The spike protein S of SARS coronavirus 2 (SARS-CoV-2) binds ACE2 on host cells to initiate entry, and soluble ACE2 is a therapeutic candidate that neutralizes infection by acting as a decoy. Using deep mutagenesis, mutations in ACE2 that increase S binding are found across the interaction surface, in the N90-glycosylation motif and at buried sites. The mutational landscape provides a blueprint for understanding the specificity of the interaction between ACE2 and S and for engineering high affinity decoy receptors. Combining mutations gives ACE2 variants with affinities that rival monoclonal antibodies. A stable dimeric variant shows potent SARS-CoV-2 and -1 neutralization in vitro. The engineered receptor is catalytically active and its close similarity with the native receptor may limit the potential for viral escape.

Almost 30 years have passed since the term ‘tissue engineering’ was created to represent a new concept that focuses on the regeneration of neotissues from cells with the support of biomaterials and growth factors. This interdisciplinary engineering has attracted much attention as a new therapeutic means that may overcome the drawbacks involved in the current artificial organs and organ transplantation that have also been aiming at replacing lost or severely damaged tissues or organs. However, the tissues regenerated by tissue engineering and widely applied to patients are still minimal, including skin, bone, cartilage, capillary, and periodontal tissues. What are the reasons for such slow advances in clinical applications of tissue engineering? This article gives a brief overview of the current state of tissue engineering, covering the fundamentals and applications. The fundamentals of tissue engineering involve cell sources, scaffolds for cell expansion and differentiation, as well as carriers for growth factors. Animal and human trials are a major part of the applications. Based on these results, some critical problems to be resolved for the advances of tissue engineering are addressed from the engineering point of view, emphasizing the close collaboration between medical doctors and biomaterials scientists.

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