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Translational Roadmap for the Organs-On-A-Chip Industry Toward Broad Adoption

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Translational Roadmap for the Organs-On-A-Chip Industry Toward Broad Adoption bioengineering Review Translational Roadmap for the Organs-on-a-Chip Industry toward Broad Adoption Vanessa Allwardt 1, Alexander J. Ainscough 2, Priyalakshmi Viswanathan 3, Stacy D. Sherrod 1, John A. McLean 1,4, Malcolm Haddrick 3 and Virginia Pensabene 5,* 1 Center for Innovative Technology, Department of Chemistry, Vanderbilt University, Nashville, TN 37212, USA; [email protected] (V.A.); [email protected] (S.D.S.); [email protected] (J.A.M.) 2 National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK; [email protected] 3 Medicines Discovery Catapult, Alderley Park, Alderley Edge, Macclesfield SK10 4TG, UK; [email protected] (P.V.); [email protected] (M.H.) 4 Vanderbilt Institute of Chemical Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN 37235, USA 5 School of Electronic and Electrical Engineering, School of Medicine, Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds LS2 9JT, UK * Correspondence: [email protected] Received: 19 August 2020; Accepted: 14 September 2020; Published: 16 September 2020 Abstract: Organs-on-a-Chip (OOAC) is a disruptive technology with widely recognized potential to change the efficiency, effectiveness, and costs of the drug discovery process; to advance insights into human biology; to enable clinical research where human trials are not feasible. However, further development is needed for the successful adoption and acceptance of this technology. Areas for improvement include technological maturity, more robust validation of translational and predictive in vivo-like biology, and requirements of tighter quality standards for commercial viability. In this review, we reported on the consensus around existing challenges and necessary performance benchmarks that are required toward the broader adoption of OOACs in the next five years, and we defined a potential roadmap for future translational development of OOAC technology. We provided a clear snapshot of the current developmental stage of OOAC commercialization, including existing platforms, ancillary technologies, and tools required for the use of OOAC devices, and analyze their technology readiness levels. Using data gathered from OOAC developers and end-users, we identified prevalent challenges faced by the community, strategic trends and requirements driving OOAC technology development, and existing technological bottlenecks that could be outsourced or leveraged by active collaborations with academia. Keywords: organ-on-a-chip; technology-led strategy; gap analysis; validation; translation; quality management; body-on-a-chip; organotypic culture models; microphysiological systems 1. Introduction The organ-on-a-chip (OOAC) concept emerged about 10 years ago when scientists combined fluidic systems, cell culture techniques, analytical methods, and single, 2D, and 3D cell culture protocols into new in vitro models. OOAC systems were developed to recapitulate typical functions of human organs in microliter volumes. The potential of these models, also defined as “microphysiological systems”, attracted research groups and pharmaceutical companies looking for more effective, efficient, and cost-saving techniques to reduce drug development failures. Subsequently, a multitude of different microfluidic systems have been designed and successfully developed, as depicted in Figure1. Bioengineering 2020, 7, 112; doi:10.3390/bioengineering7030112 www.mdpi.com/journal/bioengineering Bioengineering 2020, 7, x FOR PEER REVIEW 2 of 27 Bioengineering 2020, 7, 112 2 of 27 and cost-saving techniques to reduce drug development failures. Subsequently, a multitude of different microfluidic systems have been designed and successfully developed, as depicted in Figure 1. While Whilesome examples some examples have already have already advanced advanced our unders our understandingtanding of human of human physiology, physiology, pharmacology, pharmacology, and andtoxicology, toxicology, a large a large percentage percentage of OOAC of OOAC models models areare still still far farfrom from optimization, optimization, and and their their application application is isonly only guaranteed guaranteed in invery very limited limited and and specific specific working working conditions. conditions. Figure 1.1. Examples of organs-on-a-chip models, recreating ( a) the blood-brain barrier and (b) thethe perivascular environment in the human endometriumendometrium (Adapted and Reprinted from [[1],1], with the permission ofof AIPAIP PublishingPublishing and and from from [2 [2],], both both licensed licensed under under a Creativea Creative Commons Commons Attribution—CC Attribution— BYCC license).BY license). The OOACOOAC market market has has been been recently recently valued valued at 21 at Million 21 Million US$ andUS$ is and projected is projected to reach to 220 reach Million 220 US$Million by US$ 2025 by [3 2025]. Most [3]. Most of the of companiesthe companies (start-ups (start-ups and and large large companies) companies) reside reside in in thethe UnitedUnited States, UK, The The Netherlands, Netherlands, and and France, France, while while new new research research is sprouting is sprouting in South in South Korea, Korea, Japan, Japan, and andTaiwan. Taiwan. The Thehighest highest development development has has been been seen seen in inheart-on-chip, heart-on-chip, human-on-chip, human-on-chip, intestine-on-chip, intestine-on-chip, kidney-on-chip, liver-on-chip, andand lungs-on-chiplungs-on-chip [[4].4]. The technology development path is commonly non-linear in academic academic research, research, and and naturally, naturally, many projects stop at thethe proofproof ofof conceptconcept stage.stage. The eeffectiveffective industrialindustrial development of a product needs, instead, to steadily proceed and be completedcompleted in the shortestshortest possible time before the publicpublic and commercial interests deflatedeflate and new solutionssolutions appear on thethe market.market. A key factor to a linear technology development pathway is to definedefine the valuevalue proposition, to promptlypromptly transitiontransition from anan R&D-only stage to the validationvalidation phase, and finallyfinally move to optimizationoptimization and scale-up for rapidrapid adoption. TheseThese steps steps are are necessary necessary to deliverto deliver the promisedthe promised benefits benefits and to and successfully to successfully exploit fundingexploit sourcesfunding andsources investments and investments [5]. Mistakes [5]. andMistakes delays an alongd delays this path along lead this to continuouspath lead to technological continuous challengestechnological and challenges revisions ofand the revisions business of model, the busine but mostss model, importantly, but most risk importantly, attenuating risk the attenuating interest of end-usersthe interest and of end-users reduce future and fundingreduce future opportunities. funding opportunities. Using the organs-on-a-chip technologies network, established inin the United Kingdom in 2018 as an indicativeindicative collectioncollection ofof expertsexperts in in the the field field of of OOAC, OOAC, and and the the 3DbioNet 3DbioNet network, network, started started in in 2019 2019 in thein the United United Kingdom Kingdom under under the the technology technology touching touching life life initiative, initiative, we we surveyedsurveyed end-users,end-users, experts, and developers from both academia and industry aboutabout the existing stage of development, the faced challenges, and the limitationslimitations ofof organs-on-a-chip.organs-on-a-chip. From the responses, we aimedaimed toto identifyidentify essentialessential values ofof thethe OOACOOAC technologytechnology recognized by active users and researchers in the field,field, to complementcomplement these with an analysis of the most developed and most promising models in the peer-reviewedpeer-reviewed literature.literature. This review also focused on the specificspecific technologicaltechnological expectations,expectations, characteristicscharacteristics defined defined as “needed” by the users, and their comparison withwith the the products products and and technological technological challenges challenges recognized recognized by developers by developers in the academic in the andacademic industrial and industrial fields. fields. By interviewing interviewing both both academics academics and product and product development development specialists specialists in the industry, in the this industry, review thisprovided review an provided analysis of an the analysis perceived of the hindrances perceived to hindrances translation toand translation commercialization. and commercialization. Technological Bioengineering 2020, 7, 112 3 of 27 Technological aspects, integration activities, and requirements for adoption and acceptance by the pharmaceutical industry were identified and discussed, as well as describing the potential focus of future joint collaborations between academia and industry to translate OOAC into commercial success. 2. Translational OOAC Company and End-User Survey For the anonymously conducted expert survey, data were sampled and collected in two stages. First, we identified and contacted 64 companies currently developing OOAC technology, as well as over 270 end-users from the pharmaceutical industry, European and the United States
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