Application of lung microphysiological systems to COVID-19 modeling and drug discovery:a review

There is a pressing need for effective therapeutics for coronavirus disease 2019(COVID-19),the respiratory disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The process of drug development is a costly and meticulously paced process,where progress is often hindered by the failure of initially promising leads.To aid this chal-lenge,in vitro human microphysiological systems need to be refined and adapted for mechanistic studies and drug screening,thereby saving valuable time and resources during a pandemic crisis.The SARS-CoV-2 virus attacks the lung,an organ where the unique three-dimensional(3D)structure of its functional units is critical for proper respiratory function.The in vitro lung models essentially recapitulate the distinct tissue structure and the dynamic mechanical and biological interactions between different cell types.Current model systems include Transwell,organoid and organ-on-a-chip or microphysiological systems(MPSs).We review models that have direct relevance toward modeling the pathology of COVID-19,including the processes of inflammation,edema,coagulation,as well as lung immune function.We also consider the practical issues that may influence the design and fabrication of MPS.The role of lung MPS is addressed in the context of multi-organ models,and it is discussed how high-throughput screening and artificial intelligence can be integrated with lung MPS to accelerate drug development for COVID-19 and other infectious diseases.

Viable cryopreserved umbilical tissue (vCUT) reduces post-operative adhesions in a rabbit abdominal adhesion model

Post-operative adhesions,a common complication of surgery,cause pain,impair organ functionality,and often require additional surgical interventions.Control of inflammation,protection of injured tissue,and rapid tissue repair are critical for adhesion prevention.Adhesion barriers are biomaterials used to prevent adhesions by physical separation of opposing injured tissues.Current adhesion barriers have poor anti-inflammatory and tissue regenerative properties.Umbilical cord tissue(UT),a part of the placenta,is inherently soft,conforming,biocompatible,and biodegradable,with antimicrobial,anti-inflammatory,and antifibrotic properties,making it an attractive alternative to currently available adhesion barriers.While use of fresh tissue is preferable,availability and short storage time limit its clinical use.A viable cryopreserved UT(vCUT)“point of care”allograft has recently become available.vCUT retains the extracellular matrix,growth factors,and native viable cells with the added advantage of a long shelf life at−80℃.In this study,vCUT's anti-adhesion property was evaluated in a rabbit abdominal adhesion model.The cecum was abraded on two opposing sides,and vCUT was sutured to the abdominal wall on the treatment side;whereas the contralateral side of the abdomen served as an internal untreated control.Gross and histological evaluation was performed at 7,28,and 67 days post-surgery.No adhesions were detectable on the vCUT treated side at all time points.Histological scores for adhesion,inflammation,and fibrosis were lower on the vCUT treated side as compared to the control side.In conclusion,the data supports the use of vCUT as an adhesion barrier in surgical procedures.