Photon upconversion crystals doped bacterial cellulose composite films as recyclable photonic bioplastics.

Biopolymers currently utilized as substitutes for synthetic polymers in photonics applications are predominantly confined to linear optical color responses. Herein we expand their applications in non-linear optics by integrating with triplet-triplet annihilation photon upconversion crystals. A photon upconverting biomaterial is prepared by cultivating Pd(II) meso-tetraphenyl tetrabenzoporphine: 9,10-diphenyl anthracene (sensitizer: annihilator) crystals on bacterial cellulose hydrogel that serves both as host and template for the crystallization of photon upconversion chromophores. Coating with gelatin improves the material's optical transparency by adjusting the refractive indices. The prepared material shows an upconversion of 633 nm red light to 443 nm blue light, indicated by quadratic to linear dependence on excitation power density (non-linearly). Notably, components of this material are physically dis-assembled to retrieve 66 ± 1% of annihilator, at the end of life. Whereas, the residual clean biomass is subjected to biodegradation, showcasing the sustainability of the developed photonics material.

Priming Mesenchymal Stem Cells with Lipopolysaccharide Boosts the Immunomodulatory and Regenerative Activity of Secreted Extracellular Vesicles.

Background: Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been proposed as an alternative to live-cell administration for Acute Respiratory Distress Syndrome (ARDS). MSC-EVs can be chiefly influenced by the environment to which the MSCs are exposed. Here, lipopolysaccharide (LPS) priming of MSCs was used as a strategy to boost the natural therapeutic potential of the EVs in acute lung injury (ALI). Methods: The regenerative and immunemodulatory effect of LPS-primed MSC-EVs (LPS-EVs) and non-primed MSC-EVs (C-EVs) were evaluated in vitro on alveolar epithelial cells and macrophage-like THP-1 cells. In vivo, ALI was induced in adult male rats by the intrapulmonary instillation of HCl and LPS. Rats (n = 8 to 22/group) were randomized to receive a single bolus (1 × 108 particles) of LPS-EVs, C-EVs, or saline. Lung injury severity was assessed at 72 h in lung tissue and bronchoalveolar lavage. Results: In vitro, LPS-EVs improved wound regeneration and attenuated the inflammatory response triggered by the P. aeruginosa infection, enhancing the M2 macrophage phenotype. In in vivo studies, LPS-EVs, but not C-EVs, significantly decreased the neutrophilic infiltration and myeloperoxidase (MPO) activity in lung tissue. Alveolar macrophages from LPS-EVs-treated animals exhibited a reduced expression of CXCL-1, a key neutrophil chemoattractant. However, both C-EVs and LPS-EVs reduced alveolar epithelial and endothelial permeability, mitigating lung damage. Conclusions: EVs from LPS-primed MSCs resulted in a better resolution of ALI, achieving a greater balance in neutrophil infiltration and activation, while avoiding the complete disruption of the alveolar barrier. This opens new avenues, paving the way for the clinical implementation of cell-based therapies.

In situ shaping of intricated 3D bacterial cellulose constructs using sacrificial agarose and diverted oxygen inflow.

Bacterial cellulose (BC) is gathering increased attention due to its remarkable physico-chemical features. The high biocompatibility, hydrophilicity, and mechanical and thermal stability endorse BC as a suitable candidate for biomedical applications. Nonetheless, exploiting BC for tissue regeneration demands three-dimensional, intricately shaped implants, a highly ambitious endeavor. This challenge is addressed here by growing BC within a sacrificial viscoelastic medium consisting of an agarose gel cast inside polydimethylsiloxane (PDMS) molds imprinted with the features of the desired implant. BC produced with and without agarose has been compared through SEM, TGA, FTIR, and XRD, probing the mild impact of the agarose on the BC properties. As a first proof of concept, a PDMS mold shaped as a doll's ear was used to produce a BC perfect replica, even for the smallest features. The second trial comprised a doll face imprinted on a PDMS mold. In that case, the BC production included consecutive deactivation and activation of the aerial oxygen stream. The resulting BC face clone fitted perfectly and conformally with the template doll face, while its rheological properties were comparable to those of collagen. This streamlining concept conveys to the biosynthesized nanocelluloses broader opportunities for more advanced prosthetics and soft tissue engineering uses.

Acceptability of multimodal and multidisciplinary group-based program for chronic low back pain: a qualitative study.

BACKGROUND: The Programa d'Atenció Integral pels Pacients amb Dolor Crònic (PAINDOC) is a multimodal and multidisciplinary group-based program that integrates pain neuroscience education, mindfulness meditation, pain psychotherapy, Empowered Relief, and therapeutic exercise. It serves as a therapeutic option for individuals with chronic low back pain, providing them with comprehensive adaptive strategies for pain management. OBJECTIVE: This qualitative study explores participants' retrospective acceptability of the PAINDOC Program. METHODS: To ensure demographic variability and information power, a purposive sampling approach was applied. Twelve participants were interviewed through three focus groups, supplemented with four individual semi-structured interviews. Data was analyzed using reflexive thematic analysis and evaluated based on the Therapeutic Framework of Acceptability. RESULTS: Participants provide positive feedback regarding active pain coping strategies and improved self-management. While certain aspects of the Program were more emphasized, participants integrated tools from all components. Strategies included pain reconceptualization, positive self-talk, or problem-solving. The Program's ethicality was closely linked to individual values and may also be influenced by time constraints of certain program elements, the immediate effects of specific approaches, participant perceptions, and individual preferences. CONCLUSIONS: The findings provide valuable insights into the acceptability of the PAINDOC Program, guiding future improvements and the development of similar interventions.

Multidisciplinary approaches to chronic pain management have been explored and are recognized as an effective way to address the complexity of chronic pain conditions. These approaches often involve the collaboration of healthcare professionals from various disciplines.Multimodal pain management programs typically combine various treatment modalities, including physical therapy, cognitive-behavioral therapy, medication, and exercise.Studies have shown that multidisciplinary and multimodal interventions can be effective in reducing pain intensity, improving physical function, and enhancing quality of life in chronic low back pain patients. What does this study add? The multidisciplinary and multimodal group-based PAINDOC Program is acceptable for chronic low back pain patients.Participants noted the effectiveness of the program in helping them adopt active pain coping strategies and improve self-management.The ethicality of the multimodal Program depends on individual personal value systems, as certain program components may be less suitable for some participants.There might be some barriers to program adherence, including limited available time, the higher physical demands of exercise, the immediate effects of certain approaches, participants' perceptions, and individual needs and preferences.

The European Polysaccharide Network of Excellence (EPNOE) research roadmap 2040: Advanced strategies for exploiting the vast potential of polysaccharides as renewable bioresources.

Polysaccharides are among the most abundant bioresources on earth and consequently need to play a pivotal role when addressing existential scientific challenges like climate change and the shift from fossil-based to sustainable biobased materials. The Research Roadmap 2040 of the European Polysaccharide Network of Excellence (EPNOE) provides an expert's view on how future research and development strategies need to evolve to fully exploit the vast potential of polysaccharides as renewable bioresources. It is addressed to academic researchers, companies, as well as policymakers and covers five strategic areas that are of great importance in the context of polysaccharide related research: (I) Materials & Engineering, (II) Food & Nutrition, (III) Biomedical Applications, (IV) Chemistry, Biology & Physics, and (V) Skills & Education. Each section summarizes the state of research, identifies challenges that are currently faced, project achievements and developments that are expected in the upcoming 20 years, and finally provides outlines on how future research activities need to evolve.

Cell-Laden 3D Hydrogels of Type I Collagen Incorporating Bacterial Nanocellulose Fibers.

There is a growing interest in developing natural hydrogel-based scaffolds to culture cells in a three-dimensional (3D) millieu that better mimics the in vivo cells' microenvironment. A promising approach is to use hydrogels from animal tissues, such as decellularized extracellular matrices; however, they usually exhibit suboptimal mechanical properties compared to native tissue and their composition with hundreds of different protein complicates to elucidate which stimulus triggers cell's responses. As simpler scaffolds, type I collagen hydrogels are used to study cell behavior in mechanobiology even though they are also softer than native tissues. In this work, type I collagen is mixed with bacterial nanocellulose fibers (BCf) to develop reinforced scaffolds with mechanical properties suitable for 3D cell culture. BCf were produced from blended pellicles biosynthesized from Komagataeibacter xylinus. Then, BCf were mixed with concentrated collagen from rat-tail tendons to form composite hydrogels. Confocal laser scanning microscopy and scanning electron microscopy images confirmed the homogeneous macro- and microdistribution of both natural polymers. Porosity analysis confirmed that BCf do not disrupt the scaffold structure. Tensile strength and rheology measurements demonstrated the reinforcement action of BCf (43% increased stiffness) compared to the collagen hydrogel while maintaining the same viscoelastic response. Additionally, this reinforcement of collagen hydrogels with BCf offers the possibility to mix cells before gelation and then proceed to the culture of the 3D cell scaffolds. We obtained scaffolds with human bone marrow-derived mesenchymal stromal cells or human fibroblasts within the composite hydrogels, allowing a homogeneous 3D viable culture for at least 7 days. A smaller surface shrinkage in the reinforced hydrogels compared to type I collagen hydrogels confirmed the strengthening of the composite hydrogels. These collagen hydrogels reinforced with BCf might emerge as a promising platform for 3D in vitro organ modeling, tissue-engineering applications, and suitable to conduct fundamental mechanobiology studies.

Ce1-xZrxO2 nanoparticles in bacterial cellulose, bio-based composites with self-regenerating antioxidant capabilities.

Bacterial cellulose (BC) is an emerging biopolymer with ever-widening uses in the biomedical field due to its purity, mechanical stability, conformability, moisture control, and biocompatibility. In the wet form, its highly porous nanofibrillar structure and abundant surface hydroxyl groups enable the functionalisation of BC with inorganic nanoparticles (NPs), granting the material additional purposive capabilities. As oxidative stress caused by reactive oxygen species (ROS) negatively affects various cellular structures, the functionalisation of BC with CeO2 NPs, known antioxidants, is pursued in this work to achieve composites capable of minimising inflammation and tissue damage. We report on low-temperature in situ syntheses of CeO2 NPs in BC enabling the formation of BC-CeO2 composites that exhibit self-regenerating antioxidant properties, as verified by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays and studies of the evolution in the CeO2 absorption edge (indicative of the Ce3+ and Ce4+ fractions). X-Ray photoelectron spectroscopy (XPS) further reveals that incorporation of zirconium into the CeO2 lattice leads to a four-fold increase in the Ce3+: Ce4+ ratio, thereby enhancing the composite antioxidant performance as exemplified by BC-Ce0.6Zr0.4O2 recording the highest %DPPH scavenging per unit mass of NPs among the BC-Ce1-xZrxO2 studied systems.

Bioengineered extracellular vesicles: future of precision medicine for sepsis.

Sepsis is a syndromic response to infection and is frequently a final common pathway to death from many infectious diseases worldwide. The complexity and high heterogeneity of sepsis hinder the possibility to treat all patients with the same protocol, requiring personalized management. The versatility of extracellular vesicles (EVs) and their contribution to sepsis progression bring along promises for one-to-one tailoring sepsis treatment and diagnosis. In this article, we critically review the endogenous role of EVs in sepsis progression and how current advancements have improved EVs-based therapies toward their translational future clinical application, with innovative strategies to enhance EVs effect. More complex approaches, including hybrid and fully synthetic nanocarriers that mimic EVs, are also discussed. Several pre-clinical and clinical studies are examined through the review to offer a general outlook of the current and future perspectives of EV-based sepsis diagnosis and treatment.

Epidemiological and Genomic Analysis of a Large SARS-CoV-2 Outbreak in a Long-Term Care Facility in Catalonia, Spain.

Limiting outbreaks in long-term care facilities (LTCFs) is a cornerstone strategy to avoid an excess of COVID-19-related morbidity and mortality and to reduce its burden on the health system. We studied a large outbreak that occurred at an LTCF, combining methods of classical and genomic epidemiology analysis. The outbreak lasted for 31 days among residents, with an attack rate of 98% and 57% among residents and staff, respectively. The case fatality rate among residents was 16% (n = 15). Phylogenetic analysis of 59 SARS-CoV-2 isolates revealed the presence of two closely related viral variants in all cases (B.1.177 lineage), revealing a far more complex outbreak than initially thought and suggesting an initial spread driven by staff members. In turn, our results suggest that resident relocations to mitigate viral spread might have increased the risk of infection for staff members, creating secondary chains of transmission that were responsible for prolonging the outbreak. Our results highlight the importance of considering unnoticed chains of transmission early during an outbreak and making an adequate use and interpretation of diagnostic tests. Outbreak containment measures should be carefully tailored to each LTCF. IMPORTANCE The impact of COVID-19 on long-term care facilities (LTCFs) has been disproportionately large due to the high frailty of the residents. Here, we report epidemiological and genomic findings of a large outbreak that occurred at an LTCF, which ultimately affected almost all residents and nearly half of staff members. We found that the outbreak was initially driven by staff members; however, later resident relocation to limit the outbreak resulted in transmission from residents to staff members, evidencing the complexity and different phases of the outbreak. The phylogenetic analysis of SARS-CoV-2 isolates indicated that two closely related variants were responsible for the large outbreak. Our study highlights the importance of combining methods of classical and genomic epidemiology to take appropriate outbreak containment measures in LTCFs.

Bioevaluation of magnetic mesoporous silica rods: cytotoxicity, cell uptake and biodistribution in zebrafish and rodents.

Mesoporous silica nanoparticles (MSN) characterized by large surface area, pore volume, tunable chemistry, and biocompatibility have been widely studied in nanomedicine as imaging and therapeutic carriers. Most of these studies focused on spherical particles. In contrast, mesoporous silica rods (MSR) that are more challenging to prepare have been less investigated in terms of toxicity, cellular uptake, or biodistribution. Interestingly, previous studies showed that silica rods penetrate fibrous tissues or mucus layers more efficiently than their spherical counterparts. Recently, we reported the synthesis of MSR with distinct aspect ratios and validated their use in multiple imaging modalities by loading the pores with maghemite nanocrystals and functionalizing the silica surface with green and red fluorophores. Herein, based on an initial hypothesis of high liver accumulation of the MSR and a future vision that they could be used for early diagnosis or therapy in fibrotic liver diseases; the cytotoxicity and cellular uptake of MSR were assessed in zebrafish liver (ZFL) cells and the in vivo safety and biodistribution was investigated via fluorescence molecular imaging (FMI) and magnetic resonance imaging (MRI) employing zebrafish larvae and rodents. The selection of these animal models was prompted by the well-established fatty diet protocols inducing fibrotic liver in zebrafish or rodents that serve to investigate highly prevalent liver conditions such as non-alcoholic fatty liver disease (NAFLD). Our study demonstrated that magnetic MSR do not cause cytotoxicity in ZFL cells regardless of the rods' length and surface charge (for concentrations up to 50 µg ml-1, 6 h) and that MSR are taken up by the ZFL cells in large amounts despite their length of ∼1 µm. In zebrafish larvae, it was observed that they could be safely exposed to high MSR concentrations (up to 1 mg ml-1 for 96 h) and that the rods pass through the liver without causing toxicity. The high accumulation of MSR in rodents' livers at short post-injection times (20% of the administered dose) was confirmed by both FMI and MRI, highlighting the utility of the MSR for liver imaging by both techniques. Our results could open new avenues for the use of rod-shaped silica particles in the diagnosis of pathological liver conditions.

Riboflavin-citrate conjugate multicore SPIONs with enhanced magnetic responses and cellular uptake in breast cancer cells.

Breast cancer accounts for up to 10% of the newly diagnosed cancer cases worldwide, making it the most common cancer found in women. The use of superparamagnetic iron oxide nanoparticles (SPIONs) has been beneficial in the advancement of contrast agents and magnetic hyperthermia (MH) for the diagnosis and treatment of cancers. To achieve delivery of SPIONs to cancer cells, surface functionalization with specific ligands are required. Riboflavin carrier protein (RCP) has been identified as an alternative target for breast cancer cells. Here, we report a novel riboflavin (Rf)-based ligand that provides SPIONs with enhanced colloidal stability and high uptake potential in breast cancer cells. This is achieved by synthesizing an Rf-citrate ligand. The ligand was tested in a multicore SPION system, and affinity to RCP was assessed by isothermal titration calorimetry which showed a specific, entropy-driven binding. MRI and MH responses of the coated Rf-SPIONs were tested to evaluate the suitability of this system as a theranostic platform. Finally, interaction of the Rf-SPIONs with breast cancer cells was evaluated by in vitro cellular uptake in MCF-7 breast cancer cells. The overall characterization of the Rf-SPIONs highlighted the excellent performance of this platform for theranostic applications in breast cancer.

Fluorescent PLGA Nanocarriers for Pulmonary Administration: Influence of the Surface Charge.

Nearly four million yearly deaths can be attributed to respiratory diseases, prompting a huge worldwide health emergency. Additionally, the COVID-19 pandemic's death toll has surpassed six million, significantly increasing respiratory disease morbidity and mortality rates. Despite recent advances, it is still challenging for many drugs to be homogeneously distributed throughout the lungs, and specifically to reach the lower respiratory tract with an accurate sustained dose and minimal systemic side effects. Engineered nanocarriers can provide increased therapeutic efficacy while lessening potential biochemical adverse reactions. Poly(lactic-co-glycolic acid) (PLGA), a biodegradable polymer, has attracted significant interest as an inhalable drug delivery system. However, the influence of the nanocarrier surface charge and its intratracheal instillation has not been addressed so far. In this study, we fabricated red fluorescent PLGA nanocapsules (NCs)-Cy5/PLGA-with either positive (Cy5/PLGA+) or negative surface charge (Cy5/PLGA-). We report here on their excellent colloidal stability in culture and biological media, and after cryo-storage. Their lack of cytotoxicity in two relevant lung cell types, even for concentrations as high as 10 mg/mL, is also reported. More importantly, differences in the NCs' cell uptake rates and internalization capacity were identified. The uptake of the anionic system was faster and in much higher amounts-10-fold and 2.5-fold in macrophages and epithelial alveolar cells, respectively. The in vivo study demonstrated that anionic PLGA NCs were retained in all lung lobules after 1 h of being intratracheally instilled, and were found to accumulate in lung macrophages after 24 h, making those nanocarriers especially suitable as a pulmonary immunomodulatory delivery system with a marked translational character.

One-step double network hydrogels of photocurable monomers and bacterial cellulose fibers.

Soft-tissue replacements are challenging due to the stringent compliance requirements for the implanted materials in terms of biocompatibility, durability, high wear resistance, low friction, and water content. Acrylate hydrogels are worth considering as soft tissue implants as they can be photocurable and sustain customized shapes through 3D bioprinting. However, acrylate-based hydrogels present weak mechanical properties and significant dimensional changes when immersed in liquids. To address these obstacles, we fabricated double network (DN) hydrogels composed of polyacrylic acid (PAA) and bacterial cellulose nanofibers (BCNFs) by one fast UV photopolymerization step. BCNFs/PAA hydrogels with a 0.5 wt% BCNFs content present an increased stiffness and a lower, non-pH-dependent swelling than PAA hydrogels or PAA hydrogels with cellulose nanocrystals. Besides, BCNFs/PAA hydrogels are biocompatible and can be frozen/thawed. Those characteristics endorse these hybrid hydrogels as potential candidates for vascular and cartilage tissue implants.

Magnetic Mesoporous Silica Nanorods Loaded with Ceria and Functionalized with Fluorophores for Multimodal Imaging.

Multifunctional magnetic nanocomposites based on mesoporous silica have a wide range of potential applications in catalysis, biomedicine, or sensing. Such particles combine responsiveness to external magnetic fields with other functionalities endowed by the agents loaded inside the pores or conjugated to the particle surface. Different applications might benefit from specific particle morphologies. In the case of biomedical applications, mesoporous silica nanospheres have been extensively studied while nanorods, with a more challenging preparation, have attracted much less attention despite the positive impact on the therapeutic performance shown by seminal studies. Here, we report on a sol-gel synthesis of mesoporous rodlike silica particles of two distinct lengths (1.4 and 0.9 µm) and aspect ratios (4.7 and 2.2) using Pluronic P123 as a structure-directing template and rendering ∼1 g of rods per batch. Iron oxide nanoparticles have been synthesized within the pores yielding maghemite (γ-Fe2O3) nanocrystals of elongated shape (∼7 nm × 5 nm) with a [110] preferential orientation along the rod axis and a superparamagnetic character. The performance of the rods as T2-weighted MRI contrast agents has also been confirmed. In a subsequent step, the mesoporous silica rods were loaded with a cerium compound and their surface was functionalized with fluorophores (fluorescamine and Cyanine5) emitting at λ = 525 and 730 nm, respectively, thus highlighting the possibility of multiple imaging modalities. The biocompatibility of the rods was evaluated in vitro in a zebrafish (Danio rerio) liver cell line (ZFL), with results showing that neither long nor short rods with magnetic particles caused cytotoxicity in ZFL cells for concentrations up to 50 µg/ml. We advocate that such nanocomposites can find applications in medical imaging and therapy, where the influence of shape on performance can be also assessed.

Endovascular administration of magnetized nanocarriers targeting brain delivery after stroke.

The increasing use of mechanical thrombectomy in stroke management has opened the window to local intraarterial brain delivery of therapeutic agents. In this context, the use of nanomedicine could further improve the delivery of new treatments for specific brain targeting, tracking and guidance. In this study we take advantage of this new endovascular approach to deliver biocompatible poly(D-L-lactic-co-glycolic acid) (PLGA) nanocapsules functionalized with superparamagnetic iron oxide nanoparticles and Cy7.5 for magnetic targeting, magnetic resonance and fluorescent molecular imaging. A complete biodistribution study in naïve (n = 59) and ischemic (n = 51) mice receiving intravenous or intraarterial nanocapsules, with two different magnet devices and imaged from 30 min to 48 h, showed an extraordinary advantage of the intraarterial route for brain delivery with a specific improvement in cortical targeting when using a magnetic device in both control and ischemic conditions. Safety was evaluated in ischemic mice (n = 69) showing no signs of systemic toxicity nor increasing mortality, infarct lesions or hemorrhages. In conclusion, the challenging brain delivery of therapeutic nanomaterials could be efficiently and safely overcome with a controlled endovascular administration and magnetic targeting, which could be considered in the context of endovascular interventions for the delivery of multiple treatments for stroke.

One-Step Biosynthesis of Soft Magnetic Bacterial Cellulose Spheres with Localized Nanoparticle Functionalization.

Actuated structures are becoming relevant in medical fields; however, they call for flexible/soft-base materials that comply with biological tissues and can be synthesized in simple fabrication steps. In this work, we extend the palette of techniques to afford soft, actuable spherical structures taking advantage of the biosynthesis process of bacterial cellulose. Bacterial cellulose spheres (BCS) with localized magnetic nanoparticles (NPs) have been biosynthesized using two different one-pot processes: in agitation and on hydrophobic surface-supported static culture, achieving core-shell or hollow spheres, respectively. Magnetic actuability is conferred by superparamagnetic iron oxide NPs (SPIONs), and their location within the structure was finely tuned with high precision. The size, structure, flexibility and magnetic response of the spheres have been characterized. In addition, the versatility of the methodology allows us to produce actuated spherical structures adding other NPs (Au and Pt) in specific locations, creating Janus structures. The combination of Pt NPs and SPIONs provides moving composite structures driven both by a magnetic field and a H2O2 oxidation reaction. Janus Pt/SPIONs increased by five times the directionality and movement of these structures in comparison to the controls.

[Elements influencing the election of Family and Community Medicine]. / Factores que influyen en la elección de la especialidad de Medicina Familiar y Comunitaria.

AIM: To analyze the perceptions, motives and reasons that influence the election of Family and Community Medicine (FCM) speciality, thus exploring possible proposals for change in the health system model and university training. DESIGN: Descriptive-interpretative qualitative research from a socio-constructivist perspective. EMPLACEMENT: Medical speciality training departments in the Metropolitan Area of Barcelona. PARTICIPANTS AND CONTEXT: 55 first year junior doctors belonging to the FCM Barcelona Ciutat ICS training department were contacted; 25 agreed to participate. They were segmented into two groups depending on if the choice of FCM had been their first option or not. Through snowball sampling 11 more junior doctors from other specialities were recruited. METHOD: Three focus groups were formed: (a) first choice FCM, (b) not first choice FCM and (c) other specialities. Semi-structured 2-h long interviews took place with each of the groups. Literal transcription and inductive codification with a first triangulation within each group and a second one between the three of them and thematic content analyses. RESULTS: The choice of speciality is lived as an academic milestone and is thought determining professional and personally. It is a complex weave of influencing elements but some of main factors were university training, health system model, professional prospects and the social appreciation of the speciality. Analyzing the relation between these elements puts light on a phenomena we have called "the discredit of Primary Care (PC)". CONCLUSION: The FCM specialty will not be attractive in a hospital-centric health and training system that does not bet on PC organizationally or economically.

Sciatic nerve regeneration after traumatic injury using magnetic targeted adipose-derived mesenchymal stem cells.

Traumatic peripheral nerve injuries constitute a huge concern to public health. Nerve damage leads to a decrease or even loss of mobility of the innervated area. Adult stem cell therapies have shown some encouraging results and have been identified as promising treatment candidates for nerve regeneration. A major obstacle to that approach is securing a sufficient number of cells at the injured site to produce measurable therapeutic effects. The present work tackles this issue and demonstrates enhanced nerve regeneration ability promoted by magnetic targeted cell therapy in an in vivo Wallerian degeneration model. To this end, adipose-derived mesenchymal stem cells (AdMSC) were loaded with citric acid coated superparamagnetic iron oxide nanoparticles (SPIONs), systemically transplanted and magnetically recruited to the injured sciatic nerve. AdMSC arrival to the injured nerve was significantly increased using magnetic targeting and their beneficial effects surpassed the regenerative properties of the stand-alone cell therapy. AdMSC-SPIONs group showed a partially conserved nerve structure with many intact myelinated axons. Also, a very remarkable restoration in myelin basic protein organization, indicative of remyelination, was observed. This resulted in an improvement in nerve conduction, demonstrating functional recovery. In summary, our results demonstrate that magnetically assisted delivery of AdMSC, using a non-invasive and non-traumatic method, is a highly promising strategy to promote cell recruitment and sciatic nerve regeneration after traumatic injury. Last but not least, our results validate magnetic targeting in vivo exceeding previous reports in less complex models through cell magnetic targeting in vitro and ex vivo. STATEMENT OF SIGNIFICANCE: Traumatic peripheral nerve injuries constitute a huge public health concern. They can lead to a decrease or even loss of mobility of innervated areas. Due to their complex pathophysiology, current pharmacological and surgical approaches are only partially effective. Cell-based therapies have emerged as a useful tool to achieve full tissue regeneration. However, a major bottleneck is securing enough cells at injured sites. Therefore, our proposal combining biological (adipose derived mesenchymal stem cells) and nanotechnological strategies (magnetic targeting) is of great relevance, reporting the first in vivo experiments involving "magnetic stem cell" targeting for peripheral nerve regeneration. Using a non-invasive and non-traumatic method, cell recruitment in the injured nerve was improved, fostering nerve remyelination and functional recovery.