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.

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.

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

Wet-tissue adhesives have long been attractive materials for realizing complicated biomedical functions. However, the hydration film on wet tissues can generate a boundary, forming hydrogen bonds with the adhesives that weaken adhesive strength. Introducing black phosphorus (BP) is believed to enhance the water absorption capacity of tape-type adhesives and effectively eliminate hydration layers between the tissue and adhesive. This study reports a composite patch integrated with BP nanosheets (CPB) for wet-tissue adhesion. The patch's improved water absorption and mechanical properties ensure its immediate and robust adhesion to wet tissues. Various bioapplications of CPB are demonstrated, such as rapid hemostasis (within ~1-2 seconds), monitoring of physical-activity and prevention of tumour-recurrence, all validated via in vivo studies. Given the good practicability, histocompatibility and biodegradability of CPB, the proposed patches hold significant promise for a wide range of 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.

Sprayable tissue adhesive microparticle-magnetic nanoparticle composites for local cancer hyperthermia.

Incomplete removal of early-stage gastrointestinal cancers by endoscopic treatments often leads to recurrence induced by residual cancer cells. To completely remove or kill cancer tissues and cells and prevent recurrence, chemotherapy, radiotherapy, and hyperthermia using biomaterials with drugs or nanomaterials are usually administered following endoscopic treatments. However, there are few biomaterials that can be applied using endoscopic devices to locally kill cancer tissues and cells. We previously reported that decyl group-modified Alaska pollock gelatin-based microparticles (denoted C10MPs) can adhere to gastrointestinal tissues under wet conditions through the formation of a colloidal gel driven by hydrophobic interactions. In this study, we combined C10MPs with superparamagnetic iron oxide nanoparticles (SPIONs) to develop a sprayable heat-generating nanomaterial (denoted SP/C10MP) for local hyperthermia of gastrointestinal cancers. The rheological property, tissue adhesion strength, burst strength, and underwater stability of SP/C10MP were improved through decyl group modification and SPION addition. Moreover, SP/C10MP that adhered to gastrointestinal tissues formed a colloidal gel, which locally generated heat in response to an alternating magnetic field. SP/C10MP successfully killed cancer tissues and cells in colon cancer-bearing mouse models in vitro and in vivo. Therefore, SP/C10MP has the potential to locally kill residual cancer tissues and cells after endoscopic treatments.

Laponite nanoparticle-crosslinked carboxymethyl cellulose-based injectable hydrogels with efficient underwater-specific adhesion for rapid hemostasis.

Tissue adhesives have attracted intense and increasing interest due to their multiple biomedical applications. Despite the rapid development of adhesive hydrogels, huge challenges remain for materials that can ensure strong adhesion and seal hemostasis in aqueous and blood environments. To address this issue, we have developed an innovative design of PAA-based coacervate hydrogel with strong wet adhesion capability through a simple mixture of PAA copolymers with oxidized-carboxymethylcellulose (OCMC), and tannic acid (TA) as the main components, and structurally enhanced with natural clays (Laponite XLG). The absorbed TA provides solid adhesion to dry and wet substrates via multiple interactions, which endows the XLG-enhanced coacervate with the desired underwater adhesive strength. More importantly, the dielectric constant is introduced to evaluate the polarity of the tested samples, which may be used as guidance for the design of mussel-inspired adhesives with even better underwater adhesive properties. In vivo hemorrhage experiments further confirmed that the hydrogel adhesive dramatically shortened the hemostatic time to tens of seconds. Overall, the persistent adhesion and acceptable cytocompatibility of the hydrogel nanocomposite make it a promising alternative suture-free approach for rapid hemostasis at different length scales and is expected to be extended to clinical application for other organ injuries.

Injectable Asymmetric Adhesive-Antifouling Bifunctional Hydrogel for Peritoneal Adhesion Prevention.

Peritoneal adhesion is a common problem after abdominal surgery and can lead to various medical problems. In response to the lack of in situ retention and pro-wound healing properties of existing anti-adhesion barriers, this work reports an injectable adhesive-antifouling bifunctional hydrogel (AAB-hydrogel). This AAB-hydrogel can be constructed by "two-step" injection. The tissue adhesive hydrogel based on gallic acid-modified chitosan and aldehyde-modified dextran is prepared as the bottom hydrogel (B-hydrogel) by Schiff base reaction. The aldehyde-modified zwitterionic dextran/carboxymethyl chitosan-based hydrogel is formed on the B-hydrogel surface as the antifouling top hydrogel (T-hydrogel). The AAB-hydrogel exhibits good bilayer binding and asymmetric properties, including tissue adhesive, antifouling, and antimicrobial properties. To evaluate the anti-adhesion effect in vivo, the prepared hydrogels are injected onto the wound surface of a mouse abdominal wall abrasion-cecum defect model. Results suggest that the AAB-hydrogel has antioxidant capacity and can reduce the postoperative inflammatory response by modulating the macrophage phenotype. Moreover, the AAB-hydrogel could effectively inhibit the formation of postoperative adhesions by reducing protein deposition, and resisting fibroblast adhesions and bacteria attacking. Therefore, AAB-hydrogel is a promising candidate for the prevention of postoperative peritoneal adhesions.

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.

A Nonswelling Hydrogel with Regenerable High Wet Tissue Adhesion for Bioelectronics.

Reducing the swelling of tissue-adhesive hydrogels is crucial for maintaining stable tissue adhesion and inhibiting tissue inflammation. However, reported strategies for reducing swelling always result in a simultaneous decrease in the tissue adhesive strength of the hydrogel. Furthermore, once the covalent bonds break in the currently reported hydrogels, they cannot be rebuilt, and the hydrogel loses its tissue adhesive ability. In this work, a nonswelling hydrogel (named as "PAACP") possessing regenerable high tissue adhesion is synthesized by copolymerizing and crosslinking poly(vinyl butyral) with acrylic acid, gelatin, and chitosan-grafted N-acetyl-l-cysteine. The tissue adhesive strength of the obtained PAACP reaches 211.4 kPa, which is approximately ten times higher than that of the reported nonswelling hydrogels, and the hydrogel can be reused for multiple cycles. The as-prepared hydrogel shows great potential in soft bioelectronics, as muscle fatigue is successfully monitored via the electrode array and strain sensor integrated on PAACP substrates. The success of these bioelectronics offers potential applicability in the long-term diagnosis of muscle-related health conditions and prosthetic manipulations.

An Instant Underwater Tissue Adhesive Composed of Catechin-Chondroitin Sulfate and Cholesterol-Polyethyleneimine.

Due to the safety issue and poor underwater adhesion of current commercially available bioadhesives, they are hard to apply to in vivo physiological environments and more diverse medical use conditions. In this study, a novel and facile bioadhesive for underwater medical applications are designed based on the coacervation of electrostatic interactions and hydrophobic interactions, with the introduction of catechin as a provider of catechol moieties for adhesion to surrounding tissues. The orange-colored bio-adhesive, named PcC, is generated within seconds by mixing catechin-modified chondroitin sulfate and cholesterol chloroformate-modified polyethyleneimine with agitation. In vitro mechanical measurements prove that this novel PcC bio-adhesive is superior in underwater adhesion performance when applied to cartilage. Animal experiments in a rat mastectomy model and rat cartilage graft implantation model demonstrate its potential for diverse medical purposes, such as closing surgical incisions, reducing the formation of seroma, and tissue adhesive applied in orthopedic or cartilage surgery.

A double crosslinking adhesion mechanism for developing tough hydrogel adhesives.

Tough hydrogel adhesives that consist of a robust gel network and can strongly adhere to wet tissues have shown great promise as the next generation of bioadhesives. While a variety of chemistries can be utilized to construct the tough gel network, the covalent conjugation methods for tissue adhesion are still limited. Here we report, for the first time, the use of side product-free amine-thiolactone chemistry which initiates a double crosslinking adhesion mechanism to develop tough gel adhesives. Thiolactone groups can conjugate with tissue-surface amines via a ring-opening reaction. The resultant thiol end groups can be further crosslinked into disulfide linkages, enabling the formation of a robust and stable adhesion layer. The thiolactone-bearing tough hydrogel composed of methacrylate-modified gelatin, acrylic acid, and thiolacone acrylamide exhibited good biocompatibility and mechanical properties, and strong adhesion to various types of engineering solids and tissues. We also demonstrated its ability to function as a tissue sealant and drug depot. The novel adhesion mechanism will diversify future design of bioadhesives for hemostasis, drug delivery, tissue repair, and other applications. STATEMENT OF SIGNIFICANCE: Tough hydrogel adhesives with excellent tissue-adhesive and mechanical properties have demonstrated tremendous promise for hemostasis, tissue repair, and drug delivery applications. However, the covalent chemistry for tissue adhesion has been limited, which narrows the choice of materials for the design of bioadhesives and may pose a safety concern. Here, for the first time, we report the use of side product-free amine-thiolactone chemistry, which involves a double crosslinking adhesion mechanism, for developing tough hydrogel adhesives. We demonstrate that thiolactone-bearing tough hydrogels exhibit favorable biocompatibility and mechanical properties, and superior adhesion to both engineering solids and tissues. Our new adhesion technology will greatly facilitate future development of advanced bioadhesives for numerous biomedical applications.