adhesion strength (21.41 kPa) over the commercial fibrin glue. This kind of HA-based mussel biomimetic self-healing hydrogel is expected to be used as a multifunctional tissue adhesive material.

Autologous fibrin glue versus sutures for conjunctival autograft in primary pterygium: a randomized clinical trial.

To describe and compare the autologous fibrin glue and traditional sutures for conjunctival graft attachment in patients undergoing primary pterygium excision surgery. A randomized clinical trial included patients who underwent pterygium surgery with conjunctival autologous graft (CAG). Using randomization, a single-trained surgeon performed graft fixation with autologous glue or sutures. The glue was prepared immediately before the surgery, using the patient's blood components. After centrifugation, the plasma was collected and enhanced with calcium gluconate. Postoperative assessments were performed on Days 1, 7, 21, 30 and 180. The study evaluated postoperative edema and pain and complications. The mean surgical time was compared. Recurrence of the pterygium was assessed 6months postoperatively. The study evaluated 61 eyes. Thirty-three eyes underwent pterygium surgery using the glue technique, and 28 underwent the traditional suture technique. Fifty-one patients (83.60%) had successful graft adhered to at the end of follow-up. Ten patients (10/33) lost their graft in the glue group, and only 69.70% maintained graft presence in the fourth week versus 100% of the patients in the suture group (p = 0.001). Pain scores were lower in the glue group, and clinical edema was significantly higher. There was no significant difference in graft retraction or the presence of granuloma, necrosis or postoperative infection. Autologous fibrin glue is an affordable option for CAG fixation in particular contexts where commercial fibrin glue is unavailable, and it could offer advantages compared to sutures. A higher graft loss rate was observed and might be related to topical anesthesia, and improvements to the technique are needed. gov Identifier: NCT04151017. https://clinicaltrials.gov/ct2/show/NCT04151017?term=20170467&draw=1&rank=1 .

A Dual-network Nerve Adhesive with Enhanced Adhesion Strength Promotes Transected Peripheral Nerve Repair.

Peripheral nerve transection has a high prevalence and results in functional loss of affected limbs. The current clinical treatment using suture anastomosis significantly limits nerve recovery due to severe inflammation, secondary damage, and fibrosis. Fibrin glue, a commercial nerve adhesive as an alternative, avoids secondary damage but suffers from poor adhesion strength. To address their limitations, a highly efficacious nerve adhesive based on dual-crosslinking of dopamine-isothiocyanate modified hyaluronic acid and decellularized nerve matrix is reported in this paper. This dual-network nerve adhesive (DNNA) shows controllable gelation behaviors feasible for surgical applications, robust adhesion strength, and promoted axonal outgrowth in vitro. The in vivo therapeutic efficacy is tested using a rat-based sciatic nerve transection model. The DNNA decreases fibrosis and accelerates axon/myelin debris clearance at 10 days post-surgery, compared to suture and commercial fibrin glue treatments. At 10 weeks post-surgery, the strong adhesion and bioactivity allow DNNA to significantly decrease intraneural inflammation and fibrosis, enhance axon connection and remyelination, aid motor and sensory function recovery, as well as improve muscle contraction, compared to suture and fibrin treatments. Overall, this dual-network hydrogel with robust adhesion provides a rapid and highly efficacious nerve transection treatment to facilitate nerve repair and neuromuscular function recovery.

A Simple, Safe, and Effective Method for Preparing Autologous Bio-Based Fibrin Glue for Ophthalmic Use.

This study proposes a method to prepare autologous bio-based fibrin glue (FG) for use in ophthalmic surgery. FGs containing three fibrinogen concentrations and a thrombin concentrate were prepared using human blood from five donors (FG1: physiological fibrinogen concentration; FG2 and FG3: concentrated fibrinogen). The adhesion strength was tested, and the clinical safety and efficacy were studied in rabbit eyes in conjunctival surgery. A commercial FG was used as a control. From each donor, 2 mL of FG was prepared, containing 1 mL of 3.49 ± 0.78 (FG1), 17.74 ± 4.66 (FG2), or 47.46 ± 9.36 mg/mL (FG3) of fibrinogen and 1 mL of 2248.12 ± 604.20 UI/mL of thrombin. The average adhesion strength increased with the fibrinogen concentration, from 1.49 ± 0.39 kPa (FG1) to 3.14 ± 1.09 kPa (FG3). FG1 showed poor results when used for autograft adhesion. In contrast, the conjunctival autografts were successfully grafted using FG2 and FG3, revealing equivalent adhesion properties compared with commercial FG, but with less inflammation. In conclusion, FGs could be prepared on demand within minutes from small volumes of human blood, using a method that results in FGs which exhibit good adhesion capacity and are also safe and effective in a preclinical study.

Single-component hyaluronic acid hydrogel adhesive based on phenylboronic ester bonds for hemostasis and wound closure

Hydrogel tissue adhesives that currently available are often fabricated by mixing two or more polymeric components. Single-component hydrogels afford injectability, strong and reversible adhesion remain a formidable challenge. This research describes the creation of the first single-component hyaluronic acid hydrogel adhesive-based on phenylboronic acid-diol ester linkages. Phenylboronic acid can not only serve as a cross-linker to form hydrogel, but also act as an adhesion site for glycosyl compounds found in biological cell membranes. The rheological and compressive tests for the hydrogel show that it has excellent self-healing properties, good injectability and strong compressive strength. Adhesion tests demonstrated that the hydrogel has significantly greater adhesion strength than commercial fibrin glue. These findings suggest that the rational design of hydrogel precursors facilitates the formation of single-component networks and multiple functionalities. In vivo studies further proved the hydrogel was an ideal bio-adhesive with biocompatibility, absorbed wound exudate and hemostasis, and accelerated wound closure.

Temperature-sensitive mussel-inspired citrate-based tissue adhesives with low-swelling

ABSTRACT Mussel-inspired tissue adhesives have been widely studied in recent years because of their excellent underwater adhesion. Our recent study has synthesized a series of tissue adhesives with citric acid, dopamine, 1,8-octanediol and poly(ethylene oxide) (PEO), and found that amphiphilic adhesives showed an efficient underwater adhesion mechanism. Poly(propylene oxide)-poly(ethylene oxide) block copolymer (PEO-PPO-PEO) is a thermosensitive amphiphilic material, widely used in medical field. Herein, we replaced PEO with PEO-PPO-PEO to introduce temperature-sensitivity into adhesives, and utilized the hydrophilic-to-hydrophobic transition of PEO-PPO-PEO to reduce the swelling at human temperature. Fortunately, we got positive results that all the synthetized adhesives showed obvious temperature-sensitivity. The transition from low temperature to room temperature of the high concentrated uncured adhesive dispersion made it potentially injectable. After crosslinking, the swelling ratio of cured adhesives showed a significant decrease from 4°C to 37°C. And all the swelling ratios under 37°C were low, ranging from 8.4% to 22.5%. Additionally, the lap-shear adhesion strength on wet porcine skin was in the range of 29.2–67.1 kPa, which was higher than that of commercial fibrin glue (9–15 kPa). By selecting different (PEO)y(PPO)x(PEO)y, we could obtain adhesives with wide mechanical properties and broaden the scope of use of the adhesives.

Development of an In Situ Printing System With Human Platelet Lysate-Based Bio-Adhesive to Treat Corneal Perforations.

PurposeCorneal perforation is a clinical emergency that can result in blindness. Currently corneal perforations are treated either by cyanoacrylate glue which is toxic to corneal cells, or by using commercial fibrin glue for small perforations. Both methods use manual delivery which lead to uncontrolled application of the glues to the corneal surface. Therefore, there is a need to develop a safe and effective alternative to artificial adhesives.MethodsPreviously, our group developed a transparent human platelet lysate (hPL)-based biomaterial that accelerated corneal epithelial cells healing in vitro. This biomaterial was further characterized in this study using rheometry and adhesive test, and a two-component delivery system was developed for its application. An animal trial (5 New Zealand white rabbits) to compare impact of the biomaterial and cyanoacrylate glue (control group) on a 2 mm perforation was conducted to evaluate safety and efficacy.ResultsThe hPL-based biomaterial showed higher adhesiveness compared to commercial fibrin glue. Treatment rabbits had lower pain scores and faster recovery, despite generating similar scar-forming structure compared to controls. No secondary corneal ulcer was generated in rabbits treated with the bio-adhesive.ConclusionsThis study reports an in situ printing system capable of delivering a hPL-based, transparent bio-adhesive and successfully treating small corneal perforations. The bio-adhesive-treated rabbits recovered faster and required no additional analgesia.Translational RelevanceThe developed in situ hPL bio-adhesives treatment represents a new format of treating corneal perforation that is easy to use, allows for accurate application, and can be a potentially effective and pain relief treatment.

In situ forming hydrogel recombination with tissue adhesion and antibacterial property for tissue adhesive.

In situ forming hydrogels with strong adhesive strength and antibacterial activity are of great interest to serve as tissue adhesive in fields like wound dressing and mass hemorrhage. In this study, hybrid hydrogel (GOHA) based on gelatin and oxidized hyaluronic acid was developed and endowed with excellent mechanical strength and tissue adhesion. According to our results, GOHA hydrogel exhibits a fast gelation time of around 60 s, robust compression strength of 223.43 ± 24.28kPa, and strong adhesion of 14.33 ± 0.78kPa to porcine skin, which is much higher than that of commercial fibrin glue (around 1.00kPa). Meanwhile, through the loading of levofloxacin, obvious antibacterial activity can be obtained for wider applications. Notably, it would not compromise the hemocompatibility and cytocompatibility in vitro. In summary, this kind of hybrid hydrogel shows great potential as tissue adhesive in biomedical fields.

Multi-crosslinking hydrogels with robust bio-adhesion and pro-coagulant activity for first-aid hemostasis and infected wound healing

Bio-adhesive polysaccharide-based hydrogels have attracted much attention in first-aid hemostasis and wound healing for excellent biocompatibility, antibacterial property and pro-healing bioactivity. Yet, the inadequate mechanical properties and bio-adhesion limit their applications. Herein, based on dynamic covalent bonds, photo-triggered covalent bonds and hydrogen bonds, multifunctional bio-adhesive hydrogels comprising modified carboxymethyl chitosan, modified sodium alginate and tannic acid are developed. Multi-crosslinking strategy endows hydrogels with improved strength and flexibility simultaneously. Owing to cohesion enhancement strategy and self-healing ability, considerable bio-adhesion is presented by the hydrogel with a maximal adhesion strength of 162.6 kPa, 12.3-fold that of commercial fibrin glue. Based on bio-adhesion and pro-coagulant activity (e.g., the stimulative aggregation and adhesion of erythrocytes and platelets), the hydrogel reveals superior hemostatic performance in rabbit liver injury model with blood loss of 0.32 g, only 54.2% of that in fibrin glue. The healing efficiency of hydrogel for infected wounds is markedly better than commercial EGF Gel and Ag+ Gel due to the enhanced antibacterial and antioxidant properties. Through the multi-crosslinking strategy, the hydrogels show enhanced mechanical properties, fabulous bio-adhesion, superior hemostatic performance and promoting healing ability, thereby have an appealing application value for the first-aid hemostasis and infected wound healing.

Multi-Crosslinked Hydrogels with Instant Self-Healing and Tissue Adhesive Properties for Biomedical Applications.

Due to the defects like long gelling time, inferior mechanical properties and weak adhesion, in situ forming hydrogels are still restricted in biomedical applications like viscera rupture and targeted therapy. To address these problems, a new kind of multi-crosslinked hydrogel (G-OKG-DA) consisting of gelatin, oxidized konjac glucomannan (OKG), and dopamine (DA) is proposed in this study. The resulting hybrid hydrogel is endowed with a short gelling time (≈3min) and injectable capacity. According to the mechanical and adhesive tests, G-OKG-DA hydrogel shows a robust tensile strength of 23.94kPa, as well as a higher adhesive strength (≈150kPa) than commercial fibrin glue. In addition, an instant self-healing behavior of G-OKG-DA hydrogel can be found, which is attributed to multi-cross-linking reactions including Schiff-based dynamic covalent bonds between OKG and gelatin, oxidative polymerization of DA, and catechol-mediated chemistry like Michael addition and DA-quinone coupling. Importantly, the multi-crosslinked hydrogel will not compromise its hemocompatibility and cytocompatibility in vitro, suggesting potential applications in biomedical fields as tissue adhesive and implants.

Facile Preparation of Tunicate-Inspired Chitosan Hydrogel Adhesive with Self-Healing and Antibacterial Properties.

In order to replace traditional wound treatments such as sutures, tissue adhesives with strong wet tissue adhesion and biocompatibility have attracted more attention to the applications of non-invasive wound closure. Herein, inspired by tunicate adhesive protein, a series of 2,3,4-trihydroxybenzaldehyde (TBA)-modified chitosan hydrogels (CS-TBA-Fe) were prepared by easily mixing the solutions of chitosan-FeCl3 and TBA via the Schiff-base reaction and the coordination between Fe3+ and pyrogallol groups. The gelation time was greatly shortened to only several seconds after induced even trace Fe3+. The hydrogel (CS-TBA-Fe) exhibited ~12-fold enhanced wet tissue adhesion strength (60.3 kPa) over the commercial fibrin glue. Meanwhile, the hydrogel also showed robust adhesion to various substrates such as wood, PMMA, and aluminum. The swelling ratio and rheological property can be simply controlled by changing the concentrations of chitosan, TBA, and Fe3+. Moreover, the hydrogel displayed a rapid and highly efficient self-healing ability and an excellent antibacterial activity against E. coli. The overall results show that the CS-TBA-Fe hydrogel with enhanced wet adhesiveness will be a promising tissue adhesive material.