Tissue engineering and regenerative medicine research - how can it contribute to fight future pandemics?

Understanding the pathogenesis of viral infection is of paramount importance for the development of better therapies. In the particular case of COVID-19, the mechanism of infection is highly complex and involves a critical cascade of events, which can lead to the death of the patient. Intense research is currently being performed to gain mechanistic insights about the virus etiology and to evaluate new therapeutic approaches. The development of point-of-care diagnostic tools, predictive drug screening platforms, and biomimetic models of the disease could play a key role in understanding the cellular and molecular mechanism of viral infection and its response to drugs. In this regard, specific tissue engineering and regenerative medicine approaches, such as microfluidics and organ-on-a-chip technologies, as well as bioprinted in vitro disease models, could be used to develop a technological platform to fight COVID-19, and other virus pandemics yet to come. Herein, we briefly discuss about how such approaches can contribute to address current and future viral pandemics by highlighting recent successful examples.D. Caballero acknowledges the financial support from the Portuguese Foundation for Science and Technology under the program CEEC Individual 2017 (CEECIND/00352/2017) and the project 2MATCH (02/SAICT/2017 - nº 028070) funded by the Programa Operacional Regional do Norte supported by FEDER. M. Carvalho would like to acknowledge IET Harvey Research Prize 2017. The authors also acknowledge the financial support from the EU Framework Programme for Research and Innovation Horizon 2020 on Forefront Research in 3D Disease Cancer Models as in vitro Screening Technologies (FoReCaST- no. 668983), the Portuguese Foundation for Science and Technology (FCT) distinction attributed to J. M. Oliveira (IF/00423/2012, IF/01285/2015) and FCT, Fundo Europeu de Desenvolvimento Regional (FEDER) and Programa Operacional Competitividade e Internacionalização (POCI) for funding the projects B-Liver (PTDC/EMD-EMD/29139/2017), Hierarchitech (M-ERA-NET/0001/2014) and 3BioMeD (JICAM/0001/2017)

Rare A-Type, Spiro-Type, and Highly Oligomeric Proanthocyanidins from \u3cem\u3ePinus massoniana\u3c/em\u3e

An investigation of the dental bioactive proanthocyanidin (PAC) oligomer fractions led to three structurally distinct new PACs (1–3) from pine bark. Pinutwindoublin (1) is the first reported trimer with double A-type interflavanyl linkages (2α→O→5,4α→6 and 2α→O→7,4α→8). Pinuspirotetrin (2) represents the first reported PAC tetramer with a heterodimeric framework consisting of one spiro-type and one A-type dimer. Pinumassohexin (3) was elucidated as a mixed A + B-type hexamer that consists of a peanut-derived tetramer, peanut procyanidin E, and an A-type dimer (5). Compound 3 increased the modulus of elasticity of dentin by an impressive 4.3 times at a concentration of 0.65%

Stem cell-containing hyaluronic acid-based spongy hydrogels for integrated diabetic wound healing

The detailed pathophysiology of diabetic foot ulcers is yet to be established and improved treatments are still required. We propose a strategy that directs inflammation, neovascularization, and neoinnervation of diabetic wounds. Aiming to potentiate a relevant secretome for nerve regeneration, stem cells were precultured in hyaluronic acid-based spongy hydrogels under neurogenic/standard media before transplantation into diabetic mice full-thickness wounds. Acellular spongy hydrogels and empty wounds were used as controls. Reepithelialization was attained 4 weeks after transplantation independently of the test groups, whereas a thicker and more differentiated epidermis was observed for the cellular spongy hydrogels. A switch from the inflammatory to the proliferative phase of wound healing was revealed for all the experimental groups 2 weeks after injury, but a significantly higher M2(CD163 þ )/M1(CD86 þ ) subtype ratio was observed in the neurogenic preconditioned group that also failed to promote neoinnervation. A higher number of intraepidermal nerve fibers were observed for the unconditioned group probably due to a more controlled transition from the inflammatory to the proliferative phase. Overall, stem cell-containing spongy hydrogels represent a promising approach to enhance diabetic wound healing by positively impacting re-epithelialization and by modulating the inflammatory response to promote a successful neoinnervation.The authors would like to acknowledge Gene2Skin Project (H2020-TWINN2015-692221) and Fundac¸a˜o para a Cieˆncia e Tecnologia for SFRH/BD/ 78025/2011 (LPdS), SFRH/BPD/96611/2013 (MTC), SFRH/BPD/101886/2014 (RPP), SFRH/BPD/101952/2014 (TCS) grants. Moreover, the authors would also like to acknowledge Teresa Oliveira for histology support, Andreia Carvalho for hASCs supply, Luca Gasperini for cell profiler analysis, and Manuela E. L. Lago and Carla M. Abreu for intraepidermal nerve fiber quantification.info:eu-repo/semantics/publishedVersio

Evaluation of novel dendrimer-gold complex nanoparticles for theranostic application in oncology

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/nnm-2023-0355Aim: Despite some successful examples of therapeutic nanoparticles reaching clinical stages, there is still a significant need for novel formulations in order to improve the selectivity and efficacy of cancer treatment. Methods: The authors developed two novel dendrimerâ gold (Au) complex-based nanoparticles using twodifferent synthesis routes: complexation method (formulation A) and precipitation method (formulation B). Using a biomimetic cancer-on-a-chip model, the authors evaluated the possible cytotoxicity and internalization by colorectal cancer cells of dendrimerâ Au complex-based nanoparticles. Results: The results showed promising capabilities of these nanoparticles for selectively targeting cancer cells and delivering drugs, particularly for the formulation A nanoparticles. Conclusion: This work highlights the potential of dendrimerâ Au complex-based nanoparticles as a new strategy to improve the targeting of anticancer drugs.This work is financially supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 952603 (http://sgabu.eu/). This article reflects only the author’s view. The Commission is not responsible for any use that may be made of the information it contains. For the experimental part of the study, we acknowledge BIONECA project – Biomaterials and advanced physical techniques for regenerative cardiology and neurology (CA16122) – and the FEDER funded project 2IQBIONEURO (0624 2IQBIONEURO 6 E). M Carvalho acknowledges her postdoctoral contract TERM RES Hub – Scientific infrastructure for Tissue Engineering and Regenerative Medicine Ref Norte-01-0145-FEDER-02219015. D Caballero acknowledges the financial support from the Portuguese Foundation for Science and Technology (FCT) under the program CEEC Individual 2017 (CEECIND/00352/2017), and the project 2MATCH (PTDC/BTM-ORG/28070/2017) funded by the Programa Operacional Regional do Norte supported by European Regional Development Funds (ERDF). This work was partially supported by IET A. F. Harvey Engineering Research Award 2018 (ENG The Cancer). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed

Antimicrobial properties of membrane-active dodecapeptides derived from MSI-78

Antimicrobial peptides (AMPs) are a class of broad-spectrum antibiotics known by their ability to disrupt bacterial membranes and their low tendency to induce bacterial resistance, arising as excellent candidates to fight bacterial infections. In this study we aimed at designing short 12-mer AMPs, derived from a highly effective and broad spectrum synthetic AMP, MSI-78 (22 residues), by truncating this peptide at the N- and/or C-termini while spanning its entire sequence with 1 amino add (aa) shifts. These designed peptides were evaluated regarding antimicrobial activity against selected gram-positive Staphylococcus strains and the gram-negative Pseudomonas aeruginosa (P. aeruginosa). The short 12-mer peptide CEM1 (GIGMFLKKAKICF) was identified as an excellent candidate to fight P. aeruginosa infections as it displays antimicrobial activity against this strain and selectivity, with negligible toxicity to mammalian cells even at high concentrations. However, in general most of the short 12-mer peptides tested showed a reduction in antimicrobial activity, an effect that was more pronounced for gram-positive Staphylococcus strains. Interestingly, CEM1 and a highly similar peptide differing by only one aa-shift (CEM2: IGKFLKKAKICFG), showed a remarkably contrasting AMP activity. These two peptides were chosen for a more detailed study regarding their mechanism of action, using several biophysical assays and simple membrane models that mimic the mammalian and bacterial lipid composition. We confirmed the correlation between peptide helicity and antimicrobial activity and propose a mechanism of action based on the disruption of the bacterial membrane permeability barrier

Silk hydrogels from non-mulberry and mulberry silkworm cocoons processed with ionic liquids

Matrices based on silk fibroin from the non-mulberry silkworm Antheraea mylitta and the mulberry silkworm Bombyx mori have demonstrated good applicability in regenerative medicine. However, the cocoons of A. mylitta are underutilized in part due to their lack of solubility in traditional organic solvents. Therefore, the present work investigates the solubilization and processing of degummed fibers obtained from the cocoons of both silkworm species into hydrogels using ionic liquids (ILs). The developed hydrogels exhibited a rubbery consistency, viscoelastic behavior and rapid degradation in the presence of protease XIV. Scanning electron and confocal microscopy images suggest that human adipose stem cells (hASCs) are able to adhere to and migrate at different levels within the hydrogel structures. Moreover, the MTS assay demonstrated the maintenance of cell metabolic activity for up to 28days, while DNA quantification showed that hASCs were able to proliferate on the seeded hydrogels. The findings indicate that complete IL removal from the fabricated hydrogels results in a positive hASCs cellular response. Thus the present approach provides a unique opportunity to broaden the processability and application of silk fibroin obtained from A. mylitta cocoons for regenerative medicine, namely cartilage regeneration.The authors acknowledge financial support from the Portuguese Foundation for Science and Technology (Grants SFRH/BPD/45307/2008 and SFRH/BD/64070/2009), the Fundo Social Europeu, and the Programa Diferencial de Potencial Humano. This work was partially supported by the FEDER through POCTEP 0330_IBERO-MARE_1_P and also by the Department of Biotechnology, Government of India. S.C.K. is grateful to R.L.R. and S.S.S. for their excellent hospitality during his stay at the 3B's laboratory, Guimaraes, Portugal. R.L.R. also offers his sincere thanks to S.C.K. for providing hospitality during his short visits to his laboratory in the Indian Institute of Technology, Kharagpur

Tri- and Tetrameric Proanthocyanidins with Dentin Bioactivities from \u3cem\u3ePinus massoniana\u3c/em\u3e

Guided by dentin biomechanical bioactivity, this phytochemical study led to the elucidation of an extended set of structurally demanding proanthocyanidins (PACs). Unambiguous structure determination involved detailed spectroscopic and chemical characterization of four A-type dimers (2 and 4–6), seven trimers (10–16), and six tetramers (17–22). New outcomes confirm the feasibility of determining the absolute configuration of the catechol monomers in oligomeric PACs by one-dimensional (1D) and two-dimensional (2D) NMR. Electronic circular dichroism as well as phloroglucinolysis followed by mass spectrometry and chiral phase high-performance liquid chromatography (HPLC) analysis generated the necessary chiral reference data. In the context of previously reported dentin-bioactive PACs, accurately and precisely assigned 13C NMR resonances enabled absolute stereochemical assignments of PAC monomers via (i) inclusion of the 13C NMR γ-gauche effect and (ii) determination of differential 13C chemical shift values (ΔδC) in comparison with those of the terminal monomer (unit II) in the dimers 2 and 4–6. Among the 13 fully elucidated PACs, eight were identified as new, and one structure (11) was revised based on new knowledge gained regarding the subtle, stereospecific spectroscopic properties of PACs

Simultaneous Separation of Antioxidants and Carbohydrates From Food Wastes Using Aqueous Biphasic Systems Formed by Cholinium-Derived Ionic Liquids

project CICECO-Aveiro Institute of Materials, UID/CTM/50011/2019. Associate Laboratory for Green Chemistry-LAQV, FCT Ref. UID/QUI/50006/2019. POCI-01-0145-FEDER-016403. Investigator FCT project IF/00621/2015. Programa Mais Centro under project CENTRO-07-ST24-FEDER-002008. COMPETE: PEst-C/SAU/UI0709/2011.The food industry produces significant amounts of waste, many of them rich in valuable compounds that could be recovered and reused in the framework of circular economy. The development of sustainable and cost-effective technologies to recover these value added compounds will contribute to a significant decrease of the environmental footprint and economic burden of this industry sector. Accordingly, in this work, aqueous biphasic systems (ABS) composed of cholinium-derived bistriflimide ionic liquids (ILs) and carbohydrates were investigated as an alternative process to simultaneously separate and recover antioxidants and carbohydrates from food waste. Aiming at improving the biocompatible character of the studied ILs and proposed process, cholinium-derived bistriflimide ILs were chosen, which were properly designed by playing with the cation alkyl side chain and the number of functional groups attached to the cation to be able to create ABS with carbohydrates. These ILs were characterized by cytotoxicity assays toward human intestinal epithelial cells (Caco-2 cell line), demonstrating to have a significantly lower toxicity than other well-known and commonly used fluorinated ILs. The capability of these ILs to form ABS with a series of carbohydrates, namely monosaccharides, disaccharides and polyols, was then appraised by the determination of the respective ternary liquid-liquid phase diagrams at 25 degrees C. The studied ABS were finally used to separate carbohydrates and antioxidants from real food waste samples, using an expired vanilla pudding as an example. With the studied systems, the separation of the two products occurs in one-step, where carbohydrates are enriched in the carbohydrate-rich phase and antioxidants are mainly present in the IL-rich phase. Extraction efficiencies of carbohydrates ranging between 89 and 92% to the carbohydrate-rich phase, and antioxidant relative activities ranging between 65 and 75% in the IL-rich phase were obtained. Furthermore, antioxidants from the IL-rich phase were recovered by solid-phase extraction, and the IL was recycled for two more times with no losses on the ABS separation performance. Overall, the obtained results show that the investigated ABS are promising platforms to simultaneously separate carbohydrates and antioxidants from real food waste samples, and could be used in further related applications foreseeing industrial food waste valorization.publishersversionpublishe