Advances in the slow freezing cryopreservation of microencapsulated cells

Over the past few decades, the use of cell microencapsulation technology has been promoted for a wide range of applications as sustained drug delivery systems or as cells containing biosystems for regenerative medicine. However, difficulty in their preservation and storage has limited their availability to healthcare centers. Because the preservation in cryogenic temperatures poses many biological and biophysical challenges and that the technology has not been well understood, the slow cooling cryopreservation, which is the most used technique worldwide, has not given full measure of its full potential application yet. This review will discuss the different steps that should be understood and taken into account to preserve microencapsulated cells by slow freezing in a successful and simple manner. Moreover, it will review the slow freezing preservation of alginate-based microencapsulated cells and discuss some recommendations that the research community may pursue to optimize the preservation of microencapsulated cells, enabling the therapy translate from bench to the clinic

Sol-gel coatings for metallic prosthesis from methyl-modified alkoxysilanes: balance between protection and bioactivation

The reported osteogenic properties of the hybrid silica sol-gel materials make these compositions perfect candidates for bone tissue engineering applications. The aim of this study was the synthesis and characterisation of hybrid silica coatings, obtained using mixtures of tetraethyl orthosilicate (TEOS) and three different methyl-modified alkoxysilanes: trimethoxymethylsilane (MTMS), dimethyldiethoxysilane (DMDES) or polydimethylsiloxane (PDMS). A comparison of the properties of these materials can reveal the best candidate for the coatings on metallic prostheses. After optimising the synthesis parameters, the developed coatings were characterised using Fourier transform infrared spectrometry (FT-IR), 1H and 29Si solid-state nuclear magnetic resonance (1H-NMR and 29Si-MNR), cross-cut tests, scanning electron microscopy (SEM), contact angle measurements, optical profilometry, hydrolytic degradation tests and electrochemical corrosion analysis. Homogeneous and well-adhering coatings were obtained using the three methyl-modified reagents. However, different degrees of protection against corrosion, different hydrophilicity and varying degradation kinetics were observed for different precursors. The MTMS-based coating showed the highest hydrophilicity and degradation kinetics; these properties can be associated with increased bioactivity (Si release). In contrast, the PDMS and DMDES-based coatings showed augmented resistance to corrosion and lower permeability to water and, consequently, improved protection of metallic surfaces. From the physicochemical point of view, all these materials displayed interesting characteristics, relevant for coatings to be used in biomedical applications

Type 1 Diabetes Mellitus reversal via implantation of magnetically purified microencapsulated pseudoislets

[Abstract] Microencapsulation of pancreatic islets for the treatment of Type I Diabetes Mellitus (T1DM) generates a high quantity of empty microcapsules, resulting in high therapeutic graft volumes that can enhance the host’s immune response. We report a 3D printed microfluidic magnetic sorting device for microcapsules purification with the objective to reduce the number of empty microcapsules prior transplantation. In this study, INS1E pseudoislets were microencapsulated within alginate (A) and alginate-poly-L-lysine-alginate (APA) microcapsules and purified through the microfluidic device. APA microcapsules demonstrated higher mechanical integrity and stability than A microcapsules, showing better pseudoislets viability and biological function. Importantly, we obtained a reduction of the graft volume of 77.5% for A microcapsules and 78.6% for APA microcapsules. After subcutaneous implantation of induced diabetic Wistar rats with magnetically purified APA microencapsulated pseudoislets, blood glucose levels were restored into normoglycemia (<200 mg/dL) for almost 17 weeks. In conclusion, our described microfluidic magnetic sorting device represents a great alternative approach for the graft volume reduction of microencapsulated pseudoislets and its application in T1DM disease.Universidad del País Vasco; ESPPOC 16/65Universidad del País vasco; EHUa16/06Gobierno Vasco; IT907-16Gobierno Vasco; KK-2017/0000088Gobierno Vasco; 307616FKA4Ministerio de Economía y Competitividad; RYC-2012-1079

Designing stem-cell-based dopamine cell replacement trials for Parkinson's disease

Clinical studies of Parkinson’s disease (PD) using a dopamine cell replacment strategy have been tried for more than 30 years. The outcomes following transplantation of human fetal ventral mesencephalic tissue (hfVM) have been variable, with some patients coming off their anti-PD treatment for many years and others not responding and/or developing significant side effects, including graft-induced dyskinesia. This led to a re-appraisal of the best way to do such trials, which resulted in a new European-Union-funded allograft trial with fetal dopamine cells across several centers in Europe. This new trial, TRANSEURO (NCT01898390), is an open-label study in which some individuals in a large observational cohort of patients with mild PD who were undergoing identical assessments were randomly selected to receive transplants of hfVM. The TRANSEURO trial is currently ongoing as researchers have completed both recruitment into a large multicenter observational study of younger onset early-stage PD and transplantation of hfVM in 11 patients. While completion of TRANSEURO is not expected until 2021, we feel that sharing the rationale for the design of TRANSEURO, along with the lessons we have learned along the way, can help inform researchers and facilitate planning of transplants of dopamine-producing cells derived from human pluripotent stem cells for future clinical trials

Implementation of Active Power Substation for Harvesting Regenerative Braking Energy in Italian 3 kV Railway Systems

In line with the overall goals of EU climate commitments and railway operators, the reduction of CO2 emissions and the development of more eco-friendly transport systems with increased energy efficiency have become paramount. This paper focuses on the utilization of regenerative braking energy (RBE) and explores the potential of adopting active power substations as a solution. Active power substations enable bidirectional power flow, facilitating the feedback of RBE into the upstream grid. The paper presents a case study of the Italian railway system, which operates on 3 kV DC voltage and currently utilizes diode rectifiers in its traction substations. This configuration hinders power reversibility and prevents RBE, resulting in the wasteful dissipation of electric energy through braking rheostats. To overcome this limitation, the paper proposes a bidirectional electric substation configuration based on NPC parallel-connected converters. A control strategy is proposed and simulation results are provided to demonstrate the feasibility and benefits of the proposed approach