TISSUE ENGINEERING BIOREACTORS: POTENTIAL APPLICATIONS AND SCALE UP STRATEGY

Tissue engineering bioreactors have been used in order to achieve production of artificial tissue, increasing cell proliferation capacity and yield and/or in vitro tissue/disease modelling. Although it is still discussing how to obtain functional and vascular tissue with these bioreactors, preclinical and clinical studies are ongoing. Tissue engineering bioreactors have been used as lab-scale bioreactors until now. Crucial potential application areas can be created by increasing the production capacity and bioprocess efficiency of these bioreactors. In this review, recent bioreactor technologies such as spinner flask, rotating wall/bed, hollow fiber membrane, perfusion and mechanical stimuli bioreactors are briefly presented in terms of their potential applications in medical field especially in the scope of scale-up approaches such as bubble column, stirred tank, membrane, air lift, fluidized packed and bed bioreactors.           Peer Review History: Received 1 May 2020; Revised 11  June; Accepted 6 July, Available online 15 July 2020 Academic Editor: Dr. Asia Selman Abdullah, Al-Razi university, Department of Pharmacy, Yemen, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file:                Reviewer's Comments: Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 8.0/10 Reviewer(s) detail: Dr. Sally A. El-Zahaby, Pharos University in Alexandria, Egypt, [email protected] Dr. Viney Chawla, University Institute of Pharmaceutical Sciences, Baba Farid University of Health Sciences, Sadiq Road, Faridkot-Punjab 151203, [email protected]

High-Throughput Assessment of Drug Cardiac Safety Using a High-Speed Impedance Detection Technology-Based Heart-on-a-Chip

Drug cardiac safety assessments play a significant role in drug discovery. Drug-induced cardiotoxicity is one of the main reasons for drug attrition, even when antiarrhythmic drugs can otherwise effectively treat the arrhythmias. Consequently, efficient drug preclinical assessments are needed in the drug industry. However, most drug efficacy assessments are performed based on electrophysiological tests of cardiomyocytes in vitro and cannot effectively provide information on drug-induced dysfunction of cardiomyocyte beating. Here we present a heart-on-a-chip device for evaluating the drug cardiac efficacy using a high-speed impedance detection technology. Verapamil and doxorubicin were utilized to test this heart-on-a-chip, and multiple parameters of cardiomyocyte beating status are used to reveal the effects of drugs. The results show that drug efficacy or cardiotoxicity can be determined by this heart-on-a-chip. We believe this heart-on-a-chip will be a promising tool for the preclinical assessment of drug cardiac efficacy

Development of a Plasmonic On-Chip System to Characterize Changes from External Perturbations in Cardiomyocytes

Today’s heart-on-a-chip devices are hoped to be the state-of-the-art cell and tissue characterizing tool, in clinically applicable regenerative medicine and cardiac tissue engineering. Due to the coupled electromechanical activity of cardiomyocytes (CM), a comprehensive heart-on-a-chip device as a cell characterizing tool must encompass the capability to quantify cellular contractility, conductivity, excitability, and rhythmicity. This dissertation focuses on developing a successful and statistically relevant surface plasmon resonance (SPR) biosensor for simultaneous recording of neonatal rat cardiomyocytes’ electrophysiological profile and mechanical motion under normal and perturbed conditions. The surface plasmon resonance technique can quantify (1) molecular binding onto a metal film, (2) bulk refractive index changes of the medium near (nm) the metal film, and (3) dielectric property changes of the metal film. We used thin gold metal films (also called chips) as our plasmonic sensor and obtained a periodic signal from spontaneously contracting CMs on the chip. Furthermore, we took advantage of a microfluidic module for controlled drug delivery to CMs on-chip, inhibiting and promoting their signaling pathways under dynamic flow. We identified that ionic channel activity of each contraction period of a live CM syncytium on a gold metal sensor would account for the non-specific ion adsorption onto the metal surface in a periodic manner. Moreover, the contraction of cardiomyocytes following their ion channel activity displaces the medium, changing its bulk refractive index near the metal surface. Hence, the real-time electromechanical activity of CMs using SPR sensors may be extracted as a time series we call the Plasmonic Cardio-Eukaryography Signal (P-CeG). The P-CeG signal render opportunities, where state-of-the-art heart-on-a-chip device complexities may subside to a simpler, faster and cheaper platform for label-free, non-invasive, and high throughput cellular characterization

Elucidating and Utilising the Mechanisms Used by Pseudomonas aeruginosa to Develop Resistance to Bacteriophages to Aid Therapeutic Formulation and Application in Cystic Fibrosis

Antimicrobial resistance (AMR) is one of the greatest threats to human healthcare and this thesis explored the use of bacteriophages to treat Pseudomonas aeruginosa infections. Firstly, responses of clinical isolates of P. aeruginosa to phage treatments were investigated and mechanisms of resistance identified. Potential of phage-antibiotic pairings to prevent the emergence of phage resistance was then explored as well as safety of these combinations using a 3-dimensional cell model of the lung