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Plasma-Synthesized Polypyrrole (PSPy) has been reported as a biomaterial suitable for cell growth in vitro and in vivo. An experimental duplicate was carried out that showed the growth of cardiomyocytes with PSPy, following a protocol previously reported by the working group. The cardiomyocytes cultured with the biomaterial retained their native morphological characteristics, a fundamental key to improving cardiac cell therapy procedures. Such observations motivated us to investigate the molecular characteristics of the biomaterial and the type of interactions that could be occurring (mainly electrostatic, hydrogen bonds, and non-polar). Additionally, PSPy has been studied to establish the probable mechanisms of action of the biomaterial, in particular, its action on a group of cell membrane proteins, integrins, which we know participate in the adhesion of cells to the extracellular matrix, in adhesion between cells and as bidirectional signal transducer mechanisms. In this work, we carried out studies of the interactions established between cardiac integrins α2ß1 and α5ß1 with different PSPy models by molecular docking studies and binding free energies (ΔGb) calculations. The models based on a previously reported PSPy molecule have three variable terminal chemical groups, with the purpose of exploring the differences in the type of interaction that will be established by modifying the position of an amino (-NH2), a hydroxyl (-OH), and a nitrile (C≡N) in (fixed) groups, as well as the length of the terminal chains (a long/short -NH2). A model with short chains for the -OH and -NH2 (lateral) group was the model with the best interactions with cardiac integrins. We experimentally verified the direct interaction of cardiomyocytes with the PSPy biomaterial observed in rat primary cultures, allowing us to validate the favorable interactions predicted by the computational analysis.

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Biological treatments involve the application of metallic material coatings to enhance biocompatibility and properties. In invasive therapies, metallic electrodes are utilized, which are implanted in patients. One of these invasive therapeutic procedures is deep brain stimulation (DBS), an effective therapy for addressing the motor disorders observed in patients with Parkinson's disease (PD). This therapy involves the implantation of electrodes (IEs) into the subthalamic nucleus (STN). However, there is still a need for the optimization of these electrodes. Plasma-synthesized polypyrrole doped with iodine (PPPy/I) has been reported as a biocompatible and anti-inflammatory biomaterial that promotes nervous system regeneration. Given this information, the objective of the present study was to develop and characterize a PPPy/I-coated electrode for implantation into the STN. The characterization results indicate a uniform coating along the electrode, and physical-chemical characterization studies were conducted on the polymer. Subsequently, the IEs, both coated and uncoated with PPPy/I, were implanted into the STN of male rats of the Wistar strain to conduct an electrographic recording (EG-R) study. The results demonstrate that the IE coated with PPPy/I exhibited superior power and frequency signals over time compared to the uncoated IE (p < 0.05). Based on these findings, we conclude that an IE coated with PPPy/I has optimized functional performance, with enhanced integrity and superior signal quality compared to an uncoated IE. Therefore, we consider this a promising technological development that could significantly improve functional outcomes for patients undergoing invasive brain therapies.

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Introduction: Spinal cord injury (SCI) can cause paralysis, for which effective therapeutic strategies have not been developed yet. The only accepted strategy for patients is rehabilitation (RB), although this does not allow complete recovery of lost functions, which makes it necessary to combine it with strategies such as plasma-synthesized polypyrrole/iodine (PPy/I), a biopolymer with different physicochemical properties than PPy synthesized by conventional methods. After SCI in rats, PPy/I promotes functional recovery. Therefore, the purpose of this study was to increase the beneficial effects of both strategies and identify which genes activate PPy/I when applied alone or in combination with a mixed scheme of RB by swimming and enriched environment (SW/EE) in rats with SCI. Methods: Microarray analysis was performed to identify mechanisms of action underlying the effects of PPy/I and PPy/I+SW/EE on motor function recovery as evaluated by the BBB scale. Results: Results showed robust upregulation by PPy/I in genes related to the developmental process, biogenesis, synapse, and synaptic vesicle trafficking. In addition, PPy/I+SW/EE increased the expression of genes related to proliferation, biogenesis, cell development, morphogenesis, cell differentiation, neurogenesis, neuron development, and synapse formation processes. Immunofluorescence analysis showed the expression of ß-III tubulin in all groups, a decreased expression of caspase-3 in the PPy/I group and GFAP in the PPy/I+SW/EE group (p < 0.05). Better preservation of nerve tissue was observed in PPy/I and PPy/SW/EE groups (p < 0.05). In the BBB scale, the control group scored 1.72 ± 0.41, animals with PPy/I treatment scored 4.23 ± 0.33, and those with PPy/I+SW/EE scored 9.13 ± 0.43 1 month after follow-up. Conclusion: Thus, PPy/I+SW/EE could represent a therapeutic alternative for motor function recovery after SCI.

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In spinal cord injury (SCI) there is damage to the nervous tissue, due to the initial damage and pathophysiological processes that are triggered subsequently. There is no effective therapeutic strategy for motor functional recovery derived from the injury. Several studies have demonstrated neurons growth in cell cultures on polymers synthesized by plasma derived from pyrrole, and the increased recovery of motor function in rats by implanting the polymer in acute states of the SCI in contusion and transection models. In the process of transferring these advances towards humans it is recommended to test in mayor species, such as nonhuman primates, prioritizing the use of non-invasive techniques to evaluate the injury progression with the applied treatments. This work shows the ability of diffusion tensor imaging (DTI) to evaluate the evolution of the SCI in nonhuman primates through the fraction of anisotropy (FA) analysis and the diffusion tensor tractography (DTT) calculus. The injury progression was analysed up to 3 months after the injury day by FA and DTT. The FA recovery and the DTT re-stabilization were observed in the experimental implanted subject with the polymer, in contrast with the non-implanted subject. The parameters derived from DTI are concordant with the histology and the motor functional behaviour.

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OBJECTIVE: Brain metabolic processes are not fully characterized in the kainic acid (KA)-induced Status Epilepticus (KASE). Thus, we evaluated the usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) as an experimental strategy to evaluate in vivo, in a non-invasive way, the glucose consumption in several brain regions, in a semi-quantitative study to compare and to correlate with data from electroencephalography and histology studies. METHODS: Sixteen male Wistar rats underwent FDG-PET scans at basal state and after KA injection. FDG-PET images were normalized to an MRI-based atlas and segmented to locate regions. Standardized uptake values (SUV) were obtained at several time points. EEGs and cell viability by histological analysis, were also evaluated. RESULTS: FDG-PET data showed changes in regions such as: amygdala, hippocampus, accumbens, entorhinal cortex, motor cortex and hypothalamus. Remarkably, hippocampal hypermetabolism was found (mean SUV = 2.66 ± 0.057) 2 h after KA administration, while hypometabolism at 24 h (mean SUV = 1.83 ± 0.056) vs basal values (mean SUV = 2.19 ± 0.057). EEG showed increased spectral power values 2 h post-KA administration. Hippocampal viable-cell counting 24 h after KA was decreased, while Fluoro-Jade B-positive cells were increased, as compared to control rats, coinciding with the hypometabolism detected in the same region by semi-quantitative FDG-PET at 24 h after KASE. CONCLUSIONS: PET is suitable to measure metabolic brain changes in the rat model of status epilepticus induced by KA (KASE) at the first 24 h, compared to that of EEG; PET data may also be sensitive to cell viability.

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Composite biomaterials are solids that contain two or more different materials, combining the properties of their components to restore or improve the function of tissues. In this study, we report the generation of electrospun matrices with osteoconductive properties and porosity using the combination of a biodegradable polyester, polylactic acid (PLA), and hydroxyapatite (HA). Additionally, we report the effects of modifying these matrices through plasma polymerization of pyrrole on the growth and osteogenic differentiation of rabbit bone marrow stem cells. Cells were isolated, seeded and cultured on biomaterials for periods between 7 and 28 days. The matrices we obtained were formed by nano and microfibers containing up to 35.7 wt% HA, presenting a variety of apparent pore sizes to allow for the passage of nutrients to bone cells. Scanning electron microscopy showed that the fibers were coated with polypyrrole doped with iodine, and MTT assay demonstrated this increased cell proliferation and significantly improved cell viability due to the adhesive properties of the polymer. Our results show that PLA/HA/Pyrrole/Iodine matrices are favorable for bone tissue engineering.

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INTRODUCTION: Classic post-transplant complications are highly studied and monitored; however, other unusual complications may occur due to immunosuppression. The objective of this study is to show these rare complications in a kidney transplant center. MATERIAL AND METHODS: Retrospective, observational, longitudinal study of renal transplants carried out from 2013 to 2017 in the Renal Transplant Unit of the National Medical Center Siglo XXI. A total of 790 transplants were performed, with surveillance for 1 year and rare events described. An analysis of frequencies and percentages of the events was performed using the statistical package SPSS version 25. RESULTS: Of the 790 patients, 110 (13.92%) experienced rare events, classified into 9 types of complications. DISCUSSION AND CONCLUSIONS: Complications exist in renal transplantation that are often ignored or minimized. A considerable number have been observed in this study, 110 events (13.92%); this result allows us to consider multiple possibilities in a kidney transplant program, especially infectious complications (34 patients) and surgical complications (29 cases). With the increase in diabetic receptor transplantation, metabolic complications will surely increase in the coming years.

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BACKGROUND: Bone mineral disease after transplantation persists and is an issue that must be addressed owing to the cardiovascular impact it presents. The objective of this study is to present the behavior of calcium, phosphorus, and parathormone (PTH) before renal transplantation (RT) and throughout the 12 months after transplant surgery. METHODS: A longitudinal observational study of RT patients was performed from 2013 to 2017 in 2 renal transplant units in Mexico. In total, 1009 records of patients with RT were analyzed. Calcium, phosphorus, and PTH levels were studied before transplantation and for 12 months after. Central tendency and dispersion were measured, the difference of means was established with chi square or student t tests, and the significant value of P was set at <.05. We also used the SPSS statistical package, version 25. RESULTS: Phosphorus had a median pre-RT of 5.73, which decreased to 2.8 in the first month post-transplant and then increased to 3.41 at 12 months post-RT. The median PTH, on the other hand, started at 420.60 and decreased to 67.45. Calcium began at 9.04 and hit a plateau of 9.58 during month 12 after the surgical event. CONCLUSIONS: Of the 3 biochemical parameters evaluated, phosphorus was the one that most corrected itself after transplantation. Despite a tendency toward hypophosphatemia in the first month after transplantation, it began to normalize from month 6 on. Meanwhile, calcium was the biochemical value that changed the least after transplantation.

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Protein-engineered biomaterials represent a powerful approach to increase biofunctional activity like tissue repair and celular proliferation. Among these materials, integrins and the development of their specific interactions with plasma-polymerized pyrrole (PPPy) are promising biomaterial for tissue regeneration. In this paper, we studied the molecular recognition in the active site of three integrins (α5ß1, αvß3 and αIIbß3) with PPPy using the structure proposed by Kumar et al. PPPy molecule has three sites to incorporate different species, we worked mainly with the functional groups, -NH2 and -OH groups according to our IR spectroscopic results. We carried out docking studies to find the better conformational couplings and to determine electrostatic (ΔGelec) and non-electrostatic (ΔGnon-elec) contributions to the binding free energy (ΔGb) of these complexes we used Adaptive Poisson-Bolztmann program (APBS). Our results indicated that when incorporating -1H-azirine, -NH2 or -OH group in PPPy structure, interactions with integrins were favorable, as indicated by correspondent ΔGb values. These interactions were mainly triggered by Coulomb interactions, an important term in the electrostatic component. Furthermore, our studies suggest that some residues of integrins α5ß1, αvß3 and αIIbß3 like aspartates are important for the binding to PPPy structures. Detailed interactions between integrin α5ß1 and PPPy structures were revealed by molecular dynamics simulations. We used this particular integrin structure because of its favorable ΔGb as well as its major cellular receptor for the extracellular matrix protein fibronectin. Clustering analysis allowed us to carry out focused docking studies and to determine the time evolution of the ΔGb values. By incorporating -NH2 into PPPy structure, ΔGb values were very favorable during the course of the dynamics simulations by the establishment of hydrogen bonds with Asn224 and/orAsp227 residues, which are part of the integrin α5ß1 pocket. However, for the integrin α5ß1-PPPy-1H-azirine complex and the rest of the functional groups, the ΔGb values were less favorable, although PPPy was found at a distance of less than 5 Å from the active site residues. This work is complementary to the previous studies made employing PPPy nanoparticles for a variety of tissue engineering applications, and were done to enlighten the role played by the amino group of the PPPy in its integrin recognition process.

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Traumatic spinal cord injury (TSCI) is a health problem for which there is currently no treatment or definitive therapy. Medicine has explored therapeutic options for patients with TSCI with the aim to improve their quality of life. One alternative has been the development of biomaterials that offer neuroprotection or neuroregeneration of damaged nerve tissue. The microinjection of iodine-doped polypyrrole particles synthesised by plasma (PPPy/I) has shown neuroprotective effects that favour motor function recovery in experimental animals with TSCI. However, their ability to migrate into the tissue has led to the need to test a suspension vehicle that enables the concentration of particles at the site of injury. To achieve this, two biomaterials of PPPy/I (P1 and P2) were studied. The superficial physicochemical characterisation of the polymers was performed by infrared spectroscopy, X-ray photoelectron spectroscopy and contact angle. The rheological performance under oscillatory shear rate of suspensions containing both polymers alone and in combination with bovine serum albumin was also studied. In vivo tests were performed on animals with and without TSCI that were microinjected with particles of P1 or P2 in suspension using a solution of rat serum albumin. Exposure to the protein solutions generates a protein multilayer on the surface of the biomaterials that can drastically change the behaviour of both P1 and P2, which led to severe repercussions in the in vivo assays. The results showed that surface chemistry plays an important role in the performance and that it is possible to treat TSCI with these materials. The interaction of the surface of materials PPPy/I.1 (P1) and PPPy/I.2 (P2) with bovine serum albumin (BSA) resulted in a series of changes in the surface chemistry of both biomaterials. The contact angle study (Fig. A) showed the presence of a critical BSA concentration ([BSA]c), in which a monolayer was formed on both polymers and then a stable protein multilayer, as evidenced by the establishment of a plateau in the determination of the contact angle. In vivo tests showed that this interaction may be beneficial in the treatment of traumatic spinal cord injury (TSCI), depending on the surface characteristics with or without rat serum albumin (RSA). The TSCI + P1 and TSCI + P2 + RSA groups obtained significant differences in functional recovery compared with the control group according to the Basso, Beattie and Bresnahan scale (BBB).

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Currently, there is no universally accepted treatment for traumatic spinal cord injury (TSCI), a pathology that can cause paraplegia or quadriplegia. Due to the complexity of TSCI, more than one therapeutic strategy may be necessary to regain lost functions. Therefore, the present study proposes the use of implants of mesoparticles (MPs) of polypyrrole/iodine (PPy/I) synthesized by plasma for neuroprotection promotion and functional recovery in combination with treadmill training (TT) for neuroplasticity promotion and maintenance of muscle tone. PPy/I films were synthesized by plasma and pulverized to obtain MPs. Rats with a TSCI produced by the NYU impactor were divided into four groups: Vehicle (saline solution); MPs (PPy/I implant); Vehicle-TT (saline solution + TT); and MPs-TT (PPy/I implant + TT). The vehicle or MPs (30 µL) were injected into the lesion site 48 h after a TSCI. Four days later, TT was carried out 5 days a week for 2 months. Functional recovery was evaluated weekly using the BBB motor scale for 9 weeks and tissue protection using histological and morphometric analysis thereafter. Although the MPs of PPy/I increased nerve tissue preservation (P = 0.03) and promoted functional recovery (P = 0.015), combination with TT did not produce better neuroprotection, but significantly improved functional results (P = 0.000) when comparing with the vehicle group. So, use these therapeutic strategies by separately could stimulate specific mechanisms of neuroprotection and neuroregeneration, but when using together they could mainly potentiate different mechanisms of neuronal plasticity in the preserved spinal cord tissue after a TSCI and produce a significant functional recovery. The implant of mesoparticles of polypyrrole/iodine into the injured spinal cord displayed good integration into the nervous tissue without a response of rejection, as well as an increased in the amount of preserved tissue and a better functional recovery than the group without transplant after a traumatic spinal cord injury by contusion in rats. The relevance of the present results is that polypyrrole/iodine implants were synthesized by plasma instead by conventional chemical or electrochemical methods. Synthesis by plasma modifies physicochemical properties of polypyrrole/iodine implants, which can be responsible of the histological response and functional results. Furthermore, no additional molecules or trophic factors or cells were added to the implant for obtain such results. Even more, when the implant was used together with physical rehabilitation, better functional recovery was obtained than that observed when these strategies were used by separately.

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We studied the use of three biocompatible materials obtained by plasma polymerization of pyrrole (PPy), pyrrole doped with iodine (PPy/I) and a copolymer formed with pyrrole and polyethylene glycol (PPy/PEG), implanted, separately, after a complete spinal cord transection in rats. Motor function assessed with the BBB scale and somatosensory evoked potentials (SEPs) in the implanted rats were studied. Results showed that the highest motor recovery was obtained in rats with PPy/I implants. They also showed a significant reduction in the latency of SEPs. Histological analyses showed no signs of implant rejection; on the contrary, implants based on PPy improved the SEPs conduction and motor function after lesion.

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Most of the biomaterials used nowadays for the reconstruction of the spinal cord (SC) tissue after an injury, tested in animals, have obtained modest results. This work presents a study about the compatibility of two novel, non-biodegradable, semi-conductive materials, obtained by plasma polymerization: iodine-doped pyrrole (PPy/I) and pyrrole-polyethylene glycol (PPy/PEG). Both polymers, separately, were implanted in the SC tissue of rats after a transection. Prior to implantation, the elemental composition and the physico-chemical properties of polymers were studied by electron scanning microscopy, IR Spectroscopy and thermogravimetric analysis. We used adult female Long Evans rats, subjected to SC transection. Animals were randomized to be allocated in one of the treatment groups and were killed four weeks after the lesion for histology study. Results showed that both implants were integrated to the SC tissue, as inflammatory and gliotic responses, similar to those observed in the control group, and rejection of the implant, were not evident. Moreover, the immediate effect of PPy/I or PPy/PEG in the injured SC prevented secondary tissue destruction, as compared to non-implanted control animals. In conclusion, implants of semi-conductive polymers were well-tolerated and integrated favorably to SC tissue after transection.

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