Tissue Adhesives Research Articles

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

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

Janus Nanofibrous Patch with In Situ Grown Superlubricated Skin for Soft Tissue Repair with Inhibited Postoperative Adhesion.

The patch with a superlubricated surface shows great potential for the prevention of postoperative adhesion during soft tissue repair. However, the existing patches suffer from the destruction of topography during superlubrication coating and lack of pro-healing capability. Herein, we demonstrate a facile and versatile strategy to develop a Janus nanofibrous patch (J-NFP) with antiadhesion and reactive oxygen species (ROS) scavenging functions. Specifically, sequential electrospinning is performed with initiators and CeO2 nanoparticles (CeNPs) embedded on the different sides, followed by subsurface-initiated atom transfer radical polymerization for grafting zwitterionic polymer brushes, introducing superlubricated skin on the surface of single nanofibers. The poly(sulfobetaine methacrylate) brush-grafted patch retains fibrous topography and shows a coefficient of friction of around 0.12, which is reduced by 77% compared with the pristine fibrous patch. Additionally, a significant reduction in protein, platelet, bacteria, and cell adhesion is observed. More importantly, the CeNPs-embedded patch enables ROS scavenging as well as inhibits pro-inflammatory cytokine secretion and promotes anti-inflammatory cytokine levels. Furthermore, the J-NFP can inhibit tissue adhesion and promote repair of both rat skin wounds and intrauterine injuries. The present strategy for developing the Janus patch exhibits enormous prospects for facilitating soft tissue repair.

New dynamic suture material for tendon transfer surgeries in the upper extremity – a biomechanical comparative analysis

BackgroundEarly mobilization after tendon surgery is crucial to avoid commonly observed postoperative soft tissue adhesions. Recently, a new suture was introduced (DYNACORD; DC) with a salt-infused silicone core designed to minimize laxity and preserve consistent tissue approximation in order to avoid gap formation and allow early mobilization.AimsTo compare the biomechanical competence of DC against a conventional high strength suture (FiberWire; FW) in a human cadaveric tendon transfer model with an early rehabilitation protocol.MethodsSixteen tendon transfers (flexor digitorum superficialis (FDS) IV to flexor pollicis longus (FPL)) were performed in 8 pairs human cadaveric forearms using either DC or FW. Markings were set 0.8 cm proximally and 0.7 cm distally to the level of the interweaving zone of the transfer. All specimens underwent repetitive thumb flexion against resistance in 9 intermittent series of 300 cycles each, simulating an aggressive postoperative rehabilitation protocol. After each series, the distance of the proximal marker to the interweaving zone (proximal), the length of the interweaving zone (intermediate) and the distance of the distal marker to the interweaving zone (distal) were measured.ResultsPooled data over all nine series, normalized to the immediate postoperative status, demonstrated no significant differences between FW and DC (p ≥ 0.355) for the proximal and distal markers. However, at the intermediate zone, DC was associated with significant length shortening (p < 0.001) compared to FW without significant length changes (p = 0.351). Load to catastrophic failure demonstrated significant higher forces in FW (p = 0.011). Nevertheless, due to failure mainly proximal or distal of the transfer zone, these loads are not informative.ConclusionFrom a biomechanical perspective, DC preserved tissue approximation and might be considered as a valid alternative to conventional high-strength sutures in tendon transfer surgery. DC might allow for a shorter interweaving zone and a more aggressive early postoperative rehabilitation program, possibly avoiding commonly observed postoperative soft tissue adhesions and stiffness.

The Effect of Infrared (IR) and Mirror Exercise on Increasing Muscle Strength and Functional Ability in Bell's Palsy Cases

Bell's Palsy is an acute, ipsilateral facial nerve (VII) paralysis. Bell's palsy is alsocaused by swelling and pressure on the nerve in the stylomastoid foramen whichcauses damage to the facial nerve. Problems that sufferers often experience after realizing facial muscle weakness from a physiotherapy perspective include facial asymmetry, a feeling of stiffness and thickness on the affected side of the face and decreased facial muscles. force on the affected side has the potential for spasm and tissue adhesions, as well as potential irritation to the affected side of the eye. The population of this study consisted of 30 respondents. Special examination for Bell's palsy sufferers using the Ugo Fisch scale and a treatment program using infrared (IR) and mirror exercise methods. This action aims to increase facial muscle strength, reduce muscle spasm, increase functional activity of facial muscles, and increase functional activity. The sample for this research consisted of 20 respondents. From the results of the hypothesis test, a p-value of 0.000 (alpha &lt; 0.05) is obtained as a critical limit, which means that H0 is rejected and Ha is accepted. So, the results of this therapy show a significant increase in facial muscle strength and functional ability between before and after therapy. Based on these results, the intervention given in the form of infrared (IR) and mirror exercise was effective in increasing muscle strength and functional ability as well as improving the participants' nerves.

An injectable hydrogel of Enteromorpha polysaccharide/gelatin–derivatives inspired by siderophores and biocatalysis for addressing all phases of chronic diabetic wound healing

Given that chronic diabetic wounds are difficult to cure because of disruptions in the four healing phases (hemostasis, immune regulation, cell proliferation, and tissue regeneration), wound dressings promoting all of these phases and thus accelerating diabetic wound healing are highly desirable. To address this need, inspired by siderophore-Fe3+ chelation and horseradish peroxidase (HRP) catalysis, we synthesized a tyramine-modified Enteromorpha prolifera polysaccharide and dopamine-modified gelatin and used them to fabricate an injectable hydrogel (PG-Fe) featuring interpenetrating polymer networks facilitated by catecholate/carboxylate-Fe3+ coordination bonding and HRP-mediated covalent bonding between phenolic groups. PG-Fe exhibited good injectability, rapid gelation (11.5 s), suitable mechanical properties, enhanced tissue adhesiveness (50.5 kPa), and rapid self-healing (60 s) because of its intrinsic moieties and introduced modifications. Furthermore, it exhibited enhanced antioxidant, anti-inflammatory, cell adhesion, and migration effects. Consequently, PG-Fe simultaneously addressed all four wound healing phases, thereby shortening the closure time of normal and chronic diabetic wounds to 21 days. Following application, PG-Fe could be decomposed using a desferrioxamine solution and easily removed. Taken together, our study provides a novel strategy for fabricating injectable hydrogels that exhibit desirable physicochemical properties and enhanced biological functions to accelerate all phases of chronic diabetic wound healing.

Diamond-Like Carbon Depositing on the Surface of Polylactide Membrane for Prevention of Adhesion Formation During Tendon Repair

HighlightsThe anti-adhesion effect of polylactic acid (PLA) membrane with diamond-like carbon (DLC) depositing is 44.72%, enhanced by 23.11% compared to PLA.DLC deposited on PLA membranes has been shown to effectively reduce the levels of reactive oxygen species, leading to a decrease in the expression of pro-inflammatory cytokines within peritendinous adhesion tissue.DLC decelerates PLA biodegradation and lactic production, which reduces the number of CD68+CD206+ macrophages within peritendinous adhesion tissue.

Eggshell membrane powder reinforces adhesive polysaccharide hydrogels for wound repair

Multifunctional polysaccharide hydrogels with strong tissue adhesion, and antimicrobial and hemostatic properties are attractive wound healing materials. In this study, a chitosan-based hydrogel (HCS) was designed, and its properties were enhanced by incorporating oxidized eggshell membrane (OEM). Hydrogel characterization and testing results showed that the hydrogel had excellent antimicrobial properties, cytocompatibility, satisfactory adhesion properties on common substrates, and wet-state adhesion capacity. A rat liver injury model confirmed the significant hemostatic effect of the hydrogel. Finally, the ability of the hydrogel to promote wound healing was verified using rat skin wound repair experiments. Our findings indicate that HCS/OEM hydrogels with added eggshell membrane fibers have better self-healing properties, mechanical strength, adhesion, hemostatic properties, and biocompatibility than HCS hydrogels, in addition to having superior repair performance in wound repair experiments. Overall, the multifunctional polysaccharide hydrogels fabricated in this study are ideal for wound repair.

Endoscopic repair of tracheoesophageal fistulas: A contemporary multi-institutional case series and literature review

ObjectivesRecurrent and primary tracheoesophageal fistulas (TEFs) are a challenging surgical pathology to treat, as standard open surgical approaches are associated with high morbidity and mortality. As such, endoscopic modalities have gained interest as an alluring alternative, yet variable success rates have been reported in the literature. The aim of this study was to provide a contemporary update of the literature and describe our institutional experience with the bronchoscopic obliteration of recurrent and primary TEFs. MethodsRetrospective chart review of all pediatric patients having undergone endoscopic TEF repair at two pediatric academic centers in Montreal, Canada and Lille, France between January 1, 2008 to December 31, 2020. Results28 patients with TEFs (20 recurrent, 8 primary) underwent a total of 48 endoscopic procedures. TEF repair was performed under endoscopic guidance using various combinations of techniques, including fistula de-epithelialization (endoscopic brush, thulium laser, trichloroacetic acid-soaked pledgets or electrocautery), tissue adhesives, submucosal augmentation, esophageal clip and stenting. Successful closure was achieved in 16 patients (57 %), while 12 (43 %) required eventual open or thoracoscopic repair. The mean number of endoscopic procedures was 1.7. There were no major treatment-related complications such as pneumothorax, mediastinitis or death (mean follow-up 50.8 months). ConclusionsEndoscopic repair of recurrent or primary TEFs is a valuable component of our therapeutic armamentarium and may contribute to decreased surgical morbidity in this complex patient population. Families should be counselled that endoscopic results may be more modest than with open or thoracoscopic approaches, and multiple procedures may be required.

Liquid Metal‐Enhanced Highly Adhesive Electrodes for Multifunctional Epidermal Bioelectronics

AbstractLiquid metal (LM) bioelectronics find widespread uses in healthcare devices and medical implants. However, the current LM‐based electrodes suffer from achieving a combination of features including stable conductivity, high tissue adhesion, stability, good biocompatibility, degradability, and recyclability. In this work, a stable LM electrode is prepared with an extremely high adhesion strength (8.9 MPa), which is tunable in a wide range by introducing an adhesive ureidopyrimidinone (UPy)‐based polymer to harvest the abovementioned properties. With the help of dynamic LM particle‐polymer interactions in the polymer matrix, LMs can not only enhance the adhesion properties but also form a percolated network at a low LM loading (38 vol%) to achieve a high conductance stability (R/R0 = 0.76 at 100% strain). The high adhesion strength provides a highly stable electrical connection with rigid components with a high stretchability of 1154% when mounting a resistor, while a relatively low adhesion makes it a comfortable wounded skin‐interfaced electrode for accelerating wound healing. Taking advantage of their tunable surface adhesion and biocompatibility, the as‐prepared LM electrodes provide a more reliable and friendly approach to the development of healthcare devices.

Silver nitrate-assisted photo-crosslinking for enhancing the mechanical properties of an alginate/silk fibroin-based 3D scaffold

Scaffolds play a pivotal role in tissue engineering and serve as vital biological substitutes, providing structural support for cell adhesion and subsequent tissue development. An ideal scaffold must possess mechanical properties suitable for tissue function and exhibit biodegradability. Although synthetic polymer scaffolds offer high rigidity and elasticity owing to their reactive side groups, which facilitate tailored mechanical and rheological properties, they may lack biological cues and cause persistent side effects during degradation. To address these challenges, natural polymers have garnered attention owing to their inherent bioactivity and biocompatibility. However, natural polymers such as silk fibroin (SF) and tyramine-modified alginate (AT) have limitations, including uncontrolled mechanical properties and weak structural integrity. In this study, we developed a blend of SF and AT as a printable biomaterial for extrusion-based 3D printing. Using photocrosslinkable SF/AT inks facilitated the fabrication of complex scaffolds with high printability, thereby enhancing their structural stability. The incorporation of silver nitrate facilitated the tunability of mechanical and rheological behaviors. SF/AT scaffolds with varying stiffness in the physiologically relevant range for soft tissues (51–246 kPa) exhibited excellent biocompatibility, indicating their promising potential for diverse applications in tissue engineering.

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

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

Anti-adhesion study of three-dimensional reconstructed carbon coatings

This research study focuses on the investigation of a three-dimensional reconstructed carbon coating based on stainless steel. The investigation encompasses the assessment of surface structure, elemental composition, cytotoxicity, and impact on wound healing. The findings indicate that the carbon coating possesses an approximate thickness of 700 nm, exhibiting a distinctive porous structure. Moreover, the surface water contact angle measures 97.7°, representing a 48.4° increase compared to uncoated stainless steel. Energy-dispersive spectroscopy (EDS) analysis confirms the uniform distribution of diverse elements on the coating’s surface. Additionally, X-ray photoelectron spectroscopy (XPS) verifies a substantial carbon accumulation. The electrical resistance of the stainless steel remains largely intact after the application of the coating, as demonstrated by the four-probe method. Notably, ex vivo porcine liver tissue cutting experiments using carbon-coated electrosurgical pencil electrodes showed a significant anti-adhesion effect, with a reduction in tissue adhesions of 81.3%. Furthermore, the MTT test indicates no significant cytotoxicity associated with the carbon coating. Rat skin-cutting experiments further validate that the coating does not impede the process of wound healing. Overall, this study successfully validated the desirable properties of stainless steel-based 3D reconstructed carbon coatings, such as enhanced surface properties, improved anti-adhesion efficacy, negligible cytotoxicity, and compatibility with wound healing. These findings are important for advancing medical device technology and improving patient outcomes.

Efficacy of Endoscopic Tissue Adhesive in Patients with Gastrointestinal Tumor Bleeding

BackgroundGastrointestinal tumors bleeding remains a significantly clinical challenge due to its resistance to conventional endoscopic hemostasis methods. While the efficacy of endoscopic tissue adhesives (ETA) in variceal bleeding has been established, its role in gastrointestinal tumor bleeding (GITB) remains ambiguous.AimsThis study aims to assess the feasibility and effectiveness of ETA in the treatment of GITB.MethodsThe study enrolled 30 patients with GITB who underwent hemostasis through Histoacryl® tissue glue injection. Hemostasis success rates, ETA-related adverse events, and re-bleeding rates were evaluated.ResultsETA application achieved successful hemostasis at all tumor bleeding sites, with immediate hemostasis observed in all 30 (100.0%) patients. Among the initially hemostasis cases, 5 patients (17.0%) experienced re-bleeding within 30 days, and the 60 day re-bleeding rate was 20.0% (6/30). Expect for one case of vascular embolism, no adverse events related with ETA application were reported. The 6 month survival was 93%.ConclusionETA demonstrated excellent immediate hemostasis success rate in GITB cases and showed promising outcomes in prevention re-bleeding.

NIR‐Responsive injectable hydrogel cross-linked by homobifunctional PEG for photo-hyperthermia of melanoma, antibacterial wound healing, and preventing post-operative adhesion

Current therapeutic approaches for skin cancer face significant challenges, including wound infection, delayed skin regeneration, and tumor recurrence. To overcome these challenges, an injectable adhesive near-infrared (NIR)-responsive hydrogel with time-dependent enhancement in viscosity is developed for combined melanoma therapy and antibacterial wound healing acceleration. The multifunctional hydrogel is prepared through the chemical crosslinking between poly(methyl vinyl ether-alt-maleic acid) and gelatin, followed by the incorporation of CuO nanosheets and allantoin. The synergistic inherent antibacterial potential of CuO nanosheets, the regenerative and smoothing effect of allantoin, the extracellular matrix-mimicking effect of gelatin, and the desirable swelling behavior of the hydrogel results in fast wound recovery after photothermal ablation of the tumor. Additionally, the hydrogel can serve as an alternative to sutures owing to its tissue adhesiveness ability, which can further render it the merits for accelerated repair of abdominal lesions while acting as a biocompatible barrier to prevent peritoneal adhesion.

Bypass-Assisted Microsurgical Clipping for an Endovascular Treatment-Resistant Ruptured Internal Carotid-Posterior Communicating Artery Aneurysm, Recurring Two Decades Postinitial Clipping: 2-Dimensional Operative Video.

Salvage treatment of postclipping recurrent aneurysms remains challenging.1,2 The salvage microsurgical clipping is a possible intervention but sometimes difficult because of tissue adhesions around the aneurysm and previously installed clips; therefore, salvage coil embolization may have certain advantages.1-5 However, when coil embolization is not applicable,6 microsurgical clipping is a stand-alone curative treatment, requiring proficient and reliable microsurgical techniques. This article describes a unique case of a 70-year-old female patient complaining of a severe headache with subarachnoid hemorrhage due to a recurrent ruptured left internal carotid-posterior communicating artery aneurysm after microsurgical clipping 23 years ago. An initial attempt at coil embolization proved unsuccessful because of the aneurysm shape. Consequently, the salvage microsurgical clipping was planned. Given the additional time for trapping the internal carotid artery for the old clip removal, a superficial temporal artery-middle cerebral artery bypass was also planned. The operation entailed a superficial temporal artery-middle cerebral artery bypass, a Sylvian fissure dissection, the old clip removal, and aneurysm clipping. Intraoperatively, the complete aneurysm neck clipping was successfully performed without any complication, and patient postoperative course was uneventful. A wide surgical field should be obtained to be able to manipulate the aneurysm and old clip safely under a microscope. It is also important to temporarily trap the main artery to ensure removal of old clips and to prepare for intraprocedural ischemia using bypass after a precise assessment of hemodynamics before surgery. The patient provided informed consent for the procedure and the publication of the case along with its pertinent imaging, and this report was approved by the institutional review board at our hospital.

A multifunctional conductive organohydrogel as a flexible sensor for synchronous real-time monitoring of traumatic wounds and pro-healing process

Ion-conductive hydrogels (ICHs) offer promising applications in the realm of flexible bioelectronics due to their attributes, such as transparency, flexibility, tissue adhesion, and self-healing. However, it remains a challenge to integrate excellent material properties and bio-properties into ICHs-based smart wearables for intricate biomedical applications. Herein, a multifunctional conductive C-CST/PMC organohydrogel with stretchability, anti-freezing, self-healing, antibacterial, antioxidant, and biocompatibility was synthesized by catechol-conjugated chitosan (C-CS), silk nanofibrils (SNFs), tannic acid (TA), MgCl2/CaCl2, and polyvinyl alcohol (PVA), with a binary solvent system composed of ethylene glycol (EG) and H2O. The C-CST/PMC exhibited excellent mechanical properties (175 kPa stress and 330 % strain), anti-freezing capacity, moisture retention, self-healing performance, and high conductivity (1.76 mS/cm at 25 °C and 1.43 mS/cm at –18 °C). Moreover, we have employed this organohydrogel as a flexible strain sensor for monitoring human movements, achieving a high sensitivity (gauge factor (GF) = 1.20 at 100 % strain) and glorious fatigue resistance (>1000 cycles). Furthermore, the C-CST/PMC displayed good antibacterial, antioxidant, hemo-, and cytocompatibility. In vivo tests on diabetic rats have demonstrated that the C-CST/PMC organohydrogel effectively reduces inflammatory responses and promotes angiogenesis, consequently expediting wound healing. Notably, trials involving the use of this flexible sensor in a medical silicone bionic shoulder have indicated its potential as a wearable electronic device for real-time monitoring of human wound healing progress. Overall, this research contributes novel insights to the design and fabrication of multifunctional flexible sensors that synchronous pro-healing and real-time monitoring of traumatic skin.

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

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

Lecithin-complexed oregano essential oil-encapsulated fibrous barriers prevent postoperative adhesions by regulating Nrf2/NF-κB signaling pathways

Postoperative adhesions are prone to a variety of complications, which can adversely affect the quality of life (QOL) of patients. While anti-adhesion scaffolds rapidly degrade, foreign body reactions (FBR), exaggerated inflammatory reactions, and oxidative stress may increase tissue adhesions. This necessitates the development of anti-adhesion scaffolds with multifunctional anti-inflammatory, anti-bacterial, and anti-oxidative characteristics. The objective of this study was to simultaneously leverage natural antimicrobial and anti-oxidative bioactive molecules, such as lecithin (L) and Oregano essential oil (O) to afford poly(lactic-co-glycolic acid) (PLGA)-based electrospun membranes for postoperative anti-adhesion management. A series of assays revealed a beneficial effect of L and O co-loaded membranes (P@LO) to suppress bacterial growth, reduce the proliferation of fibroblasts, and confer anti-oxidative and anti-inflammatory functionalities to membranes than that of the control (P) or only a single cue-loaded groups (P@L and P@O). The underlying molecular mechanism of the anti-inflammatory effect may be an upregulation of the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation. An assessment of membranes in an abdominal and a tendon adhesion model showed a significant effect of P@LO membranes to prevent post-operative tissue adhesion. The P@LO membranes were found to up-regulate the phosphorylation of Nrf2 while down-regulate the phosphorylation of nuclear factor kappa-B (NF-κB) P65. This resulted in lower expression of collagen Ⅰ (Col-Ⅰ), collagen Ⅲ (Col-Ⅲ), and alpha-smooth muscle actin (α-SMA) alongside inflammation resolution and less transition of fibroblasts to myofibroblasts. Taken together, these multifunctional scaffolds may have broad implications for postoperative adhesion management.

A TLR4-Targeting Bioactive Peptide Hydrogel to Regulate Immune-Microenvironment for Diabetic Wound Repair.

Persistent inflammation and disrupted immunoregulation are critical factors in impeding diabetic wound healing. While immunoregulatory hydrogel dressings hold significant promise for clinical applications in diabetic wound healing, the current application often demands intricate interventions and high-cost treatments involving cytokines and cell therapies. The development of single component immunoregulatory hydrogels remains a complex challenge. To address this issue, an active peptide hydrogel with immunoregulatory properties targeting the TLR4/NF-kB pathway, aiming to promote rapid diabetic wound healing, is engineered. The hydrogel sequence comprises naphthalene derivative, phenylalanine, and glycine to modulate hydrophilic/hydrophobic characteristics. The amino group on arginine contributes to tissue adhesion and regulation of intermolecular forces, ultimately yielding stable gels. The results underscore the formation of the peptide hydrogel (NFA) via the physical crosslinking of self-assembled nanofibers in water, thereby affording both excellent injectability and tissue adhesion. Notably, NFA demonstrates significant potential in promoting wound healing in a mouse model with full-thickness wounds by regulating macrophage responses in the inflammatory microenvironment through the TLR4/NF-kB pathway.

Spermidine-Functionalized Injectable Hydrogel Reduces Inflammation and Enhances Healing of Acute and Diabetic Wounds In Situ.

The inflammatory response is a key factor affecting tissue regeneration. Inspired by the immunomodulatory role of spermidine, an injectable double network hydrogel functionalized with spermidine (DN-SPD) is developed, where the first and second networks are formed by dynamic imine bonds and non-dynamic photo-crosslinked bonds respectively. The single network hydrogel before photo-crosslinking exhibits excellent injectability and thus can be printed and photo-crosslinked in situ to form double network hydrogels. DN-SPD hydrogel has demonstrated desirable mechanical properties and tissue adhesion. More importantly, an "operando" comparison of hydrogels loaded with spermidine or diethylenetriamine (DETA), a sham molecule resembling spermidine, has shown similar physical properties, but quite different biological functions. Specifically, the outcomes of 3 sets of in vivo animal experiments demonstrate that DN-SPD hydrogel can not only reduce inflammation caused by implanted exogenous biomaterials and reactive oxygen species but also promote the polarization of macrophages toward regenerative M2 phenotype, in comparison with DN-DETA hydrogel. Moreover, the immunoregulation by spermidine can also translate into faster and more natural healing of both acute wounds and diabetic wounds. Hence, the local administration of spermidine affords a simple but elegant approach to attenuate foreign body reactions induced by exogenous biomaterials to treat chronic refractory wounds.