RESUMEN
ABSTRACT: Fostamatinib, a recently approved Syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here, 138 patients with ITP (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively. The median age of our cohort (55.8% women) was 66 years (interquartile range [IQR], 56-80). The median time since ITP diagnosis at fostamatinib initiation was 51 months (IQR, 10-166). The median number of therapies before fostamatinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%), and IV immunoglobulins (44.2%). Fifty-eight patients (42.0%) had signs/symptoms of bleeding in the month before treatment initiation. Seventy-nine percent of patients responded to fostamatinib with 53.6% complete responses (platelet count > 100 × 109/L). Eighty-three patients (60.1%) received fostamatinib monotherapy, achieving a high response rate (85.4%). The proportion of time in response during the 27-month period examined was 83.3%. The median time to platelet response was 11 days (IQR, 7-21). Sixty-seven patients (48.5%) experienced adverse events, mainly grade 1 to 2; the commonest of which were diarrhea (n = 28) and hypertension (n = 21). One patient had deep venous thrombosis, and one patient developed acute myocardial infarction. Fostamatinib was shown to be effective with good safety profile in patients with primary and secondary ITP across a wide age spectrum in this real-world study.
Asunto(s)
Aminopiridinas , Morfolinas , Oxazinas , Púrpura Trombocitopénica Idiopática , Piridinas , Pirimidinas , Humanos , Femenino , Masculino , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Anciano , Oxazinas/uso terapéutico , Oxazinas/efectos adversos , Anciano de 80 o más Años , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Morfolinas/uso terapéutico , Morfolinas/efectos adversos , Piridinas/uso terapéutico , Piridinas/efectos adversos , Aminopiridinas/uso terapéutico , Aminopiridinas/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Quinasa Syk/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Recuento de Plaquetas , Estudios ProspectivosRESUMEN
Traditional wound dressings have not been able to satisfy the needs of the regenerative medicine biomedical area. With the aim of improving tissue regeneration, nanofiber-based wound dressings fabricated by electrospinning (ES) processes have emerged as a powerful approach. Nowadays, nanofiber-based bioactive dressings are mainly developed with a combination of natural and synthetic polymers, such as polycaprolactone (PCL) and chitosan (CHI). Accordingly, herein, PCL/CHI nanofibers have been developed with varying PCL:CHI weight ratios (9:1, 8:2 and 7:3) or CHI viscosities (20, 100 and 600 mPa·s) using a novel alternating current ES (ACES) process. Such nanofibers were thoroughly characterized by determining physicochemical and nanomechanical properties, along with wettability, absorption capacity and hydrolytic plus enzymatic stability. Furthermore, PCL/CHI nanofiber biological safety was validated in terms of cytocompatibility and hemocompatibility (hemolysis < 2%), in addition to a notable antibacterial performance (bacterial reductions of 99.90% for S. aureus and 99.91% for P. aeruginosa). Lastly, the enhanced wound healing activity of PCL/CHI nanofibers was confirmed thanks to their ability to remarkably promote cell proliferation, which make them ideal candidates for long-term applications such as wound dressings.
RESUMEN
To provide insight into the subclonal architecture and co-dependency patterns of the alterations in Waldenström's macroglobulinemia (WM), we performed single-cell mutational and protein profiling of eight patients. A custom panel was designed to screen for mutations and copy number alterations at the single-cell level in samples taken from patients at diagnosis (n=5) or at disease progression (n=3). Results showed that in asymptomatic WM at diagnosis, MYD88L265P was the predominant clonal alteration; other events, if present, were secondary and subclonal to MYD88L265P. In symptomatic WM, clonal diversity was more evident, uncovering combinations of alterations that synergized to promote clonal expansion and dominance. At disease progression, a dominant clone was observed, sometimes accompanied by other less complex minor clones, which could be consistent with a clonal selection process. Clonal diversity was also reduced, probably due to the effect of treatment. Finally, we combined protein expression with mutational analysis to map somatic genotype with the immunophenotype. Our findings provide a comprehensive view of the clonality of tumor populations in WM and how clonal complexity can evolve and impact disease progression.
Asunto(s)
Evolución Clonal , Variaciones en el Número de Copia de ADN , Mutación , Macroglobulinemia de Waldenström , Macroglobulinemia de Waldenström/diagnóstico , Macroglobulinemia de Waldenström/genética , Humanos , Análisis de la Célula Individual , Análisis por Matrices de Proteínas , Factor 88 de Diferenciación Mieloide/genética , Análisis Mutacional de ADNRESUMEN
In this work, we have studied structural and magnetic properties of LaFeO3 as a function of the particle size d, from bulk (d >> 1 µm) to nanoscale (d ≈ 30 nm). A large number of twins were observed for large particles that disappear for small particle sizes. This could be related to the softening of the FeO6 distortion as particle size decreases. It was observed that the bulk sample showed spin canting that disappeared for d ~ 125 nm and can be associated with the smoothening of the orthorhombic distortion. On the other hand, for d < 60 nm, the surface/volume ratio became high and, despite the high crystallinity of the nanoparticle, a notable exchange effect bias appeared, originated by two magnetic interactions: spin glass and antiferromagnetism. This exchange bias interaction was originated by the formation of a "magnetic core-shell": the broken bonds at the surface atoms give place to a spin glass behavior, whereas the inner atoms maintain the antiferromagnetic G-type order. The LaFeO3 bulk material was synthesized by the ceramic method, whereas the LaFeO3 nanoparticles were synthesized by the sol-gel method; the particle size was varied by annealing the samples at different temperatures. The physical properties of the materials have been investigated by XRD, HRTEM, TGA, and AC and DC magnetometry.
RESUMEN
The present study aims at the integration of the "oxalic conversion" route into "green chemistry" for the synthesis of copper oxide nanoparticles (CuO-NPs) with controllable structural, morphological, and magnetic properties. Two oxalate-containing precursors (H2C2O4.2H2O and (NH4)2C2O4.H2O) and different volume ratios of a mixed water/glycerol solvent were tested. First, the copper oxalates were synthesized and then subjected to thermal decomposition in air at 400 °C to produce the CuO powders. The purity of the samples was confirmed by X-ray powder diffraction (XRPD), and the crystallite sizes were calculated using the Scherrer method. The transmission electron microscopy (TEM) images revealed oval-shaped CuO-NPs, and the scanning electron microscopy (SEM) showed that morphological features of copper oxalate precursors and their corresponding oxides were affected by the glycerol (V/V) ratio as well as the type of C2O42- starting material. The magnetic properties of CuO-NPs were determined by measuring the temperature-dependent magnetization and the hysteresis curves at 5 and 300 K. The obtained results indicate the simultaneous coexistence of dominant antiferromagnetic and weak ferromagnetic behavior.
RESUMEN
(1) Background: New therapeutic strategies have improved the prognosis of multiple myeloma (MM), changing the accepted view of this disease from being incurable to treatable. (2) Methods: We studied 1001 patients with MM between 1980 and 2020, grouping patients into ten-year periods by diagnosis 1980-1990, 1991-2000, 2001-2010 and 2011-2020. (3) Results: After 65.1 months of follow-up, the median OS of the cohort was 60.3 months, and OS increased significantly over time: 22.4 months in 1980-1990, 37.4 months in 1991-2000, 61.8 months in 2001-2010 and 103.6 months in 2011-2020 (p < 0.001). Using novel agents in the front-line setting for myeloma patients yielded a significantly better OS than in those treated with conventional therapies, especially when combinations of at least two novel agents were used. The median OS of patients treated with the combination of at least two novel agents in induction was significantly prolonged compared to those treated with a single novel agent or conventional therapy in induction: 143.3 vs. 61.0 vs. 42.2 months (p < 0.001). The improvement was apparent in all patients regardless of age at diagnosis. In addition, 132 (13.2%) patients were long-term survivors (median OS ≥ 10 years). Some independent clinical predictors of long-term survival were identified: ECOG < 1, age at diagnosis ≤ 65 years, non-IgA subtype, ISS-1 and standard-risk cytogenetic. Achieving CR and undergoing ASCT were positively associated with >10 years of survival. (4) Conclusions: The combination of novel agents appears to be the main factor for the improvement in survival in MM, which is becoming a chronic and even curable disease in a subtype of patients without high-risk features.
RESUMEN
Granular polymer hydrogels based on dynamic covalent bonds are attracting a great deal of interest for the design of injectable biomaterials. Such materials generally exhibit shear-thinning behavior and properties of self-healing/recovery after the extrusion that can be modulated through the interactions between gel microparticles. Herein, bulk macro-hydrogels based on thiolated-hyaluronic acid were produced by disulphide bond formation using oxygen as oxidant at physiological conditions and gelation kinetics were monitored. Three different thiol substitution degrees (SD%: 65%, 30% and 10%) were selected for hydrogel formation and fully characterized as to their stability in physiological medium and morphology. Then, extrusion fragmentation technique was applied to obtain hyaluronic acid microgels with dynamic disulphide bonds that were subsequently sterilized by autoclaving. The resulting granular hyaluronic hydrogels were able to form stable filaments when extruded through a syringe. Rheological characterization and cytotoxicity tests allowed to assess the potential of these materials as injectable biomaterials. The application of extrusion fragmentation for the formation of granular hyaluronic hydrogels and the understanding of the relation between the autoclaving processes and the resulting particle size and rheological properties should expand the development of injectable materials for biomedical applications.
RESUMEN
We have investigated the structural, magnetic, and electrical transport properties of Pr0.7 Sr0.3 Mn(1-x)Cox O3 nanopowders (x = 0, 0.05, 0.10 and 0.15). The Pechini Sol-gel method was used to synthesize these nanopowders. X-ray diffraction at room temperature shows that all the nano powders have an orthorhombic structure of Pnma space group crystallography. The average crystallite size of samples x = 0, 0.05, 0.10, and 0.15 are 33.78 nm, 29 nm, 33.61 nm, and 24.27 nm, respectively. Semi-quantitative chemical analysis by energy dispersive spectroscopy (EDS) confirms the expected stoichiometry of the sample. Magnetic measurements indicate that all samples show a ferromagnetic (FM) to paramagnetic (PM) transition with increasing temperature. The Curie temperature TC gradually decreases (300 K, 270 K, 250 K, and 235 K for x = 0, 0.05, 0.10, and 0.15, respectively) with increasing Co concentrations. The M-H curves for all compounds reveal the PM behavior at 300 K, while the FM behavior characterizes the magnetic hysteresis at low temperature (5 K). The electrical resistivity measurements show that all compounds exhibit metallic behavior at low temperature (T < Tρ) well fitted by the relation ρ = ρ0 + ρ2T2 + ρ4.5T4.5 and semiconductor behavior above Tρ (T > Tρ), for which the electronic transport can be explained by the variable range hopping model and the adiabatic small polaron hopping model. All samples have significant magnetoresistance (MR) values, even at room temperature. This presented research provides an innovative and practical approach to develop materials in several technological areas, such as ultra-high density magnetic recording and magneto resistive sensors.
RESUMEN
Among biomedical community, great efforts have been realized to develop antibacterial coatings that avoid implant-associated infections. To date, conventional mono-functional antibacterial strategies have not been effective enough for successful long-term implantations. Consequently, researchers have recently focused their attention on novel bifunctional or multifunctional antibacterial coatings, in which two or more antibacterial mechanisms interact synergistically. Thus, in this work different chitosan-based (CHI) hydrogel coatings were created on Ti6Al4V surface using genipin (Ti-CHIGP) and polyethylene glycol (Ti-CHIPEG) crosslinking agents. Hydrogel coatings demonstrated an exceptional in vivo biocompatibility plus a remarkable ability to promote cell proliferation and differentiation. Lastly, hydrogel coatings demonstrated an outstanding bacteria-repelling (17-28 % of S. aureus and 33-43 % of E. coli repelled) and contact killing (186-222 % of S. aureus and 72-83 % of E. coli damaged) ability. Such bifunctional antibacterial activity could be further improved by the controlled release of drugs resulting in powerful multifunctional antibacterial coatings.
Asunto(s)
Quitosano , Quitosano/farmacología , Hidrogeles/farmacología , Staphylococcus aureus , Escherichia coli , Materiales Biocompatibles Revestidos/farmacología , Antibacterianos/farmacología , Titanio/farmacologíaRESUMEN
Today, the treatment of implant-associated infections with conventional mono-functional antibacterial coatings has not been effective enough for a prosperous long-term implantation. Therefore, biomedical industry is making considerable efforts on the development of novel antibacterial coatings with a combination of more than one antibacterial strategies that interact synergistically to reinforce each other. Therefore, in this work hyaluronic acid-based (HA) hydrogel coatings were created on the surface Ti6Al4V biomaterial with 1,4-butanediol diglycidyl ether (Ti-HABDDE) and divinyl sulfone (Ti-HADVS) crosslinking agents. Hydrogel coatings displayed an extraordinary in vivo biocompatibility, a remarkable ability to promote cell proliferation, differentiation and mineralization, and capability to sustainedly release drugs. Finally, HA-based hydrogel coatings demonstrated an outstanding multifunctional antibacterial activity: bacteria-repelling (51-55 % of S. aureus and 27-40 % of E. coli), bacteria-killing (82-119 % of S. aureus and 83-87 % of E. coli) and bactericide release killing (drug-loaded hydrogel coatings, R > 2).
Asunto(s)
Materiales Biocompatibles , Hidrogeles , Antibacterianos/farmacología , Materiales Biocompatibles/farmacología , Escherichia coli , Ácido Hialurónico/farmacología , Hidrogeles/farmacología , Staphylococcus aureusRESUMEN
Great efforts have been performed on the production of advanced biomaterials with the combination of self-healing and wound healing properties in implant/tissue engineering biomedical area. Inspired by this idea, chitosan (CHI) based hydrogels can be used to treat a less investigated class of harmful chronic wounds: ulcers or pressure ulcers. Thus, CHI was crosslinked with previously synthesized polyethylene glycol diacid (PEG-diacid) to obtain different CHI-PEG hydrogel formulations with high H-bonding tendency resulting in self-repair ability. Here presented results show biocompatible, antibacterial, anti-inflammatory, and self-healing CHI-PEG hydrogels with a promising future in the treatment of ulcerated wounds by a significant improvement in metabolic activity (94.51 ± 4.38 %), collagen and elastin quantities (2.12 ± 0.63 µg collagen and 4.97 ± 0.61 µg elastin per mg dermal tissue) and histological analysis. Furthermore, cefuroxime (CFX), tetracycline (TCN) and amoxicillin (AMX) antibiotics, and acetylsalicylic acid (ASA) anti-inflammatory agent were sustainedly released for enhancing antibacterial and anti-inflammatory activities of hydrogels.
Asunto(s)
Quitosano , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Materiales Biocompatibles , Quitosano/farmacología , Colágeno/farmacología , Elastina , Humanos , Hidrogeles , Úlcera , Cicatrización de HeridasRESUMEN
Immunoparesis is the suppression of normal polyclonal immunoglobulins and is present in most patients with newly diagnosed multiple myeloma (MM). The association of immunoparesis at diagnosis, and particularly its recovery along with treatment, with survival in patients ineligible for autologous stem-cell transplantation (ASCT) has not been well established. This retrospective study evaluated the impact of immunoparesis in 431 patients diagnosed with MM, ineligible for ASCT, with a median overall survival of 36 months [95% confidence interval (CI): 31-40]. Immunoparesis was present in 81.2% of patients at diagnosis and was associated with a trend to a worse overall response rate (ORR: 84.8% vs. 74.9%; OR 1.88 (95% CI: 0.97-3.63), shorter progression-free survival (PFS) [22.0 vs. 18.2 months; hazard ratio (HR) 0.775; 95%CI: 0.590-1.018; p = 0.066], and overall survival (OS) (45.9 vs. 34.2 months; HR 0.746; 95% CI: 0.551-1.010; p = 0.057). Twenty-four per cent of patients who had immunoparesis at diagnosis recovered polyclonal immunoglobulins in the follow-up period. Interestingly, these patients had a better ORR (96.3% vs. 68.2%; OR 12.29 (95% CI: 3.77-40.06), PFS (HR 0.703; 95CI%: 0.526-0.941; p = 0.018) and OS (HR 0.678; 95 CI%: 0.503-0.913; p = 0.011) than patients who did not recover it. In summary, restoring a healthy immune system along with first-line treatment in patients with MM, not receiving ASCT, is associated with better outcomes.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Supervivencia sin Enfermedad , Humanos , Inmunoglobulinas , Mieloma Múltiple/diagnóstico , Pronóstico , Supervivencia sin Progresión , Estudios Retrospectivos , Trasplante AutólogoRESUMEN
Hyaluronic acid (HA) injectable biomaterials are currently applied in numerous biomedical areas, beyond their use as dermal fillers. However, bacterial infections and painful inflammations are associated with healthcare complications that can appear after injection, restricting their applicability. Fortunately, HA injectable hydrogels can also serve as drug delivery platforms for the controlled release of bioactive agents with a critical role in the control of certain diseases. Accordingly, herein, HA hydrogels were crosslinked with 1 4-butanediol diglycidyl ether (BDDE) loaded with cefuroxime (CFX), tetracycline (TCN), and amoxicillin (AMX) antibiotics and acetylsalicylic acid (ASA) anti-inflammatory agent in order to promote antibacterial and anti-inflammatory responses. The hydrogels were thoroughly characterized and a clear correlation between the crosslinking grade and the hydrogels' physicochemical properties was found after rheology, scanning electron microscopy (SEM), thermogravimetry (TGA), and differential scanning calorimetry (DSC) analyses. The biological safety of the hydrogels, expected due to the lack of BDDE residues observed in 1H-NMR spectroscopy, was also corroborated by an exhaustive biocompatibility test. As expected, the in vitro antibacterial and anti-inflammatory activity of the drug-loaded HA-BDDE hydrogels was confirmed against Staphylococcus aureus by significantly decreasing the pro-inflammatory cytokine levels.
RESUMEN
Chitosan (CHI) based hydrogels promote wound healing and relieve inflammations and chronic infections. However, in hardly healable ulcers with excessively painful inflammations, anti-inflammatory activity of hydrogels can be enhanced by the sustained release of non-steroidal anti-inflammatory drugs or combining them with antibiotics. Thus, CHI was crosslinked with genipin (GP) to obtain biocompatible hydrogels. Moreover, their antibacterial activity was confirmed against Staphylococcus aureus and Escherichia coli with an almost 100% bacteria reduction and a potential antibacterial efficacy (R > 2). Furthermore, hydrogels effective healing of ulcerated wounds was corroborated by a significant improvement in metabolic activity (95.58 ± 4.40%), collagen and elastin quantities (1.48 ± 0.07 µg collagen and 5.82 ± 0.73 µg elastin per mg dermal tissue) and histological analysis. Finally, the sustained release of acetylsalicylic acid (ASA), cefuroxime (CFX), tetracycline (TCN) and amoxicillin (AMX) were studied, as well as their anti-inflammatory activity. Results confirm the synergistic anti-inflammatory activity by the significant reduction in the amount of pro-inflammatory cytokines when ASA was combined with CFX (5.39 ± 0.81 ng·mL-1 TNF-α), TCN (4.70 ± 0.21 ng·mL-1 TNF-α and 49.06 ± 9.64 ng·mL-1 IL-8), and AMX (2.28 ± 0.36 ng·mL-1 TNF-α, 14.84 ± 5.57 ng·mL-1 IL-8, and total IL-6 removal).
Asunto(s)
Quitosano , Hidrogeles , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Quitosano/farmacología , Hidrogeles/farmacología , Iridoides , Cicatrización de HeridasRESUMEN
Hyaluronic acid (HA) hydrogels display a wide variety of biomedical applications ranging from tissue engineering to drug vehiculization and controlled release. To date, most of the commercially available hyaluronic acid hydrogel formulations are produced under conditions that are not compatible with physiological ones. This review compiles the currently used approaches for the development of hyaluronic acid hydrogels under physiological/mild conditions. These methods include dynamic covalent processes such as boronic ester and Schiff-base formation and click chemistry mediated reactions such as thiol chemistry processes, azide-alkyne, or Diels Alder cycloaddition. Thermoreversible gelation of HA hydrogels at physiological temperature is also discussed. Finally, the most outstanding biomedical applications are indicated for each of the HA hydrogel generation approaches.
RESUMEN
Objetivo: analizar el efecto de la simulación clínica en el nivel de ansiedad pre/post-actividad formativa en varios grupos profesionales y en estudiantes de Enfermería, y evaluar la autoconfianza percibida antes/después de la simulación en cada grupo.Métodos: estudio cuasi-experimental en profesionales sanitarios (enfermeras, técnicos en cuidados auxiliares de Enfermería o TCAE y médicos) y estudiantes de Enfermería (4º curso) sometidos por primera vez a una intervención de simulación clínica en el Hospital General Universitario de Ciudad Real. Se evaluó el nivel de ansiedad estado antes/después de la simulación mediante el cuestionario STAI de Spielberg, y se valoró la autoconfianza percibida antes/después de la simulación. Se realizó análisis descriptivo. Se usó la t de Student para la comparación de medias. Se estableció significación estadística si p< 0,05.Resultados: participaron 53 sujetos, 43 (81,2%) profesionales y 10 (18,8%) estudiantes de Enfermería. Edad media (DE) fue 39 (11,8) años; 84,9% (n= 45) mujeres. El nivel de ansiedad medio (DE) al inicio de la simulación fue mayor en los estudiantes de Enfermería 24,6 (5,4) y menor en los médicos 14,4 (5,8). Tras la intervención se redujo la media (DE) del nivel de ansiedad-estado en todos los grupos, siendo significativo (p< 0,001) en TCAE -13,1 (6,9) y enfermeras -12,5 (8,4). Hubo un aumento del nivel de autoconfianza de todos los participantes al finalizar la actividad.Conclusiones: los profesionales que participaron por primera vez en una actividad de simulación clínica presentaron alto grado de ansiedad, aunque en médicos fue inferior. Hubo un descenso de la ansiedad y aumento de la confianza al final de la simulación clínica.(AU)
Objective: to analyze the effect of clinical simulation in the level of anxiety pre- and post- training activity in different professional groups and Nursing students, and to assess the self-confidence perceived before/after the simulation in each group.Methods: a quasi-experimental study in healthcare professionals (nurses, assistant nursing technicians or TCAE, and doctors), and Nursing students (4th year), who underwent for the first time a clinical simulation intervention at the Hospital General Universitario de Ciudad Real. The level of anxiety was evaluated before/after the simulation, through Spielbergers STAI questionnaire, and the level of self-confidence perceived was also evaluated before / after the simulation. Descriptive analysis was conducted, and Students t test was used for mean comparison. Statistical significance was established at p< 0.05.Results: the study included 53 subjects: 43 (81.2%) were professionals and 10 (18.8%) were Nursing students; their mean age (SD) was 39 (11.8) years; and 84.9% (n= 45) were female. The mean anxiety level (SD) at the start of the simulation was higher in Nursing students, with 24.6 (5.4), and lower in doctors, with 14.4 (5.8). After the intervention, the mean (SD) level of anxiety-status was reduced in all groups; it was significant (p< 0.001) in the TCAE group, with -13.1 (6.9) and nurses, with -12.5 (8.4). There was an increase in the level of self-confidence in all participants by the end of the activity.Conclusions: the professionals who participated for the first time in a clinical simulation activity presented a high level of anxiety, though this was lower among doctors. There was a reduction in anxiety and increase in confidence by the end of the clinical simulation.(AU)
Asunto(s)
Humanos , Entrenamiento Simulado , Relaciones Interprofesionales , Ansiedad , Personal de Salud , Estudiantes de Enfermería , AprendizajeRESUMEN
Bacterial contamination in implanted biomedical devices is a critical daily concern. The most used material for permanent implant in biomedical field is Ti6Al4V alloy due to its beneficial mechanical properties and high biocompatibility. Accordingly, in this work different polymeric antibacterial coatings poly(N-vinyl pyrrolidone) (PVP), hyaluronic acid (HA) and chitosan (CHI) were developed and comparatively analysed for Ti6Al4V surface covering. The adhesion of these coatings to Ti6Al4V substrates were carried out after the conjugation of these polymers with the so well-known bioadhesive properties of catechol (CA) anchor group. These surface modifications were characterized by X-ray photoelectronic spectroscopy, contact angle measurements and atomic force microscopy. In addition, the stability of CA-conjugated polymeric coatings was compared with the coatings formed with unconjugated polymers. Finally, the cytocompatibility and antibacterial properties against gram-positive and gram-negative strains on coated Ti6Al4V substrates were assessed confirming the effectiveness of these polymeric coatings against bacterial infections for future applications in protecting biomedical implants.
Asunto(s)
Aleaciones/síntesis química , Antibacterianos/síntesis química , Catecoles/química , Ácido Hialurónico/química , Pirrolidinonas/química , Aleaciones/química , Aleaciones/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Línea Celular , Quitosano , Materiales Biocompatibles Revestidos/síntesis química , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Ensayo de Materiales , Pruebas de Sensibilidad Microbiana , Microscopía de Fuerza Atómica , Espectroscopía de Fotoelectrones , Prótesis e Implantes , Propiedades de Superficie , Titanio/química , Titanio/farmacologíaRESUMEN
Hyaluronic acid (HA) solutions were crosslinked with divinyl sulfone (DVS) and subsequently loaded with antibiotic molecules to obtain biocompatible and antibacterial injectable hydrogels. The crosslinking degree of the hydrogels was modulated by varying the reaction time and the HA:DVS weight ratio. Synthesized HA-DVS hydrogels were characterized by their rheological properties, pore size, swelling capacity and hydrolytic and thermal degradation. Biocompatibility was assessed by measuring pH, osmolality and by in vitro cytotoxic assay. Acetyl salicylic (AAS) loaded hydrogels display anti-inflammatory properties in vitro, whereas cefuroxime (CFX), tetracycline (TCN) and amoxicillin (AMX) loaded hydrogels show in vitro antibacterial activity against Staphylococcus aureus. The combine use of antibiotics and AAS produces a synergic effect that reduces the S. aureus population up to a log10 reduction (R) of 5.55. Overall results show that antibiotic/AAS loaded HA-DVS hydrogels could be effectively used to combat S. aureus infections and to increase the antibacterial activity of antibiotics commonly used against S. aureus.
Asunto(s)
Ácido Hialurónico , Hidrogeles , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Liberación de Fármacos , Ensayo de Materiales , Staphylococcus aureus , SulfonasRESUMEN
The transfer of some innovative technologies from the laboratory to industrial scale is many times not taken into account in the design and development of some functional materials such as hydrogels to be applied in the biomedical field. There is a lack of knowledge in the scientific field where many aspects of scaling to an industrial process are ignored, and products cannot reach the market. Injectable hydrogels are a good example that we have used in our research to show the different steps needed to follow to get a product in the market based on them. From synthesis and process validation to characterization techniques used and assays performed to ensure the safety and efficacy of the product, following regulation, several well-defined protocols must be adopted. Therefore, this paper summarized all these aspects due to the lack of knowledge that exists about the industrialization of injectable products with the great importance that it entails, and it is intended to serve as a guide on this area to non-initiated scientists. More concretely, in this work, the characteristics and requirements for the development of injectable hydrogels from the laboratory to industrial scale is presented in terms of (i) synthesis techniques employed to obtain injectable hydrogels with tunable desired properties, (ii) the most common characterization techniques to characterize hydrogels, and (iii) the necessary safety and efficacy assays and protocols to industrialize and commercialize injectable hydrogels from the regulatory point of view. Finally, this review also mentioned and explained a real example of the development of a natural hyaluronic acid hydrogel that reached the market as an injectable product.
RESUMEN
Titanium (Ti) and its alloys have been demonstrated over the last decades to play an important role as inert materials in the field of orthopedic and dental implants. Nevertheless, with the widespread use of Ti, implant-associated rejection issues have arisen. To overcome these problems, antibacterial properties, fast and adequate osseointegration and long-term stability are essential features. Indeed, surface modification is currently presented as a versatile strategy for developing Ti coatings with all these challenging requirements and achieve a successful performance of the implant. Numerous approaches have been investigated to obtain stable and well-organized Ti coatings that promote the tailoring of surface chemical functionalization regardless of the geometry and shape of the implant. However, among all the approaches available in the literature to functionalize the Ti surface, a promising strategy is the combination of surface pre-activation treatments typically followed by the development of intermediate anchoring layers (self-assembled monolayers, SAMs) that serve as the supporting linkage of a final active layer. Therefore, this paper aims to review the latest approaches in the biomedical area to obtain bioactive coatings onto Ti surfaces with a special focus on (i) the most employed methods for Ti surface hydroxylation, (ii) SAMs-mediated active coatings development, and (iii) the latest advances in active agent immobilization and polymeric coatings for controlled release on Ti surfaces.