The early career researcher's toolkit: translating tissue engineering, regenerative medicine and cell therapy products

Although the importance of translation for the development of tissue engineering, regenerative medicine and cell-based therapies is widely recognized, the process of translation is less well understood. This is particularly the case among some early career researchers who may not appreciate the intricacies of translational research or make decisions early in development which later hinders effective translation. Based on our own research and experiences as early career researchers involved in tissue engineering and regenerative medicine translation, we discuss common pitfalls associated with translational research, providing practical solutions and important considerations which will aid process and product development. Suggestions range from effective project management, consideration of key manufacturing, clinical and regulatory matters and means of exploiting research for successful commercialization

Valor de la morfina liofilizada en la revascularización miocárdica

Introduction: epidural analgesia is a mainstay in cardiac surgery. Objectives: The aim of this study was to compare the use of lyophilized morphine and epidural bupivacaine in postoperative analgesia of myocardial revascularization. Method: A comparative and prospective study was conducted in 160 patients. They were divided into two groups: group M received epidural analgesia with morphine (2 mg) associated with 100 mg of bupivacaine, and group B bupivacaine only. Results: there was a prevalence of males. The ages and the average weights of both groups were similar (p>0.05). In group M, 90% of patients had excellent analgesia eight hours after the intervention, and it was good to excellent after 12 and 24 hours. On the other hand, 50% of patients in group B talked of an average analgesia eight hours after the operation –which extended to 80% of patients after 12 hours– and, after 24 hours, all the patients in group B complained of an inadequate or poor analgesia (p0.05); el 90% de los enfermos del grupo M tenían una analgesia excelente ocho horas después de la intervención y entre buena y excelente a las 12 y 24 horas, mientras que el 50% de los pacientes del grupo B referían una analgesia regular a las ocho horas de operados -lo que se extendió al 80% de los enfermos a las 12 horas- y, a las 24 horas, la totalidad de los enfermos del grupo B se aquejaban de una analgesia insuficiente o mala (p<0.05); el promedio de analgesia postoperatoria obtenida del grupo M fue de 29,41 horas y del grupo B de 9,76 horas (p<0.01) y los principales efectos adversos fueron la hipotensión arterial y la bradicardia. Conclusiones: la morfina demostró su utilidad como agente analgésico en la operación de las arterias coronarias. Los pacientes con bupivacaína y morfina epidural tuvieron mejor analgesia con tiempos más prolongados que los tratados con bupivacaína

The early career researcher's toolkit:translating tissue engineering, regenerative medicine and cell therapy products

Although the importance of translation for the development of tissue engineering, regenerative medicine and cell-based therapies is widely recognized, the process of translation is less well understood. This is particularly the case among some early career researchers who may not appreciate the intricacies of translational research or make decisions early in development which later hinders effective translation. Based on our own research and experiences as early career researchers involved in tissue engineering and regenerative medicine translation, we discuss common pitfalls associated with translational research, providing practical solutions and important considerations which will aid process and product development. Suggestions range from effective project management, consideration of key manufacturing, clinical and regulatory matters and means of exploiting research for successful commercialization

Selective laser melting–enabled electrospinning: Introducing complexity within electrospun membranes

Additive manufacturing technologies enable the creation of very precise and well-defined structures that can mimic hierarchical features of natural tissues. In this article, we describe the development of a manufacturing technology platform to produce innovative biodegradable membranes that are enhanced with controlled microenvironments produced via a combination of selective laser melting techniques and conventional electrospinning. This work underpins the manufacture of a new generation of biomaterial devices that have significant potential for use as both basic research tools and components of therapeutic implants. The membranes were successfully manufactured and a total of three microenvironment designs (niches) were chosen for thorough characterisation. Scanning electron microscopy analysis demonstrated differences in fibre diameters within different areas of the niche structures as well as differences in fibre density. We also showed the potential of using the microfabricated membranes for supporting mesenchymal stromal cell culture and proliferation. We demonstrated that mesenchymal stromal cells grow and populate the membranes penetrating within the niche-like structures. These findings demonstrate the creation of a very versatile tool that can be used in a variety of tissue regeneration applications including bone healing

Urease Functionalized Silica: A Biohybrid Substrate To Drive Self-Mineralization

The present work explores the enzymatic driven biomineralization of a model silica substrate. Jack Bean Urease was covalently anchored onto synthetic aminopropyl-capped silica spheres. After several hours of aging at physiological temperatures in the presence of urea, Ca(II) and phosphate ions, homogeneous nanoparticulated hydroxyapatite-like shells were obtained.Fil: Ortega, Ilida. Consejo Superior de Investigaciones Científicas; España. Instituto de Ciencia de Materiales de Madrid; EspañaFil: Jobbagy, Matias. Consejo Superior de Investigaciones Científicas; España. Instituto de Ciencia de Materiales de Madrid; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Centro de Investigación en Nanociencia y Nanotecnología (CIN2); EspañaFil: Ferrer, María Luisa. Instituto de Ciencia de Materiales de Madrid; EspañaFil: del Monte, Francisco. Instituto de Ciencia de Materiales de Madrid; Españ

Proof-of-concept study of electrospun PLGA membrane in the treatment of limbal stem cell deficiency.

ObjectiveThe aim of this study was to assess the safety of poly-lactic co-glycolic acid (PLGA) electrospun membranes as carriers for limbal tissue explants for treatment of limbal stem cell deficiency (LSCD).Methods and analysisApproval was obtained for a first in-man study from the Drug Controller General of India. PLGA membranes were applied to the affected eye of five patients after removal of the vascular pannus. Simple limbal epithelial transplantation was performed and limbal explants were secured on the membrane using fibrin glue followed by a bandage contact lens. Patients were followed up for 1 year with ocular exams including slit lamp exam, corneal thickness measurements, intraocular pressure measurements and recording of corneal vascularisation and visual acuity. Systemic examinations included pain grading, clinical laboratory assessment, blood chemistry and urine analysis at baseline, 3 and 6 months after surgery.ResultsPLGA membranes completely degraded by 8 weeks post-transplantation without any infection or inflammation. In all five patients, the epithelium regenerated by 3 months. In two in five patients, there was a sustained two-line improvement in vision. In one in five patients, the vision improvement was limited due to an underlying stromal scarring. There was recurrence of pannus and LSCD in two in five patients 6 months after surgery which was not attributable to the membrane. The ocular surface remained clear with no epithelial defects in three in five subjects at 12 months.ConclusionPLGA electrospun membranes show promise as carrier for limbal epithelial cells in the treatment of LSCD

Náuseas y vómitos postoperatorios con morfina liofilizada epidural. Su relacióncon algunasvariables

Introduction and Objectives: Postoperative complications associated with epidural use of opioids limit its wider use as an analgesic method. The purpose of this research was to describe the behavior of postoperative nausea and vomiting with the application of lyophilized morphine in epidural anesthesia. Method: Prospective, observational and single-blind study, where 3 groups, of 20 patients each, were randomly formed: Group I received preoperative medication with 10 mg of metoclopramide, Group II received 4 mg of ondansetron and Group III received no preoperative medication. Results: Postoperative nausea and vomiting occurred in the sample with an incidence of 20,6 %. There were no significant differences between metoclopramide and ondansetron regarding the incidence of nausea and vomiting. These effects occurred more frequently in those patients who were mobilized in the first 12 hours in which they had oral intake during the same period of time. Conclusions: Postoperative nausea and vomiting were relatively frequent side effects as a result of applying lyophilized morphine to the epidural anesthesia. Metoclopramide was as effective as ondansetron in its antiemetic effect. Nausea and vomiting were more common in patients who were mobilized and had oral intake in the first 12 hours, and in those who received no antiemetic premedication.Introducción y objetivos: Las complicaciones postoperatorias asociadas al empleo epidural de opiáceos, limitan su mayor uso como método analgésico. El objetivo de esta investigación fue describir el comportamiento de las náuseas y vómitos postoperatorios con la aplicación de morfina liofilizada en la anestesia epidural. Método: Estudio prospectivo, observacional y a simple ciegas, donde se conformaron aleatoriamente 3 grupos de 20 pacientes cada uno: Grupo I recibió medicación preoperatoria con 10 mg de metoclopramida, Grupo II con 4 mg de ondansetrón y el Grupo III no recibió ninguna medicación preoperatoria. Resultados: Las náuseas y vómitos postoperatorios se presentaron en la muestra estudiada con una incidencia de 20,6 %. No hubo diferencias significativas entre la metoclopramida y el ondansetrón en la incidencia de náuseas y vómitos; efectos que se presentaron con mayor frecuencia en aquellas pacientes que se movilizaron en las primeras 12 horas y en las que tuvieron ingesta oral en ese mismo período de tiempo. Conclusiones: Las náuseas y vómitos postoperatorios fueron efectos adversos, relativamente frecuentes, al aplicar morfina liofilizada a la anestesia epidural. La metoclopramida fue tan efectiva como el ondansetrón en su efecto antiemético. Las náuseas y vómitos fueron más habituales en los pacientes que se movilizaron y tuvieron ingesta oral en las primeras 12 horas, y en los que no recibieron premedicación antiemética

Multifunctional hybrid materials for combined photo and chemotherapyof cancer

[EN] Combined chemo and photothermal therapy in in vitro testing has been achieved by means of multifunctional nanoparticles formed by plasmonic gold nanoclusters with a protecting shell of porous silica that contains an antitumor drug. We propose a therapeutic nanoplatform that associates the optical activity of small gold nanoparticles aggregates with the cytotoxic activity of 20(S)-camptothecin simultaneously released for the efficient destruction of cancer cells. For this purpose, a method was used for the controlled assembly of gold nanoparticles into stable clusters with a tailored absorption crosssection in the vis/NIR spectrum, which involves aggregation in alkaline medium of 15 nm diameter gold colloids protected with a thin silica layer. Clusters were further encapsulated in an ordered homogeneous mesoporous silica coating that provides biocompatibility and stability in physiological fluids. After internalization in 42-MG-BA human glioma cells, these protected gold nanoclusters were able to produce effective photothermolysis under femtosecond pulse laser irradiation of 790 nm. Cell death occurred by combination of a thermal mechanism and mechanical disruption of the membrane cell due to induced generation of micrometer-scale bubbles by vaporizing the water inside the channels of the mesoporous silica coating. Moreover, the incorporation of 20(S)-camptothecin within the pores of the external shell, which was released during the process, provoked significant cell death increase. This therapeutic model could be of interest for application in the treatment and suppression of non-solid tumors.This work was financially supported by Comision Interministerial de Ciencia y Tecnologia of Spain through the projects FIS2006-09319, SAF2008-03694, MAT2006-14274-C02-01 and MULTICAT (Consolider-Ingenio 2010). CM thanks the Spanish "Ministerio de Economia y Competitividad" for a FDU Ph D studentship (AP2008-02851).Botella Asuncion, P.; Ortega, I.; Quesada Vilar, M.; Madrigal Madrigal, RF.; Muniesa Lajara, C.; Fimia Gil, A.; Fernandez Jover, E.... (2012). Multifunctional hybrid materials for combined photo and chemotherapyof cancer. Dalton Transactions. 41(31):9243-9554. https://doi.org/10.1039/c2dt30381gS92439554413

Valor de la morfina liofilizada intratecal en la revascularización miocárdica quirúrgica

Introduction: Subarachnoid analgesia is a useful therapeutic method in cardiac sur-gery. Objective: To compare the use of subarachnoid and intravenous morphine for post-operative analgesia in coronary artery bypass surgery. Method: A comparative longitudinal study was conducted in 40 patients, divided into two groups. The subarachnoid analgesia group received 15 mcg/kg of lyophilized mor-phine, and the intravenous morphine group received 0.3 mg/kg before and after sur-gery. Results: Female patients predominated. The average age and weights of both groups were similar (p > 0.05). In the subarachnoid morphine group, 90% of patients had excellent analgesia at 8 hours after surgery, and it ranged between excellent and good at 12 and 24 hours, respectively. On the other hand, only 50% of patients with intravenous morphine expressed they had a good analgesia at 8 hours after the operation; and at 24 hours they all complained of inadequate or poor analgesia (p < 0.05). The average total time of postoperative analgesia in the intrathecal morphine group was 24.41 hours, while in the intravenous morphine group it was 8.76 hours (p < 0.01). The main side effects were itching, for both groups, and hypotension and bradycardia for the intravenous morphine group, although differences were not sig-nificant. Conclusions: Subarachnoid morphine proved to be useful as an analgesic in coronary artery bypass surgery, with better and more prolonged analgesia than in those pa-tients who were treated with intravenous morphine.Introducción: La analgesia subaracnoidea constituye un método terapéutico útil en la cirugía cardíaca. Objetivo: Comparar el uso de la morfina subaracnoidea e intravenosa para la analge-sia postoperatoria de la revascularización miocárdica quirúrgica. Método: Se realizó un estudio comparativo, longitudinal en 40 pacientes, divididos en dos grupos. El de analgesia subaracnoidea recibió morfina liofilizada 15 mcg/kg, y el grupo de morfina intravenosa, 0,3 mg/kg previo y posterior a la cirugía. Resultados: Predominó el sexo femenino, las edades y los pesos promedio de ambos grupos fueron similares (p > 0.05). El 90 % de los enfermos del grupo de morfina sub-aracnoidea tuvo una analgesia excelente a las 8 horas de la intervención, y se mantu-vo entre buena y excelente a las 12 y 24 horas posteriores, respectivamente; mientras que solo el 50 % de los pacientes de morfina intravenosa refirió una analgesia buena a las 8 horas de operados; y a las 24 horas, todos se quejaron de una analgesia insufi-ciente o mala (p < 0.05). El tiempo total promedio de analgesia postoperatoria obteni-da en el grupo de morfina intratecal fue de 24,41 horas y en el de morfina intraveno-sa, de 8,76 horas (p < 0.01). Los principales efectos adversos fueron el prurito para ambos grupos, y la hipotensión y la bradicardia para el grupo con morfina intraveno-sa, aunque las diferencias no fueron significativas. Conclusiones: La morfina subaracnoidea demostró su utilidad como agente analgési-co en la revascularización miocárdica quirúrgica, con mejor y más prolongada analge-sia que los enfermos tratados con morfina intravenosa