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 challenge, 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.
Infectious diseases remain a public healthcare concern worldwide. Amidst the pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, increasing resources have been diverted to investigate the therapeutics targeting COVID-19 Spike glycoprotein and to develop various classes of vaccines. Most of the current investigations employ two-dimensional (2D) cell culture and animal models. However, 2D culture negates the multicellular interactions and 3D microenvironment, and animal models cannot mimic human physiology because of interspecies differences. On the other hand, organ-on-a-chip (OoC) research devices introduce a game-changer to model viral infections in human tissues, facilitating high-throughput screening of antiviral therapeutics. In this context, this review provides an overview of the in vitro OoC-based modeling of viral infection, highlighting the strengths and challenges for the future directions.
Secreted phosphoprotein 24 kDa (spp24) is a bone morphogenetic protein (BMP)/transforming growth factor-β cytokine-binding protein. The spp24 BMP-2-binding/transforming growth factor receptor II homology-1 (TRH1) domain is a highly conserved N-to-C terminally disulfide-bonded 19-amino acid residue loop similar to those in fetuin and the BMP receptor II. TRH1 domains exhibit a characteristic BTB or β-pleated sheet/turn/β-pleated sheet secondary structure. Our objective was to identify amino acid residues in the spp24 TRH1 domain that bind BMP-2, starting with the nine invariant mammalian residues. Alanine scanning (substitution of Ala for a native residue) was conducted for Cys(110), Arg(111), Ser(112), Thr(113), Val(114), Ser(117), Val(121), Val(124), and Cys(128) of recombinant bovine spp24 (residues 24-203). Binding to rhBMP-2 was assessed by surface plasmon resonance, and the equilibrium binding constants were calculated assuming 1:1 binding between spp24 or its mutants and rhBMP-2, so that affinity = K(D) = k(d)/k(a). Replacing Arg(111) (a positively charged basic residue), polar residues Thr(113) and Ser(117), and the nonpolar Cys(128) with Ala had little effect on BMP-2 binding. Replacing Val(114) or Val(121) with Ala increased binding affinity, whereas replacing Cys(110), Ser(112), Val(124), or both Cys(110) and Cys(128) with Ala decreased it. The kinetics of spp24 binding to BMP-2 can be manipulated by replacing invariant TRH1 residues. Decreasing the relative degree of hydrophobicity in the β-pleated sheet secondary structural motif of the TRH1 domain by replacing key Val residues with Ala increased the affinity for BMP-2 whereas altering the composition of the α-helical turn did not. Thus, the β-pleated sheets play a greater role in BMP-2 binding than the α-helical turn.
Currently, there are more than 1.5 million knee and hip replacement procedures carried out in the United States. Implants have a 10–15-year lifespan with up to 30% of revision surgeries showing complications with osteomyelitis. Titanium and titanium alloys are the favored implant materials because they are lightweight and have high mechanical strength. However, this increased strength can be associated with decreased bone density around the implant, leading to implant loosening and failure. To avoid this, current strategies include plasma-spraying titanium surfaces and foaming titanium. Both techniques give the titanium a rough and irregular finish that improves biocompatibility. Recently, researchers have also sought to surface-conjugate proteins to titanium to induce osteointegration. Cell adhesion-promoting proteins can be conjugated to methacrylate groups and crosslinked using a variety of methods. Methacrylated proteins can be conjugated to titanium surfaces through atom transfer radical polymerization (ATRP). However, surface conjugation of proteins increases biocompatibility non-specifically to bone cells, adding to the risk of biofouling which may result in osteomyelitis that causes implant failure. In this work, we analyze the factors contributing to biofouling when coating titanium to improve biocompatibility, and design an experimental scheme to evaluate optimal coating parameters.
The pace of research and development in neuroscience, neurotechnology, and neurorehabilitation is rapidly accelerating, with the number of publications doubling every 4.2 years. Maintaining this progress requires technological standards and scientific reporting guidelines to provide frameworks for communication and interoperability. The present lack of such neurotechnology standards limits the transparency, repro-ducibility, and meta-analysis of this growing body of literature, posing an ongoing barrier to research, clinical, and commercial objectives. Continued neurotechnological innovation requires the development of some minimal standards to promote integration between this broad spectrum of technologies and therapies. To preserve design freedom and accelerate the translation of research into safe and effective technologies with maximal user benefit, such standards must be collaboratively co-developed by the full range of neuroscience and neurotechnology stakeholders. This paper summarizes the preliminary recommendations of IEEE P2794 Standards Working Group, developing a Reporting Standard for in-vivo Neural Interface Research (RSNIR).
The pace of research and development in neuroscience, neurotechnology, and neurorehabilitation is rapidly accelerating, with the number of publications doubling every 4.2 years. Maintaining this progress requires technological standards and scientific reporting guidelines to provide frameworks for communication and interoperability. The present lack of such standards for neurotechnologies limits the transparency, reproducibility, and meta-analysis of this growing body of research, posing an ongoing barrier to research, clinical, and commercial objectives.Continued neurotechnological innovation requires the development of some minimal standards to promote integration between this broad spectrum of technologies and therapies. To preserve design freedom and accelerate the translation of research into safe and effective technologies with maximal user benefit, such standards must be collaboratively co-developed by a full spectrum of neuroscience and neurotechnology stakeholders. This paper summarizes the preliminary recommendations of IEEE Working Group P2794, developing a Reporting Standard for in-vivo Neural Interface Research (RSNIR).Impact StatementThis work provides a preliminary set of reporting guidelines for implantable neural interface research, developed by IEEE WG P2794 in open collaboration between a range of stakeholders to accelerate the research, development, and integration of innovative neurotechnologies.
Neuromotor Deficits were simulated using an embedded navigation system. The Arduino platform-based robot follows a predetermined route. A stochastic term modifies the compensatory movement the system uses to correct for route deviations. Excessive and insufficient compensation results in unique movement patterns.
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