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.

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.

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.

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.

Enhanced ROS scavenging and tissue adhesive abilities in injectable hydrogels by protein modification with oligoethyleneimine.

Postsurgical treatment comprehensively benefits from the application of tissue-adhesive injectable hydrogels, which reduce postoperative complications by promoting wound closure and tissue regeneration. Although various hydrogels have been employed as clinical tissue adhesives, many exhibit deficiencies in adhesive strength under wet conditions or in immunomodulatory functions. Herein, we report the development of reactive oxygen species (ROS) scavenging and tissue-adhesive injectable hydrogels composed of polyamine-modified gelatin crosslinked with the 4-arm poly (ethylene glycol) crosslinker. Polyamine-modified gelatin was particularly potent in suppressing the secretion of proinflammatory cytokines from stimulated primary macrophages. This effect is attributed to its ability to scavenge ROS and inhibit the nuclear translocation of nuclear factor kappa-B. Polyamine-modified gelatin-based hydrogels exhibited ROS scavenging abilities and enhanced tissue adhesive strength on collagen casing. Notably, the hydrogel demonstrated exceptional tissue adhesive properties in a wet environment, as evidenced by its performance using porcine small intestine tissue. This approach holds significant promise for designing immunomodulatory hydrogels with superior tissue adhesion strength compared to conventional medical materials, thereby contributing to advancements in minimally invasive surgical techniques.

ECM-based bioadhesive hydrogel for sutureless repair of deep anterior corneal defects.

Corneal transplantation is the gold standard treatment for corneal-related blindness; however, this strategy faces challenges such as limited donor cornea, graft rejection, suture-related complications, and the need for specialized equipment and advanced surgical skills. Development of tissue adhesives for corneal regeneration is of great clinical value. However, currently available corneal tissue sealants pose challenges, such as lack of safety, biocompatibility, and desired mechanical properties. To meet these requirements simultaneously, a bovine stromal corneal extracellular matrix (dCor) was used to design a bioadhesive photocurable hydrogel based on gelatin methacrylate (GelMA) and polyethylene glycol diacrylate (PEGDA) hydrogels (dCor/Gel-PEG). Integration of dCor into the dual networks of GelMA and PEGDA (Gel-PEG) led to a bioadhesive hydrogel for curing corneal defects, which could be crosslinked by Irgacure 2959 within 5 min ultraviolet irradiation. The viability of corneal stromal stem cells (CSSCs) was improved on the dCor/Gel-PEG hydrogel in comparison to the Gel-PEG hydrogel. The gene expression profile supported the keratocyte differentiation of CSSCs seeded on dCor/Gel-PEG via increased KERA and ALDH, with inhibited myofibroblast transdifferentiation via decreased α-SMA due to the presence of dCor. Interestingly, the dCor/Gel-PEG hydrogel exhibited favorable mechanical performance in terms of elasticity and bioadherence to the host corneal stroma. Ex vivo and in vivo examinations proved the feasibility of this hydrogel for the sutureless reconstruction of deep anterior corneal defects with promising histopathological results.

A tough bioadhesive hydrogel supports sutureless sealing of the dural membrane in porcine and ex vivo human tissue.

Complete sequestration of central nervous system tissue and cerebrospinal fluid by the dural membrane is fundamental to maintaining homeostasis and proper organ function, making reconstruction of this layer an essential step during neurosurgery. Primary closure of the dura by suture repair is the current standard, despite facing technical, microenvironmental, and anatomic challenges. Here, we apply a mechanically tough hydrogel paired with a bioadhesive for intraoperative sealing of the dural membrane in rodent, porcine, and human central nervous system tissue. Tensile testing demonstrated that this dural tough adhesive (DTA) exhibited greater toughness with higher maximum stress and stretch compared with commercial sealants in aqueous environments. To evaluate the performance of DTA in the range of intracranial pressure typical of healthy and disease states, ex vivo burst pressure testing was conducted until failure after DTA or commercial sealant application on ex vivo porcine dura with a punch biopsy injury. In contrast to commercial sealants, DTA remained adhered to the porcine dura through increasing pressure up to 300 millimeters of mercury and achieved a greater maximum burst pressure. Feasibility of DTA to repair cerebrospinal fluid leak in a simulated surgical context was evaluated in postmortem human dural tissue. DTA supported effective sutureless repair of the porcine thecal sac in vivo. Biocompatibility and adhesion of DTA was maintained for up to 4 weeks in rodents after implantation. The findings suggest the potential of DTA to augment or perhaps even supplant suture repair and warrant further exploration.

Improved hydration property of tissue adhesive/hemostatic microparticle based on hydrophobically-modified Alaska pollock gelatin.

The management of bleeding is an important aspect of endoscopic surgery to avoid excessive blood loss and minimize pain. In clinical settings, sprayable hemostatic particles are used for their easy delivery, adaptability to irregular shapes, and rapid hydration. However, conventional hemostatic particles present challenges associated with tissue adhesion. In a previous study, we reported tissue adhesive microparticles (C10-sa-MPs) derived from Alaska pollock gelatin modified with decyl groups (C10-sa-ApGltn) using secondary amines as linkages. The C10-sa-MPs adhere to soft tissues through a hydration mechanism. However, their application as a hemostatic agent was limited by their long hydration times, attributed to their high hydrophobicity. In this study, we present a new type microparticle, C10-am-MPs, synthesized by incorporating decanoyl group modifications into ApGltn (C10-am-ApGltn), using amide bonds as linkages. C10-am-MPs exhibited enhanced hydration characteristics compared to C10-sa-MPs, attributed to superior water absorption facilitated by amide bonds rather than secondary amines. Furthermore, C10-am-MPs demonstrated comparable tissue adhesion properties and underwater adhesion stability to C10-sa-MPs. Notably, C10-am-MPs exhibited accelerated blood coagulation in vitro compared to C10-sa-MPs. The application of C10-am-MPs in an in vivo rat liver hemorrhage model resulted in a hemostatic effect comparable to a commercially available hemostatic particle. These findings highlight the potential utility of C10-am-MPs as an effective hemostatic agent for endoscopic procedures and surgical interventions.

Sprayable Hydrogel Sealant for Gastrointestinal Wound Shielding.

Naturally occurring internal bleeding, such as in stomach ulcers, and complications following interventions, such as polyp resection post-colonoscopy, may result in delayed (5-7 days) post-operative adverse events-such as bleeding, intestinal wall perforation, and leakage. Current solutions for controlling intra- and post-procedural complications are limited in effectiveness. Hemostatic powders only provide a temporary solution due to their short-term adhesion to GI mucosal tissues (less than 48 h). In this study, a sprayable adhesive hydrogel for facile application and sustained adhesion to GI lesions is developed using clinically available endoscopes. Upon spraying, the biomaterial (based on polyethyleneimine-modified Pluronic micelles precursor and oxidized dextran) instantly gels upon contact with the tissue, forming an adhesive shield. In vitro and in vivo studies in guinea pigs, rabbits, and pig models confirm the safety and efficacy of this biomaterial in colonic and acidic stomach lesions. The authors' findings highlight that this family of hydrogels ensures prolonged tissue protection (3-7 days), facilitates wound healing, and minimizes the risk of delayed complications. Overall, this technology offers a readily adoptable approach for gastrointestinal wound management.

Natural Polymer-Polyphenol Bioadhesive Coacervate with Stable Wet Adhesion, Antibacterial Activity, and On-Demand Detachment.

Medical adhesives are emerging as an important clinical tool as adjuvants for sutures and staples in wound closure and healing and in the achievement of hemostasis. However, clinical adhesives combining cytocompatibility, as well as strong and stable adhesion in physiological conditions, are still in demand. Herein, a mussel-inspired strategy is explored to produce adhesive coacervates using tannic acid (TA) and methacrylate pullulan (PUL-MA). TA|PUL-MA coacervates mainly comprise van der Waals forces and hydrophobic interactions. The methacrylic groups in the PUL backbone increase the number of interactions in the adhesives matrix, resulting in enhanced cohesion and adhesion strength (72.7 Jm-2), compared to the non-methacrylated coacervate. The adhesive properties are kept in physiologic-mimetic solutions (72.8 Jm-2) for 72 h. The photopolymerization of TA|PUL-MA enables the on-demand detachment of the adhesive. The poor cytocompatibility associated with the use of phenolic groups is here circumvented by mixing reactive oxygen species-degrading enzyme in the adhesive coacervate. This addition does not hamper the adhesive character of the materials, nor their anti-microbial or hemostatic properties. This affordable and straightforward methodology, together with the tailorable adhesivity even in wet environments, high cytocompatibility, and anti-bacterial activity, enables foresee TA|PUL-MA as a promising ready-to-use bioadhesive for biomedical applications.

Lung-Mimetic Hydrofoam Sealant to Treat Pulmonary Air Leak.

Pulmonary air leak is the most common complication of lung surgery, contributing to post-operative morbidity in up to 60% of patients; yet, there is no reliable treatment. Available surgical sealants do not match the demanding deformation mechanics of lung tissue; and therefore, fail to seal air leak. To address this therapeutic gap, a sealant with structural and mechanical similarity to subpleural lung is designed, developed, and systematically evaluated. This "lung-mimetic" sealant is a hydrofoam material that has alveolar-like porous ultrastructure, lung-like viscoelastic properties (adhesive, compressive, tensile), and lung extracellular matrix-derived signals (matrikines) to support tissue repair. In biocompatibility testing, the lung-mimetic sealant shows minimal cytotoxicity and immunogenicity in vitro. Human primary monocytes exposed to sealant matrikines in vitro upregulate key genes (MARCO, PDGFB, VEGF) known to correlate with pleural wound healing and tissue repair in vivo. In rat and swine models of pulmonary air leak, this lung-mimetic sealant rapidly seals air leak and restores baseline lung mechanics. Altogether, these data indicate that the lung-mimetic sealant can effectively seal pulmonary air leak and promote a favorable cellular response in vitro.

Injectable-Hydrogel-Based Tissue Sealant for Hemostasis, Bacteria Inhibition, and Pro-Angiogenesis in Organ Bleeding Wounds and Therapeutic Outcome Monitoring Via NIR-II Optical Imaging.

Sudden hemorrhage stemming from internal organ wounds poses a grave and potentially fatal risk if left untreated. Injectable-hydrogel-based tissue sealants featuring multiple actions, including fit-to-shape in situ gelation, rapid hemostasis, pro-angiogenic, anti-bacterial and outcome tracking, are ideal for the management of organ trauma wounds. Herein, an injectable-hydrogel tissue sealant AN@CD-PEG&TQ which consists of four-arm 4-arm poly(ethylene glycol) (PEG-SC) succinimidyl carbonate), AN@CD nanoprobe, and two bioactive peptides (anti-microbial peptide Tet213 and pro-angiogenic peptide QK) is developed. Among them, AN@CD nanoparticles form through host/guest complexation of amino-group-containing ß-cyclodextrin and adamantyl group, enabling in situ biomarker (NO)-activatable optoacoustic/NIR-II: Near-infrared second biological window fluorescent imaging. The ample ─NH2 groups on the surface of AN@CD readily engage in rapid cross-linking with succinimidyl ester groups located at the ends of four-arm PEG-SC. This cross-linking expedites the gelation process without necessitating additional initiators or cross-linking agents; thus, significantly enhancing both hydrogel's application convenience and biocompatibility. Bioactive peptides (Tet213 and QK) safeguard against possible bacterial infections, facilitate angiogenesis, and eventually, improve organ wounds healing. This hydrogel-based tissue sealant demonstrates superior therapeutic and bioimaging performance in various mouse models including liver hemorrhage, gastric perforation, and bacterial-infected skin wound mouse models, highlighting its potential as a high-performance wound sealant for organ bleeding wound management.

The role of tissue adhesives and sealants in colorectal anastomotic healing-a scoping review.

PURPOSE: Anastomotic leakage (AL) after colorectal resection is a serious postoperative complication with grave consequences for patients. Despite several efforts to reduce its incidence, AL is still seen among 2-20% of colorectal cancer patients receiving an anastomosis. The use of tissue adhesives and sealants as an extra layer of protection around the anastomosis has shown promising results. We conducted a scoping review to provide an overview of the current knowledge on the effect of tissue adhesives and sealants on colorectal anastomosis healing, as well as their effect on the postoperative outcome. METHODS: The databases of PubMed, Embase, and Cochrane Library were systematically searched on 14/10/2022. Studies addressing the use of a tissue adhesive or tissue sealant applied around a colorectal anastomosis, with the goal to prevent AL or to decrease AL-related complications, were included. We presented an overview of the available studies and summarized their results narratively. RESULTS: Seven studies were included out of the 846 screened. All authors reported the rate of AL in their interventions group. Five of the studies found a decreased rate of AL compared to the control group. One study had no incidences of AL, while the last study had a seemingly low rate of AL but no comparison group. Information on secondary outcomes was sparingly reported, but the results hinted at a positive effect. CONCLUSION: Tissue adhesives and sealants might have a beneficial effect on colorectal anastomosis healing. The literature is sparse, and this review has shown the need for further clinical studies.

Double-Cross-Linked Hydrogel with Long-Lasting Underwater Adhesion: Enhancement of Maxillofacial In Situ and Onlay Bone Retention.

Bone retention is a usual clinical problem existing in a lot of maxillofacial surgeries involving bone reconstruction and bone transplantation, which puts forward the requirements for bone adhesives that are stable, durable, biosafe, and biodegradable in wet environment. To relieve the suffering of patients during maxillofacial surgery with one-step operation and satisfying repair, herein, we developed a double-cross-linked A-O hydrogel named by its two components: [(3-Aminopropyl) methacrylamide]-co-{[Tris(hydroxymethyl) methyl] acrylamide} and oxidated methylcellulose. With excellent bone adhesion ability, it can maintain long-lasting stable underwater bone adhesion for over 14 days, holding a maximum adhesion strength of 2.32 MPa. Schiff-base reaction and high-density hydrogen bonds endow the hydrogel with strong cohesion and adhesion performance as well as maneuverable properties such as easy formation and injectability. A-O hydrogel not only presents rarely reported long-lasting underwater adhesion of hard tissue but also owns inherent biocompatibility and biodegradation properties with a porous structure that facilitates the survival of bone graft. Compared to the commercial cyanoacrylate adhesive (3 M Vetbond Tissue Adhesive), the A-O hydrogel is confirmed to be safer, more stable, and more effective in calvarial in situ bone retention model and onlay bone retention model of rat, providing a practical solution for the everyday scenario of clinical bone retention.

Andrias Davidianus Mucus-Based Bioadhesive with Enhanced Adhesion and Wound Healing Properties.

The skin secretion of Andrias davidianus (SSAD) is a novel biological adhesive raw material under development. This material exhibits robust adhesion while maintaining the flexibility of the wound. It also has the potential for large-scale production, making it promising for practical application explore. Hence, in-depth research on methods to fine-tune SSAD properties is of great importance to promote its practical applications. Herein, we aim to enhance the adhesive and healing properties of SSAD by incorporating functional components. To achieve this goal, we selected 3,4-dihydroxy-l-phenylalanine and vaccarin as the functional components and mixed them with SSAD, resulting in a new bioadhesive, namely, a formulation termed "enhanced SSAD" (ESSAD). We found that the ESSAD exhibited superior adhesive properties, and its adhesive strength was improved compared with the SSAD. Moreover, ESSAD demonstrated a remarkable ability to promote wound healing. This study presents an SSAD-based bioadhesive formulation with enhanced properties, affirming the feasibility of developing SSAD-based adhesive materials with excellent performance and providing new evidence for the application of SSAD. This study also aims to show that SSAD can be mixed with other substances, and addition of effective components to SSAD can be studied to further adjust or improve its performance.

Highly Tough and Biodegradable Poly(ethylene glycol)-Based Bioadhesives for Large-Scaled Liver Injury Hemostasis and Tissue Regeneration.

Conventional tissue adhesives face challenges for hemostasis and tissue regeneration in large-scaled hemorrhage and capillary hypobaric bleeding due to weak adhesion, and inability to degrade at specific sites. Herein, convenient and injectable poly(ethylene glycol) (PEG)-based adhesives are developed to address the issues for liver hemostasis. The PEG-bioadhesives are composed of tetra-armed PEG succinimide glutarate (PEG-SG), tetra-armed PEG amine (PEG-NH2 ), and tri-lysine. By mixing the components, the PEG-bioadhesives can be rapidly formulated for use of liver bleeding closure in hepatectomy. The PEG-bioadhesives also possess mechanical compliance to native tissues (elastic modulus ≈40 kPa) and tough tissue adhesion (≈28 kPa), which enables sufficient adhering to the injured tissues and promotes liver regeneration with the PEG-bioadhesive degradation. In both rats of liver injury and pigs of large-scaled hepatic hemorrhage, the PEG-bioadhesives show effective hemostasis with superior blood loss than conventional tissue adhesives. Due to biocompatibility and degradability, the PEG-bioadhesive is advantageous for liver regeneration, while commercial adhesives (e.g., N-octyl cyanoacrylate) display adhesion failure and limited liver reconstructions. These PEG-bioadhesive components are FDA-approved, and demonstrate excellent adhesion to various tissues not only for liver hemostasis, it is a promising candidate in biomedical translations and clinical applications.

How to test adhesive strength: a biomechanical testing for aortic glue used in type a dissection repair.

OBJECTIVES: The aim of this study was to develop a method to quantify the peel force in an in vitro model simulating repair of ascending aortic dissections with tissue glue (Bioglue). METHODS: This study adapted an adhesive T-Peel test for the determination of the peel strength of adhesives by measuring the peeling force of a T-shaped bonded tissue. Measurements were performed on iatrogenic dissected ascending porcine aorta, which has been repaired with Bioglue using different pressure levels. Four conditions were tested: zero sample pressure according to the manufacturer's recommendation (n = 10), low (504 Pa; n = 11), moderate pressure (1711 Pa; n = 24) and pressure applied by a round shaped vascular 'Borst clamp' (1764 Pa; n = 23). Non-parametric one-way analysis of variance was applied for statistical significance. RESULTS: The median peel force (lower quartile, upper quartile) of aortic samples increased depending on the applied pressure: [no pressure 0.030 N/mm (0.016, 0.057), low pressure 0.040 N/mm (0.032, 0.070) and moderate pressure 0.214 N/mm (0.050, 0.304)]. Samples pressurized with the Borst clamp reached 0.078 N/mm (0.046, 0.152), which was comparable to the peel force of the unpeeled controls [0.107 N/mm (0.087, 0.124)]. Compared to samples without pressure, Bioglue with the application of the Borst clamp (P = 0.021) and with moderate pressure (P = 0.0007) performed significantly better. CONCLUSIONS: The novel T-Peel test offers an attractive method to test tissue glues in defined in vitro environments. Bioglue peel force increased with pressure on the aortic sample in contrast to low or no pressure as per the manufacturer's recommendation. Modifying current recommended use may aid in increasing effectiveness of this approach.

An Adhesive/Anti-Adhesive Janus Tissue Patch for Efficient Closure of Bleeding Tissue with Inhibited Postoperative Adhesion.

Most of the current bioadhesives cannot perform well on bleeding tissues while postoperative adhesion is a general but serious clinical issue. Here, a three-layer biodegradable Janus tissue patch (J-TP) that is able to simultaneously enable efficient closure of bleeding wounds with significantly promoted clotting ability and suppressed postoperative adhesion of tissues is reported. A dry adhesive hydrogel bottom layer of the J-TP can form rapid (within 15 s) and strong (tensile strength up to 98 kPa) adhesion to bleeding/wet tissues with high bursting pressure (about 312.5 mmHg on a sealed porcine skin) through hydrogen binding and covalent conjugation between the carboxyl & N-hydroxy succinimide (NHS) groups of hydrogel and the primary amine groups of tissues, while the phosphonic motifs can significantly reduce blood loss (by 81% on a rat bleeding liver model) of bleeding wounds. A thin polylactic acid (PLA) middle layer can improve the tensile strength (by 132%) of the J-TP in wet conditions while the grafted zwitterionic polymers can effectively prevent postoperative tissue adhesion and inflammatory reaction. This J-TP may be a promising tissue patch to assist the clinical treatment of injured bleeding tissues with inhibited postoperative adhesion.

Comparison of Tissue Adhesive Glue with Subcuticular Absorbable Suture for Skin Closure Following Thyroid Surgery: A single-blinded randomised controlled trial.

Objectives: This study aimed to compare the skin closure time, postoperative pain and the scar outcome between tissue adhesive and sub-cuticular sutures in thyroid surgery. Methods: This study was conducted in Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, a tertiary care hospital in India from March 2017 to December 2019. Adult patients undergoing thyroid surgery were included while those with previous neck surgery, history of keloids/hypertrophic scars and those undergoing concomitant neck dissections were excluded. Following platysma closure, patients were randomised into two groups (tissue adhesive and subcuticular sutures) using the Serially Numbered Opaque Sealed Envelopes technique. A sample size of 64 in each group was calculated for this prospective, single-blinded and randomised controlled trial. The primary outcome was the skin closure time. The secondary outcomes were postoperative pain at 24 hours and scar scoring at 1st and 3rd postoperative month. Statistical analysis was done using SPSS software. Results: A total sample of 124 patients were included in this study, with 61 patients assigned to the suture group and 63 assigned to the tissue adhesive group. The median skin closure time and postoperative pain was significantly lower in the tissue adhesive group as compared to the suture group (P <0.01). There was no statistically significant difference in scar outcome at the 1st or 3rd months between both groups (P = 0.088 and 0.137, respectively). There were no wound-related complications in either group. When a subgroup analysis was conducted, no difference was seen in the scar outcome or wound-related complications in patients with comorbidities. There were no instances of allergic contact dermatitis to the tissue adhesive. Conclusion: The use of tissue adhesive leads to lower operative time and less postoperative pain in thyroid surgeries. The scar outcome is comparable between tissue adhesives and subcuticular sutures.