RESUMEN
The healing of chronic diabetic wounds remains a formidable challenge in modern times. In this study, a novel traditional Chinese medicine microneedle patch was designed based on the physiological characteristics of wounds, with properties including hemostasis, anti-inflammatory, antioxidant, antimicrobial, and induction of angiogenesis. Initially, white peony polysaccharide (BSP) with hemostatic properties and carboxymethyl chitosan (CMCS) with antimicrobial capabilities were used as materials for microneedle fabrication. To endow it with antimicrobial, procoagulant, and adhesive properties. Among them, loaded with ROS-sensitive nanoparticles of Astragalus polysaccharides (APS) based on effective components baicalein (Bai) and berberine (Ber) from Scutellaria baicalensis (SB) and Coptis chinensis (CC) drugs (APB@Ber). Together, they are constructed into multifunctional traditional Chinese medicine composite microneedles (C/B@APB@Ber). Bai and Ber synergistically exert anti-inflammatory and antimicrobial effects. Microneedle patches loaded with BSP and APS exhibited significant effects on cell proliferation and angiogenesis induction. The combination of composite polysaccharides enabled the microneedles to adhere stably to wounds and provide sufficient strength to penetrate the biofilm and induce dispersion. The combination of composite polysaccharides enabled the microneedles to adhere stably to wounds and provide sufficient strength to penetrate the biofilm and induce dispersion. Therefore, traditional Chinese medicine multifunctional microneedle patches offer potential medical value in promoting the healing of diabetic wounds.
Asunto(s)
Astragalus propinquus , FN-kappa B , Nanopartículas , Polisacáridos , Especies Reactivas de Oxígeno , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/administración & dosificación , Astragalus propinquus/química , Ratones , Nanopartículas/química , Especies Reactivas de Oxígeno/metabolismo , FN-kappa B/metabolismo , Células RAW 264.7 , Agujas , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/administración & dosificación , Quitosano/química , Quitosano/farmacología , Proliferación Celular/efectos de los fármacosRESUMEN
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/métodosRESUMEN
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 , PeriostioRESUMEN
Thermal burns are the most common type of burn injuries. Medical treatment for burns is crucial, especially for third-degree burns and when a significant surface area of the body is affected. One of the most pressing issues in modern medicine is the search for new effective means to accelerate the healing of burn wounds. Oxygen radicals play a significant role in maintaining homeostasis, forming the body's resistance to infection, and ensuring the regeneration of organs and tissues. In this study, a superoxide (O2-)-producing enzyme (SPE) from raspberries was applied (topically to the skin, injected under the wound surface, with solution concentrations of 12.75% and 5%) after a third-degree thermal burn to determine its reparative effects on the skin. To assess the condition of the animals that had suffered burn injuries and the healing process, blood parameters were analyzed, and cytogenetic indices of bone marrow from the femur of the animals were studied: mitotic index, number of polyploid cells, and chromosomal aberrations. When analyzing hematological, cytogenetic, and histological parameters, significant differences were found between the «clean burn¼ groups and the groups in which SPE was used in different concentrations and methods of application. The use of SPE in both concentrations contributed to a reduction in the area of burn wounds compared to a «clean burn¼. The survival rate of animals for 30 days (before the end of the experiment) was 100% when using a 12.75% SPE solution and 50% when using a 5% SPE solution. The use of SPE led to significant differences in hematological parameters from the «clean burn¼ group throughout the entire duration of the experiment, showing a tendency to normalize the parameters. Under the influence of the 12.75% SPE solution, there was a tendency toward normalization of the mitotic index, along with a significant reduction in the percentage of polyploid cells and chromosomal aberrations, which may indicate its beneficial effects. This study found that a 12.75% SPE solution derived from raspberries was more effective and had healing properties on third-degree thermal burns, promoting rapid healing of the burn wound.
Asunto(s)
Quemaduras , Rubus , Superóxidos , Cicatrización de Heridas , Quemaduras/patología , Quemaduras/tratamiento farmacológico , Animales , Ratas , Rubus/química , Cicatrización de Heridas/efectos de los fármacos , Superóxidos/metabolismo , Masculino , Aberraciones Cromosómicas/efectos de los fármacos , Ratas Wistar , Piel/efectos de los fármacos , Piel/patología , Piel/lesiones , Índice MitóticoRESUMEN
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/lesionesRESUMEN
Konjac glucomannan (KGM) as an emerging natural polymer has attracted increasing interests owing to its film-forming properties, excellent gelation, non-toxic characteristics, strong adhesion, good biocompatibility, and easy biodegradability. Benefiting from these superior performances, KGM has been widely applied in the construction of multiple composite materials to further improve their intrinsic performances (e.g., mechanical strength and properties). Up to now, KGM-based composite materials have obtained widespread applications in diverse fields, especially in the field of biomedical. Therefore, a timely review of relevant research progresses is important for promoting the development of KGM-based composite materials. Innovatively, firstly, this review briefly introduced the structure properties and functions of KGMs based on the unique perspective of the biomedical field. Then, the latest advances on the preparation and properties of KGM-based composite materials (i.e., gels, microspheres, films, nanofibers, nanoparticles, etc.) were comprehensively summarized. Finally, the promising applications of KGM-based composite materials in the field of biomedical are comprehensively summarized and discussed, involving drug delivery, wound healing, tissue engineering, antibacterial, tumor treatment, etc. Impressively, the remaining challenges and opportunities in this promising field were put forward. This review can provide a reference for guiding and promoting the design and biomedical applications of KGM-based composites.
Asunto(s)
Materiales Biocompatibles , Mananos , Ingeniería de Tejidos , Mananos/química , Humanos , Materiales Biocompatibles/química , Ingeniería de Tejidos/métodos , Animales , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/química , Antibacterianos/farmacología , Sistemas de Liberación de MedicamentosRESUMEN
An ideal adhesive hydrogel must possess high adhesion to the native tissue, biocompatibility, eligible biodegradability, and good mechanical compliance with the substrate tissues. We constructed an interpenetrating double-network hydrogel containing polysaccharides (alginate and dextran) and nanosized spherical dendrimer by both physical and chemical crosslinking, thus endowing the hydrogel with a broad range of mechanical properties, adhesive properties, and biological functions. The double-network hydrogel has moderate pore sizes and swelling properties. The chelation of calcium ions significantly enhances the tensile and compressive properties. The incorporation of dendrimer improves both the mechanical and adhesive properties. This multicomponent interpenetrating network hydrogel has excellent biocompatibility, tunable mechanical and adhesive properties, and satisfied multi-functions to meet the complex requirements of wound healing and tissue engineering. The hydrogel exhibits promising corneal adhesion capabilities in vitro, potentially supplanting the need for sutures in corneal stromal surgery and mitigating the risks associated with donor corneal damage and graft rejection during corneal transplantation. This novel polysaccharide and dendrimer hydrogel also shows good results in sutureless keratoplasty, with high efficiency and reliability. Based on the clinical requirements for tissue bonding and wound closure, the hydrogel provides insight into solving the mechanical properties and adhesive strength of tissue adhesives.
Asunto(s)
Alginatos , Dendrímeros , Dextranos , Hidrogeles , Adhesivos Tisulares , Alginatos/química , Hidrogeles/química , Dextranos/química , Dendrímeros/química , Adhesivos Tisulares/química , Animales , Trasplante de Córnea/métodos , Humanos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Resistencia a la Tracción , Conejos , Córnea/cirugía , Cicatrización de Heridas/efectos de los fármacos , Reactivos de Enlaces Cruzados/químicaRESUMEN
Rapid regeneration of the injured tissue or organs is necessary to achieve the usual functionalities of the damaged parts. However, bacterial infections delay the regeneration process, a severe challenge in the personalized healthcare sector. To overcome these challenges, 3D-printable multifunctional hydrogels of Zn/tannic acid-reinforced glycol functionalized chitosan for rapid wound healing were developed. Polyphenol strengthened intermolecular connections, while glutaraldehyde stabilized 3D-printed structures. The hydrogel exhibited enhanced viscoelasticity (G'; 1.96 × 104 Pa) and adhesiveness (210 kPa). The dual-crosslinked scaffolds showed remarkable antibacterial activity against Bacillus subtilis (â¼81 %) and Escherichia coli (92.75 %). The hydrogels showed no adverse effects on human dermal fibroblasts (HDFs) and macrophages (RAW 264.7), indicating their superior biocompatibility. The Zn/TA-reinforced hydrogels accelerate M2 polarization of macrophages through the activation of anti-inflammatory transcription factors (Arg-1, VEGF, CD163, and IL-10), suggesting better immunomodulatory effects, which is favorable for rapid wound regeneration. Higher collagen deposition and rapid re-epithelialization occurred in scaffold-treated rat groups vis-à-vis controls, demonstrating superior wound healing. Taken together, the developed multifunctional hydrogels have great potential for rapidly regenerating bacteria-infected wounds in the personalized healthcare sector.
Asunto(s)
Antibacterianos , Biopelículas , Quitosano , Escherichia coli , Hidrogeles , Impresión Tridimensional , Cicatrización de Heridas , Quitosano/química , Quitosano/farmacología , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología , Ratones , Animales , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Biopelículas/efectos de los fármacos , Células RAW 264.7 , Escherichia coli/efectos de los fármacos , Zinc/química , Zinc/farmacología , Ratas , Bacillus subtilis/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Masculino , Macrófagos/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Reactivos de Enlaces Cruzados/química , Ratas Sprague-DawleyRESUMEN
Failure rate after chronic rotator cuff repair is considerably high. Moreover, diabetes mellitus is known as a compromising factor of rotator cuff tear. The effect of Polydeoxyribonucleotide (PDRN) and polynucleotide (PN) on tendon healing and fatty infiltration is unclear as tissue regeneration activator in diabetic state. Therefore, a diabetic rat model with chronic rotator cuff tear was made for mechanical, histologic and blood tests. In the animal study using a diabetic rat cuff repair model, the administration of PDRN and PN increased the load to failure of repaired cuffs and improved tendon healing and decreased fatty infiltration. Also, the plasma levels of vascular endothelial growth factor and fibroblast growth factor were elevated in PDRN and PN administrated groups. We concluded that PDRN and PN appear to boost tendon recovery and reduce the presence of fatty infiltration following cuff repair in diabetic state. Also, PN showed a later onset and a longer duration than PDRN associated with the mean plasma growth factors.
Asunto(s)
Diabetes Mellitus Experimental , Polidesoxirribonucleótidos , Polinucleótidos , Lesiones del Manguito de los Rotadores , Cicatrización de Heridas , Animales , Polidesoxirribonucleótidos/farmacología , Polidesoxirribonucleótidos/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Ratas , Cicatrización de Heridas/efectos de los fármacos , Lesiones del Manguito de los Rotadores/tratamiento farmacológico , Lesiones del Manguito de los Rotadores/patología , Lesiones del Manguito de los Rotadores/metabolismo , Masculino , Polinucleótidos/farmacología , Manguito de los Rotadores/patología , Manguito de los Rotadores/efectos de los fármacos , Modelos Animales de Enfermedad , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/sangre , Ratas Sprague-Dawley , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Tejido Adiposo/patologíaRESUMEN
Wounds are most commonly caused by accidents, surgery and burns, and can be internal or external. Naturally, the wound healing process can take a long time and lead to scarring. In this study we present a technique to shorten wound healing time and prevent or mitigate scarring using D-mannose that is applied directly on the wound. The results showed that the healing time is almost halved compared to treatment with povidone-iodine solution which is an antiseptic widely used in surgery. D-Mannose is neither an antisepsis nor an antibiotic. We propose a posssible mechanism by which D-mannose binds to D-mannose binding lectin and immediately activates the innate immune system that ultimately phagocytizes pathogens and clears the wound of degraded cells and materials, which reduces inflammation and implicitly wound healing time. D-Mannose also intervenes in the coagulation process by binding to fibrinogen, generating a finer and denser fibrin, which visibly reduces collagen scars. Our findings show that applying D-mannose directly on the wound as a powder shortens wound healing time and visibly attenuates scarring. Apart from the unaesthetic appearance, these scars can also cause a certain tissue dysfunction, regardless of the affected organ.
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Cicatriz , Lectina de Unión a Manosa , Manosa , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Cicatriz/patología , Cicatriz/prevención & control , Lectina de Unión a Manosa/metabolismo , Animales , Humanos , Masculino , Piel/patología , Piel/efectos de los fármacos , Piel/metabolismo , Femenino , Inmunidad Innata/efectos de los fármacosRESUMEN
BACKGROUND: Boswellic acids (BAs) showed promising effects in cancer treatment, immune response regulation, and anti-inflammatory therapy. We aimed to assess the roles of alpha-BA (α-BA) in treating acute wound healing. METHODS: In vivo wound-healing models were established to evaluate the therapeutic effects of α-BA. Cell assays were conducted to assess the impact of α-BA on cellular biological functions. Western blot analysis was employed to validate the potential mechanisms of action of α-BA. RESULTS: Animal models indicated that wound healing was notably accelerated in the α-BA group compared to the control group (P < 0.01). Hematoxylin and eosin (HE) staining and enzyme-linked immunosorbent assay (ELISA) assay preliminarily suggested that α-BA may accelerate wound healing by inhibiting excessive inflammatory reactions and increasing the protein levels of growth factors. Cell function experiments demonstrated that α-BA suppressed the proliferation and migration ability of human hypertrophic scar fibroblasts (HSFBs), thereby favoring wound healing. Additionally, α-BA exerted a significant impact on cell cycle progression. Mechanistically, the protein levels of key genes in nuclear factor kappa beta (NF-κB) signaling pathway, including cyclin D1, p65, IκBα, and p-IκBα, were downregulated by α-BA. CONCLUSIONS: α-BA demonstrated the ability to counteract the abnormal proliferation of skin scar tissues, consequently expediting wound healing. These findings suggest its potential for development as a new agent for treating acute wound healing.
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Proliferación Celular , FN-kappa B , Transducción de Señal , Triterpenos , Cicatrización de Heridas , Triterpenos/farmacología , Cicatrización de Heridas/efectos de los fármacos , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Humanos , Proliferación Celular/efectos de los fármacos , Masculino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Movimiento Celular/efectos de los fármacos , Cicatriz Hipertrófica/tratamiento farmacológico , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/patología , RatonesRESUMEN
The impact of ustekinumab (UST) on mucosal- and fistula healing and extraintestinal manifestations (EIM) in Crohn's disease (CD) were not fully elucidated in the registration trials. In this prospective, multicenter study (EudraCT number: 2017-005151-83) we evaluated the German label real-world-effectiveness of UST to achieve the primary endpoint of combined clinical and endoscopic response at week 52 and several secondary endpoints. Of 79 screened we enrolled 52 patients (female n = 28, bionaïve n = 13, biologic n = 39). At week 52 (per protocol analysis), 52% (n = 13/25) of patients achieved the primary endpoint [50% (n = 3/6) in the bionaïve, 45.5% (n = 5/11) biologic, 62.5% (n = 5/8 ) multiple biologics cohorts, respectively with age as independent predictor [OR 95% CI 0.933 (0.873, 0.998) p = 0.043], 60% (n = 15/25) achieved endoscopic response [50% (n = 3/6) in the bionaïve, 54.5% (n = 6/11) biologic, 75% (n = 6/8) multiple biologics cohorts, respectively], 36% (n = 9/25) achieved endoscopic remission [50% (n = 3/6) in the bionaïve, 27.3% (n = 3/11) biologic, 37.5% (n = 3/8) multiple biologics cohorts, respectively], 48% (n = 12/25) achieved mucosal healing [50% (n = 3/6) in the bionaïve, 36.4% (n = 4/11) biologic, 62.5% (n = 5/8) multiple biologics cohorts, respectively]. All achieved a fistula response and 33.3% (n = 1/3) in the multiple biologics group fistula remission at week 52. EIM decreased (week 0 28.2% vs. week 52 8%). CRP, FCP, PRO-2, EQ-5D-5L improved throughout. 36 patients (69.2%) experienced ≥ 1 treatment emergent adverse event, in 8 (15.4%) cases rated as severe and in 5 (9.6%) leading to UST discontinuation, but no very severe events or deaths. The effectiveness of UST was better than in the registration trials.
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Enfermedad de Crohn , Mucosa Intestinal , Ustekinumab , Humanos , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/patología , Ustekinumab/uso terapéutico , Femenino , Masculino , Alemania , Adulto , Persona de Mediana Edad , Estudios Prospectivos , Mucosa Intestinal/patología , Mucosa Intestinal/efectos de los fármacos , Resultado del Tratamiento , Cicatrización de Heridas/efectos de los fármacosRESUMEN
BACKGROUND: The AGEs levels in tissues of diabetics and elderly tend to be higher than in normal individuals. This study aims to determine the effects of AGEs on Achilles tendon repair. MATERIALS AND METHODS: Thirty-six male eight-week-old Sprague Dawley rats were selected in this study. The rats were randomly divided into two experimental groups and a control group after the transection of the Achilles tendon. During the tendon repair, the experimental groups were injected around the Achilles tendon with 350mmol/L (low dose group) and 1000mmol/L (high dose group) D-ribose 0.2 ml respectively to increase the AGEs level, while in the control group were given the same amount of PBS. The injections were given twice a week for six weeks. Collagen-I, TNF-α, and IL-6 expression in the healed Achilles tendon was assessed. Additionally, macroscopic, pathological, and biomechanical evaluations of Achilles tendon repair were conducted. RESULTS: The repaired Achilles tendons in the high dose group showed severe swelling and distinctive adhesions. The histological score went up with the increase of the AGEs in the Achilles tendon (p<0.001). TNF- α and IL-6 in the Achilles tendon increased (p<0.001, p<0.001), and the production of collagen-I decreased with the accumulation of AGEs in the repaired Achilles tendon (p<0.001). The tensile strength of Achilles tendon in the high dose group was impaired significantly. CONCLUSION: In current study, the compromised tendon repair model induced by AGEs was successfully established in rat. The study demonstrated that AGEs significantly impair Achilles tendon repair.
Asunto(s)
Tendón Calcáneo , Productos Finales de Glicación Avanzada , Ratas Sprague-Dawley , Traumatismos de los Tendones , Cicatrización de Heridas , Animales , Masculino , Tendón Calcáneo/lesiones , Tendón Calcáneo/patología , Tendón Calcáneo/metabolismo , Tendón Calcáneo/cirugía , Tendón Calcáneo/efectos de los fármacos , Productos Finales de Glicación Avanzada/metabolismo , Traumatismos de los Tendones/metabolismo , Traumatismos de los Tendones/patología , Traumatismos de los Tendones/fisiopatología , Ratas , Cicatrización de Heridas/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Colágeno Tipo I/metabolismo , Interleucina-6/metabolismo , Modelos Animales de EnfermedadRESUMEN
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/lesionesRESUMEN
Royal sun medicinal mushroom Agaricus brasiliensis KA21 has various beneficial pharmacological effects; however, these effects are influenced by its cultivation conditions. A. brasiliensis KA21 is rich in ß-glucan, which promotes wound healing. This study evaluated the wound healing-promoting effects of A. brasiliensis KA21 and the influence of cultivation conditions on these effects. Upon evaluation of its effect on wound healing, the outdoor-cultivated A. brasiliensis KA21 (KAOD) promoted wound healing in mice, and the effect of KAOD was stronger than that of the indoor-cultivated one (KAID). In addition, A. brasiliensis KA21 promoted the synthesis of collagen I and III, which are involved in promoting wound healing; KAOD strongly induced collagen III production. Furthermore, KAOD suppressed the decrease in skin elasticity after acetone application in our mouse model, which was not observed for KAID. These results show that KAOD is useful as a supplement in surgery and injury healing for humans and animals, improving immunity against pathogens in wound areas and promoting wound healing. In addition, KAOD may be useful in the field of skin aesthetics for repairing skin damage and maintaining skin elasticity.
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Agaricus , Piel , Cicatrización de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Agaricus/química , Ratones , Piel/efectos de los fármacos , Elasticidad/efectos de los fármacos , Masculino , Humanos , Modelos Animales de EnfermedadRESUMEN
Lipids play an essential role in skin barrier health. With age, there is a natural reduction of physiological lipids such as fatty acids, ceramides, and cholesterol. The triple lipid restore cream is a moisturizer that contains an optimized lipid ratio for aging skin. The cream contains a 2:4:2 ratio of ceramides, cholesterol, and fatty acids that have been shown to best support aging skin. The triple lipid restore cream has been used in combination with energy-based procedures, to provide patients with comprehensive integrated skincare regimens. With limited clinical data and guidelines available in regenerative medicine, real-world cases serve as an invaluable guide for patients and dermatologists in navigating rejuvenation treatment plans. J Drugs Dermatol. 2024;23:9(Suppl 1):s3-14.
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Rejuvenecimiento , Envejecimiento de la Piel , Crema para la Piel , Humanos , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiación , Crema para la Piel/administración & dosificación , Crema para la Piel/química , Femenino , Persona de Mediana Edad , Ceramidas/administración & dosificación , Colesterol/administración & dosificación , Resultado del Tratamiento , Técnicas Cosméticas , Terapia por Radiofrecuencia/métodos , Ácidos Grasos/administración & dosificación , Ácidos Grasos/química , Administración Cutánea , Terapia por Láser/métodos , Cicatrización de Heridas/efectos de los fármacos , Anciano , Masculino , Agujas , Inducción Percutánea del ColágenoRESUMEN
INTRODUCTION: Oral lesions are a common clinical symptom arising from various etiologies and disrupt the patient's quality of life. However, no definite treatment is not yet possible, due to the constantly changing environment of the mouth. In recent years, herbal treatments have gained popularity among patients and physicians due to their availability, safety, affordability, and antimicrobial properties. This research aims to investigate the therapeutic effects of a nano-emulsion of Plantago major standardized extract (PMSE) on oral ulcers in a Wistar rat model using histomorphometry and stereological parameters. MATERIALS AND METHODS: The study involved 72 Wistar rats divided randomly into 24 groups of 3 each: groups A1 to A4 received one dose to 4 doses of 5% PMSE nano emulsion, groups B1 to B4 received one dose to 4 doses of 10% PMSE nano emulsion, and groups C1 to C4 received one dose to 4 doses of 20% PMSE nano emulsion, groups D1 to D4 received one dose to 4 doses of nano-emulsion without PMSE, groups E1 to E4 received one dose to 4 doses of PMSE, and group F served as the control group. An incision measuring 2 mm in diameter was made in the animals' hard palate using a biopsy punch. A swab containing the necessary material was used to administer the medication orally to the wound. Histological samples were collected on days 2, 4, 6, and 8 and sent to the pathology laboratory for examination. Data analysis was performed using SPSS 26 and setting statistical significance at p < 0.05. RESULTS: Group A showed a high rate of complete and normal re-epithelialization of the wound at 66.7%, compared to the other groups. Group D had a re-epithelialization rate of 50%, while groups C, E, and F had rates of 7.41% and group B had 7.16%. In terms of inflammation reduction, 23.88% of group A had no inflammation, a higher percentage compared to the other groups. Group B and D had no inflammation in 3.33% of cases, lower than the other groups. The study evaluated frequency of re-epithelialization and inflammation levels in different groups on days 2, 4, 6, and 8 after four doses of the drug with no significant differences found among the groups. CONCLUSION: None of the nano emulsions or PMSE enhanced the healing rate of oral ulcers. However, a 5% PMSE nano emulsion displayed an increase in lesion re-epithelialization.
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Modelos Animales de Enfermedad , Emulsiones , Extractos Vegetales , Plantago , Ratas Wistar , Cicatrización de Heridas , Animales , Extractos Vegetales/farmacología , Ratas , Cicatrización de Heridas/efectos de los fármacos , Plantago/química , Úlceras Bucales/tratamiento farmacológico , MasculinoRESUMEN
Purpose: In this study, wound dressings were designed using zinc-modified marine collagen porous scaffold as host for wild bilberry (WB) leaves extract immobilized in functionalized mesoporous silica nanoparticles (MSN). These new composites were developed as an alternative to conventional wound dressings. In addition to the antibacterial activity of classic antibiotics, a polyphenolic extract could act as an antioxidant and/or an anti-inflammatory agent as well. Methods: Wild bilberry leaves extract was prepared by ultrasound-assisted extraction in ethanol and its properties were evaluated by UV-Vis spectroscopy (radical scavenging activity, total amount of polyphenols, flavonoids, anthocyanins, and condensed tannins). The extract components were identified by HPLC, and the antidiabetic properties of the extract were evaluated via α-glucosidase inhibitory activity. Spherical MSN were modified with propionic acid or proline moieties by post-synthesis method and used as carriers for the WB leaves extract. The textural and structural features of functionalized MSN were assessed by nitrogen adsorption/desorption isotherms, small-angle XRD, SEM, TEM, and FTIR spectroscopy. The composite porous scaffolds were prepared by freeze drying of the zinc-modified collagen suspension containing WB extract loaded silica nanoparticles. Results: The properties of the new composites demonstrated enhanced properties in terms of thermal stability of the zinc-collagen scaffold, without altering the protein conformation, and stimulation of NCTC fibroblasts mobility. The results of the scratch assay showed contributions of both zinc ions from collagen and the polyphenolic extract incorporated in functionalized silica in the wound healing process. The extract encapsulated in functionalized MSN proved enhanced biological activities compared to the extract alone: better inhibition of P. aeruginosa and S. aureus strains, higher biocompatibility on HaCaT keratinocytes, and anti-inflammatory potential demonstrated by reduced IL-1ß and TNF-α levels. Conclusion: The experimental data shows that the novel composites can be used for the development of effective wound dressings.
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Vendajes , Colágeno , Nanopartículas , Extractos Vegetales , Hojas de la Planta , Dióxido de Silicio , Cicatrización de Heridas , Zinc , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Dióxido de Silicio/química , Dióxido de Silicio/farmacología , Colágeno/química , Colágeno/farmacología , Zinc/química , Zinc/farmacología , Nanopartículas/química , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Andamios del Tejido/química , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/química , Línea Celular , Porosidad , Fibroblastos/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/químicaRESUMEN
Endogenous stem cell homing refers to the transport of endogenous mesenchymal stem cells (MSCs) to damaged tissue. The paradigm of using well-designed biomaterials to induce resident stem cells to home in to the injured site while coordinating their behavior and function to promote tissue regeneration is known as endogenous regenerative medicine (ERM). ERM is a promising new avenue in regenerative therapy research, and it involves the mobilizing of endogenous stem cells for homing as the principal means through which to achieve it. Comprehending how mesenchymal stem cells home in and grasp the influencing factors of mesenchymal stem cell homing is essential for the understanding and design of tissue engineering. This review summarizes the process of MSC homing, the factors influencing the homing process, analyses endogenous stem cell homing studies of interest in the field of skin tissue repair, explores the integration of endogenous homing promotion strategies with cellular therapies and details tissue engineering strategies that can be used to modulate endogenous homing of stem cells. In addition to providing more systematic theories and ideas for improved materials for endogenous tissue repair, this review provides new perspectives to explore the complex process of tissue remodeling to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.
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Materiales Biocompatibles , Células Madre Mesenquimatosas , Ingeniería de Tejidos , Cicatrización de Heridas , Humanos , Células Madre Mesenquimatosas/citología , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/fisiología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ingeniería de Tejidos/métodos , Animales , Medicina Regenerativa/métodos , Andamios del Tejido/química , Movimiento Celular/efectos de los fármacos , Piel , Trasplante de Células Madre Mesenquimatosas/métodosRESUMEN
Pressure ulcers (PU) are caused by persistent long-term pressure, which compromises the integrity of the epidermis, dermis, and subcutaneous adipose tissue layer by layer, making it difficult to heal. Platelet products such as platelet lysate (PL) can promote tissue regeneration by secreting numerous growth factors based on clinical studies on skin wound healing. However, the components of PL are difficult to retain in wounds. Gelatin methacrylate (GelMA) is a photopolymerizable hydrogel that has lately emerged as a promising material for tissue engineering and regenerative medicine. The PL liquid was extracted, flow cytometrically detected for CD41a markers, and evenly dispersed in the GelMA hydrogel to produce a surplus growth factor hydrogel system (PL@GM). The microstructure of the hydrogel system was observed under a scanning electron microscope, and its sustained release efficiency and biological safety were tested in vitro. Cell viability and migration of human dermal fibroblasts, and tube formation assays of human umbilical vein endothelial cells were applied to evaluate the ability of PL to promote wound healing and regeneration in vitro. Real-time polymerase chain reaction (PCR) and western blot analyses were performed to elucidate the skin regeneration mechanism of PL. We verified PL's therapeutic effectiveness and histological analysis on the PU model. PL promoted cell viability, migration, wound healing and angiogenesis in vitro. Real-time PCR and western blot indicated PL suppressed inflammation and promoted collagen I synthesis by activating STAT3. PL@GM hydrogel system demonstrated optimal biocompatibility and favorable effects on essential cells for wound healing. PL@GM also significantly stimulated PU healing, skin regeneration, and the formation of subcutaneous collagen and blood vessels. PL@GM could accelerate PU healing by promoting fibroblasts to migrate and secrete collagen and endothelial cells to vascularize. PL@GM promises to be an effective and convenient treatment modality for PU, like chronic wound treatment.