FBXW7 circular RNA repress glioma tumorigenesis

Polymethylmethacrylate (PMMA) bone cement, commonly used for the fixation of joint prostheses and also for orthopaedic devices, may be colonised by Gram positive cocci. The use of antibiotic-loaded PMMA should prevent bacterial colonisation of cement surfaces. Biofilm formation on bone cement could be more effectively reduced by incorporation of a second antibiotic The aim of our study was to evaluate the in vitro effects of gentamicin (G)- and vancomycin (V)-loaded PMMA cement specimens on the bacterial adhesion of multi-resistant clinical isolates staphylococci

Skin Tissue Models

Skin Tissue Models provides a translational link for biomedical researchers on the interdisciplinary approaches to skin regeneration. As the skin is the largest organ in the body, engineered substitutes have critical medical application to patients with disease and injury - from burn wounds and surgical scars, to vitiligo, psoriasis and even plastic surgery. This volume offers readers preliminary description of the normal structure and function of mammalian skin, exposure to clinical problems and disease, coverage of potential therapeutic molecules and testing, skin substitutes, models as study platforms of skin biology and emerging technologies. The editors have created a table of contents which frames the relevance of skin tissue models for researchers as platforms to study skin biology and therapeutic approaches for different skin diseases, for clinicians as tissue substitutes, and for cosmetic and pharmaceutical industries as alternative test substrates that can replace animal models. Offers descriptions of the normal structure/function of mammalian skin, exposure to clinical problems, and more Presents coverage of skin diseases (cancer, genodermatoses, vitiligo and psoriasis) that extends to clinical requirements and skin diseases in vitro models Addresses legal requirements and ethical concerns in drugs and cosmetics in vitro testing Edited and authored by internationally renowned group of researchers, presenting the broadest coverage possible. © 2018 Elsevier Inc. All rights reserved.(undefined)info:eu-repo/semantics/publishedVersio

Evaluating biomaterial-and microfluidic-based 3D tumor models

Cancer is a major cause of morbidity and mortality worldwide, with a disease burden estimated to increase in the coming decades. Disease heterogeneity and limited information on cancer biology and disease mechanisms are aspects that 2D cell cultures fail to address. We review the current "state-of-the-art" in 3D Tissue Engineering (TE) models developed for and used in cancer research. Scaffold-based TE models and microfluidics, are assessed for their potential to fill the gap between 2D models and clinical application. Recent advances in combining the principles of 3D TE models and microfluidics are discussed, with a special focus on biomaterials and the most promising chip-based 3D models.The authors would like to thank the European Union's Seventh Framework Program (FP7/2007-2013) under grant agreement no REGPOT-CT2012-316331-POLARIS, and QREN (ON.2 - NORTE-01-0124-FEDER-000016) co-financed by North Portugal Regional Operational Program (ON.2 - O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF) for providing financial support to this project. The FCT distinction attributed to J.M.O. under the Investigator FCT program (IF/00423/2012) Is also greatly acknowledged

Investigation of Dendrimer-based nanoparticles cellular uptake and cell tracking in a semiautomated microfluidic platform

A microfluidic device such as Kima Pump and Vena8 biochip is able to realize functions that are not easily imaginable in conventional biological analysis, such as highly parallel, sophisticated high-throughput analysis and single-cell analysis in a well-defined manner [1]. Cancer cell tracking within the microfluidic model will be achieved by grafting fluorescent label probe Fluorescein-5(6)-isothiocyanate (FITC) to dendrimer nanoparticles allowing cell visualization by immunofluorescent staining followed by fluorescence microscopy. In this study, synthesis and physicochemical characterization of Carboxymethyl-chitosan/poly(amidoamine) dendrimer nanoparticles (CMCht/PAMAM NPâ s) were performed[2].  Several cancer cell lines such as a HeLA (cervical carcinoma cell line), HTTC-116 (Colon Carcinoma) and Glioblastome cell line (GBM) were exposed to different concentrations of CMCht/PAMAM dendrimer nanoparticles over a period of 7d. After finding the adequate NP concentration, the internalization efficiency was tested, as well as cellular trafficking, in static and dynamic conditions (Kima Pump bioreactor).Portuguese Foundation for Science and Technology (FCT) through the project PEst­C/SAU/LA0026/20

Pre-selection of fibroblasts subsets prompt prevascularization of tissue engineered skin analogues

The papillary and reticular dermis harbors phenotypically distinct fibroblasts, whose functions such as maintenance of skin's microvasculature are also distinct. Thus, we hypothesized that pre-selection of the subpopulations of fibroblasts would benefit the generation of skin tissue engineered (TE) constructs, promoting their prevascularization in vitro. We first isolated papillary and reticular fibroblasts using fluorescence-activated cell sorting and studied the effect of their secretome and extracellular matrix (ECM) on human dermal microvascular endothelial cell (hDMEC) organization. Subsequently, we developed a bilayered 3D polymeric structure with distinct layer-associated features to house the subpopulations of fibroblasts, to generate a skin analogue. Both papillary and reticular fibroblasts were able to stimulate capillary-like network formation in a Matrigel assay. However, the secretome of the two subpopulations was substantially different, being enriched in VEGF, IGF-1, and Angio-1 in the case of papillary fibroblasts and in HGF and FGF-2 for the reticular subset. In addition, the fibroblast subpopulations deposited varied levels of ECM proteins, more collagen I and laminin was produced by the reticular subset, but these differences did not impact hDMEC organization. Vessel-like structures with lumens were observed earlier in the 3D skin analogue prepared with the sorted fibroblasts, although ECM deposition was not affected by the cell's pre-selection. Moreover, a more differentiated epidermal layer was obtained in the skin analogue formed by the sorted fibroblasts, confirming that its whole structure was not affected. Overall, we provide evidence that pre-selection of papillary and reticular fibroblasts is relevant for promoting the in vitro prevascularization of skin TE constructs.The authors would like to acknowledge the financial support from the Consolidator Grant “ECM_INK” (ERC-2016- COG-726061), to the FSE/POCH (Fundo Social Europeu através do Programa Operacional do Capital Humano) under the scope of the PD/169/2013, NORTE-08-5369-FSE-000037 (H.R. M.)

Longitudinally aligned inner-patterned silk fibroin conduits for peripheral nerve regeneration

Published 18 April 2023Peripheral nerve injuries represent a major clinical challenge, if nerve ends retract, there is no spontaneous regeneration, and grafts are required to proximate the nerve ends and give continuity to the nerve. The nerve guidance conduits (NGCs) presented in this work are silk fibroin (SF)-based, which is biocompatible and very versatile. The formation of conduits is obtained by forming a covalently cross-linked hydrogel in two concentric moulds, and the inner longitudinally aligned pattern of the SF NGCs is obtained through the use of a patterned inner mould. SF NGCs with two wall thicknesses of ~ 200 to ~ 400 μm are synthesized. Their physicochemical and mechanical characteristics have shown improved properties when the wall thickness is thicker such as resistance to kinking, which is of special importance as conduits might also be used to substitute nerves in flexible body parts. The Young modulus is higher for conduits with inner pattern, and none of the conduits has shown any salt deposition in presence of simulated body fluid, meaning they do not calcify; thus, the regeneration does not get impaired when conduits have contact with body fluids. In vitro studies demonstrated the biocompatibility of the SF NGCs; proliferation is enhanced when iSCs are cultured on top of conduits with longitudinally aligned pattern. BJ fibroblasts cannot infiltrate through the SF wall, avoiding scar tissue formation on the lumen of the graft when used in vivo. These conduits have been demonstrated to be very versatile and fulfil with the requirements for their use in PNR.Open access funding provided by FCT|FCCN (b-on)

Dendrimers in tissue engineering

Dendrimers are highly branched and multivalent, and monodispersive making them perfect candidates for a myriad of controlled drug delivery applications. Dendrimers possess many other advantages, such as the possibility of modulating surface chemistry and charge, and biodegradation rate and to be processed as scaffolds that can emulate natural extracellular matrices thus opening up unique applications in tissue engineering. The combination of dendrimers and other macromolecules (proteins and carbohydrates), as well as other traditional scaffold polymers, has led to the creation of hybrid scaffolds with new physical, mechanical, and biochemical properties. However, despite the widespread use of dendrimers in biomedical applications, their use in the fabrication of tissue engineering scaffolds remains some-how narrow. The most promising applications of dendritic macromolecules in TE area such as drug delivery strategies, cell differentiation and/or tissue regeneration, 3D/Dynamic platforms and ex vivo/in vivo testing are overviewed and discussed herein.JMO for the financial support provided under the program “Investigador FCT” (IF/01285/2015). MCR acknowledges the IET Institution of Engineering and Technology for the financial support provided under the IET Harvey Research Prize 2017. IMO thanks the financial support under the Norte2020 project (“NORTE-08-5369-FSE-000044”)

A semiautomated microfluidic platform for real-time investigation of nanoparticles' cellular uptake and cancer cells' tracking

Aims: develop a platform composed of labeled dendrimer nanoparticles and a microfluidic device for real-time monitoring of cancer cells fate. Materials and Methods: The physicochemical and biological characterization of the developed Carboxymethyl-chitosan/poly(amidoamine) (CMCht/PAMAM) dendrimer nanoparticles were performed using TEM, AFM, Zeta Sizer, DSC and cytotoxicity screening. Cancer cell lines derived from different tumor types, including HeLa (Cervical Carcinoma), HCT-116 (Colon Carcinoma) and U87MG (Glioblastoma), were exposed to different concentrations of CMCht/PAMAM dendrimer nanoparticles over a period of 3 days (MTS/DNA). Results: Nanoparticles were successfully modified with an average size of 50 nm. Internalization levels go from 87% to 100% in static and from 95% to 100% in dynamic conditions. Viability levels range from 95% to 100% in static and from 90% to 100% in dynamic conditions, being HCT the most sensitive to the presence of the NP. Conclusions: the results show different responses to the presence of 0.5 mg.mL-1 dendrimer nanoparticles when comparing static to dynamic conditions, with a tendency towards higher sensitivity when subjected to confinement. This work demonstrated that the proposed microfluidic-based platform allows real-time cell monitoring, which, upon more studies, namely the assessment of the drug release effect, could be used for cancer theranostics.FR Maia acknowledges ERC-2012-ADG 20120216–321266 (ComplexiTE) for her Postdoc scholarship. JM Oliveira thanks Portuguese Foundation for Science and Technology (FCT) for his distinction attributed under the FCT Investigator program (IF/00423/2012). BM Costa also thanks Portuguese Foundation for Science and Technology (PTDC/SAU-GMG/113795/2009 and IF/00601/2012 to BM Costa), Fundação Calouste Gulbenkian (BM Costa) and Liga Portuguesa Contra o Cancro (BM Costa). MR Carvalho also thanks the funding through the LA ICVS/3Bs project (UID/Multi/50026/2013). 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.info:eu-repo/semantics/publishedVersio

Semipermeable capsules wrapping a multifunctional and self-regulated co-culture microenvironment for osteogenic differentiation

A new concept of semipermeable reservoirs containing co-cultures of cells and supporting microparticles is presented, inspired by the multi-phenotypic cellular environment of bone. Based on the deconstruction of the â stem cell nicheâ , the developed capsules are designed to drive a self-regulated osteogenesis. PLLA microparticles functionalized with collagen I, and a co-culture of adipose stem (ASCs) and endothelial (ECs) cells are immobilized in spherical liquified capsules. The capsules are coated with multilayers of poly(L-lysine), alginate, and chitosan nano-assembled through layer-by-layer. Capsules encapsulating ASCs alone or in a co-culture with ECs are cultured in endothelial medium with or without osteogenic differentiation factors. Results show that osteogenesis is enhanced by the co-encapsulation, which occurs even in the absence of differentiation factors. These findings are supported by an increased ALP activity and matrix mineralization, osteopontin detection, and the up regulation of BMP-2, RUNX2 and BSP. The liquified co-capsules also act as a VEGF and BMP-2 cytokines release system. The proposed liquified capsules might be a valuable injectable self-regulated system for bone regeneration employing highly translational cell sources.The authors acknowledge the financial support by the Portuguese Foundation for Science and Technology (FCT) through the Ph.D. (SFRH/BD/69529/2010-Clara R. Correia) and the Post-doc grants (SFRH/BPD/96611/2013- Mariana T. Cerqueira), and the funding of RL3-TECT-NORTE-01-0124-FEDER-000020 for Rogério P. Pirraco. This work was also supported by European Research Council grant agreement ERC-2014-ADG-669858 for project ATLAS