RESUMEN

The rising prevalence of bone injuries has increased the demand for minimally invasive treatments. Microbead hydrogels, renowned for cell encapsulation, provide a versatile substrate for bone tissue regeneration. They deliver bioactive agents, support cell growth, and promote osteogenesis, aiding bone repair and regeneration. In this study, we synthesized superparamagnetic iron oxide nanoparticles (Sp) coated with a calcium phosphate layer (m-Sp), achieving a distinctive flower-like micro-cluster morphology. Subsequently, sodium alginate (SA) microbead hydrogels containing m-Sp (McSa@m-Sp) were fabricated using a dropping gelation strategy. McSa@m-Sp is magnetically targetable, enhance cross-linking, control degradation rates, and provide strong antibacterial activity. Encapsulation studies with MC3T3-E1 cells revealed enhanced viability and proliferation. These studies also indicated significantly elevated alkaline phosphatase (ALP) activity and mineralization in MC3T3-E1 cells, as confirmed by Alizarin Red S (ARS) and Von Kossa staining, along with increased collagen production within the McSa@m-Sp microbead hydrogels. Immunocytochemistry (ICC) and gene expression studies supported the osteoinductive potential of McSa@m-Sp, showing increased expression of osteogenic markers including RUNX-2, collagen-I, osteopontin, and osteocalcin. Thus, McSa@m-Sp microbead hydrogels offer a promising strategy for multifunctional scaffolds in bone tissue engineering.

Asunto(s)

Alginatos , Regeneración Ósea , Fosfatos de Calcio , Proliferación Celular , Hidrogeles , Osteogénesis , Alginatos/química , Alginatos/farmacología , Animales , Ratones , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Osteogénesis/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Regeneración Ósea/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ingeniería de Tejidos/métodos , Línea Celular , Nanopartículas Magnéticas de Óxido de Hierro/química , Antibacterianos/farmacología , Antibacterianos/química

RESUMEN

The impact of electrical stimulation has been widely investigated on the wound healing process; however, its practicality is still challenging. This study explores the effect of electrical stimulation on fibroblasts in a culture medium containing different electrically-charged polysaccharide derivatives including alginate, hyaluronate, and chitosan derivatives. For this aim, an electrical stimulation, provided by a zigzag triboelectric nanogenerator (TENG), was exerted on fibroblasts in the presence of polysaccharides' solutions. The analyses showed a significant increase in cell proliferation and an improvement in wound closure (160 % and 90 %, respectively) for the hyaluronate-containing medium by a potential of 3 V after 48 h. In the next step, a photo-crosslinkable hydrogel was prepared based on hyaluronic acid methacrylate (HAMA). Then, the cells were cultured on HAMA hydrogel and treated by an electrical stimulation. Surprisingly, the results showed a remarkable increase in cell growth (280 %) and migration (82 %) after 24 h. Attributed to the electroosmosis phenomenon and an amplified transfer of soluble growth factors, a dramatic promotion was underscored in cell activities. These findings highlight the role of electroosmosis in wound healing, where TENG-based electrical stimulation is combined with bioactive polysaccharide-based hydrogels to promote wound healing.

Asunto(s)

Alginatos , Proliferación Celular , Fibroblastos , Ácido Hialurónico , Hidrogeles , Cicatrización de Heridas , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Alginatos/química , Proliferación Celular/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fibroblastos/citología , Hidrogeles/química , Hidrogeles/farmacología , Cicatrización de Heridas/efectos de los fármacos , Estimulación Eléctrica , Polielectrolitos/química , Animales , Ratones , Quitosano/química , Movimiento Celular/efectos de los fármacos , Humanos , Células 3T3 NIH

RESUMEN

Tumor vaccines have become a promising approach for cancer treatment by triggering antigen-specific responses against tumors. However, autophagy and immunosuppressive tumor microenvironment (TME) reduce antigen exposure and immunogenicity, which limit the effect of tumor vaccines. Here, we develop fucoidan (Fuc) based chlorin e6 (Ce6)-chloroquine (CQ) self-assembly hydrogels (CCFG) as in situ vaccines. Ce6 triggers immune response in situ by photodynamic therapy (PDT) induced immunogenic cell death (ICD) effect, which is further enhanced by macrophage polarization of Fuc and autophagy inhibition of CQ. In vivo studies show that CCFG effectively enhances antigen presentation under laser irradiation, which induces a powerful in situ vaccine effect and significantly inhibits tumor metastasis and recurrence. Our study provides a novel approach for enhancing tumor immunotherapy and inhibiting tumor recurrence and metastasis.

Asunto(s)

Autofagia , Vacunas contra el Cáncer , Clorofilidas , Cloroquina , Hidrogeles , Inmunoterapia , Macrófagos , Fotoquimioterapia , Polisacáridos , Porfirinas , Animales , Polisacáridos/farmacología , Polisacáridos/química , Ratones , Vacunas contra el Cáncer/farmacología , Vacunas contra el Cáncer/inmunología , Porfirinas/química , Porfirinas/farmacología , Porfirinas/uso terapéutico , Autofagia/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Inmunoterapia/métodos , Fotoquimioterapia/métodos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Cloroquina/farmacología , Ratones Endogámicos C57BL , Microambiente Tumoral/efectos de los fármacos , Células RAW 264.7 , Línea Celular Tumoral , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/uso terapéutico , Ratones Endogámicos BALB C , Femenino

RESUMEN

Oral conditions, such as recurrent aphthous stomatitis, are chronic inflammatory disorders that significantly affect the life quality. This study aims to develop a novel buccal mucoadhesive based on methacrylate hydroxypropyl methylcellulose (M-HPMC) and methacrylate lignin (M-SLS) encapsulated with nanostructured lipid carriers (NLCs) for controlled release of alpha-pinene (α-pinene). NLCs with particle sizes of 152 ± 3 nm were prepared by using stearic acid and oleic acid as solid and liquid lipids, respectively. Following the successful synthesis of M-HPMC and M-SLS, various concentrations of α-pinene loaded NLCs (0, 18, 38, and 50 wt%) were encapsulated in M-HPMC/M-SLS hydrogel. It was demonstrated that the physiological and mechanical performances of hydrogels were changed, depending on the NLC content. Remarkably, the incorporation of 18 wt% NLC improved the compressive strength (143 ± 14 kPa) and toughness (17 ± 1 kJ/m3) of M-HPMC/M-SLS hydrogel. This nanocomposite hydrogel considerably decreased dissipated energy from 1.64 kJ/m3 to 0.99 kJ/m3, after a five-cycle compression test. The nanocomposite hydrogel exhibited controlled α-pinene release for up to 96 h which could significantly improve the antioxidant activity of M-HPMC/M-SLS matrix. Moreover, the reinforcing M-HPMC/M-SLS hydrogel with α-pinene-loaded NLCs resulted in increased adhesive strength (113.5 ± 7.5 kPa) to bovine buccal mucosa and cytocompatibility in contact with fibroblasts.

Asunto(s)

Monoterpenos Bicíclicos , Hidrogeles , Derivados de la Hipromelosa , Lignina , Nanocompuestos , Lignina/química , Monoterpenos Bicíclicos/química , Monoterpenos Bicíclicos/farmacología , Hidrogeles/química , Hidrogeles/síntesis química , Hidrogeles/farmacología , Nanocompuestos/química , Animales , Derivados de la Hipromelosa/química , Ratones , Metacrilatos/química , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/síntesis química , Antioxidantes/administración & dosificación , Fibroblastos/efectos de los fármacos

RESUMEN

Bone defects caused by trauma, infection and congenital diseases still face great challenges. Dihydromyricetin (DHM) is a kind of flavone extracted from Ampelopsis grossedentata, a traditional Chinese medicine. DHM can enhance the osteogenic differentiation of human bone marrow mesenchymal stem cells with the potential to promote bone regeneration. Hydrogel can be used as a carrier of DHM to promote bone regeneration due to its unique biochemical characteristics and three-dimensional structure. In this study, oxidized phellinus igniarius polysaccharides (OP) and L-arginine chitosan (CA) are used to develop hydrogel. The pore size and gel strength of the hydrogel can be changed by adjusting the oxidation degree of oxidized phellinus igniarius polysaccharides. The addition of DHM further reduce the pore size of the hydrogel (213 µm), increase the mechanical properties of the hydrogel, and increase the antioxidant and antibacterial activities of the hydrogel. The scavenging rate of DPPH are 72.30 ± 0.33 %, and the inhibition rate of E.coli and S.aureus are 93.12 ± 0.38 % and 94.49 ± 1.57 %, respectively. In addition, PCAD has good adhesion and biocompatibility, and its extract can effectively promote the osteogenic differentiation of MC3T3-E1 cells. Network pharmacology and molecular docking show that the promoting effect of DHM on osteogenesis may be achieved by activating the PI3K/AKT and MAPK signaling pathways. This is confirmed through in vitro cell experiments and in vivo animal experiments.

Asunto(s)

Regeneración Ósea , Quitosano , Flavonoles , Hidrogeles , Sistema de Señalización de MAP Quinasas , Osteogénesis , Fosfatidilinositol 3-Quinasas , Polisacáridos , Proteínas Proto-Oncogénicas c-akt , Quitosano/química , Quitosano/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Flavonoles/farmacología , Flavonoles/química , Ratones , Hidrogeles/química , Hidrogeles/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Polisacáridos/química , Polisacáridos/farmacología , Osteogénesis/efectos de los fármacos , Regeneración Ósea/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Arginina/química , Arginina/farmacología , Oxidación-Reducción/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Escherichia coli/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Humanos , Antioxidantes/farmacología , Antioxidantes/química , Adhesivos/química , Adhesivos/farmacología

RESUMEN

Frequent occurrence of wound infection caused by multiple-resistant bacteria (MRB) has posed a serious challenge to the current healthcare system relying on antibiotics. The development of novel antimicrobial materials with high safety and efficacy to heal wound infection is of great importance in combating this crisis. Herein, we prepared a promising antibacterial hydrogel by cross-linking ferrous ions (Fe2+) with the deprotonated carboxyl anion in sodium alginate (Na-ALG) to cure wound infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Interestingly, ferrous-modified Na-ALG (Fe-ALG) hydrogel demonstrated better properties compared to the traditional Na-ALG-based hydrogels, including injectability, self-healing, appropriate fluidity, high-water retention, potent MRSA-killing efficacy, and excellent biocompatibility. Importantly, the addition of Fe2+ enhances the antibacterial efficacy of the Na-ALG hydrogel, enabling it to effectively eliminate MRSA and accelerate the healing of antibiotic-resistant bacterial-infected wounds in a remarkably short period (10 days). This modification not only facilitates wound closure and fur generation, but also mitigates systemic inflammation, thereby effectively impeding the spread of MRSA to the lungs. Taken together, Fe-ALG hydrogel is a promising therapeutic material for treating wound infections by Staphylococcus aureus, especially by antibiotic-resistant strains like MRSA.

Asunto(s)

Alginatos , Antibacterianos , Compuestos Ferrosos , Hidrogeles , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Cicatrización de Heridas , Infección de Heridas , Alginatos/química , Alginatos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Compuestos Ferrosos/química , Compuestos Ferrosos/farmacología , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Animales , Infecciones Estafilocócicas/tratamiento farmacológico , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Ratones , Pruebas de Sensibilidad Microbiana , Masculino

RESUMEN

Non-healing skin wounds pose significant clinical challenges, with biologic products like exosomes showing promise for wound healing. Saliva and saliva-derived exosomes, known to accelerate wound repair, yet their extraction is difficult due to the complex environment of oral cavity. In this study, as a viable alternative, we established human minor salivary gland organoids (hMSG-ORG) to produce exosomes (MsOrg-Exo). In vitro, MsOrg-Exo significantly enhanced cell proliferation, migration, and angiogenesis. When incorporated into a GelMA-based controlled-release system, MsOrg-Exo demonstrated controlled release, effectively improving wound closure, collagen synthesis, angiogenesis, and cellular proliferation in a murine skin wound model. Further molecular analyses revealed that MsOrg-Exo promotes proliferation, angiogenesis and the secretion of growth factors in wound sites. Proteomic profiling showed that MsOrg-Exo's protein composition is similar to human saliva and enriched in proteins essential for wound repair, immune modulation, and coagulation. Additionally, MsOrg-Exo was found to modulate macrophage polarization, inducing a shift towards M1 and M2 phenotypes in vitro within 48 h and predominantly towards the M2 phenotype in vivo after 15 days. In conclusion, our study successfully extracted MsOrg-Exo from hMSG-ORGs, confirmed the effectiveness of the controlled-release system combining MsOrg-Exo with GelMA in promoting skin wound healing, and explored the potential role of macrophages in this action.

Asunto(s)

Exosomas , Macrófagos , Organoides , Cicatrización de Heridas , Exosomas/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Humanos , Animales , Macrófagos/metabolismo , Organoides/metabolismo , Ratones , Proliferación Celular , Hidrogeles/química , Hidrogeles/farmacología , Glándulas Salivales/metabolismo , Saliva/química , Saliva/metabolismo , Movimiento Celular , Piel/metabolismo , Piel/lesiones

RESUMEN

Breast cancer is a malignant tumor that poses a significant threat to women's health and single therapy fails to play a good oncological therapeutic effect. Synergistic treatment with multiple strategies may make up for the deficiencies and has gained widespread attention. In this study, sulfhydryl-modified hyaluronic acid (HA-SH) was covalently crosslinked with polydopamine (PDA) via a Michael addition reaction to develop an injectable hydrogel, in which PDA can be used not only as a matrix but also as a photothermal agent. After HSA and paclitaxel were spontaneously organized into nanoparticles via hydrophobic interaction, hyaluronic acid with low molecular weight was covalently linked to HSA, thus conferring effectively delivery. This photothermal injectable hydrogel incorporates PTX@HSA-HA nanoparticles, thereby initiating a thermochemotherapeutic response to target malignancy. Our results demonstrated that this injectable hydrogel possesses consistent drug delivery capability in a murine breast cancer model, collaborating with photothermal therapy to effectively suppress tumor growth, represented by low expression of Ki-67 and increasing apoptosis. Photothermal therapy (PTT) can effectively stimulate immune response by increasing IL-6 and TNF-α. Notably, the treatment did not elicit any indications of toxicity. This injectable hydrogel holds significant promise as a multifaceted therapeutic agent that integrates photothermal and chemotherapeutic modalities.

Asunto(s)

Neoplasias de la Mama , Ácido Hialurónico , Hidrogeles , Paclitaxel , Terapia Fototérmica , Animales , Ácido Hialurónico/química , Hidrogeles/química , Hidrogeles/farmacología , Femenino , Neoplasias de la Mama/terapia , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Ratones , Terapia Fototérmica/métodos , Paclitaxel/farmacología , Paclitaxel/química , Paclitaxel/administración & dosificación , Humanos , Indoles/química , Indoles/farmacología , Ratones Endogámicos BALB C , Polímeros/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Nanopartículas/química , Portadores de Fármacos/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Fototerapia/métodos

RESUMEN

Burns are the fourth most common type of civilian trauma worldwide, and the management of severe irregular scald wounds remains a significant challenge. Herein, crocin-1 laden hydroxybutyl chitosan (CRO-HBC) thermosensitive hydrogel with smart anti-inflammatory performance was developed for accelerating full-thickness burn healing. The injectable and shape adaptability of the CRO-HBC gel make it a promising candidate for effectively filling scald wounds with irregular shapes, while simultaneously providing protection against external pathogens. The CRO-HBC gel network formed by hydrophobic interactions exhibited an initial burst release of crocin-1, followed by a gradual and sustained release over time. The excessive release of ROS and pro-inflammatory cytokines should be effectively regulated in the early stage of wound healing. The controlled release of crocin-1 from the CRO-HBC gel adequately addresses this requirement for wound healing. The CRO-HBC hydrogel also exhibited an excellent biocompatibility, an appropriate biodegradability, keratinocyte migration facilitation properties, and a reactive oxygen species scavenging capability. The composite CRO-HBC hydrogel intelligently mitigated inflammatory responses, promoted angiogenesis, and exhibited a commendable efficacy for tissue regeneration in a full-thickness scalding model. Overall, this innovative temperature-sensitive CRO-HBC injectable hydrogel dressing with smart anti-inflammatory performance has enormous potential for managing severe scald wounds.

Asunto(s)

Antiinflamatorios , Quemaduras , Carotenoides , Quitosano , Hidrogeles , Cicatrización de Heridas , Quitosano/química , Quitosano/farmacología , Quitosano/análogos & derivados , Quemaduras/tratamiento farmacológico , Cicatrización de Heridas/efectos de los fármacos , Carotenoides/farmacología , Carotenoides/química , Carotenoides/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Hidrogeles/química , Hidrogeles/farmacología , Animales , Humanos , Ratones , Temperatura , Masculino , Especies Reactivas de Oxígeno/metabolismo , Ratas , Ratas Sprague-Dawley

RESUMEN

Bleeding and bacterial infection are common problems associated with wound treatment, while effective blood clotting and vessel regeneration promotion are the primary considerations to design the wound dressing materials. This research presents a chitosan-based hydrogel with grafted quaternary ammonium and polyphosphate (QCSP hydrogel) as the antibacterial hemostatic dressing to achieve burn wound treatment. The tissue adhesion of the hydrogel sealed the blood flow and the polyphosphate grafted to the chitosan promoted the activation of coagulation factor V to enhance the hemostasis. At the same time, the grafted quaternary ammonium enhanced the antibacterial ability of the biodegradable hydrogel wound dressing. In addition, the polydopamine as a photothermal agent was composited into the hydrogel to enhance the antibacterial and reactive oxygen scavenging performance. The in vivo hemostasis experiment proved the polyphosphate enhanced the coagulation property. Moreover, this photothermal property of the composite hydrogel enhanced the burn wound repairing rate combined with the NIR stimulus. As a result, this hydrogel could have potential application in clinic as dressing material for hemostasis and infection prone would repairing.

Asunto(s)

Antibacterianos , Quemaduras , Quitosano , Hemostasis , Hidrogeles , Indoles , Polímeros , Cicatrización de Heridas , Quitosano/química , Quitosano/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Quemaduras/tratamiento farmacológico , Quemaduras/terapia , Polímeros/química , Polímeros/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Animales , Indoles/química , Indoles/farmacología , Cicatrización de Heridas/efectos de los fármacos , Hemostasis/efectos de los fármacos , Ratones , Hemostáticos/química , Hemostáticos/farmacología , Vendajes , Masculino , Ratas , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Ratas Sprague-Dawley , Pruebas de Sensibilidad Microbiana , Terapia Fototérmica/métodos

RESUMEN

Hydrogels are highly sought-after absorbent materials for absorbent pads; however, it is still challenging to achieve a satisfactory balance between mechanical performance, water absorption capacity, and active functionalities. In this work, we presented double-network hydrogels synthesized through acrylic acid (AA) polymerization in the presence of quaternized cellulose nanofibrils (QCNF) and Fe3+. Spectroscopic and microscopic analyses revealed that the combined QCNF and Fe3+ facilitated the formation of double-network hydrogels with combined chemical and physical crosslinking. The synergistic effect of QCNF and Fe3+ resulted in impressive mechanical properties, including tensile strength of 1.98 MPa, fracture elongation of 838.8 %, toughness of 7.47 MJ m-3, and elastic modulus of 0.35 MPa. In comparison to the single-network PAA hydrogel, the PAA/QCNF/Fe3+ (PQFe) hydrogels showed higher and relatively stable swelling ratios under varying pH levels and saline conditions. The PQFe hydrogels exhibited notable antioxidant activity, as evidenced by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and demonstrated effective antibacterial activity against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). These hydrogels show promising potential as an absorbent interlayer in absorbent pads for active food packaging.

Asunto(s)

Resinas Acrílicas , Antibacterianos , Celulosa , Escherichia coli , Hidrogeles , Hierro , Nanofibras , Staphylococcus aureus , Resistencia a la Tracción , Hidrogeles/química , Hidrogeles/farmacología , Celulosa/química , Staphylococcus aureus/efectos de los fármacos , Resinas Acrílicas/química , Escherichia coli/efectos de los fármacos , Nanofibras/química , Hierro/química , Antibacterianos/farmacología , Antibacterianos/química , Antioxidantes/química , Antioxidantes/farmacología , Módulo de Elasticidad

RESUMEN

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.

Asunto(s)

Quitosano , Gelatina , Hidrogeles , Ensayo de Materiales , Cicatrización de Heridas , Hidrogeles/química , Hidrogeles/farmacología , Cicatrización de Heridas/efectos de los fármacos , Quitosano/química , Quitosano/farmacología , Gelatina/química , Animales , Humanos , Cerámica/química , Cerámica/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Periostio

RESUMEN

Background: The formation of adhesion after tendon injury represents a major obstacle to tendon repair, and currently there is no effective anti-adhesion method in clinical practice. Oxidative stress, inflammation, and fibrosis can occur in tendon injury and these factors can lead to tendon adhesion. Antioxidant carbon dots and ursolic acid (UA) both possess antioxidant and anti-inflammatory properties. In this experiment, we have for the first time created RCDs/UA@Lipo-HAMA using red fluorescent carbon dots and UA co-encapsulated liposomes composite hyaluronic acid methacryloyl hydrogel. We found that RCDs/UA@Lipo-HAMA could better attenuate adhesion formation and enhance tendon healing in tendon injury. Materials and Methods: RCDs/UA@Lipo-HAMA were prepared and characterized. In vitro experiments on cellular oxidative stress and fibrosis were performed. Reactive oxygen species (ROS), and immunofluorescent staining of collagens type I (COL I), collagens type III (COL III), and α-smooth muscle actin (α-SMA) were used to evaluate anti-oxidative and anti-fibrotic abilities. In vivo models of Achilles tendon injury repair (ATI) and flexor digitorum profundus tendon injury repair (FDPI) were established. The major organs and blood biochemical indicators of rats were tested to determine the toxicity of RCDs/UA@Lipo-HAMA. Biomechanical testing, motor function analysis, immunofluorescence, and immunohistochemical staining were performed to assess the tendon adhesion and repair after tendon injury. Results: In vitro, the RCDs/UA@Lipo group scavenged excessive ROS, stabilized the mitochondrial membrane potential (ΔΨm), and reduced the expression of COL I, COL III, and α-SMA. In vivo, assessment results showed that the RCDs/UA@Lipo-HAMA group improved collagen arrangement and biomechanical properties, reduced tendon adhesion, and promoted motor function after tendon injury. Additionally, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the RCDs/UA@Lipo-HAMA group increased; the levels of cluster of differentiation 68 (CD68), inducible Nitric Oxide Synthase (iNOS), COL III, α-SMA, Vimentin, and matrix metallopeptidase 2 (MMP2) decreased. Conclusion: In this study, the RCDs/UA@Lipo-HAMA alleviated tendon adhesion formation and enhanced tendon healing by attenuating oxidative stress, inflammation, and fibrosis. This study provided a novel therapeutic approach for the clinical treatment of tendon injury.

Asunto(s)

Antioxidantes , Carbono , Hidrogeles , Liposomas , Ratas Sprague-Dawley , Traumatismos de los Tendones , Triterpenos , Ácido Ursólico , Animales , Triterpenos/farmacología , Triterpenos/química , Antioxidantes/farmacología , Antioxidantes/química , Liposomas/química , Traumatismos de los Tendones/tratamiento farmacológico , Adherencias Tisulares/tratamiento farmacológico , Carbono/química , Carbono/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Ratas , Estrés Oxidativo/efectos de los fármacos , Masculino , Cicatrización de Heridas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Puntos Cuánticos/química , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Tendón Calcáneo/efectos de los fármacos , Tendón Calcáneo/lesiones

RESUMEN

Introduction: Graphene oxide (GO) nanoparticles have emerged as a compelling photothermal agent (PHTA) in the realm of photothermal antibacterial therapy, owing to their cost-effectiveness, facile synthesis, and remarkable photostability. Nevertheless, the therapeutic efficacy of GO nanoparticles is commonly hindered by their inherent drawback of low photothermal conversion efficiency (PCE). Methods: Herein, we engineer the Ag/GO-GelMA platform by growing the Ag on the surface of GO and encapsulating the Ag/GO nanoparticles into the GelMA hydrogels. Results: The resulting Ag/GO-GelMA platform demonstrates a significantly enhanced PCE (47.6%), surpassing that of pure GO (11.8%) by more than fourfold. As expected, the Ag/GO-GelMA platform, which was designed to integrate the benefits of Ag/GO nanoparticles (high PCE) and hydrogel (slowly releasing Ag+ to exert an inherent antibacterial effect), has been shown to exhibit exceptional antibacterial efficacy. Furthermore, transcriptome analyses demonstrated that the Ag/GO-GelMA platform could significantly down-regulate pathways linked to inflammation (the MAPK and PI3K-Akt pathways) and had the ability to promote cell migration. Discussion: Taken together, this study presents the design of a potent photothermal antibacterial platform (Ag/GO-GelMA) aimed at enhancing the healing of infectious wounds. The platform utilizes a handy method to enhance the PCE of GO, thereby making notable progress in the utilization of GO nano-PHTAs.

Asunto(s)

Antibacterianos , Grafito , Hidrogeles , Plata , Cicatrización de Heridas , Grafito/química , Grafito/farmacología , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Plata/química , Plata/farmacología , Hidrogeles/química , Hidrogeles/farmacología , Animales , Humanos , Ratones , Terapia Fototérmica/métodos , Nanopartículas/química , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Movimiento Celular/efectos de los fármacos

RESUMEN

Preserving pulp viability and promoting pulp regeneration in pulpitis have attracted widespread attention. Restricted by the oxidative stress microenvironment of dental pulpitis, excessive reactive oxygen and nitrogen species (RONS) trigger uncontrolled inflammation and exacerbate pulp tissue destruction. However, modulating redox homeostasis in inflamed pulp tissue to promote pulp regeneration remains a great challenge. Herein, this work proposes an effective antioxidative system (C-NZ/GelMA) consisting of carbon dot nanozymes (C-NZ) with gelatin methacryloyl (GelMA) to modulate the pulpitis microenvironment for dental pulp regeneration by utilizing the antioxidant properties of C-NZ and the mechanical support of an injectable GelMA hydrogel. This system effectively scavenges RONS to normalize intracellular redox homeostasis, relieving oxidative stress damage. Impressively, it can dramatically enhance the polarization of regenerative M2 macrophages. This study revealed that the C-NZ/GelMA hydrogel promoted pulp regeneration and dentin repair through its outstanding antioxidant, antiapoptotic, and anti-inflammatory effects, suggesting that the C-NZ/GelMA hydrogel is highly valuable for pulpitis treatment.

Asunto(s)

Antioxidantes , Carbono , Pulpa Dental , Gelatina , Hidrogeles , Estrés Oxidativo , Pulpitis , Regeneración , Estrés Oxidativo/efectos de los fármacos , Pulpa Dental/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Animales , Carbono/química , Carbono/farmacología , Pulpitis/tratamiento farmacológico , Regeneración/efectos de los fármacos , Ratones , Antioxidantes/farmacología , Antioxidantes/química , Gelatina/química , Gelatina/farmacología , Especies Reactivas de Oxígeno/metabolismo , Humanos , Masculino , Ratas , Células RAW 264.7 , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Metacrilatos

RESUMEN

Graphitic carbon nitride (g-C3N4, CN) has emerged as a promising photocatalytic material due to its inherent stability, antibacterial properties, and eco-friendliness. However, its tendency to aggregate and limited dispersion hinder its efficacy in practical antibacterial applications. To address these limitations, this study focuses on developing a composite hydrogel coating, in which sodium alginate (SA) molecules interact electrostatically and through hydrogen bonding to anchor CN, thereby significantly improving its dispersion. The optimal CN loading of 35% results in a hydrogel with a tensile strength of 120 MPa and an antibacterial rate of 99.87% within 6 h. The enhanced mechanical properties are attributed to hydrogen bonding between the -NH2 groups of CN and the -OH groups of SA, while the -OH groups of SA facilitate the attraction of photogenerated holes from CN, promoting carrier transfer and separation, thereby strengthening the antibacterial action. Moreover, the hydrogel coating exhibits excellent antibacterial and corrosion resistance capabilities against Pseudomonas aeruginosa on 316L stainless steel (316L SS), laying the foundation for advanced antimicrobial and anticorrosion hydrogel systems.

Asunto(s)

Alginatos , Antibacterianos , Grafito , Hidrogeles , Pseudomonas aeruginosa , Alginatos/química , Antibacterianos/farmacología , Antibacterianos/química , Pseudomonas aeruginosa/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Grafito/química , Grafito/farmacología , Compuestos de Nitrógeno/química , Compuestos de Nitrógeno/farmacología , Corrosión , Pruebas de Sensibilidad Microbiana , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Enlace de Hidrógeno , Acero Inoxidable/química

RESUMEN

The use of hydrogels to mimic natural cartilage implantation can effectively solve the current problems of insufficient cartilage donors and low rate of injury healing. In particular, injectable hydrogels are less invasive in clinical applications and better able to fill uneven injury surfaces. Here, we prepared NorCS and CS-SH by modifying chitosan with 5-norbornene-2-carboxylic acid and N-Acetyl-L-cysteine, respectively. Dual-network hydrogels were prepared by using UV-triggered thiol-ene click reaction between NorCS and CS-SH and the metal coordination between SA and Ca2+. The prepared hydrogels can be cross-linked quickly and exhibit excellent degradability, self-healing and injectable properties. At the same time, the hydrogel also showed good cytocompatibility and could significantly restore the motor function of mice. This study provides an effective strategy for preparing injectable hydrogels capable of rapid cross-linking.

Asunto(s)

Quitosano , Química Clic , Hidrogeles , Compuestos de Sulfhidrilo , Rayos Ultravioleta , Hidrogeles/química , Hidrogeles/farmacología , Animales , Ratones , Compuestos de Sulfhidrilo/química , Quitosano/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología

RESUMEN

The antimicrobial and pro-healing properties remain critical clinical objectives for skin wound management. However, the escalating problem of antibiotic overuse and the corresponding rise in bacterial resistance necessitates an urgent shift towards an antibiotic-free approach to antibacterial treatment. The quest for antimicrobial efficacy while accelerating wound healing without antibiotic treatment have emerged as innovative strategies in skin wound treatment. Here, a dual-function hydrogel with antimicrobial and enhanced tissue-healing properties was developed by utilizing cyclodextrin, ferrocene, polyethyleneimine (PEI), and Bletilla striata polysaccharide (BSP), through multiple non-covalent interactions, which can intelligently release BSP by recognizing the wound inflammatory microenvironment through the cyclodextrin-ferrocene unit. Moreover, the porosity (65 % - 85 %), Young's modulus (400 KPa - 140 KPa), and DPPH scavenge rate (18 % - 40 %) of the hydrogel are modulated by varying the BSP content. The hydrogel exhibits outstanding antibacterial properties (98.3 % reduction of Escherichia coli observed after exposure to HTFC@BSP-20 for 24 h) and favorable biocompatibility. Furthermore, in a rat full-thickness skin wound model, the dual-function hydrogel significantly accelerates wound healing, increased CD31 expression promotes vascular regeneration, reduced TNF-α express and inhibited the inflammation. This multifunctional ROS responsive hydrogel provides a new perspective for antibiotics-free treatment of skin injuries.

Asunto(s)

Antibacterianos , Vendajes , Hidrogeles , Polisacáridos , Especies Reactivas de Oxígeno , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Animales , Polisacáridos/química , Polisacáridos/farmacología , Ratas , Especies Reactivas de Oxígeno/metabolismo , Antibacterianos/farmacología , Antibacterianos/química , Inflamación/tratamiento farmacológico , Orchidaceae/química , Escherichia coli/efectos de los fármacos , Humanos , Piel/efectos de los fármacos , Ciclodextrinas/química , Ciclodextrinas/farmacología , Ratas Sprague-Dawley , Masculino , Compuestos Ferrosos/química , Compuestos Ferrosos/farmacología , Metalocenos

RESUMEN

Rapid hemostasis, potent antimicrobial activity, and efficient wound management are critical factors in enhancing the survival of trauma patients. Chitosan, as a green and sustainable biomaterial with low cost, degradability and biocompatibility, is widely used in the biomedical field. However, chitosan dissolves in an acidic environment, which is not conducive to wound healing. In this study, chitosan was chemically modified to address this limitation. A mussel-inspired hydrogel composed of caffeic acid-grafted chitosan, gallic acid-grafted chitosan, and oxidized microcrystalline cellulose (CHI-C/CSG/OMCC) was designed. This hydrogel exhibits blood-responsive gelation behavior and offers a synergistic combination of tissue adhesion, antimicrobial properties, and tissue repair capabilities. The carboxyl, hydroxyl, phenolic hydroxyl and aldehyde groups within the hydrogel system endowed the hydrogel with excellent adhesion properties (53.1 kPa adhesion strength to porcine skin-adherent tissues), biocompatibility, and excellent antimicrobial properties. Surprisingly, this hydrogel not only achieved rapid and effective hemostasis, but also effectively promoted wound healing in a mouse skin injury model. In addition, its remarkable efficacy in stopping bleeding within approximately 2 min without rebleeding was demonstrated in a porcine model of acute gastrointestinal hemorrhage in the esophagus, stomach, and intestines. This blood-responsive ternary hydrogel offers a promising alternative to wound management materials due to its excellent overall performance and superior efficacy in all phases of wound healing.

Asunto(s)

Antibacterianos , Bivalvos , Hemostasis , Hidrogeles , Cicatrización de Heridas , Hidrogeles/química , Hidrogeles/farmacología , Animales , Cicatrización de Heridas/efectos de los fármacos , Hemostasis/efectos de los fármacos , Ratones , Bivalvos/química , Antibacterianos/farmacología , Antibacterianos/química , Quitosano/química , Quitosano/farmacología , Porcinos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Celulosa/química , Celulosa/farmacología , Ácidos Cafeicos/farmacología , Ácidos Cafeicos/química

RESUMEN

Traumatic spinal cord injury (tSCI) has complex pathophysiological events that begin after the initial trauma. One such event is fibroglial scar formation by fibroblasts and reactive astrocytes. A strong inhibition of axonal growth is caused by the activated astroglial cells as a component of fibroglial scarring through the production of inhibitory molecules, such as chondroitin sulfate proteoglycans or myelin-associated proteins. Here, we used neural precursor cells (aldynoglia) as promoters of axonal growth and a fibrin hydrogel gelled under alkaline conditions to support and guide neuronal cell growth, respectively. We added Tol-51 sulfoglycolipid as a synthetic inhibitor of astrocyte and microglia in order to test its effect on the axonal growth-promoting function of aldynoglia precursor cells. We obtained an increase in GFAP expression corresponding to the expected glial phenotype for aldynoglia cells cultured in alkaline fibrin. In co-cultures of dorsal root ganglia (DRG) and aldynoglia, the axonal growth promotion of DRG neurons by aldynoglia was not affected. We observed that the neural precursor cells first clustered together and then formed niches from which aldynoglia cells grew and connected to groups of adjacent cells. We conclude that the combination of alkaline fibrin with synthetic sulfoglycolipid Tol-51 increased cell adhesion, cell migration, fasciculation, and axonal growth capacity, promoted by aldynoglia cells. There was no negative effect on the behavior of aldynoglia cells after the addition of sulfoglycolipid Tol-51, suggesting that a combination of aldynoglia plus alkaline fibrin and Tol-51 compound could be useful as a therapeutic strategy for tSCI repair.

Asunto(s)

Axones , Fibrina , Ganglios Espinales , Animales , Ganglios Espinales/efectos de los fármacos , Ganglios Espinales/metabolismo , Ganglios Espinales/citología , Axones/metabolismo , Axones/efectos de los fármacos , Fibrina/metabolismo , Hidrogeles/química , Hidrogeles/farmacología , Ratas , Glucolípidos/farmacología , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/metabolismo , Células-Madre Neurales/citología , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Células Cultivadas , Técnicas de Cocultivo , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/patología , Neuroglía/efectos de los fármacos , Neuroglía/metabolismo , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Médula Espinal/metabolismo , Médula Espinal/efectos de los fármacos , Médula Espinal/citología , Movimiento Celular/efectos de los fármacos