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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Biomimetic Gradient Scaffolds Containing Hyaluronic Acid and Sr/Zn Folates for Osteochondral Tissue Engineering.

Regenerative therapies based on tissue engineering are becoming the most promising alternative for the treatment of osteoarthritis and rheumatoid arthritis. However, regeneration of full-thickness articular osteochondral defects that reproduces the complexity of native cartilage and osteochondral interface still remains challenging. Hence, in this work, we present the fabrication, physic-chemical characterization, and in vitro and in vivo evaluation of biomimetic hierarchical scaffolds that mimic both the spatial organization and composition of cartilage and the osteochondral interface. The scaffold is composed of a composite porous support obtained by cryopolymerization of poly(ethylene glycol) dimethacrylate (PEGDMA) in the presence of biodegradable poly(D,L-lactide-co-glycolide) (PLGA), bioactive tricalcium phosphate ß-TCP and the bone promoting strontium folate (SrFO), with a gradient biomimetic photo-polymerized methacrylated hyaluronic acid (HAMA) based hydrogel containing the bioactive zinc folic acid derivative (ZnFO). Microscopical analysis of hierarchical scaffolds showed an open interconnected porous open microstructure and the in vitro behaviour results indicated high swelling capacity with a sustained degradation rate. In vitro release studies during 3 weeks indicated the sustained leaching of bioactive compounds, i.e., Sr2+, Zn2+ and folic acid, within a biologically active range without negative effects on human osteoblast cells (hOBs) and human articular cartilage cells (hACs) cultures. In vitro co-cultures of hOBs and hACs revealed guided cell colonization and proliferation according to the matrix microstructure and composition. In vivo rabbit-condyle experiments in a critical-sized defect model showed the ability of the biomimetic scaffold to promote the regeneration of cartilage-like tissue over the scaffold and neoformation of osteochondral tissue.

Influence of the chitosan morphology on the properties of acrylic cements and their biocompatibility.

Acrylic bone cements (ABC) are materials widely used in orthopedics and biomedical applications. Several active compounds have been introduced to ABC formulations to improve their mechanical properties and bifunctionality. In this research, we studied the effect of the addition of chitosan (CS) microspheres and chitosan sheets on ABC formulations. For mechanical performance optimization, the compression strength was taken as a response variable using an extreme vertices mixing design with fraction by weight of CS and poly(methyl methacrylate) (PMMA) as the variable factors. According to the statistical analysis, the control samples (without CS), samples with 7% (wt.) of CS sheets, and samples with 17% (wt.) of CS spheres presented the best compression properties: 90.6 MPa and 95.6 MPa, respectively. The study of these formulations confirmed that CS spheres allow a higher amount of loading on the formulation, maintaining comparable compression strength. By 1H-NMR, it was observed that the residual monomer was similar in all wording. The hydrolytic degradation assay in simulated body fluid (SBF) determined that the sphere incorporation increased by 50% and 35% for the water uptake and weight loss values, respectively, when compared with the reported values with CS sheets. By morphological analysis via SEM, it was observed that the porosity increased considerably in the presence of CS spheres throughout the immersion time in SBF. The subdermal implant results demonstrated excellent compatibility between the cement studied and the biological environment.

Achievements in the Topographic Design of Commercial Titanium Dental Implants: Towards Anti-Peri-Implantitis Surfaces.

Titanium and its alloys constitute the gold standard materials for oral implantology in which their performance is mainly conditioned by their osseointegration capacity in the host's bone. We aim to provide an overview of the advances in surface modification of commercial dental implants analyzing and comparing the osseointegration capacity and the clinical outcome exhibited by different surfaces. Besides, the development of peri-implantitis constitutes one of the most common causes of implant loss due to bacteria colonization. Thus, a synergic response from industry and materials scientists is needed to provide reliable technical and commercial solutions to this issue. The second part of the review focuses on an update of the recent findings toward the development of new materials with osteogenic and antibacterial capacity that are most likely to be marketed, and their correlation with implant geometry, biomechanical behavior, biomaterials features, and clinical outcomes.

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.

HDPE/Chitosan Composites Modified with PE-g-MA. Thermal, Morphological and Antibacterial Analysis.

In this work, composites of high density polyethylene (HDPE) with chitosan were prepared by melt compounding in a laboratory internal mixer. Maleic anhydride grafted HDPE (PE-g-MA) in a concentration up to 25 phr was used as a compatibilizer to enhance the dispersing effect of chitosan in the HDPE matrix. The degree of crystallinity was investigated by X-ray diffraction (XRD) and the thermal properties were analyzed by differential scanning calorimetry (DSC) and thermogravimetry (TG). The morphology was investigated by optical microscopy (OM) and scanning electron microscopy (SEM). The integrity of composites was evaluated by mechanical properties and antibacterial properties were assessed against Escherichia coli (DH5a). Neither crystallinity nor HDPE's melting parameters changed upon addition of chitosan and PE-g-MA. Chitosan aggregates were observed, which were dispersed upon addition of PE-g-MA, which also provided improved mechanical performance. Chitosan significantly improved the bacteriostatic effect of HDPE compounds preventing bacteria to colonize thus reducing the number of viable colony-forming units (CFU). This study revealed that HDPE/chitosan composites could be obtained by melt compounding, at lower cost and additionally having antibacterial properties, which might provide a new formulation option for developing antimicrobial film for food packaging.

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.

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.