Abstract
A proper validation of an engineered brain microenvironment requires a trade of between the complexity of a cellular construct within the in vitro platform and the simple implementation of the investigational tool. The present work aims to accomplish this challenging balance by setting up an innovative membrane platform that represents a good compromise between a proper mimicked brain tissue analogue combined with an easily accessible and implemented membrane system. Another key aspect of the in vitro modelling disease is the identification of a precise phenotypic onset as a definite hallmark of the pathology that needs to be recapitulated within the implemented membrane system. On the basis of these assumptions, we propose a multiplex membrane system in which the recapitulation of specific neuro-pathological onsets related to Alzheimer’s disease pathologies, namely oxidative stress and β-amyloid1–42 toxicity, allowed us to test the neuroprotective effects of trans-crocetin on damaged neurons. The proposed multiplex membrane platform is therefore quite a versatile tool that allows the integration of neuronal pathological events in combination with the testing of new molecules. The present paper explores the use of this alternative methodology, which, relying on membrane technology approach, allows us to study the basic physiological and pathological behaviour of differentiated neuronal cells, as well as their changing behaviour, in response to new potential therapeutic treatment.
Highlights
Advancements in tissue engineering technologies rely on the development of biomimetic models, which recapitulate the main distinctive tissue features for applications in basic research and the screening of new therapeutic treatments.Nowadays, the global burden of neurological disease is huge, and quite often the methods of assessing cell behaviour in response to a new drug are insufficient
We present a PLGA multiplex membrane platform, which features several fundamental prerequisites for an efficient investigational platform. It consists of a continuous array of PLGA membrane chambers, where each membrane spot allows for dedicated investigation inherent to the case of study
Considering the early stages of apoptosis are characterized by the loss of mitochondrial membrane potential (MMP), we investigated the effect of trans-crocetin on the Amyloid β peptide (Aβ)-induced decrease of MMP using a potential-sensing fluorescence probe (JC-1) in LSCM
Summary
Advancements in tissue engineering technologies rely on the development of biomimetic models, which recapitulate the main distinctive tissue features for applications in basic research and the screening of new therapeutic treatments.Nowadays, the global burden of neurological disease is huge, and quite often the methods of assessing cell behaviour in response to a new drug are insufficient. The key aspect for a high throughput therapeutic screening platform is the creation of a defined cellular microenvironment and specific interactions between cells, offering reliable tools for in vitro observations [1,2,3,4] This challenging aspect is satisfied by the use of in vitro tools based on a membrane technology approach, which has been widely demonstrated to act as proper platform to model physiological and pathological conditions [5,6,7,8,9]. The present work aims to accomplish such a challenging balance by setting up an innovative membrane platform that represents a good compromise between a proper mimicked brain tissue analogue combined with an accessible and implemented membrane system
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