The Effects of Fucoidan Derived from Sargassum filipendula and Fucus vesiculosus on the Survival and Mineralisation of Osteogenic Progenitors.

Osteosarcoma is a bone cancer primarily affecting teenagers. It has a poor prognosis and diminished quality of life after treatment due to chemotherapy side effects, surgical complications and post-surgical osteoporosis risks. The sulphated polysaccharide fucoidan, derived from brown algae, has been a subject of interest for its potential anti-cancer properties and its impact on bone regeneration. This study explores the influence of crude, low-molecular-weight (LMW, 10-50 kDa), medium-molecular-weight (MMW, 50-100 kDa) and high-molecular-weight (HMW, >100 kDa) fractions from Sargassum filipendula, harvested from the Colombian sea coast, as well as crude fucoidan from Fucus vesiculosus, on a specific human osteoprogenitor cell type, human embryonic-derived mesenchymal stem cells. Fourier transform infrared spectroscopy coupled with attenuated total reflection (FTIR-ATR) results showed the highest sulphation levels and lowest uronic acid content in crude extract from F. vesiculosus. There was a dose-dependent drop in focal adhesion formation, proliferation and osteogenic differentiation of cells for all fucoidan types, but the least toxicity was observed for LMW and MMW. Transmission electron microscopy (TEM), JC-1 (5,50,6,60-tetrachloro-1,10,3,30-tetraethylbenzimi-dazolylcarbocyanine iodide) staining and cytochrome c analyses confirmed mitochondrial damage, swollen ER and upregulated autophagy due to fucoidans, with the highest severity in the case of F. vesiculosus fucoidan. Stress-induced apoptosis-like cell death by F. vesiculosus fucoidan and stress-induced necrosis-like cell death by S. filipendula fucoidans were also confirmed. LMW and MMW doses of <200 ng/mL were the least toxic and showed potential osteoinductivity. This research underscores the multifaceted impact of fucoidans on osteoprogenitor cells and highlights the delicate balance between potential therapeutic benefits and the challenges involved in using fucoidans for post-surgery treatments in patients with osteosarcoma.

Indocyanine green and iohexol loaded hydroxyapatite in poly(L-lactide-co-caprolactone)-based composite for bimodal near-infrared fluorescence- and X-ray-based imaging.

This study aimed to develop material for multimodal imaging by means of X-ray and near-infrared containing FDA- and EMA-approved iohexol and indocyanine green (ICG). The mentioned contrast agents (CAs) are hydrophilic and amphiphilic, respectively, which creates difficulties in fabrication of functional polymeric composites for fiducial markers (FMs) with usage thereof. Therefore, this study exploited for the first time the possibility of enhancing the radiopacity and introduction of the NIR fluorescence of FMs by adsorption of the CAs on hydroxyapatite (HAp) nanoparticles. The particles were embedded in the poly(L-lactide-co-caprolactone) (P[LAcoCL]) matrix resulting in the composite material for bimodal near-infrared fluorescence- and X-ray-based imaging. The applied method of material preparation provided homogenous distribution of both CAs with high iohexol loading efficiency and improved fluorescence signal due to hindered ICG aggregation. The material possessed profound contrasting properties for both imaging modalities. Its stability was evaluated during in vitro experiments in phosphate-buffered saline (PBS) and foetal bovine serum (FBS) solutions. The addition of HAp nanoparticles had significant effect on the fluorescence signal. The X-ray radiopacity was stable within minimum 11 weeks, even though the addition of ICG contributed to a faster release of iohexol. The stiffness of the material was not affected by iohexol or ICG, but incorporation of HAp nanoparticles elevated the values of bending modulus by approximately 70%. Moreover, the performed cell study revealed that all tested materials were not cytotoxic. Thus, the developed material can be successfully used for fabrication of FMs.

Surgical Management of Tophaceous Gout in the Upper Limb.

PURPOSE: Gouty tophi are a clinical manifestation of hyperuricemia in advanced stages. They can produce pain, functional limitation, and severe deformities. Patients with severe symptoms require short-term symptomatic solutions that standard medical management is not able to provide. The objective of this study was to present the results obtained with the surgical management of tophaceous gout in the upper limb, as well as present a detailed characterization of the disease in the upper limb. METHODS: Databases of the hand surgery service of a quaternary care hospital were reviewed to identify patients aged >18 years old undergoing tophi resection in the upper limbs between 2014 and 2020. Medical history records were reviewed retrospectively, and the relevant data were extracted to establish demographic profile, clinical presentation, anatomic distribution, postoperative outcomes, and additional procedures required. RESULTS: The most frequent symptom was pain (83%), followed by limited range of motion (56%), deformity (50%), and daily living/occupational activity limitation (28%). The main indications for surgical management were the presence of deformity, pain, and/or limited range of motion. The most frequently affected anatomic sites were the metacarpophalangeal joints, followed by the elbows, proximal interphalangeal joints, and proximal phalanges. The postoperative complication rate was 28%. The most common complications were operative site infections and wound dehiscence. Decreased pain was associated with surgical resection. Additional procedures, such as extensor tenorrhaphy and local flaps, were required in 47.2% of patients. CONCLUSION: Surgical resection of tophi can decrease pain. Although surgery is associated with a high rate of complications, most are minor. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

In vitro and in vivo degradation behavior of Mg-0.45Zn-0.45Ca (ZX00) screws for orthopedic applications.

Magnesium (Mg) alloys have become a potential material for orthopedic implants due to their unnecessary implant removal, biocompatibility, and mechanical integrity until fracture healing. This study examined the in vitro and in vivo degradation of an Mg fixation screw composed of Mg-0.45Zn-0.45Ca (ZX00, in wt.%). With ZX00 human-sized implants, in vitro immersion tests up to 28 days under physiological conditions, along with electrochemical measurements were performed for the first time. In addition, ZX00 screws were implanted in the diaphysis of sheep for 6, 12, and 24 weeks to assess the degradation and biocompatibility of the screws in vivo. Using scanning electron microscopy (SEM) coupled with energy dispersive X-ray spectroscopy (EDX), micro-computed tomography (µCT), X-ray photoelectron spectroscopy (XPS), and histology, the surface and cross-sectional morphologies of the corrosion layers formed, as well as the bone-corrosion-layer-implant interfaces, were analyzed. Our findings from in vivo testing demonstrated that ZX00 alloy promotes bone healing and the formation of new bone in direct contact with the corrosion products. In addition, the same elemental composition of corrosion products was observed for in vitro and in vivo experiments; however, their elemental distribution and thicknesses differ depending on the implant location. Our findings suggest that the corrosion resistance was microstructure-dependent. The head zone was the least corrosion-resistant, indicating that the production procedure could impact the corrosion performance of the implant. In spite of this, the formation of new bone and no adverse effects on the surrounding tissues demonstrated that the ZX00 is a suitable Mg-based alloy for temporary bone implants.

Magnesium implant degradation provides immunomodulatory and proangiogenic effects and attenuates peri-implant fibrosis in soft tissues.

Implants made of magnesium (Mg) are increasingly employed in patients to achieve osteosynthesis while degrading in situ. Since Mg implants and Mg2+ have been suggested to possess anti-inflammatory properties, the clinically observed soft tissue inflammation around Mg implants is enigmatic. Here, using a rat soft tissue model and a 1-28 d observation period, we determined the temporo-spatial cell distribution and behavior in relation to sequential changes of pure Mg implant surface properties and Mg2+ release. Compared to nondegradable titanium (Ti) implants, Mg degradation exacerbated initial inflammation. Release of Mg degradation products at the tissue-implant interface, culminating at 3 d, actively initiated chemotaxis and upregulated mRNA and protein immunomodulatory markers, particularly inducible nitric oxide synthase and toll-like receptor-4 up to 6 d, yet without a cytotoxic effect. Increased vascularization was demonstrated morphologically, preceded by high expression of vascular endothelial growth factor. The transition to appropriate tissue repair coincided with implant surface enrichment of Ca and P and reduced peri-implant Mg2+ concentration. Mg implants revealed a thinner fibrous encapsulation compared with Ti. The detailed understanding of the relationship between Mg material properties and the spatial and time-resolved cellular processes provides a basis for the interpretation of clinical observations and future tailoring of Mg implants.

The combined effect of zinc and calcium on the biodegradation of ultrahigh-purity magnesium implants.

Magnesium (Mg)-based implants are promising candidates for orthopedic interventions, because of their biocompatibility, good mechanical features, and ability to degrade completely in the body, eliminating the need for an additional removal surgery. In the present study, we synthesized and investigated two Mg-based materials, ultrahigh-purity ZX00 (Mg-Zn-Ca; <0.5 wt% Zn and <0.5 wt% Ca, in wt%; Fe-content <1 ppm) and ultrahigh-purity Mg (XHP-Mg, >99.999 wt% Mg; Fe-content <1 ppm), in vitro and in vivo in juvenile healthy rats to clarify the effect of the alloying elements Zn and Ca on mechanical properties, microstructure, cytocompatibility and degradation rate. Potential differences in bone formation and bone in-growth were also assessed and compared with state-of-the-art non-degradable titanium (Ti)-implanted, sham-operated, and control (non-intervention) groups, using micro-computed tomography, histology and scanning electron microscopy. At 6 and 24 weeks after implantation, serum alkaline phosphatase (ALP), calcium (Ca), and Mg level were measured and bone marrow stromal cells (BMSCs) were isolated for real-time PCR analysis. Results show that ZX00 implants have smaller grain size and superior mechanical properties than XHP-Mg, and that both reveal good biocompatibility in cytocompatibilty tests. ZX00 homogenously degraded with an increased gas accumulation 12 and 24 weeks after implantation, whereas XHP-Mg exhibited higher gas accumulation already at 2 weeks. Serum ALP, Ca, and Mg levels were comparable among all groups and both Mg-based implants led to similar relative expression levels of Alp, Runx2, and Bmp-2 genes at weeks 6 and 24. Histologically, Mg-based implants are superior for new bone tissue formation and bone in-growth compared to Ti implants. Furthermore, by tracking the sequence of multicolor fluorochrome labels, we observed higher mineral apposition rate at week 2 in both Mg-based implants compared to the control groups. Our findings suggest that (i) ZX00 and XHP-Mg support bone formation and remodeling, (ii) both Mg-based implants are superior to Ti implants in terms of new bone tissue formation and osseointegration, and (iii) ZX00 is more favorable due to its lower degradation rate and moderate gas accumulation.

Lesiones y muertes no intencionales en el departamento de Antioquia, Colombia. Estudio observacional descriptivo, 2016 y 2017 / Unintentional injuries and deaths in the department of Antioquia, Colombia. An observational descriptive study, 2016 - 2017

Introducción: la Organización Mundial de la Salud considera a las lesiones accidentales o lesiones no intencionales (LNI) como un problema de salud pública por su efecto sobre la discapacidad y mortalidad en la población general. Objetivo: presentar y analizar los datos de LNI y muertes accidentales registrados por el Instituto Nacional de Medicina Legal y Ciencias Forenses en el departamento de Antioquia, durante los años 2016 y 2017. Métodos: estudio descriptivo basado en la información recolectada por el Instituto Nacional de Medicina Legal y Ciencias Forenses. Se calcula ron las tasas de lesionados y muertes por 100.000 habitantes/año y el análisis estadístico se realizó con el paquete estadístico SPSS® versión 24.0. Resultados: durante 2016 y 2017 se registró una tasa de morbilidad de LNI de 7,86 y 7,21 casos por 100.000 habitantes, respectivamente, similar a la del promedio nacional. Fue mayor el número de casos en hombres que en mujeres, principalmente entre los 18 y los 34 años. La tasa de mortalidad reportada fue de 10,10 y 11,05 por cada 100.000 habitantes para el mismo periodo. Las LNI fueron más frecuentes en personas con bajo nivel educativo, del área urbana, y el mecanismo traumático más frecuente fue el contundente. Conclusiones: este estudio evidencia disminución en las tasas de LNI y aumento de la mortalidad accidental en Antioquia, comparada con años anteriores. Dicho comportamiento es diferente a lo reportado por la literatura internacional. Se requieren investigaciones que analicen otras fuentes generadoras de información acerca de las LNI, con la finalidad de estimar con mayor precisión la ocurrencia del fenómeno y sus variables asociadas.

Background: The World Health Organization con siders unintentional injuries (UI) as an international public health problem, due to their effect on disability and mortality in the general population. Objective: To present and analyze the data on UI and accidental death collected by the National Institute of Legal Medicine and Forensic Sciences in the Department of Antioquia, Colombia, between 2016 and 2017. Methods: Descriptive study based on the information collected by the National Institute of Legal Medicine and Forensic Sciences. The rates of injuries and deaths per 100,000 inhabitants / year were calculated, and the statistical analysis was made using SPSS® version 24.0. Results: In the years 2016 and 2017, there was a morbidity rate of UI of 7.86 and 7.21 cases per 100,000 inhabitants, respectively, similar to the national average. The number of cases was greater in men than in women, mainly between 18 and 34 years of age. The reported accidental mortality rate was 10.10 and 11.05 per 100,000 inhabitants for the years 2016 and 2017, respectively. The UI were more frequent in people with low educational level, from the urban area, and the most frequent traumatic mechanism was the blunt one. Conclusions: This study shows a reduction in the rates of UI and an increase of the rates of accidental death in Antioquia compared to the previous years. This trend is different to the previously reported on international literature. More studies analyzing other sources of information on variables like UI are needed in this field, in order to precisely estimate the occurrence of this event and its associated variables.

Fucoidan Inhibition of Osteosarcoma Cells Is Species and Molecular Weight Dependent.

Fucoidan is a brown algae-derived polysaccharide having several biomedical applications. This study simultaneously compares the anti-cancer activities of crude fucoidans from Fucus vesiculosus and Sargassum filipendula, and effects of low (LMW, 10-50 kDa), medium (MMW, 50-100 kDa) and high (HMW, >100 kDa) molecular weight fractions of S. filipendula fucoidan against osteosarcoma cells. Glucose, fucose and acid levels were lower and sulphation was higher in F. vesiculosus crude fucoidan compared to S. filipendula crude fucoidan. MMW had the highest levels of sugars, acids and sulphation among molecular weight fractions. There was a dose-dependent drop in focal adhesion formation and proliferation of cells for all fucoidan-types, but F. vesiculosus fucoidan and HMW had the strongest effects. G1-phase arrest was induced by F. vesiculosus fucoidan, MMW and HMW, however F. vesiculosus fucoidan treatment also caused accumulation in the sub-G1-phase. Mitochondrial damage occurred for all fucoidan-types, however F. vesiculosus fucoidan led to mitochondrial fragmentation. Annexin V/PI, TUNEL and cytochrome c staining confirmed stress-induced apoptosis-like cell death for F. vesiculosus fucoidan and features of stress-induced necrosis-like cell death for S. filipendula fucoidans. There was also variation in penetrability of different fucoidans inside the cell. These differences in anti-cancer activity of fucoidans are applicable for osteosarcoma treatment.