Mn-based methacrylated gellan gum hydrogels for MRI-guided cell delivery and imaging

This work aims to engineer a new stable injectable Mn-based methacrylated gellan gum (Mn/GG-MA) hydrogel for real-time monitored cell delivery into the central nervous system. To enable the hydrogel visualization under Magnetic Resonance Imaging (MRI), GG-MA solutions were supplemented with paramagnetic Mn2+ ions before its ionic crosslink with artificial cerebrospinal fluid (aCSF). The resulting formulations were stable, detectable by T1-weighted MRI scans and also injectable. Cell-laden hydrogels were prepared using the Mn/GG-MA formulations, extruded into aCSF for crosslink, and after 7 days of culture, the encapsulated human adipose-derived stem cells remained viable, as assessed by Live/Dead assay. In vivo tests, using double mutant MBPshi/shi/rag2 immunocompromised mice, showed that the injection of Mn/GG-MA solutions resulted in a continuous and traceable hydrogel, visible on MRI scans. Summing up, the developed formulations are suitable for both non-invasive cell delivery techniques and image-guided neurointerventions, paving the way for new therapeutic procedures.Sílvia Vieira acknowledges the FCT Ph.D. scholarship (SFRH/BD/102710/2014). J. Miguel Oliveira and J. Silva-Correia acknowledge the FCT grants under the Investigator FCT program (IF/01285/2015 and IF/00115/2015, respectively). The authors also acknowledge the funds provided under the project NanoTech4ALS, funded under the EU FP7 M-ERA.NET program, and ESF (POWR.03.02.00-00-I028/17-00)

Forensic electrochemistry: simultaneous voltammetric detection of MDMA and its fatal counterpart "Dr Death" (PMA)

The simultaneous detection of substances present in drugs of abuse is increasingly important since some materials are known for their high mortality rate. One drug that received considerable attention is para-methoxyamphetamine (PMA), commonly known as ‘Dr Death’ – this substance is linked with several deaths internationally and can often be found together with 3,4-methylenedioxymethamphetamine (MDMA) in drugs sold under the alias “ecstasy”, a very popular drug of abuse. This work reports for the first time the detection and quantification of MDMA and PMA simultaneously through an electrochemical technique using screen-printed graphite electrodes (SPEs). The electroanalytical sensing of MDMA/PMA, MDMA and PMA are explored directly at bare unmodified SPEs yielding a detection limit (3σ) corresponding to 0.25 μg mL−1/0.14 μg mL−1 for MDMA/PMA, 0.04 μg mL−1 MDMA and 0.03 μg mL−1 PMA. Raman spectroscopy and presumptive colour tests were also performed on MDMA/PMA, MDMA and PMA using the Marquis, Mandelin, Simon's and Robadope tests but were found to not be able discriminate when PMA and MDMA are both present in the same samples. We report a novel electrochemical protocol for the sensing of PMA and MDMA which is independently validated in a synthetic (MDMA/PMA) sample with HPLC

Manganese-labeled alginate hydrogels for image-guided cell transplantation

Cell transplantation has been studied extensively as a therapeutic strategy for neurological disorders. However, to date, its effectiveness remains unsatisfactory due to low precision and efficacy of cell delivery; poor survival of transplanted cells; and inadequate monitoring of their fate in vivo. Fortunately, different bio-scaffolds have been proposed as cell carriers to improve the accuracy of cell delivery, survival, differentiation, and controlled release of embedded stem cells. The goal of our study was to establish hydrogel scaffolds suitable for stem cell delivery that also allow non-invasive magnetic resonance imaging (MRI). We focused on alginate-based hydrogels due to their natural origin, biocompatibility, resemblance to the extracellular matrix, and easy manipulation of gelation processes. We optimized the properties of alginate-based hydrogels, turning them into suitable carriers for transplanted cells. Human adipose-derived stem cells embedded in these hydrogels survived for at least 14 days in vitro. Alginate-based hydrogels were also modified successfully to allow their injectability via a needle. Finally, supplementing alginate hydrogels with Mn ions or Mn nanoparticles allowed for their visualization in vivo using manganese-enhanced MRI. We demonstrated that modified alginate-based hydrogels can support therapeutic cells as MRI-detectable matrices.This work was supported by NanoTech4ALS (ref. ENMed/0008/2015, 13/EuroNanoMed/ 2016), funded under the EU FP7 M-ERA.NET program, and European Social Fund (POWR.03.02.00- 00-I028/17-00). Eduarda P. Oliveira acknowledges the Ph.D. scholarship (SFRH/BD/137726/2018), attributed by the Portuguese Foundation for Science and Technology (FCT). Authors also acknowledge the R&D Project KOAT—Kefiran exopolysaccharide: Promising biopolymer for use in regenerative medicine and tissue engineering, with reference PTDC/BTMMAT/29760/2017, financed by FCT and co-financed by FEDER and POCI.

Methacrylated gellan gum and hyaluronic acid hydrogel blends for image-guided neurointerventions

Cell-based therapies deliveredviaintrathecal injection are considered as one of the most promisingsolutions for the treatment of amyotrophic lateral sclerosis (ALS). Herein, injectable manganese-basedbiocompatible hydrogel blends were developed, that can allow image-guided cell delivery. Thehydrogels can also provide physical support for cells during injection, and at the intrathecal space aftertransplantation, while assuring cell survival. In this regard, different formulations of methacrylated gellangum/hyaluronic acid hydrogel blends (GG-MA/HA) were considered as a vehicle for cell delivery. Thehydrogels blends were supplemented with paramagnetic Mn2+to allow a real-time monitorization ofhydrogel depositionvia T1-weighted magnetic resonance imaging (MRI). The developed hydrogels wereeasily extruded and formed a stable fiber upon injection into the cerebrospinal fluid. Hydrogels preparedwith a 75 : 25 GG-MA to HA ratio supplemented with MnCl2at 0.1 mM showed controlled hydrogeldegradation, suitable permeability, and a distinct MRI signalin vitroandin vivo. Additionally, human-derived adipose stem cells encapsulated in 75 : 25 GG-MA/HA hydrogels remained viable for up to14 days of culturein vitro. Therefore, the engineered hydrogels can be an excellent tool for injectableimage-guided cell delivery approaches.Sı´lvia Vieira acknowledges the FCT PhD scholarship (SFRH/BD/102710/2014). The FCT distinction attributed to J. Miguel Oliveira under the Investigator FCT program (IF/01285/2015) and J. Silva-Correia (IF/00115/2015) are also greatly acknowledged. The authors also acknowledge the funds provided under the project NanoTech4ALS, funded under the EU FP7 M-ERA.NET program, and ESF (POWR.03.02.00-00-I028/17-00)