Development of Methotrexate Complexes Endowed with New Biological Properties Envisioned for Musculoskeletal Regeneration in Rheumatoid Arthritis Environments.

Methotrexate (MTX) administration is the gold standard treatment for rheumatoid arthritis (RA), but its effects are limited to preventing the progression of the disease. Therefore, effective regenerative therapies for damaged tissues are still to be developed. In this regard, MTX complexes of general molecular formula M(MTX)·xH2O, where M = Sr, Zn, or Mg, were synthesized and physicochemically characterized by TGA, XRD, NMR, ATR-FTIR, and EDAX spectroscopies. Characterization results demonstrated the coordination between the different cations and MTX via two monodentate bonds with the carboxylate groups of MTX. Cation complexation provided MTX with new bioactive properties such as increasing the deposition of glycosaminoglycans (GAGs) and alternative anti-inflammatory capacities, without compromising the immunosuppressant properties of MTX on macrophages. Lastly, these new complexes were loaded into spray-dried chitosan microparticles as a proof of concept that they can be encapsulated and further delivered in situ in RA-affected joints, envisioning them as a suitable alternative to oral MTX therapy.

Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications.

: Bacterial, protozoan and other microbial infections share an accelerated metabolic rate. In order to ensure a proper functioning of cell replication and proteins and nucleic acids synthesis processes, folate metabolism rate is also increased in these cases. For this reason, folic acid antagonists have been used since their discovery to treat different kinds of microbial infections, taking advantage of this metabolic difference when compared with human cells. However, resistances to these compounds have emerged since then and only combined therapies are currently used in clinic. In addition, some of these compounds have been found to have an immunomodulatory behavior that allows clinicians using them as anti-inflammatory or immunosuppressive drugs. Therefore, the aim of this review is to provide an updated state-of-the-art on the use of antifolates as antibacterial and immunomodulating agents in the clinical setting, as well as to present their action mechanisms and currently investigated biomedical applications.

Biomaterials for Cleft Lip and Palate Regeneration.

Craniofacial bone defect anomalies affect both soft and hard tissues and can be caused by trauma, bone recessions from tumors and cysts, or even from congenital disorders. On this note, cleft/lip palate is the most prevalent congenital craniofacial defect caused by disturbed embryonic development of soft and hard tissues around the oral cavity and face area, resulting in most cases, of severe limitations with chewing, swallowing, and talking as well as problems of insufficient space for teeth, proper breathing, and self-esteem problems as a consequence of facial appearance. Spectacular advances in regenerative medicine have arrived, giving new hope to patients that can benefit from new tissue engineering therapies based on the supportive action of 3D biomaterials together with the synergic action of osteo-inductive molecules and recruited stem cells that can be driven to the process of bone regeneration. However, few studies have focused on the application of tissue engineering to the regeneration of the cleft/lip and only a few have reported significant advances to offer real clinical solutions. This review provides an updated and deep analysis of the studies that have reported on the use of advanced biomaterials and cell therapies for the regeneration of cleft lip and palate regeneration.

Novel Bioactive and Antibacterial Acrylic Bone Cement Nanocomposites Modified with Graphene Oxide and Chitosan.

Acrylic bone cements (ABCs) have played a key role in orthopedic surgery mainly in arthroplasties, but their use is increasingly extending to other applications, such as remodeling of cancerous bones, cranioplasties, and vertebroplasties. However, these materials present some limitations related to their inert behavior and the risk of infection after implantation, which leads to a lack of attachment and makes necessary new surgical interventions. In this research, the physicochemical, thermal, mechanical, and biological properties of ABCs modified with chitosan (CS) and graphene oxide (GO) were studied. Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (1H-NMR) scanning electron microscopy (SEM), Raman mapping, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), compression resistance, mechanical dynamic analysis (DMA), hydrolytic degradation, cell viability, alkaline phosphatase (ALP) activity with human osteoblasts (HOb), and antibacterial activity against Gram-negative bacteria Escherichia coli were used to characterize the ABCs. The results revealed good dispersion of GO nanosheets in the ABCs. GO provided an increase in antibacterial activity, roughness, and flexural behavior, while CS generated porosity, increased the rate of degradation, and decreased compression properties. All ABCs were not cytotoxic and support good cell viability of HOb. The novel formulation of ABCs containing GO and CS simultaneously, increased the thermal stability, flexural modulus, antibacterial behavior, and osteogenic activity, which gives it a high potential for its uses in orthopedic applications.

Bone Regeneration Induced by Strontium Folate Loaded Biohybrid Scaffolds.

Nowadays, regenerative medicine has paid special attention to research (in vitro and in vivo) related to bone regeneration, specifically in the treatment of bone fractures or skeletal defects, which is rising worldwide and is continually demanding new developments in the use of stem cells, growth factors, membranes and scaffolds based on novel nanomaterials, and their applications in patients by using advanced tools from molecular biology and tissue engineering. Strontium (Sr) is an element that has been investigated in recent years for its participation in the process of remodeling and bone formation. Based on these antecedents, this is a review about the Strontium Folate (SrFO), a recently developed non-protein based bone-promoting agent with interest in medical and pharmaceutical fields due to its improved features in comparison to current therapies for bone diseases.

Combination of Polymeric Supports and Drug Delivery Systems for Osteochondral Regeneration.

Musculoskeletal conditions have been defined by European National Health systems as one of the key themes which should be featured during the present decade as a consequence of the significant healthcare and social support costs. Among others, articular cartilage degeneration due to traumatic and degenerative lesion injury or other pathologies commonly results in the development of musculoskeletal disorders such as osteoarthritis and arthritis rheumatoid, eventually leading to progressive articular cartilage and joint destruction especially at osteochondral interphase, that account for more disability among the elderly than any other diseases constituting a global social challenge that needs a multidisciplinary response from the scientific community. Current treatments for damaged osteoarthritic joint cartilage include the use of disease-modifying drugs and ultimately joint arthroplasty as unavoidable surgical intervention due to the limited ability of articular cartilage to self-regenerate. However, potential future regenerative therapies based on tissue engineering strategies are likely to become more important to facilitate the recruitment of repairing cells and improve musculoskeletal metabolism. In addition, emerging bioprinting technologies in combination with implemented manufacturing techniques such electrospinning or cryogelation processes have permitted the development of new tissue substitutes with precise control of sizes and shapes to recreate the complex physiological, biomechanical and hieratical microstructure of osteochondral interphases. Thus, this chapter will provide an upgrade on the state of the art focusing the most relevant developments on polymer scaffolds and drug delivery systems for osteochondral regeneration.

Tissue Engineering Therapies Based on Folic Acid and Other Vitamin B Derivatives. Functional Mechanisms and Current Applications in Regenerative Medicine.

B-vitamins are a group of soluble vitamins which are cofactors of some of the enzymes involved in the metabolic pathways of carbohydrates, fats and proteins. These compounds participate in a number of functions as cardiovascular, brain or nervous systems. Folic acid is described as an accessible and multifunctional niche component that can be used safely, even combined with other compounds, which gives it high versatility. Also, due to its non-toxicity and great stability, folic acid has attracted much attention from researchers in the biomedical and bioengineering area, with an increasing number of works directed at using folic acid and its derivatives in tissue engineering therapies as well as regenerative medicine. Thus, this review provides an updated discussion about the most relevant advances achieved during the last five years, where folic acid and other vitamins B have been used as key bioactive compounds for enhancing the effectiveness of biomaterials' performance and biological functions for the regeneration of tissues and organs.

Risk factor assessment and counselling for 12 months reduces metabolic and cardiovascular risk in overweight or obese patients with schizophrenia spectrum disorders: The CRESSOB study.

BACKGROUND: Metabolic syndrome (MS) and cardiovascular risk factors (CRF) have been associated with patients with schizophrenia. The main objective is to assess the evolution of CRF and prevalence of MS for 12 months in a cohort of overweight patients diagnosed with schizophrenia schizophreniform disorder or schizoaffective disorder in which the recommendations for the assessment and control of metabolic and cardiovascular risk were applied. METHODS: The Control of Metabolic and Cardiovascular Risk in Patients with Schizophrenia and Overweight (CRESSOB) study is a 12-month, observational, prospective, open-label, multicentre, naturalistic study including 109 community mental health clinics of Spain. The study included a total of 403 patients, of whom we could collect all variables related to CRF and MS in 366 patients. Of these 366 patients, 286 completed the follow-up, (baseline, months 3, 6 and 12) where they underwent a complete physical examination and a blood test (glucose, cholesterol and triglycerides), they were asked about their health-related habits (smoking, diet and exercise) and they were given a series of recommendations to prevent cardiovascular risk and MS. RESULTS: A total of 403 patients were included, 63% men, mean age (mean; (SD)) 40.5 (10.5) years. After 12 months, the study showed statistically significant decrease in weight (p<0.0001), waist circumference (p<0.0001), BMI (p<0.0001), blood glucose (p=0.0034), total cholesterol (p<0.0001), HDL cholesterol (p=0.02), LDL cholesterol (p=0.0023) and triglycerides (p=0.0005). There was a significant reduction in the percentage of smokers (p=0.0057) and in the risk of heart disease at 10 years (p=0.0353). CONCLUSION: Overweight patients with schizophrenia who receive appropriate medical care, including CRF monitoring and control of health-related habits experience improvements with regard to most CRFs.

Involvement of leucocyte/endothelial cell interactions in anorexia nervosa.

BACKGROUND: Anorexia nervosa is a common psychiatric disorder in adolescence and is related to cardiovascular complications. Our aim was to study the effect of anorexia nervosa on metabolic parameters, leucocyte-endothelium interactions, adhesion molecules and proinflammatory cytokines. MATERIALS AND METHODS: This multicentre, cross-sectional, case-control study employed a population of 24 anorexic female patients and 36 controls. We evaluated anthropometric and metabolic parameters, interactions between leucocytes polymorphonuclear neutrophils (PMN) and human umbilical vein endothelial cells (HUVEC), proinflammatory cytokines such as tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and soluble cellular adhesion molecules (CAMs) including E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). RESULTS: Anorexia nervosa was related to a decrease in weight, body mass index, waist circumference, systolic blood pressure, glucose, insulin and HOMA-IR, and an increase in HDL cholesterol. These effects disappeared after adjusting for BMI. Anorexia nervosa induced a decrease in PMN rolling velocity and an increase in PMN rolling flux and PMN adhesion. Increases in IL-6 and TNF-α and adhesion molecule VCAM-1 were also observed. CONCLUSIONS: This study supports the hypothesis of an association between anorexia nervosa, inflammation and the induction of leucocyte-endothelium interactions. These findings may explain, in part at least, the increased risk of vascular disease among patients with anorexia nervosa.

[Prevalence of metabolic syndrome in Spanish patients with schizophrenia and overweight. The CRESSOB Study]. / Prevalencia del síndrome metabólico en pacientes españoles con esquizofrenia y sobrepeso. El estudio CRESSOB.

INTRODUCTION: Metabolic syndrome (MS) (visceral obesity, dyslipidemia, hyperglycemia, and hypertension), has become one of the major public-health challenges worldwide. Patients with schizophrenia are more likely to suffer from MS than the general population. OBJECTIVE: The primary aim of this study was to analyze the prevalence of MS in Spanish patients with schizophrenia and overweight and to compare the best method to calculate the MS prevalence in this population. A secondary aim of the CRESSOB study was to determine whether the presence of the metabolic syndrome (MS) is associated or not with clinical remission of schizophrenia. METHODS: The Control of Metabolic and Cardiovascular Risk in Patients with Schizophrenia and Overweight (CRESSOB) study is a 12-month, prospective, naturalistic study including 110 community mental health clinics selected at random. Each site enrolled four consecutive patients with a diagnosis of schizophrenia, according to DSM-IV TR criteria, and who were overweight (Body Mass Index (BMI) >25 kg/m2). To assess the prevalence of MS we analyzed the baseline results of the CRESSOB study. The National Cholesterol Education Program (NCEP-ATP III), the International Diabetes Federation (IDF) and the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) definitions were used to establish the presence of MS. The Positive and Negative Syndrome Scale (PANSS) was used to determine the percentage of patients in remission. Psychosocial functioning was measured by the Global Assessment of Functioning (GAF) scale. RESULTS: A total of 391 patients were enrolled in the study (mean age 40.5 years, 63.8% men). 75.9% of the patients did not meet criteria for remission, using the selected PANSS items. The mean GAF score was 52.7 (Standard Deviation (SD) 15.4). Overall, 59.0% of males and 58.3% of females fulfilled the NCEP-ATP III criteria, 71.1% of males and 65.8% of females fulfilled the IDF criteria and 70.1% of males and 65.1% of females fulfilled the AHA/ NHLBI criteria. The patients who fulfilled remission criteria were younger, had a lower BMI, and a higher GAF score. CONCLUSIONS: MS is highly prevalent in Spanish patients with schizophrenia who are overweight. Given that metabolic syndrome is an important risk factor for cardiovascular disease, these patients should receive appropriate clinical monitoring for this syndrome.

Europium-tannic acid nanocomplexes devised for bone regeneration under oxidative or inflammatory environments.

Europium ions (Eu3+) are gaining attention in the field of regenerative medicine due to increasing evidence of their osteogenic properties. However, inflammatory and oxidative environments present in many bone diseases, such as osteoporosis or rheumatoid arthritis, are known to hinder this regenerative process. Herein, we describe a straightforward synthetic procedure to prepare Eu3+-tannic acid nanocomplexes (EuTA NCs) with modulable physicochemical characteristics, as well as antioxidant, anti-inflammatory, and osteogenic properties. EuTA NCs were rationally synthesized to present different contents of Eu3+ on their structure to evaluate the effect of the cation on the biological properties of the formulations. In all the cases, EuTA NCs were stable in distilled water at physiological pH, had a highly negative surface charge (ζ ≈ -25.4 mV), and controllable size (80 < Dh < 160 nm). In vitro antioxidant tests revealed that Eu3+ complexation did not significantly alter the total radical scavenging activity (RSA) of TA but enhanced its ability to scavenge H2O2 and ferrous ions, thus improving its overall antioxidant potential. At the cellular level, EuTA NCs reduced the instantaneous toxicity of high concentrations of free TA, resulting in better antioxidant (13.3% increase of RSA vs. TA) and anti-inflammatory responses (17.6% reduction of nitric oxide production vs. TA) on cultures of H2O2- and LPS-stimulated macrophages, respectively. Furthermore, the short-term treatment of osteoblasts with EuTA NCs was found to increase their alkaline phosphatase activity and their matrix mineralization capacity. Overall, this simple and tunable platform is a potential candidate to promote bone growth in complex environments by simultaneously targeting multiple pathophysiological mechanisms of disease.

[Factors associated with abandoning from the Kangaroo Mother Program between years 2019 and 2021]. / Factores asociados al abandono del Programa Madre Canguro entre los años 2019-2021 en Colombia.

OBJECTIVE: The abandonment of the Kangaroo Mother Program is a public health problem that affects the health of premature infants. The objective of this study was to determine the factors associated with the abandonment of mothers or caregivers of premature infants in the first stage of the Kangaroo Mother Program of a Health Promoting Company (EPS) in the department of Antioquia (Colombia), between 2019 and 2021. METHODS: An observational, cross-sectional, and analytical study was carried out, where information was collected on admissions to the program (N=1,344) between 2019 and 2021. The Chi-Square likelihood ratio test was performed with crude prevalence ratio, a generalized linear model of robust variance was applied with the adjusted prevalence ratio. RESULTS: When adjusting for dropout with the independent variables, a higher probability of dropout was evidenced: with respect to the year 2020 (PR 2.44, 95% CI: 1.94-3.08, p-value=0.0001), marital status alone with support (PR 1.60, 95% CI: 0.84-3.04, p-value=0. 147), primary school completed or incomplete (PR 1.48, 95% CI 1.11-1.97, p-value=0.006), monthly income less than the current legal monthly minimum wage (CLMMW) (PR 1.26, 95% CI: 1.00-1.59, p-value=0.004) and area of residence living outside Medellin (PR 1.25, 95% CI: 1.06-1.46, p-value=0.006). CONCLUSIONS: The findings of this study can be very useful to carry out interventions in families belonging to Kangaroo Programs, with the aim of intervening risk factors associated with program dropout.

OBJECTIVE: El abandono del Programa Madre Canguro es un problema de Salud Pública, que afecta la salud de los menores prematuros. El objetivo de este estudio fue determinar los factores asociados con el abandono de las madres o cuidadores de los menores prematuros en la primera etapa del Programa Madre Canguro de una Empresa Promotora de Salud (EPS) del departamento de Antioquia (Colombia) entre 2019 y 2021. METHODS: Se realizó un estudio observacional, transversal y analítico, donde se recopiló información de los ingresos al programa (N=1.344) entre 2019 y 2021. Se realizó la prueba Chi-Cuadrado, razón de verosimilitud con razón de prevalencias crudas, se aplicó un modelo lineal generalizado de varianza robusta con la razón de prevalencias ajustadas. RESULTS: Al ajustar el abandono con las variables independientes, se evidenció mayor probabilidad de abandono: con respecto al año 2020 (RP 2,44, IC 95%: 1,94-3,08, valor p=0,0001), estado civil sola con apoyo (RP 1,60, IC 95%: 0,84-3,04, valor p=0,147), nivel académico primaria completa o incompleta (RP 1,48, IC 95% 1,11-1,97, valor p=0,006), ingreso mensual menor al salario mínimo mensual legal vigente (SMMLV) (RP 1,26, IC 95%: 1,00-1,59, valor p=0,004) y área de residencia vivir fuera de Medellín (RP 1,25, IC 95%: 1,06-1,46, valor p=0,006). CONCLUSIONS: Los hallazgos de este estudio pueden ser muy útiles para realizar intervenciones en las familias pertenecientes de los Programas Canguro, con el objetivo de intervenir factores de riesgo que se asocian con el abandono del programa.

New Insights into the In Vitro Antioxidant Routes and Osteogenic Properties of Sr/Zn Phytate Compounds.

Sr/Zn phytate compounds have been shown interest in biomaterial science, specifically in dental implantology, due to their antimicrobial effects against Streptococcus mutans and their capacity to form bioactive coatings. Phytic acid is a natural chelating compound that shows antioxidant and osteogenic properties that can play an important role in bone remodelling processes affected by oxidative stress environments, such as those produced during infections. The application of non-protein cell-signalling molecules that regulate both bone and ROS homeostasis is a promising strategy for the regeneration of bone tissues affected by oxidative stress processes. In this context, phytic acid (PA) emerged as an excellent option since its antioxidant and osteogenic properties can play an important role in bone remodelling processes. In this study, we explored the antioxidant and osteogenic properties of two metallic PA complexes bearing bioactive cations, i.e., Sr2+ (SrPhy) and Zn2+ (ZnPhy), highlighting the effect of the divalent cations anchored to phytate moieties and their capability to modulate the PA properties. The in vitro features of the complexes were analyzed and compared with those of their precursor PA. The ferrozine/FeCl2 method indicated that SrPhy exhibited a more remarkable ferrous ion affinity than ZnPhy, while the antioxidant activity demonstrated by a DPPH assay showed that only ZnPhy reduced the content of free radicals. Likewise, the antioxidant potential was assessed with RAW264.7 cell cultures. An ROS assay indicated again that ZnPhy was the only one to reduce the ROS content (20%), whereas all phytate compounds inhibited lipid peroxidation following the decreasing order of PA > SrPhy > ZnPhy. The in vitro evaluation of the phytate's osteogenic ability was performed using hMSC cells. The results showed tailored properties related to the cation bound in each complex. ZnPhy overexpressed ALP activity at 3 and 14 days, and SrPhy significantly increased calcium deposition after 21 days. This study demonstrated that Sr/Zn phytates maintained the antioxidant and osteogenic properties of PA and can be used in bone regenerative therapies involving oxidative environments, such as infected implant coatings and periodontal tissues.

Are Socially Relevant Scenes Abnormally Processed in Complex Trauma-Exposed Children?

Abnormal attentional processes to socially relevant information may underlie behavioral dysfunctional symptoms in children exposed to a complex trauma. Attentional biases to social scenes close to real-world situations and their association with behavioral symptomatology were examined in complex trauma-exposed children. A visual dot-probe task involving neutral versus emotional (i.e., threatening, sad, or happy) scenes was applied to twenty-one maltreated children (mean age 10.43; 42.8% female; 61.1% White). These children were exposed to a complex trauma (i.e., severe, repeated, multiple, prolonged, and interpersonal) and were safeguarded in a juvenile welfare home after all parental responsibility was removed. Twenty-four comparable non-maltreated children (mean age 10.13; 29.2% female; 76% White), served as control group. All participants were at risk of social exclusion and every legal representative completed the Child Behavior Checklist (CBCL). Complex trauma-exposed children showed an attentional bias toward threatening scenes, while the control group showed an attentional bias toward sad scenes. There were no differences for happy scenes between groups. Attentional bias toward threatening scenes was associated with withdrawn symptoms in complex trauma-exposed children. Children exposed to a complex trauma show an abnormal attention to threatening social situations, which can trigger maladaptive behaviors such as withdrawn. The understanding of how complex trauma-exposed children process affective environmental information may provide new targets in the social skills interventions such as diminishing maladaptive behaviors and improving coping strategies to face threatening situations.

Antimicrobial polymeric biomaterials based on synthetic, nanotechnology, and biotechnological approaches.

Antimicrobial resistance is the main threat to biomaterial failure with a huge impact on National Health Systems and patients' quality of life. Materials engineering and biotechnology have experienced great advances and have converged in the development of new and more sophisticated biomimetic systems with antimicrobial properties. In this sense, polymeric biomaterials play and will play a key role in the development of new antimicrobial devices for biomedical applications. In this Current Opinion article, we review recent and relevant advances reported in the field of polymeric biomaterials with antimicrobial properties with the potential to be applied in the clinic, that is, antimicrobial polymers, antifouling surfaces, nanodelivery systems of antibiotics and antiseptic drugs, biocide polymer-metal hybrid systems, and engineered living materials that actively interact with the pathogen. We conclude with a discussion on the implications of the results for clinical practice and future research.

Injectable Tripeptide/Polymer Nanoparticles Supramolecular Hydrogel: A Candidate for the Treatment of Inflammatory Pathologies.

Supramolecular peptide-based hydrogels attract great attention in several fields, i.e., biomedicine, catalysis, energy, and materials chemistry, due to the noncovalent nature of the self-assembly and functional tunable properties defined by the amino acid sequence. In this work, we developed an injectable hybrid supramolecular hydrogel whose formation was triggered by electrostatic interactions between a phosphorylated tripeptide, Fmoc-FFpY (F: phenylalanine, pY: phosphorylated tyrosine), and cationic polymer nanoparticles made of vinylimidazole and ketoprofen (poly(HKT-co-VI) NPs). Hydrogel formation was assessed through inverted tube tests, and its fibrillary structure, around polymer NPs, was observed by transmission electron microscopy. Interestingly, peptide self-assembly yields the formation of nontwisted and twisted fibers, which could be attributed to ß-sheets and α-helix structures, respectively, as characterized by circular dichroism and infrared spectroscopies. An increase of the elastic modulus of the Fmoc-FFpY/polymer NPs hybrid hydrogels was observed with peptide concentration as well as its injectability property, due to its shear thinning behavior and self-healing ability. After checking their stability under physiological conditions, the cytotoxicity properties of these hybrid hydrogels were evaluated in contact with human dermal fibroblasts (FBH) and murine macrophages (RAW 264.7). Finally, the Fmoc-FFpY/polymer NPs hybrid hydrogels exhibited a great nitric oxide reduction (∼67%) up to basal values of pro-inflammatory RAW 264.7 cells, thus confirming their excellent anti-inflammatory properties for the treatment of localized inflammatory pathologies.

Optimization of the Rheological Properties of Self-Assembled Tripeptide/Alginate/Cellulose Hydrogels for 3D Printing.

3D printing is an emerging and powerful technique to create shape-defined three-dimensional structures for tissue engineering applications. Herein, different alginate-cellulose formulations were optimized to be used as printable inks. Alginate (Alg) was chosen as the main component of the scaffold due to its tunable mechanical properties, rapid gelation, and non-toxicity, whereas microcrystalline cellulose (MCC) was added to the hydrogel to modulate its mechanical properties for printing. Additionally, Fmoc-FFY (Fmoc: 9-fluorenylmethoxycarbonyl; F: phenylalanine; Y: tyrosine), a self-assembled peptide that promotes cell adhesion was incorporated into the ink without modifying its rheological properties and shear-thinning behavior. Then, 3D-printed scaffolds made of Alg, 40% of MCC inks and Fmoc-FFY peptide were characterized by scanning electron microscopy and infrared spectroscopy, confirming the morphological microstructure of the hydrogel scaffolds with edged particles of MCC homogeneously distributed within the alginate matrix and the self-assembly of the peptide in a ß-sheet conformation. Finally, the cytocompatibility of the scaffolds was tested in contact with the MG63 osteosarcoma cells, confirming the absence of cytotoxic components that may compromise their viability. Interestingly, MG63 cell growth was retarded in the scaffolds containing the peptide, but cells were more likely to promote adhesive interactions with the material rather than with the other cells, indicating the benefits of the peptide in promoting biological functionality to alginate-based biomaterials.

A study on Sr/Zn phytate complexes: structural properties and antimicrobial synergistic effects against Streptococcus mutans.

Phytic acid (PA) is an abundant natural plant component that exhibits a versatility of applications benefited from its chemical structure, standing out its use as food, packing and dental additive due to its antimicrobial properties. The capacity of PA to chelate ions is also well-established and the formation and thermodynamic properties of different metallic complexes has been described. However, research studies of these compounds in terms of chemistry and biological features are still demanded in order to extend the application scope of PA complexes. The main goal of this paper is to deepen in the knowledge of the bioactive metal complexes chemistry and their bactericide activity, to extend their application in biomaterial science, specifically in oral implantology. Thus, this work presents the synthesis and structural assessment of two metallic phytate complexes bearing the bioactive cations Zn2+ and Sr2+ (ZnPhy and SrPhy respectively), along with studies on the synergic biological properties between PA and cations. Metallic phytates were synthesized in the solid-state by hydrothermal reaction leading to pure solid compounds in high yields. Their molecular formulas were C6H12024P6Sr4·5H2O and C6H12024P6Zn6·6H2O, as determined by ICP and HRES-TGA. The metal coordination bond of the solid complexes was further analysed by EDS, Raman, ATR-FTIR and solid 13C and 31P-NMR spectroscopies. Likewise, we evaluated the in vitro ability of the phytate compounds for inhibiting biofilm production of Streptococcus mutans cultures. Results indicate that all compounds significantly reduced biofilm formation (PA < SrPhy < ZnPhy), and ZnPhy even showed remarkable differences with respect to PA and SrPhy. Analysis of antimicrobial properties shows the first clues of the possible synergic effects created between PA and the corresponding cation in different cell metabolic processes. In overall, findings of this work can contribute to expand the applications of these bioactive metallic complexes in the biotechnological and biomedical fields, and they can be considered for the fabrication of anti-plaque coating systems in the dentistry field.

The Role of Polymeric Biomaterials in the Treatment of Articular Osteoarthritis.

Osteoarthritis is a high-prevalence joint disease characterized by the degradation of cartilage, subchondral bone thickening, and synovitis. Due to the inability of cartilage to self-repair, regenerative medicine strategies have become highly relevant in the management of osteoarthritis. Despite the great advances in medical and pharmaceutical sciences, current therapies stay unfulfilled, due to the inability of cartilage to repair itself. Additionally, the multifactorial etiology of the disease, including endogenous genetic dysfunctions and exogenous factors in many cases, also limits the formation of new cartilage extracellular matrix or impairs the regular recruiting of chondroprogenitor cells. Hence, current strategies for osteoarthritis management involve not only analgesics, anti-inflammatory drugs, and/or viscosupplementation but also polymeric biomaterials that are able to drive native cells to heal and repair the damaged cartilage. This review updates the most relevant research on osteoarthritis management that employs polymeric biomaterials capable of restoring the viscoelastic properties of cartilage, reducing the symptomatology, and favoring adequate cartilage regeneration properties.

Vitamin B9 derivatives as carriers of bioactive cations for musculoskeletal regeneration applications: Synthesis, characterization and biological evaluation.

The development of new drugs for musculoskeletal regeneration purposes has attracted much attention in the last decades. In this work, we present three novel vitamin B9 (folic acid)-derivatives bearing divalent cations (ZnFO, MgFO and MnFO), providing their synthesis mechanism and physicochemical characterization. In addition, a strong emphasis has been placed on evaluating their biological properties (along with our previously reported SrFO) using human mesenchymal stem cells (hMSC). In all the cases, pure folate derivatives (MFOs) with a bidentate coordination mode between the metal and the folate anion, and a 1:1 stoichiometry, were obtained in high yields. A non-cytotoxic dose of all the MFOs (50 µg/mL) was demonstrated to modulate by their own the mRNA profiles towards osteogenic-like or fibrocartilaginous-like phenotypes in basal conditions. Moreover, ZnFO increased the alkaline phosphatase activity in basal conditions, while both ZnFO and MnFO increased the matrix mineralization degree in osteoinductive conditions. Thus, we have demonstrated the bioactivity of these novel compounds and the suitability to further studied them in vivo for musculoskeletal regeneration applications.