Vancomycin-Loaded 3D-Printed Polylactic Acid-Hydroxyapatite Scaffolds for Bone Tissue Engineering.

The regeneration of bone remains one of the main challenges in the biomedical field, with the need to provide more personalized and multifunctional solutions. The other persistent challenge is related to the local prevention of infections after implantation surgery. To fulfill the first one and provide customized scaffolds with complex geometries, 3D printing is being investigated, with polylactic acid (PLA) as the biomaterial mostly used, given its thermoplastic properties. The 3D printing of PLA in combination with hydroxyapatite (HA) is also under research, to mimic the native mechanical and biological properties, providing more functional scaffolds. Finally, to fulfill the second one, antibacterial drugs locally incorporated into biodegradable scaffolds are also under investigation. This work aims to develop vancomycin-loaded 3D-printed PLA-HA scaffolds offering a dual functionality: local prevention of infections and personalized biodegradable scaffolds with osseointegrative properties. For this, the antibacterial drug vancomycin was incorporated into 3D-printed PLA-HA scaffolds using three loading methodologies: (1) dip coating, (2) drop coating, and (3) direct incorporation in the 3D printing with PLA and HA. A systematic characterization was performed, including release kinetics, Staphylococcus aureus antibacterial/antibiofilm activities and cytocompatibility. The results demonstrated the feasibility of the vancomycin-loaded 3D-printed PLA-HA scaffolds as drug-releasing vehicles with significant antibacterial effects for the three methodologies. In relation to the drug release kinetics, the (1) dip- and (2) drop-coating methodologies achieved burst release (first 60 min) of around 80-90% of the loaded vancomycin, followed by a slower release of the remaining drug for up to 48 h, while the (3) 3D printing presented an extended release beyond 7 days as the polymer degraded. The cytocompatibility of the vancomycin-loaded scaffolds was also confirmed.

Physicochemical Properties of 3D-Printed Polylactic Acid/Hydroxyapatite Scaffolds.

The reconstruction or regeneration of damaged bone tissue is one of the challenges of orthopedic surgery and tissue engineering. Among all strategies investigated, additive manufacturing by fused deposition modeling (3D-FDM printing) opens the possibility to obtain patient-specific scaffolds with controlled architectures. The present work evaluates in depth 3D direct printing, avoiding the need for a pre-fabricated filament, to obtain bone-related scaffolds from direct mixtures of polylactic acid (PLA) and hydroxyapatite (HA). For it, a systematic physicochemical characterization (SEM-EDS, FT-Raman, XRD, micro-CT and nanoindentation) was performed, using different PLA/HA ratios and percentages of infill. Results prove the versatility of this methodology with an efficient HA incorporation in the 3D-printed scaffolds up to 13 wt.% of the total mass and a uniform distribution of the HA particles in the scaffold at the macro level, both longitudinal and cross sections. Moreover, an exponential distribution of the HA particles from the surface toward the interior of the biocomposite cord (micro level), within the first 80 µm (10% of the entire cord diameter), is also confirmed, providing the scaffold with surface roughness and higher bioavailability. In relation to the pores, they can range in size from 250 to 850 µm and can represent a percentage, in relation to the total volume of the scaffold, from 24% up to 76%. The mechanical properties indicate an increase in Young's modulus with the HA content of up to ~50%, compared to the scaffolds without HA. Finally, the in vitro evaluation confirms MG63 cell proliferation on the 3D-printed PLA/HA scaffolds after up to 21 days of incubation.

Review article laser-induced hyperthermia on graphene oxide composites.

BACKGROUND: Hyperthermia-based therapies have shown great potential for clinical applications such as for the antitumor and antipathogenic activities. Within all strategies, the so-called photothermal therapy proposes to induce the hyperthermia by the remote laser radiation on a photothermal conversion agent, in contact with the target tissue. METHODS: This paper reviews the most relevant in vitro and in vivo studies focused on NIR laser-induced hyperthermia due to photoexcitation of graphene oxide (GO) and reduced graphene oxide (rGO). Relevant parameters such as the amount of GO/rGO, the influence of the laser wavelength and power density are considered. Moreover, the required temperature and exposure time for each antitumor/antipathogenic case are collected and unified in a thermal dose parameter: the CEM43. RESULTS: The calculated CEM43 thermal doses revealed a great variability for the same type of tumor/strain. In order to detect potential tendencies, the values were classified into four ranges, varying from CEM43 < 60 min to CEM43 ≥ 1 year. Thus, a preference for moderate thermal doses of CEM43 < 1 year was detected in antitumor activity, with temperatures ≤ 50 °C and exposure time ≤ 15 min. In case of the antipathogenic studies, the most used thermal dose was higher, CEM43 ≥ 1 year, with ablative hyperthermia (> 60ºC). CONCLUSIONS: The ability of GO/rGO as effective photothermal conversion agents to promote a controlled hyperthermia is proven. The variability found for the CEM43 thermal doses on the reviewed studies reveals the potentiality to evaluate, for each application, the use of lower temperatures, by modulating time and/or repetitions in the doses.

3D-Printed PLA Medical Devices: Physicochemical Changes and Biological Response after Sterilisation Treatments.

Polylactic acid (PLA) has become one of the most commonly used polymers in medical devices given its biocompatible, biodegradable and bioabsorbable properties. In addition, due to PLA's thermoplastic behaviour, these medical devices are now obtained using 3D printing technologies. Once obtained, the 3D-printed PLA devices undergo different sterilisation procedures, which are essential to prevent infections. This work was an in-depth study of the physicochemical changes caused by novel and conventional sterilisation techniques on 3D-printed PLA and their impact on the biological response in terms of toxicity. The 3D-printed PLA physicochemical (XPS, FTIR, DSC, XRD) and mechanical properties as well as the hydrophilic degree were evaluated after sterilisation using saturated steam (SS), low temperature steam with formaldehyde (LTSF), gamma irradiation (GR), hydrogen peroxide gas plasma (HPGP) and CO2 under critical conditions (SCCO). The biological response was tested in vitro (fibroblasts NCTC-929) and in vivo (embryos and larvae wild-type zebrafish Danio rerio). The results indicated that after GR sterilisation, PLA preserved the O:C ratio and the semi-crystalline structure. Significant changes in the polymer surface were found after HPGP, LTSF and SS sterilisations, with a decrease in the O:C ratio. Moreover, the FTIR, DSC and XRD analysis revealed PLA crystallisation after SS sterilisation, with a 52.9% increase in the crystallinity index. This structural change was also reflected in the mechanical properties and wettability. An increase in crystallinity was also observed after SCCO and LTSF sterilisations, although to a lesser extent. Despite these changes, the biological evaluation revealed that none of the techniques were shown to promote the release of toxic compounds or PLA modifications with toxicity effects. GR sterilisation was concluded as the least reactive technique with good perspectives in the biological response, not only at the level of toxicity but at all levels, since the 3D-printed PLA remained almost unaltered.

How to Sterilize Polylactic Acid Based Medical Devices?

How sterilization techniques accurately affect the properties of biopolymers continues to be an issue of discussion in the field of biomedical engineering, particularly now with the development of 3D-printed devices. One of the most widely used biopolymers in the manufacture of biomedical devices is the polylactic acid (PLA). Despite the large number of studies found in the literature on PLA devices, relatively few papers focus on the effects of sterilization treatments on its properties. It is well documented in the literature that conventional sterilization techniques, such as heat, gamma irradiation and ethylene oxide, can induced damages, alterations or toxic products release, due to the thermal and hydrolytical sensitivity of PLA. The purposes of this paper are, therefore, to review the published data on the most common techniques used to sterilize PLA medical devices and to analyse how they are affecting their physicochemical and biocompatible properties. Emerging and alternative sterilization methods for sensitive biomaterials are also presented.

Characterization and Cytotoxic Effect of Biosurfactants Obtained from Different Sources.

In this work, five biosurfactant extracts, obtained from different sources, all of them with demonstrated antimicrobial properties, were characterized and subjected to a cytotoxic study using mouse fibroblast cells (NCTC clone 929). Biosurfactant extracts obtained directly from corn steep water (CSW) showed similar surfactant characteristics to those of the extracellular biosurfactant extract produced by Bacillus isolated from CSW and grown in tryptic soy broth, observing that they are amphoteric, consisting of viscous and yellowish liquid with no foaming capacity. Contrarily, cell-bound biosurfactant extracts produced from Lactobacillus pentosus or produced by Bacillus sp isolated from CSW are nonionic, consisting of a white powder with foaming capacity. All the biosurfactants possess a similar fatty acid composition. The cytotoxic test revealed that the extracts under evaluation, at a concentration of 1 g/L, were not cytotoxic for fibroblasts (fibroblast growth > 90%). The biosurfactant extract obtained from CSW with ethyl acetate, at 1 g/L, showed the highest cytotoxic effect but above the cytotoxicity limit established by the UNE-EN-ISO10993-5. It is remarkable that the cell-bound biosurfactant produced by L. pentosus, at a concentration of 1 g/L, promoted the growth of the fibroblast up to 113%.

Stage progression and need for renal replacement therapy in a renal protection programme in Colombia. A cohort study. / Progreso de estadio y requerimiento de terapia de reemplazo renal en un programa de protección renal en Colombia. Estudio de cohorte.

BACKGROUND: Due to the global burden represented by chronic kidney disease (CKD), the World Health Organization encouraged the implementation of renal protection programmes (RPP) to affect its incidence through prevention and control measures. OBJECTIVES: To assess the effectiveness of a Colombian RPP in terms of its effect on the stage progression of CKD and the need for renal replacement therapy (RRT). METHODS: An analytical study that monitored 2cohorts of patients diagnosed with CKD. The study compares the behaviour of clinical and renal impairment indicators from patients exposed to a RPP with that of patients following conventional treatment (CT). The population of both intervention groups was considered when determining the sample size. The incidence rate was calculated as well as patient survival (Kaplan Meier). In addition, a multivariate analysis (Cox) was used to calculate the influence that exposure to the RPP had on the outcomes of the patients following the RPP and those following CT. RESULTS: The patients exposed to the RPP took longer to advance to the next CKD stage and require RRT. The incidence rate for progression is higher for the patients following CT (0.050, IC 95%: 0.040-0.064) compared to those in the RPP (0.034, IC 95%: 0.030-0.039). The ratio of incidence rates was 1.480 (IC 95% 1.21-1.90). The hazard of progression was lower for the RPP (HR: 0.855, IC 95%: 0.74- 0.98), as was the hazard of requiring RRT (HR: 0.797, IC 95%: 0.606-1.049). CONCLUSIONS: The RPP is a secondary prevention strategy against CKD which has an effect on the stage progression of CKD and the need for RRT. Early patient detection has a positive effect on the outcomes studied.

Progreso de estadio y requerimiento de terapia de reemplazo renal en un programa de protección renal en Colombia. Estudio de cohorte / Stage progression and need for renal replacement therapy in a renal protection programme in Colombia. A cohort study

Antecedentes: Debido a la carga global de la enfermedad renal crónica (ERC), la Organización Mundial de la Salud fomentó programas de protección renal (PPR) para impactar en su incidencia con medidas de prevención y control. Objetivos: Evaluar la efectividad de un PPR en Colombia sobre el progreso de estadio en ERC y el requerimiento de terapia de reemplazo renal (TRR). Métodos: Estudio analítico de seguimiento a 2cohortes de pacientes con diagnóstico de ERC, que compara el comportamiento de indicadores clínicos y de deterioro renal entre pacientes expuestos a un PPR versus el tratamiento convencional (TC). Como tamaño de muestra se tuvo en cuenta el censo de la población de ambas aseguradoras. Se calculó la tasa de incidencia, la supervivencia (Kaplan Meier) y la influencia de la exposición al PPR sobre los desenlaces entre PPR y TC mediante un análisis multivariado (Cox). Resultados: Los pacientes expuestos al PPR se demoraron más en hacer el primer progreso de estadio y en requerir TRR. La tasa de incidencia para progreso es mayor en TC (0,050; IC 95%: 0,040-0,064) que en PPR (0,034: IC 95%: 0,030-0,039). Razón de tasas de incidencia: 1,480 (IC 95%: 1,21-1,90). El riesgo instantáneo de progreso fue menor en PPR (HR: 0,855; IC 95%: 0,74-0,98), al igual que el riesgo de requerir TRR (HR: 0,797; IC 95%: 0,606-1,049). Conclusiones: El PPR representa una estrategia de prevención secundaria en ERC que impacta en el progreso de estadio y requerimiento de TRR. La captación temprana de pacientes mejora dichos desenlaces (AU)

Background: Due to the global burden represented by chronic kidney disease (CKD), the World Health Organization encouraged the implementation of renal protection programmes (RPP) to affect its incidence through prevention and control measures. Objectives: To assess the effectiveness of a Colombian RPP in terms of its effect on the stage progression of CKD and the need for renal replacement therapy (RRT). Methods: An analytical study that monitored 2cohorts of patients diagnosed with CKD. The study compares the behaviour of clinical and renal impairment indicators from patients exposed to a RPP with that of patients following conventional treatment (CT). The population of both intervention groups was considered when determining the sample size. The incidence rate was calculated as well as patient survival (Kaplan Meier). In addition, a multivariate analysis (Cox) was used to calculate the influence that exposure to the RPP had on the outcomes of the patients following the RPP and those following CT. Results: The patients exposed to the RPP took longer to advance to the next CKD stage and require RRT. The incidence rate for progression is higher for the patients following CT (0.050, IC 95%: 0.040-0.064) compared to those in the RPP (0.034, IC 95%: 0.030-0.039). The ratio of incidence rates was 1.480 (IC 95% 1.21-1.90). The hazard of progression was lower for the RPP (HR: 0.855, IC 95%: 0.74- 0.98), as was the hazard of requiring RRT (HR: 0.797, IC 95%: 0.606-1.049). Conclusions: The RPP is a secondary prevention strategy against CKD which has an effect on the stage progression of CKD and the need for RRT. Early patient detection has a positive effect on the outcomes studied (AU)