Organism-Inspired Antioxidant Bioadhesive with Strong Sealing Ability to Prevent Epidural Adhesion.

Epidural adhesion or epidural fibrosis is the major reason for postoperative pain, which remains a clinically challenging problem. Current physical barriers fail to provide a satisfactory therapeutic outcome mainly due to their lack of adhesion, inability to prevent fluid leakage, and exhibiting limited antioxidant properties. Herein, we fabricated a cysteine-modified bioadhesive (SECAgel) with improved sealing and antioxidant properties for epidural adhesion prevention, inspired by the organism's antioxidant systems. The resulting SECAgel showed good injectability and in situ adhesion ability, effectively covering every corner of the irregular wound. Besides, it possessed efficient sealing properties (395.2 mmHg), effectively stopping blood leakage in the rabbit carotid artery transection model. The antioxidant experiments demonstrated that the SECAgel effectively scavenged various radicals and saved the cells from oxidative stress. Two animal models were used to show that the SECAgel effectively inhibited adhesion in both situations with and without cerebrospinal fluid leakage. The RNA sequencing analysis showed that SECAgel treatment effectively inhibited the expression of key genes related to adhesion development, inflammatory response, and oxidative stress. The SECAgel, together with good biocompatibility, can be a good candidate for preventing epidural adhesion in the clinic.

Composite hydrogels with antioxidant and robust adhesive properties for the prevention of radiation-induced dermatitis.

Radiotherapy is a pivotal means of cancer treatment, but it often leads to radiation dermatitis, a skin injury caused by radiation-induced excess reactive oxygen species (ROS). Scavenging free radicals in the course of radiation therapy will be an effective means to prevent radiation dermatitis. This study demonstrates a novel double network hydrogel doped with MoS2 nanosheets for the prevention of radiation-induced dermatitis. The resultant SPM hydrogel constructed from polyacrylamide (PAM) and sodium alginate (SA) nanofiber presented favorable mechanical and adhesion properties. It could conform well to the human body's irregular contours without secondary dressing fixation, making it suitable for skin protection applications. The in vitro and in vivo experiments showed that the antioxidant properties conferred by MoS2 nanosheets enable SPM to effectively mitigate excessive ROS and reduce oxidative stress, thereby preventing radiation dermatitis caused by oxidative damage. Biosafety assessments indicated good biocompatibility of the composite hydrogel, suggesting SPM's practicality and potential as an external dressing for skin radiation protection.

Multi-dynamic-bond cross-linked antibacterial and adhesive hydrogel based on boronated chitosan derivative and loaded with peptides from Periplaneta americana with on-demand removability.

The design and development of a bio-adhesive hydrogel with on-demand removability and excellent antibacterial activities are meaningful to achieve high wound closure effectiveness and post-wound-closure care, which is desirable in clinical applications. In this work, a series of adhesive antioxidant antibacterial hydrogels containing peptides from Periplaneta americana (PAP) were prepared through multi-dynamic-bond cross-linking among 3,4-dihydroxybenzaldehyde (DBA) containing catechol and aldehyde groups and chitosan grafted with 3-carboxy-4-fluorophenylboronic acid (CS-FPBA) to enable the effective adhesion of skin tissues and prevention of bacterial infection of wound. PAP was derived from alcohol-extracted residues generated during the pharmaceutical process, aiming to minimize resource wastage and achieve the high-value development of such a medicinal insect. The hydrogel was prepared by freezing-thawing with no toxic crosslinkers. The multi-dynamic-bond cross-linking of dynamic borate ester bonds and dynamic Schiff base bonds can achieve reversible breakage and re-formation and the adhesive strength of CS-FPBA-DBA-P-gel treated with a 20 % glucose solution dramatically decreased from 3.79 kPa to 0.35 kPa within 10 s. Additionally, the newly developed hydrogel presents ideal biocompatibility, hemostasis and antibacterial activity against Staphylococcus aureus and Escherichia coli compared to commercial chitosan gel (approximately 50 % higher inhibition rate), demonstrating its great potential in dealing with infected full-thickness skin wounds.

Antibacterial Hydrogel Adhesives Based on Bifunctional Telechelic Dendritic-Linear-Dendritic Block Copolymers.

Antibiotic-resistant pathogens have been declared by the WHO as one of the major public health threats facing humanity. For that reason, there is an urgent need for materials with inherent antibacterial activity able to replace the use of antibiotics, and in this context, hydrogels have emerged as a promising strategy. Herein, we introduce the next generation of cationic hydrogels with antibacterial activity and high versatility that can be cured on demand in less than 20 s using thiol-ene click chemistry (TEC) in aqueous conditions. The approach capitalizes on a two-component system: (i) telechelic polyester-based dendritic-linear-dendritic (DLDs) block copolymers of different generations heterofunctionalized with allyl and ammonium groups, as well as (ii) polyethylene glycol (PEG) cross-linkers functionalized with thiol groups. These hydrogels resulted in highly tunable materials where the antibacterial performance can be adjusted by modifying the cross-linking density. Off-stoichiometric hydrogels showed narrow antibacterial activity directed toward Gram-negative bacteria. The presence of pending allyls opens up many possibilities for functionalization with biologically interesting molecules. As a proof-of-concept, hydrophilic cysteamine hydrochloride as well as N-hexyl-4-mercaptobutanamide, as an example of a thiol with a hydrophobic alkyl chain, generated three-component networks. In the case of cysteamine derivatives, a broader antibacterial activity was noted than the two-component networks, inhibiting the growth of Gram-positive bacteria. Additionally, these systems presented high versatility, with storage modulus values ranging from 270 to 7024 Pa and different stability profiles ranging from 1 to 56 days in swelling experiments. Good biocompatibility toward skin cells as well as strong adhesion to multiple surfaces place these hydrogels as interesting alternatives to conventional antibiotics.

Engineering Wet-Resistant and Osteogenic Nanocomposite Adhesive to Control Bleeding and Infection after Median Sternotomy.

Median sternotomy surgery stands as one of the prevailing strategies in cardiac surgery. In this study, the cutting-edge bone adhesive is designed, inspired by the impressive adhesive properties found in mussels and sandcastle worms. This work has created an osteogenic nanocomposite coacervate adhesive by integrating a cellulose-polyphosphodopamide interpenetrating network, quaternized chitosan, and zinc, gallium-doped hydroxyapatite nanoparticles. This adhesive is characterized by robust catechol-metal coordination which effectively adheres to both hard and soft tissues with a maximum adhesive strength of 900 ± 38 kPa on the sheep sternum bone, surpassing that of commercial bone adhesives. The release of zinc and gallium cations from nanocomposite adhesives and quaternized chitosan matrix imparts remarkable antibacterial properties and promotes rapid blood coagulation, in vitro and ex vivo. It is also proved that this nanocomposite adhesive exhibits significant in vitro bioactivity, stable degradability, biocompatibility, and osteogenic ability. Furthermore, the capacity of nanocomposite coacervate to adhere to bone tissue and support osteogenesis contributes to the successful healing of a sternum bone defect in a rabbit model in vivo. In summary, these nanocomposite coacervate adhesives with promising characteristics are expected to provide solutions to clinical issues faced during median sternotomy surgery.

Janus adhesive microneedle patch loaded with exosomes for intrauterine adhesion treatment.

Intrauterine adhesions (IUAs) are common sequelae of cervical mucosa damage caused by uterine curettage. Establishing an anti-adhesion barrier between the damaged endometrium with a sustained-release drug capability and hence promoting endogenous regeneration of the endometrium is an available treatment for IUA. However, current therapy lacks long-term intracavitary residence, drug-delivery permeability, and tissue anti-adhesion to the endometrium. Here, we report the design of a Janus microneedle patch consisting of two layers: an adhesive inner layer with an exosomes-loaded microneedle, which endows the patch with a tissue adhesive capability as well as transdermal drug-delivery capability; and an anti-adhesion outer layer, which prevents the intrauterine membrane from postoperative adhesion. This Janus adhesive microneedle patch firmly adhered to uterine tissue, and sustainedly released ∼80% of the total loaded exosomes in 7 days, hence promoting the expression of vascular- and endothelial-related cell signals. Furthermore, the anti-adhesive layer of the microneedle patch exhibited low cell and protein adhesion performance. In rats, the microneedle patch successfully prevented uterine adhesions, improved endometrial angiogenesis, proliferation, and hormone response levels. This study provides a stable anti-adhesion barrier as well as efficient drug-release capability treatment for intrauterine adhesion treatment.

Antibacterial adhesive based on oxidized tannic acid-chitosan for rapid hemostasis.

Currently, bacterial infections and bleeding interfere with wound healing, and multifunctional hydrogels with appropriate blood homeostasis, skin adhesion, and antibacterial activity are desirable. In this study, chitosan-based hydrogels were synthesized using oxidized tannic acid (OTA) and Fe3+ as cross-linkers (CS-OTA-Fe) by forming covalent, non-covalent, and metal coordination bonds between Fe3+ and OTA. Our results demonstrated that CS-OTA-Fe hydrogels showed antibacterial properties against Gram-positive bacteria (Staphylococcus aureus)and Gram-negative bacteria (Escherichia coli), low hemolysis rate (< 2 %), rapid blood clotting ability, in vitro (< 2 min), and in vivo (90 s) in mouse liver bleeding. Additionally, increasing the chitosan concentration from 3 wt% to 4.5 wt% enhanced cross-linking in the network, leading to a significant improvement in the strength (from 106 ± 8 kPa to 168 ± 12 kPa) and compressive modulus (from 50 ± 9 kPa to 102 ± 14 kPa) of hydrogels. Moreover, CS-OTA-Fe hydrogels revealed significant adhesive strength (87 ± 8 kPa) to the cow's skin tissue and cytocompatibility against L929 fibroblasts. Overall, multifunctional CS-OTA-Fe hydrogels with tunable mechanical properties, excellent tissue adhesive, self-healing ability, good cytocompatibility, and fast hemostasis and antibacterial properties could be promising candidates for biomedical applications.

Water-compatible cross-linked pyrrolidone acrylate pressure-sensitive adhesives with persistent adhesion for transdermal delivery: Synergistic effect of hydrogen bonding and electrostatic force.

Poor skin adhesion and mechanical properties are common problems of pressure-sensitive adhesive (PSA) in transdermal drug delivery system (TDDS). Its poor water compatibility also causes the patch to fall off after sweating or soaking in the application site. To solve this problem, poly (2-Ethylhexyl acrylate-co-N-Vinyl-2-pyrrolidone-co-N-(2-Hydroxyethyl)acrylamide) (PENH), a cross-linked pyrrolidone polyacrylate PSA, was designed to improve the adhesion and water resistance of PSA through electrostatic force and hydrogen bonding system. The structure of PENH was characterized by 1H NMR, FTIR, DSC, and other methods. The mechanism was studied by FTIR, rheological test, and molecular simulation. The results showed that the PENH patch could adhere to human skin for more than 10 days without cold flow, and it could still adhere after sweating or water contact. In contrast, the commercial PSA Duro-Tak® 87-4098 and Duro-Tak® 87-2852 fell off completely on the 3rd and 6th day, respectively, and Duro-Tak® 87-2510 showed a significant dark ring on the second day. Mechanism studies have shown that the hydrogen bond formed by 2-ethylhexyl acrylate (2-EHA), N-vinyl-2-pyrrolidinone (NVP), and N-(2-Hydroxyethyl)acrylamide (HEAA) enhances cohesion, the interaction with skin improves skin adhesion, and the electrostatic interaction with water or drug molecules enhances the ability of water absorption and drug loading. Due to the synergistic effect of hydrogen bonds and electrostatic force, PENH can maintain high cohesion after drug loading or water absorption. PENH provides a choice for the development of water-compatible patches with long-lasting adhesion. STATEMENT OF SIGNIFICANCE: Based on the synergistic effect of hydrogen bonding and electrostatic force, a hydrogen-bonded, cross-linked pyrrolidone acrylate pressure-sensitive adhesive for transdermal drug delivery was designed and synthesized, which has high adhesion and cohesive strength and is non-irritating to the skin. The patch can be applied on the skin surface continuously for more than 10 days without the phenomenon of "dark ring", and the patch can remain adherent after the patient sweats or bathes. This provides a good strategy for choosing a matrix for patches that require prolonged administration.

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.

Coagulant Protein-Free Blood Coagulation Using Catechol-Conjugated Adhesive Chitosan/Gelatin Double Layer.

Since the discovery of polyphenolic underwater adhesion in marine mussels, researchers strive to emulate this natural phenomenon in the development of adhesive hemostatic materials. In this study, bio-inspired hemostatic materials that lead to pseudo-active blood coagulation, utilizing traditionally passive polymer matrices of chitosan and gelatin are developed. The two-layer configuration, consisting of a thin, blood-clotting catechol-conjugated chitosan (CHI-C) layer and a thick, barrier-functioning gelatin (Geln) ad-layer, maximizes hemostatic capability and usability. The unique combination of coagulant protein-free condition with CHI-C showcases not only coagulopathy-independent blood clotting properties (efficacy) but also exceptional clinical potential, meeting all necessary biocompatibility evaluation (safety) without inclusion of conventional coagulation triggering proteins such as thrombin or fibrinogen. As a result, the CHI-C/Geln is approved by the Ministry of Food and Drug Safety (MFDS, Republic of Korea) as a class II medical device. Hemostatic efficacy observed in multiple animal models further demonstrates the superiority of CHI-C/Geln sponges in achieving quick hemostasis compared to standard treatments. This study not only enriches the growing body of research on mussel-inspired materials but also emphasizes the potential of biomimicry in developing advanced medical materials, contributing a promising avenue toward development of readily accessible and affordable hemostatic materials.

Nanoengineered Supramolecular Adhesive Sponge for Rapid Hemostasis and Abdominal Wall Wound Healing.

Multifunctional dressing biomaterials that can promote tissue adhesion, hemostasis, and soft-tissue wound healing are of great clinical significance. Here, we report a nanocomposite supramolecular sponge constructed by an air-in-water emulsion template composed of methacrylated gelatin (GelMA), Laponite nanoclay, and branched supramolecular polymer (PAMU). The sponge has an interconnected macroporous structure and exhibits tunable mechanical properties with varying Laponite concentration. The nanoengineered sponge is endowed with tissue adhesion by intermolecular hydrogen bonds and ionic interactions contributed by the supramolecular polymer and the Laponite nanoclay. The biocompatible sponge facilitates cell proliferation and blood coagulation in both in vitro and in vivo experiments. In addition, the results of the rat external abdominal wall defect model show that the sponge can promote angiogenesis, collagen deposition, and granulation tissue formation to accelerate wound repair. These findings suggest that the unique air-in-water templated sponge is a promising candidate for applications in hemostasis and wound healing.

Robust and Wet Adhesive Self-Gelling Powders for Rapid Hemostasis and Efficient Wound Healing.

Healing traumatic wounds is arduous, leaving miscellaneous demands for ideal wound dressings, such as rapid hemostasis, superior wet tissue adhesion, strong mechanical properties, and excellent antibacterial activity. Herein, we report a self-gelling, wet adhesive, stretchable (polyethylenimine/poly(dimethylammonium chloride)/(poly(acrylic acid)/poly(sodium styrenesulfonate)/alkylated chitosan)) ((PEI/PDDA)/(PAA/PSS)/ACS) powder as a new option. The self-gel utilizes noncovalent interactions among in situ formed PDDA/PSS nanoparticles and PEI/PAA polymetric matrices to earn sensational mechanical properties and tensile strength while incorporating ACS to obtain fast hemostasis and therapeutic capacities. The powder can form a hydrogel patch in situ within 3 s upon liquid absorption, capable of resisting pressure higher than twice the blood pressure. Deposition of the self-gelling powders on various wounds, such as rat liver and femoral artery wounds, can stop bleeding in 10 s and lessen the amount of bleeding 6-fold plus in corresponding models. Furthermore, the self-gelling powders can significantly advance the chronic wound healing process by displaying a high wound healing rate and a low inflammatory response and promoting the formation of new blood vessels and tissue regeneration. The satisfactory mechanical properties, strong wet adhesion, sufficient antibacterial properties, ease of usage, adaptability to complex wounds, rapid hemostasis, and superior therapeutic capacities of (PEI/PDDA)/(PAA/PSS)/ACS self-gelling powders render them as a profound wound dressing biomaterial.

Adhesive Nanoparticle-in-Microgel System with ROS Scavenging Capability and Hemostatic Activity for Postoperative Adhesion Prevention.

Postoperative adhesion is a noteworthy clinical complication in abdominal surgery due to the existing physical barriers are unsatisfactory and inefficient in preventing its occurrence. In this work, an elaborate nanoparticle-in-microgel system (nMGel) is presented for postoperative adhesion prevention. nMGel is facilely formed by crosslinking manganese dioxide (MnO2) nanoparticles-loaded gelatin microspheres with polydopamine using a modified emulsification-chemical crosslinking method, generating a nano-micron spherical hydrogel. After drying, powdery nMGel with sprayability can perfectly cover irregular wounds and maintains robust tissue adhesiveness even in a wet environment. Additionally, nMGel possesses prominent antioxidant and free radical scavenging activity, which protects cell viability and preserves cell biological functions in an oxidative microenvironment. Furthermore, nMGel displays superior hemostatic property as demonstrated in mouse tail amputation models and liver trauma models. Importantly, nMGel can be conveniently administrated in a mouse cecal defect model to prevent adhesion between the injured cecum and the peritoneum by reducing inflammation, oxidative stress, collagen synthesis, and angiogenesis. Thus, the bioactive nMGel offers a practical and efficient approach for ameliorating postsurgical adhesion.

A multifunctional hydrogel dressing with high tensile and adhesive strength for infected skin wound healing in joint regions.

Most hydrogel dressings are designed for skin wounds in flat areas, and few are focused on the joint skin regions which undergo frequent movement. The mismatch of mechanical properties and poor fit between a hydrogel dressing and a wound in joint skin results in hydrogel shedding, bacterial infection and delayed healing. Therefore, it is of great significance to design and prepare a multifunctional hydrogel with high tensile and tissue-adhesive strength as well as other therapeutic effects for the treatment of joint skin wounds. In this work, a multifunctional hydrogel was reasonably prepared by simply mixing polyvinyl alcohol (PVA), borax, tannic acid (TA) and iron(III) chloride in certain proportions, which was further used to treat the skin wounds at the joint of the hind limb. Acting as the physical crosslinkers, borax and TA dynamically bond with PVA and provide the resulting hydrogel with strong tensile, fast shape-adaptive and self-healing properties. The photothermal bacteriostatic activity of the hydrogel is attributed to the formation of a metallic polyphenol network (MPN) between ferric ions and TA. In addition, the hydrogel exhibits high levels of adhesion, hemostatic performance, antioxidant abilities, and biocompatibility, and shows great potential to promote joint skin wound healing.

Biomimetic, self-coacervating adhesive with tough underwater adhesion for ultrafast hemostasis and infected wound healing.

Massive bleeding and wound infection due to severe traumas pose a huge threat to the life and health of sufferers; therefore, it is of clinical importance to fabricate adhesives with rapid hemostatic and superior antibacterial capabilities. However, the weak wet adhesion and insufficient function of existing bioadhesives limits their practical application. In this study, a sandcastle worm protein inspired polyelectrolyte self-coacervate adhesive of poly-γ-glutamic acid (PGA) and lysozyme (LZM) was developed. The adhesive exhibited strong underwater adhesion to various surfaces (>250 kPa for solid plates and >50 kPa for soft tissues) and maintained a 80 kPa even when soaked in water for 7 days. Rat liver and tail defect bleeding models revealed that the hemostatic efficiency was superior to that of commercial samples. The in vitro antimicrobial tests showed that the bacterial inhibition to Staphylococcus aureus and Escherichia coli reached almost 100%. Additionally, the infected wound regeneration model demonstrated that the healing rate of the adhesive group was about 100% within 15 days, which was greater than that of the control group. In vitro and in vivo experiments proved that this facilely prepared adhesive will be a promising material to fulfil the integration functions for rapid wound closure and facilitating wound healing.

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.

A multi-crosslinking strategy of organic and inorganic compound bio-adhesive polysaccharide-based hydrogel for wound hemostasis.

Polysaccharides are naturally occurring polymers with exceptional biodegradable and biocompatible qualities that are used as hemostatic agents. In this study, photoinduced CC bond network and dynamic bond network binding was used to give polysaccharide-based hydrogels the requisite mechanical strength and tissue adhesion. The designed hydrogel was composed of modified carboxymethyl chitosan (CMCS-MA) and oxidized dextran (OD), and introduced hydrogen bond network through tannic acid (TA) doping. Halloysite nanotubes (HNTs) were also added, and the effects of various doping amount on the performance of the hydrogel were examined, in order to enhance the hemostatic property of hydrogel. Experiments on vitro degradation and swelling demonstrated the strong structural stability of hydrogels. The hydrogel has improved tissue adhesion strength, with a maximum adhesion strength of 157.9 kPa, and demonstrated improved compressive strength, with a maximum compressive strength of 80.9 kPa. Meanwhile, the hydrogel had a low hemolysis rate and had no inhibition on cell proliferation. The created hydrogel exhibited a significant aggregation effect on platelets and a reduced blood clotting index (BCI). Importantly, the hydrogel can quickly adhere to seal the wound and has good hemostatic effect in vivo. Our work successfully prepared a polysaccharide-based bio-adhesive hydrogel dressing with stable structure, appropriate mechanical strength, and good hemostatic properties.

In situ polyphenol-adhesive hydrogel enhanced the noncarcinogenic repairing of KGF on the gut epithelial barrier on TNBS-induced colitis rats.

Ulcerative colitis (UC) is a chronic recurrent disease affecting the gastrointestinal tract especially colorectum. Keratinocyte growth factor (KGF) plays the vital roles in maintaining the colonic mucosal barrier. The poor stability and off-target of KGF were two hindering factors for its clinical application. Herein, in situ hydrogel (PE) with mucoadhesive ability was constructed by using temperature-sensitive poloxamer and EGCG as hydrogel-forming material and adhesive enhancer, respectively. Incorporation of EGCG led to the slight decrease of the gelled temperature and shortened the gelled time of PE hydrogel. When the concentration of EGCG is 0.1 %, PE hydrogel exhibits the suitable viscosity of 280 ± 20 Pa·s and the strong adhesive force of 725 ± 25 mN. KGF was soluble in cold PE solution to obtain KGF-loaded PE hydrogel (KGF@PE). PE hydrogel could improve the stability of KGF in vitro. KGF@PE not only could recover greatly the body weight of TNBS-induced rats but also repair their colonic morphology and goblet cell function. Moreover, the potential of repairing the epithelial barrier was indicated by upregulating tight junction proteins. Importantly, the safety of KGF@PE hydrogel for colitis was also confirmed on AOM/DSS-induced mice models. Conclusively, KGF@PE may be a promising therapeutic platform without obvious side effect for ulcerative colitis.

Multifunctional Bioinspired Bredigite-Modified Adhesive for Bone Fracture Healing.

Despite recent advances in bone adhesives applied for full median sternotomy, the regeneration of bone defects has remained challenging since the healing process is hampered by poor adhesiveness, limited bioactivity, and lack of antibacterial functions. Bioinspired adhesives by marine organisms provide a novel concept to circumvent these problems. Herein, a dual cross-link strategy is employed in designing a multifaceted bioinspired adhesive consisting of a catechol amine-functionalized hyperbranched polymer (polydopamine-co-acrylate, PDA), bredigite (BR) nanoparticles, and Fe3+ ions. The hybrid adhesives exhibit strong adhesion to various substrates such as poly(methyl methacrylate), glass, bone, and skin tissues through synergy between irreversible covalent and reversible noncovalent cross-linking, depending on the BR content. Noticeably, the adhesion strength of hybrid adhesives containing 2 wt % BR nanoparticles to bone tissues is 2.3 ± 0.8 MPa, which is about 3 times higher than that of pure PDA adhesives. We also demonstrate that these hybrid adhesives not only are bioactive and accelerate in vitro bone-like apatite formation but also exhibit antibacterial properties against Staphylococcus aureus, depending on the BR concentration. Furthermore, the superior cellular responses in contact with hybrid adhesives, including improved human osteosarcoma MG63 cell spreading and osteogenic differentiation, are achieved owing to the appropriate ion release and flexibility of the cross-linked double-network adhesive. In summary, multifunctional hybrid PDA/BR adhesives with appreciable osteoconductive, mechanical, and antibacterial properties represent the potential applications for median sternotomy surgery as a bone tissue adhesive.

In situ photo-crosslinked adhesive hydrogel loaded with mesenchymal stem cell-derived extracellular vesicles promotes diabetic wound healing.

The delayed healing of diabetic wounds is directly affected by the disturbance of wound microenvironment, resulting from persistent inflammation, insufficient angiogenesis, and impaired cell functions. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) showed considerable therapeutic potential in diabetic wound healing. However, the low retention rate of MSC-EVs at wound sites hampers their efficacy. For skin wounds exposed to the outer environment, using a hydrogel with tissue adhesiveness under a moist wound condition is a promising strategy for wound healing. In this study, we modified methacryloyl-modified gelatin (GelMA) hydrogel with catechol motifs of dopamine to fabricate a GelMA-dopamine hydrogel. EVs isolated from MSCs were applied in the synthesized GelMA-dopamine hydrogel to prepare a GelMA-dopamine-EV hydrogel. The results demonstrated that the newly formed GelMA-dopamine hydrogel possessed improved properties of softness, adhesiveness, and absorptive capacity, as well as high biocompatibility in the working concentration (15% w/v). In addition, MSC-EVs were verified to promote cell migration and angiogenesis in vitro. In the skin wound model of diabetic rats, the GelMA-dopamine-EV hydrogel exerted prominent wound healing efficacy estimated by collagen deposition, skin appendage regeneration, and the expression of IL-6, CD31, and TGF-ß. In conclusion, this combination of MSC-EVs and the modified hydrogel not only accelerates wound closure but also promotes skin structure normalization by rescuing the homeostasis of the healing microenvironment of diabetic wounds, which provides a potential approach for the treatment of diabetic wounds.