Tissue Adhesives Research Articles

Determination of the internal loads experienced by proximal phalanx fracture fixations during rehabilitation exercises.

Phalangeal fractures are common, particularly in younger patients, leading to a large economic burden due to higher incident rates among patients of working age. In traumatic cases where the fracture may be unstable, plate fixation has grown in popularity due to its greater construct rigidity. However, these metal plates have increased reoperation rates due to inflammation of the surrounding soft tissue. To overcome these challenges, a novel osteosynthesis platform, AdhFix, has been developed. This method uses a light-curable polymer that can be shaped in situ around traditional metal screws to create a plate-like structure that has been shown to not induce soft tissue adhesions. However, to effectively evaluate any novel osteosynthesis device, the biomechanical environment must first be understood. In this study, the internal loads in a phalangeal plate osteosynthesis were measured under simulated rehabilitation exercises. In a human hand cadaver study, a plastic plate with known biomechanical properties was used to fix a 3mm osteotomy and each finger was fully flexed to mimic traditional rehabilitation exercises. The displacements of the bone fragments were tracked with a stereographic camera system and coupled with specimen specific finite element (FE) models to calculate the internal loads in the osteosynthesis. Following this, AdhFix patches were created and monotonically tested under similar conditions to determine survival of the novel technique. The internal bending moment in the osteosynthesis was 6.78 ± 1.62Nmm and none of the AdhFix patches failed under the monotonic rehabilitation exercises. This study demonstrates a method to calculate the internal loads on an osteosynthesis device during non-load bearing exercises and that the novel AdhFix solution did not fail under traditional rehabilitation protocols in this controlled setting. Further studies are required prior to clinical application.

Antimicrobial adhesive self-healing hydrogels for efficient dental biofilm removal from periodontal tissue

ObjectivesOral biofilms, including pathogens such as Porphyromonas gingivalis, are involved in the initiation and progression of various periodontal diseases. However, the treatment of these diseases is hindered by the limited efficacy of many antimicrobial materials in removing biofilms under the harsh conditions of the oral cavity. Our objective is to develop a gel-type antimicrobial agent with optimal physicochemical properties, strong tissue adhesion, prolonged antimicrobial activity, and biocompatibility to serve as an adjunctive treatment for periodontal diseases. MethodsPhenylboronic acid-conjugated alginate (Alg–PBA) was synthesized using a carbodiimide coupling agent. Alg–PBA was then combined with tannic acid (TA) to create an Alg–PBA/TA hydrogel. The composition of the hydrogel was optimized to enhance its mechanical strength and tissue adhesiveness. Additionally, the hydrogel’s self-healing ability, erosion and release profile, biocompatibility, and antimicrobial activity against P. gingivalis were thoroughly characterized. ResultsThe Alg–PBA/TA hydrogels, with a final concentration of 5 wt% TA, exhibited both mechanical properties comparable to conventional Minocycline gel and strong tissue adhesiveness. In contrast, the Minocycline gel demonstrated negligible tissue adhesion. The Alg–PBA/TA hydrogel also retained its rheological properties under repeated 5 kPa stress owing to its self-healing capability, whereas the Minocycline gel showed irreversible changes in rheology after just one stress cycle. Additionally, Alg–PBA/TA hydrogels displayed a sustained erosion and TA release profile with minimal impact on the surrounding pH. Additionally, the hydrogels exhibited potent antimicrobial activity against P. gingivalis, effectively eliminating its biofilm without compromising the viability of MG-63 cells. SignificanceThe Alg–PBA/TA hydrogel demonstrates an optimal combination of mechanical strength, self-healing ability, tissue adhesiveness, excellent biocompatibility, and sustained antimicrobial activity against P. gingivalis. These attributes make it superior to conventional Minocycline gel. Thus, the Alg–PBA/TA hydrogel is a promising antiseptic candidate for adjunctive treatment of various periodontal diseases.

Stretchable, Self-Healing, and Bioactive Hydrogel with High-Functionality N,N'-bis(acryloyl)cystamine Dynamically Bonded Ag@polydopamine Crosslinkers for Wearable Sensors.

Hydrogels present attractive opportunities as flexible sensors due to their soft nature and tunable physicochemical properties. Despite significant advances, practical application of hydrogel-based sensor is limited by the lack of general routes to fabricate materials with combination of mechanical, conductive, and biological properties. Here, a multi-functional hydrogel sensor is reported by in situ polymerizing of acrylamide (AM) with N,N'-bis(acryloyl)cystamine (BA) dynamic crosslinked silver-modified polydopamine (PDA) nanoparticles, namely PAM/BA-Ag@PDA. Compared with traditional polyacrylamide (PAM) hydrogel, the BA-Ag@PDA nanoparticles provide both high-functionality crosslinks and multiple interactions within PAM networks, thereby endowing the optimized PAM/BA-Ag@PDA hydrogel with significantly enhanced tensile/compressive strength (349.80kPa at 383.57% tensile strain, 263.08kPa at 90% compressive strain), lower hysteresis (5.2%), improved conductivity (2.51 S m-1) and excellent near-infrared (NIR) light-triggered self-healing ability. As a strain sensor, the PAM/BA-Ag@PDAhydrogel shows a good sensitivity (gauge factor of 1.86), rapid response time (138ms), and high stability. Owing to abundant reactive groups in PDA, the PAM/BA-Ag@PDA hydrogel exhibits inherent tissue adhesiveness and antioxidant, along with a synergistic antibacterial effect by PDA and Ag. Toward practical applications, the PAM/BA-Ag@PDA hydrogel can conformally adhere to skin and monitor subtle activities and large-scale movements with excellent reliability, demonstrating its promising applications as wearable sensors for healthcare.

Development and Characterization of a Novel Composite Hydrogel Biomaterial for Improved Mucoperiosteal WoundRepair.

Mucoperiosteal wound healing, as it occurs after pediatric cleft palate surgery, can be challenging due to the limitations of current treatments such as tissue flaps secured with sutures and fibrin glue. In this study, we characterized the in vitro performance of a novel composite hydrogel biomaterial designed to be employed as an in situ wound filler and enhance mucoperiosteal wound healing. We evaluated a range of photopolymerizable formulations containing methacrylated gelatin (GelMA), glycol chitosan, and bioglass microparticles. Our aim was to identify one or more formulations with an appropriate balance of properties against a set of functional requirements that we established for this application. To test the formulations against these criteria, we measured photopolymerization kinetics, mechanical properties, degradation rate, in vitro biocompatibility, and ex vivo tissue adhesion. All formulations polymerized in less than 90 s using violet light. In addition, we found that GelMA-based hydrogels were more adhesive to mucoperiosteal tissue than clinical standard fibrin glue. Inclusion of small amounts of bioglass in the formulation increased mechanical compatibility with mucoperiosteal tissue, enhanced cytoconductivity, and promoted cell proliferation. Taken together, our results support the suitability of these photopolymerized composite hydrogels as in situ mucoperiosteal wound fillers. Overall, this study lays the groundwork for investigating the in vivo, pre-clinical effectiveness of these composite hydrogels in improving mucoperiosteal wound healing outcomes.

Robust tissue adhesion in biomedical applications: enhancing polymer stability in an injectable protein-based hydrogel

Protein-based hydrogels are appealing materials for a variety of therapeutic uses because they are compatible, biodegradable, and adaptable to biological and chemical changes. Therefore, adherent varieties of hydrogels have received significant study; nevertheless, the majority of them show weak mechanical characteristics, transient adherence, poor biocompatibility activity, and low tensile strength. Here we are reporting, a two-component (BSA-gelatin) protein solution crosslinked with Tetrakis (hydroxymethyl) phosphonium chloride (THPC) to form a novel hydrogel. Compared with classical adhesive hydrogels, this hydrogel showed enhanced mechanical properties, was biocompatible with L929 cells, and had minimal invasive injectability. A considerable, high tensile strength of 73.33 ± 11.54 KPa and faultless compressive mechanical properties of 173 KPa at 75% strain were both demonstrated by this adhesive hydrogel. Moreover, this maximum tissue adhesion strength could reach 18.29 ± 2.22 kPa, significantly higher than fibrin glue. Cell viability was 97.09 ± 6.07%, which indicated that these hydrogels were non-toxic to L929. The fastest gelation time of the BSA-gelatin hydrogel was 1.25 ± 0.17 min at physiological pH and 37 °C. Therefore, the obtained novel work can potentially serve as a tissue adhesive hydrogel in the field of biomedical industries.

A dopamine-assisted antioxidative in situ-forming hydrogel with photothermal therapy for enhancing scarless burn wound healing

Burn wounds are characterized by complex physiological and pathophysiological response and the management of burn wounds is challenging. In situ-forming hydrogels and photothermal therapy (PTT) are promising treatments for wound healing. However, current research on biomaterials for burn treatment mainly focuses on either promoting healing or inhibiting scar formation, few studies have combined the two functions of one material. In this study, we prepared a multifunctional, in-situ cross-linked hydrogel termed CPOD hydrogel, which integrates carboxymethyl chitosan (CMCS), polyvinyl alcohol (PVA), oxidized hyaluronic acid (OHA), and dopamine (DA), coupled with photothermal therapy (PTT). In vitro experiments showed that the CPOD hydrogel had outstanding biocompatibility, suitable tissue adhesion and mechanical properties, excellent antimicrobial and antioxidant properties. This hydrogel showed PTT properties, which could produce mild heat in the early stage and higher temperatures in the later stage under NIR radiation. In the treatment of burn wounds of mice, application of CPOD hydrogel with PTT significantly promoted wound healing in the early stage and inhibited scar formation in the later stage, showing great potential for future innovation and application.

Electrospun Polymeric Fiber Systems Inoculated with Cyanoacrylate Tissue Adhesive: A Novel Hemostatic Alternative during Open Surgery.

Natural-based and synthetic tissue adhesives have attracted extensive attention in the last two decades for their ability to stabilize uncontrolled bleeding instances. However; these materials present several drawbacks during use that scientists have tried to minimize in order to optimize their usage. This study comprises the development of a novel wound dressing, combining the excellent properties of polylactic acid (PLA) non-woven textile, as substrate, obtained through electrospinning, and a cyanoacrylate-based (CA) tissue adhesive, for rapid hemostatic action. Thus, the fabrication of electrospun PLA membranes at three different PLA concentrations, the design and manufacturing of the support system and the production of surgical patches were carried out. SEM and FT-IR methods were employed for analyzing the morphology as well as the indicative markers for the shelf life evolution of the obtained patches. PLA fibers with well-defined structures and a mean diameter varying between 4.6 and 7.24 μm were obtained with the increase of the concentration of the PLA solutions. In vivo tests on a rat model as well as peeling tests for good patch adhesion on liver fragments harvested from the test animals, with a limit for the strength of the liver tissue of 1.5 N, were carried out. The devices exhibited excellent adhesion to the parenchymal tissue and a long enough shelf life to be used with success in surgical procedures, also facilitating prompt hemostatic action.

Can we use superglues for superfi cial lacerations?

Objectives: To compare the histopathological and cosmetic outcomes of ethyl-cyanoacrylate to n-butyl-2-cyanoacrylate in rats using an incision wound model. Methods: Two longitudinal incisions were made on the dorsal region of the back of 18 Wistar rats after ketamine anesthesia. Rats were divided into three groups of six: the incisions were closed either using medical tissue adhesive or superglue or were left for secondary wound healing. In each group, three rats were randomly euthanized on the 7th day. The rest were euthanized on the 21st day of the procedure. Tissue samples taken on days 7 and 21 were Histopathologically evaluated blindly by a histologist. The cosmetic appearance was evaluated by a plastic surgeon blinded to the method of closure using a visual analog scale. Results: Histopathological evaluation revealed impaired epithelialization, infl ammation, fi brosis, and dehiscence on connective tissue, and foreign substance reactions were worse in the ethyl-2-cyanoacrylate group when compared with the other groups. A statistically signifi cant diff erence was not found among groups regarding the cosmetic outcome. Conclusions: Cyanoacrylate glues produced for commercial purposes should not be used for the repair of skin lacerations due to their worse histopathological results of epithelialization, infl ammation, fi brosis, dehiscence on connective tissue, and foreign substance reaction. Keywords: Lacerations, Wound closure techniques, Tissue adhesives, Cyanoacrylates, Wound healing.

Self-healing hydrogel from poly(aspartic acid) and dextran with antibacterial property for burn wound healing

Designing hydrogel dressing with intrinsic antibacterial property to promote skin injury recovery remains a significant challenge. In this research, poly(aspartic hydrazide) with grafted betaine (PAHB) was designed and reacted with oxidized dextran (OD) to fabricate biodegradable PAHB/OD hydrogel and its application as wound dressing was systematically investigated. The PAHB/OD hydrogels exhibited fast gelation, strong tissue adhesion, preferable mechanical properties and biocompatibility. The grafted betaine endowed the hydrogel with antibacterial property and antibacterial rate enhanced through photothermal performance of composited CuS nanoparticles under near infrared (NIR) radiation. The CuS composited PAHB/OD hydrogel (CuS/hydrogel) with microporous morphology was used as burn wound dressing with loaded anti-inflammatory drug diclofenac sodium (DS) in mouse model. The results showed the DS loaded CuS/hydrogel (CuS@DS/hydrogel) promoted the tissue regeneration and suppressed the inflammatory response. The histological analysis and immunohistochemical expression confirmed the CuS@DS/hydrogel promote angiogenesis of the burn wound by regulating the expression of inflammatory cytokines (IL-6 and CD68) and vascular endothelial growth factor (VEGF). Overall, the CuS@DS/hydrogel hydrogel is a promising candidate as wound dressing due to its tissue adhesive, antioxidant, antibacterial and anti-inflammatory activities.

Novel injectable adhesive hydrogel loaded with exosomes for holistic repair of hemophilic articular cartilage defect

Hemophilic articular cartilage damage presents a significant challenge for surgeons, characterized by recurrent intraarticular bleeding, a severe inflammatory microenvironment, and limited self-repair capability of cartilage tissue. Currently, there is a lack of tissue engineering-based integrated therapies that address both early hemostasis, anti-inflammation, and long-lasting chondrogenesis for hemophilic articular cartilage defects. Herein, we developed an adhesive hydrogel using oxidized chondroitin sulfate and gelatin, loaded with exosomes derived from bone marrow stem cells (BMSCs) (Hydrogel-Exos). This hydrogel demonstrated favorable injectability, self-healing, biocompatibility, biodegradability, swelling, frictional and mechanical properties, providing a comprehensive approach to treating hemophilic articular cartilage defects. The adhesive hydrogel, featuring dynamic Schiff base bonds and hydrogen bonds, exhibited excellent wet tissue adhesiveness and hemostatic properties. In a pig model, the hydrogel could be smoothly injected into the knee joint cartilage defect site and gelled in situ under fluid-irrigated arthroscopic conditions. Our in vitro and in vivo experiments confirmed that the sustained release of exosomes yielded anti-inflammatory effects by modulating macrophage M2 polarization through the NF-κB pathway. This immunoregulatory effect, coupled with the extracellular matrix components provided by the adhesive hydrogel, enhanced chondrogenesis, promoted the cartilage repair and joint function restoration after hemophilic articular cartilage defects. In conclusion, our results highlight the significant application potential of Hydrogel-Exos for early hemostasis, immunoregulation, and long-term chondrogenesis in hemophilic patients with cartilage injuries. This innovative approach is well-suited for application during arthroscopic procedures, offering a promising solution for addressing the complex challenges associated with hemophilic articular cartilage damage.

Bioresponsive and transformable coacervate actuated by intestinal peristalsis for targeted treatment of intestinal bleeding and inflammation

Developing an oral in situ-forming hydrogel that targets the inflamed intestine to suppress bleeding ulcers and alleviate intestinal inflammation is crucial for effectively treating ulcerative colitis (UC). Here, inspired by sandcastle worm adhesives, we proposed a water-immiscible coacervate (EMNs-gel) with a programmed coacervate-to-hydrogel transition at inflammatory sites composed of dopa-rich silk fibroin matrix containing embedded inflammation-responsive core-shell nanoparticles. Driven by intestinal peristalsis, the EMNs-gel can be actuated forward and immediately transform into a hydrogel once contacting with the inflamed intestine to yield strong tissue adhesion, resulting from matrix metalloproteinases (MMPs)-triggered release of Fe3+ from embedded nanoparticles and rearrangement of polymer network of EMNs-gel on inflamed intestine surfaces. Extensive in vitro experiments and in vivo UC models confirmed the preferential hydrogelation behavior of EMNs-gel to inflamed intestine surfaces, achieving highly effective hemostasis, and displaying an extended residence time (> 48 h). This innovative EMNs-gel provides a non-invasive solution that accurately suppresses severe bleeding and improves intestinal homeostasis in UC, showcasing great potential for clinical applications.

Evaluation of sodium hyaluronate-based composite hydrogels for prevention of nasal adhesions.

During the healing process after intra-nasal surgery, the growth and repair of damaged tissues can result in the development of postoperative adhesions. Various techniques have been devised to minimize the occurrence of postoperative adhesions which include insertion of stents in the middle meatus, application of removable nasal packing, and utilizing biodegradable materials with antiadhesive properties. This study assesses the efficacy of two sodium hyaluronate (SH)-based freeze-dried hydrogel composites in preventing postoperative nasal adhesions, comparing them with commonly used biodegradable materials in nasal surgery. The freeze-dried hydrogels, sodium hyaluronate and collagen 1(SH-COL1) and sodium hyaluronate, carboxymethyl cellulose, and collagen 1 (SH-CMC-COL1), were evaluated for their ability to reduce bleeding time, promote wound healing, and minimize fibrous tissue formation. Results showed that SH-CMC-COL1 significantly reduced bleeding time compared to both biodegradable polyurethane foam and SH-COL1. Both SH-COL1 and SH-CMC-COL1 exhibited enhanced wound healing effects, as indicated by significantly greater wound size reduction after two weeks compared to the control. Histological analyses revealed significant differences in re-epithelialization and blood vessel count among all tested materials, suggesting variable initial wound tissue response. Although all treatment groups had more epithelial growth, with X-SCC having higher blood vessel count at 7 d post treatment, all treatment groups did not differ in all histomorphometric parameters by day 14. However, the long-term application of SH-COL1 demonstrated a notable advantage in reducing nasal adhesion formation compared to all other tested materials. This indicates the potential of SH-based hydrogels, particularly SH-COL1, in mitigating postoperative complications associated with nasal surgery. These findings underscore the versatility and efficacy of SH-based freeze-dried hydrogel composites for the management of short-term and long-term nasal bleeding with an anti-adhesion effect. Further research is warranted to optimize their clinical use, particularly in understanding the inflammatory factors influencing tissue adhesions and assessing material performance under conditions mimicking clinical settings. Such insights will be crucial for refining therapeutic approaches and optimizing biomaterial design, ultimately improving patient outcomes in nasal surgery.

A molybdenum sulfide based nitric oxide controlled release oral gel for rapid healing of oral mucosal ulcers

Oral mucosal ulcer is the most prevalent oral mucosal lesion, affecting over 25 % of general population. The current treatment regimens lack efficacy in addressing challenges such as wound bleeding, bacterial infection and inflammation on a continuous basis. Hence, a multi-functional oral gel (termed MPCST) with a long-acting duration is designed. It is based on a tannic acid-thioctic acid (TATA) supramolecular hydrogel which absorbs tissue exudate while exhibiting robust tissue adhesion properties. To form MPCST, TATA is loaded with MPCS, which are composed of polydopamine (PDA)-coated molybdenum disulfide (MoS2) nanoflakes (MoS2@PDA) with high photothermal conversion efficiency, nitric oxide (NO) precursor nitroprusside (SNP) and cerium oxide (CeO2) with high reactive oxygen species (ROS) scavenging rate. Upon exposure to 808 nm near-infrared (NIR) irradiation, MPCS rapidly heats up and releases NO to promote angiogenesis, while exhibiting strong ROS scavenging, antibacterial (including oral common Streptococcus mutans), and anti-inflammatory properties. Animal experiments show that the MPCST oral gel, composed of MPCS and TATA hydrogel, exhibits superior therapeutic efficacy compared to the commonly used dexamethasone patch.

Tough and self-adhesive zwitterionic hydrogels with mechano-responsive release of bFGF for tympanic membrane repair

The tympanic membrane (TM) is constantly in a state of vibrating. However, there is currently a lack of drug-delivery scaffolds suitable for the dynamic environment of TM perforation. In this study, a mechano-responsive tough hydrogel was developed. It consists of basic fibroblast growth factor (bFGF)-loaded sodium alginate (SA) microspheres, polysulfobetaine methacrylate (polySBMA), and gelatin methacrylate (GelMA). This hydrogel was designed to serve as a TM scaffold to promote perforation healing under dynamic conditions. bFGF was encapsulated in SA microspheres, which were then incorporated into polySBMA-GelMA hydrogels through photo-initiated free radical polymerization. The mechanical properties, tissue adhesiveness, swelling properties, and degradation of the hydrogels were evaluated before and after microsphere incorporation. It was observed that incorporating bFGF-loaded SA microspheres did not significantly impact the adhesion and degradation mechanisms of the hydrogel. The compressive strength and tensile strength of the microsphere-incorporated hydrogel were up to 6.6 MPa and 64.1 kPa, respectively, suitable for a TM scaffold. The release behavior of bFGF from the hydrogel could be controlled by vibration stimulation without significantly affecting the hydrogel's mechanical properties, indicating a mechano-responsive nature of the hydrogel. The in vitro cytotoxicity assay demonstrated that the hydrogels showed no cytotoxic effects. Moreover, cell culture assays demonstrated that vibration stimulation could enhance the release of bFGF, significantly promoting cell proliferation and migration. The results demonstrate the significant potential of the mechano-responsive hydrogel as a scaffold for repairing TM perforations.

Bi2Se3/PAAS Hydrogels with Photothermal and Antioxidant Properties for Bacterial Infection Wound Therapy by Improving Vascular Function and Regulating Glycolipid Metabolism.

Skin is the largest organ in the human body, and it is also the most important natural barrier. However, some accidents can cause skin damage. Bacterial infections and inflammatory reactions can hinder wound healing. Therefore, eliminating bacterial infections and regulating oxidative stress are essential. The use of antibiotics is no longer sufficient because of bacterial resistance. The development of new nanomaterials provides another way of thinking about bacterial drug resistance. In this study, bismuth selenide is modified with polyethylpyrrolidone to obtain a 2D nanomaterial with negligible toxicity and then added to a sodium polyacrylate hydrogel, which is nontoxic and has strong tissue adhesion and a weak antibacterial effect. To further enhance antibacterial performance, photothermal therapy is a good strategy. Under near-infrared light, Bi2Se3/PAAS shows a strong bactericidal effect. Bi2Se3/PAAS hydrogels also have certain antioxidant effects and are used to remove excess free radicals from wound infections. The effective therapeutic effect of Bi2Se3/PAAS/NIR on methicillin-resistant Staphylococcus aureus (MRSA) infection is further verified in animal models. Transcriptome analysis reveals that the Bi2Se3/PAAS hydrogel improves the function of vascular endothelial cells, regulates glucose and lipid metabolism, and promotes the healing of infected wounds.

Self-healing injectable hydrogels incorporating hyaluronic acid and phytic acid: Rheological insights and implications for regenerative medicine

Eying the increasing impact of hyaluronic acid (HA) and its multifaceted applications, this study employs a non-toxic, one-pot strategy to develop injectable, self-healing hydrogels for biomedical applications. Phytic acid (PA), a plant-derived organic acid with high biocompatibility and numerous hydroxyl groups, can act as a cross-linking agent to form hydrogen-bonded networks with the HA chains. The study examined the optimal mass ratio of HA to PA to achieve superior hydrogel performance. Fourier transform infrared spectroscopy, rheological studies, and thermal analysis confirmed the successful formation of the hydrogels, which exhibited injectability, rapid self-healing, malleability, and elasticity. The investigation of different compositions revealed a sensitive influence of PA on the self-assembly phenomena of HA during flow. SEM cross-section images of the freeze-dried gels revealed a porous surface in the form of an interconnected network of microchannels. In addition, the hydrogel exhibits good tissue adhesion properties and promotes cell proliferation in biocompatibility tests on human gingival fibroblasts. The significance of this study lies in the ability of the proposed materials to be injected, to conform to the complex 3D structure of host tissues as well as their ability to recover after damage, indicating significant potential as scaffolds for wound healing.

An in situ forming cartilage matrix mimetic hydrogel scavenges ROS and ameliorates osteoarthritis after superficial cartilage injury

Superficial cartilage defects represent the most prevalent type of cartilage injury encountered in clinical settings, posing significant treatment challenges. Here, we fabricated a cartilage extracellular matrix mimic hydrogel (GHC, consisting of Gelatin, Hyaluronic acid, and Chondroitin sulfate) to avoid the exacerbation of cartilage deterioration, which is often driven by the accumulation of reactive oxygen species (ROS) and a pro-inflammatory microenvironment. The GHC hydrogel exhibited multifunctional properties, including in situ formation, tissue adhesiveness, anti-ROS capabilities, and the promotion of chondrogenesis. The enhancement of tissue adhesion was achieved by chemically modifying hyaluronic acid and chondroitin sulfate with o-nitrobenzene, enabling a covalent connection to the cartilage surface upon light irradiation. In vitro characterization revealed that GHC hydrogel facilitated chondrocyte adhesion, migration, and differentiation into cartilage. Additionally, GHC hydrogels demonstrated the ability to scavenge ROS in vitro and inhibit the production of inflammatory factors by chondrocytes. In the animal model of superficial cartilage injury, the hydrogel effectively promoted cartilage ECM regeneration and facilitated the interface integration between the host tissue and the material. These findings suggest that the multifunctional GHC hydrogels hold considerable promise as a strategy for cartilage defect repair. Statement of significanceSuperficial cartilage defects represent the most prevalent type of cartilage injury encountered in the clinic. Previous cartilage tissue engineering materials are only suitable for full-thickness cartilage defects or osteochondral defects. Here, we developed a multifunctional GHC hydrogel composed of gelatin, hyaluronic acid, and chondroitin sulfate, which are natural cartilage extracellular matrix components. The drug-free and cell-free hydrogel not only avoids immune rejection and drug toxicity, but also shows good mechanical properties and biocompatibility. More importantly, the GHC hydrogel could adhere tightly to the superficial cartilage defects and promote cartilage regeneration while protecting against oxidation. This natural ingredients and multifunctional hydrogel is a potential material for repairing superficial cartilage defects.

Mussel-Inspired Injectable Adhesive Hydrogels for Biomedical Applications.

The impressive adhesive capacity of marine mussels has inspired various fascinating designs in biomedical fields. Mussel-inspired injectable adhesive hydrogels, as a type of promising mussel-inspired material, have attracted much attention due to their minimally invasive property and desirable functions provided by mussel-inspired components. In recent decades, various mussel-inspired injectable adhesive hydrogels have been designed and widely applied in numerous biomedical fields. The rational incorporation of mussel-inspired catechol groups endows the injectable hydrogels with the potential to exhibit many properties, including tissue adhesiveness and self-healing, antimicrobial, and antioxidant capabilities, broadening the applications of injectable hydrogels in biomedical fields. In this review, we first give a brief introduction to the adhesion mechanism of mussels and the characteristics of injectable hydrogels. Further, the typical design strategies of mussel-inspired injectable adhesive hydrogels are summarized. The methodologies for integrating catechol groups into polymers and the crosslinking methods of mussel-inspired hydrogels are discussed in this section. In addition, we systematically overview recent mussel-inspired injectable adhesive hydrogels for biomedical applications, with a focus on how the unique properties of these hydrogels benefit their applications in these fields. The challenges and perspectives of mussel-inspired injectable hydrogels are discussed in the last section. This review may provide new inspiration for the design of novel bioinspired injectable hydrogels and facilitate their application in various biomedical fields.

Chitosan-based mucoadhesive films loaded with curcumin for topical treatment of oral cancer

This study aimed to develop mucoadhesive chitosan-based films capable of enhancing the curcumin penetration into the oral mucosa to treat oral cancers. We developed three films containing medium molecular weight chitosan (190–310 KDa) and other excipients (polyvinyl alcohol, Poloxamer®407, and propylene glycol) that have proven to be compatible with each other and with curcumin in thermal analyses. The films were smooth, flexible, and precipitates free, with uniform weight and thickness, pH compatible with the oral mucosa, resistance to traction, and entrapped curcumin in a high proportion. They also exhibited necessary swelling and mucoadhesion for tissue adherence. Ex vivo penetration studies proved that the films significantly increased the penetration of curcumin into the oral mucosa compared to control, even when the mucosa was subjected to a condition of simulated salivation. Curcumin exhibited cytotoxic activity in vitro in the two head and neck cancer cell lines (FaDu, SCC-9) at doses close to those found in penetration studies with the films. When combined with radiotherapy, curcumin demonstrated superiority over single doses of radiotherapy at 4, 8, and 12 Gy. Therefore, the developed films may represent a promising alternative for the topical treatment of oral tumors.

Sprayable biomimetic double mask with rapid autophasing and hierarchical programming for scarless wound healing.

Current sprayable hydrogel masks lack the stepwise protection, cleansing, and nourishment of extensive wounds, leading to delayed healing with scarring. Here, we develop a sprayable biomimetic double wound mask (BDM) with rapid autophasing and hierarchical programming for scarless wound healing. The BDMs comprise hydrophobic poly (lactide-co-propylene glycol-co-lactide) dimethacrylate (PLD) as top layer and hydrophilic gelatin methacrylate (GelMA) hydrogel as bottom layer, enabling swift autophasing into bilayered structure. After photocrosslinking, BDMs rapidly solidify with strong interfacial bonding, robust tissue adhesion, and excellent joint adaptiveness. Upon implementation, the bottom GelMA layer could immediately release calcium ion for rapid hemostasis, while the top PLD layer could maintain a moist, breathable, and sterile environment. These traits synergistically suppress the inflammatory tumor necrosis factor-α pathway while coordinating the cyclic guanosine monophosphate/protein kinase G-Wnt/calcium ion signaling pathways to nourish angiogenesis. Collectively, our BDMs with self-regulated construction of bilayered structure could hierarchically program the healing progression with transformative potential for scarless wound healing.