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Alastair Stewart
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University of Melbourne

Abstract: Microphysiological systems (MPS) are increasingly being used together with other Novel alternative approach methodologies (NAMs) in the drug regulatory process. The absence of specific guidance on preclinical efficacy assessment allows a lower evidentiary hurdle for the use of NAMs in the regulatory pathway. Thus, NAMs may typically be deployed where the target is human-specific or where animal models are unreliable predictors of clinical efficacy. The MPS field aspires to emulate human organ function for predictive fidelity. We have advocated that such models incorporate static and dynamic biomechanical features that recapitulate the tissues of MPS origin (Krishnan et al 2016). Our attention recently turned to the media used to superfuse or perfuse MPS, identifying that hyper-nutritional aspects of the most commonly-used commercial media distort pharmacological assessments (Zhang et al, 2024; Stewart et al., 2025). One of the barriers to adoption of physiological media is the rapidity of nutrient levels falling below physiological levels in static systems, such as multi-well plate environments. However, such barriers may be addressed by continuous or intermittent flow using highly multiplexed microfluidic pumps (Gao et al., 2023), which may be used in conjunction with biosensors (Yang et al, 2024) to continuously qualify cell culture media.

 

References:

1. Krishnan, R., Park, J-A., Seow, C.Y., Lee, P.V.S., Stewart, A.G., 2016). Cellular biomechanics in drug screening and evaluation: Mechanopharmacology. Trends in Pharmacological Sciences 37:87-100.

2. Gao, Xumei; Wu, Yanqi; Cheng, Tianhong; Stewart, Alastair (2022). Comprehensive Multiplexed Superfusion System Enables Physiological Emulation in Cell Culture: Exemplification by Persistent Circadian Entrainment. Lab on a Chip DOI: 10.1039/D1LC00841B.

3. Yiling Yang, Xumei Gao, Bryce Widdicombe, Xiaodan Zhang, Jana Lorraine Zielinski, Tianhong Cheng, Avanka Gunatilaka, Kaylyn K Leung, Kevin W Plaxco, Ranjith Rajasekharan Unnithan, Alastair G Stewart (2024)

4. Dual-Purpose Aptamer-Based Sensors for Real-Time, Multiplexable Monitoring of Metabolites in Cell Culture Media. ACS Nano. DOI:10.1021/acsnano.4c06813

5. Xiaodan Zhang, Tianhong Cheng, Ellie Cho, Wenjia Lu, Delphine Denoyer, Paul McMillan, Kalyan Shobhana, Swati Varshney, Nicholas A Williamson, Alastair G Stewart. (2024). Nutritionally physiological cell culture medium and 3D culture influence breast tumour proteomics and anti-cancer drug effectiveness. Pharmacological Research.

6. Alastair G. Stewart, Avanka Gunatilaka & Bryan Gao (2025). Should culture media for

microphysiological systems be nutritionally physiological? Nature Reviews Bioengineering. https://doi.org/10.1038/s44222-025-00290-w


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Date Time Local Time Room Forum Session Role Topic
2025-10-16 17:00-17:20 2025-10-16,17:00-17:20Room 1- Guobin Hall 1 Symposium Program (Session)

Session 07: Organoids and Organ-on-a-chip in Toxicology

Speaker Qualifying the soluble and mechanical environments of microphysiological systems for enhanced regulatory utility