Pappalardo, F. | bioRxiv Science

bioRxiv2020

In Silico Trial to test COVID-19 candidate vaccines: a case study with UISS platform

SARS-CoV-2 is a severe respiratory infection that infects humans. Its outburst entitled it as a pandemic emergence. To get a grip on this outbreak, specific preventive and therapeutic interventions are urgently needed. It must be said that, until now, there are no existing vaccines for coronaviruses. To promptly and rapidly respond to pandemic events, the application of in silico trials can be used for designing and testing medicines against SARS-CoV-2 and speed-up the vaccine discovery pipeline, predicting any therapeutic failure and minimizing undesired effects. Here, we present an in silico platform that showed to be in very good agreement with the latest literature in predicting SARS-CoV-2 dynamics and related immune system host response. Moreover, it has been used to predict the outcome of one of the latest suggested approach to design an effective vaccine, based on monoclonal antibody. Universal Immune System Simulator (UISS) in silico platform is potentially ready to be used as an in silico trial platform to predict the outcome of vaccination strategy against SARS-CoV-2.

bioinformatics↗

bioRxiv2020

Designing Topographically Textured Microparticles For Induction and Modulation of Osteogenesis in Mesenchymal Stem Cell Engineering

Mesenchymal stem cells have been the focus of intense research in bone development and regeneration. We demonstrate the potential of microparticles as modulating moieties of osteogenic response by utilizing their architectural features. Topographically textured microparticles of varying microscale features were produced by exploiting phase-separation of a readily-soluble sacrificial component from polylactic acid. The influence of varying topographical features on primary human mesenchymal stem cell attachment, proliferation and markers of osteogenesis was investigated. In the absence of osteoinductive supplements, cells cultured on textured microparticles exhibited notably increased expression of osteogenic markers relative to conventional smooth microparticles. They also exhibited varying morphological, attachment and proliferation responses. Significantly altered gene expression and metabolic profiles were observed, with varying histological characteristics in vivo. This study highlights how tailoring topographical design offers cell-instructive 3D microenvironments which allow manipulation of stem cell fate by eliciting the desired downstream response without use of exogenous osteoinductive factors.

bioengineering↗