Engineering tissue patterning in human stem cell-based embryo models

Human embryonic development is challenging to study in vitro as animal models inadequately represent human biology, while use of natural human embryos is both ethically and technically limited. Stem cell-based embryo models (SCBEMs) have emerged as a powerful alternative, enabling faithful recapitulation of early human development. However, current approaches predominantly rely on stochastic self-organisation with globally delivered signals, producing variable and often non-recapitulative structures. This review addresses this gap by introducing the first engineering-anchored taxonomy of human SCBEMs, systematically organizing the literature by their underlying technical platform rather than biological outcome alone. We demonstrate how five key engineering approaches - micropatterning, biomaterials, microwells, microfluidics, and dynamic culture - constrain morpho-and-histogenic patterning to determine developmental fidelity. We identify metabolic constraints limiting current models to ∼1 mm diameter as the primary bottleneck and demonstrate how vascular engineering and perfusion systems offer solutions. Finally, we propose standardisation metrics linking technical parameters to biological outcomes and establish an ethical framework defined by engineering choices.

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Publication Details

Journal
Advanced Drug Delivery Reviews
Published
2025-12-20
DOI
https://doi.org/10.1016/j.addr.2025.115765
Primary Topic
3D Printing in Biomedical Research
Type
article
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article

Engineering tissue patterning in human stem cell-based embryo models

Peter Newman, K. Kilian, Sara Romanazzo, Ella G. Lambert
Advanced Drug Delivery Reviews
3D Printing in Biomedical Research
article

Engineering tissue patterning in human stem cell-based embryo models

Peter Newman, K. Kilian, Sara Romanazzo, Ella G. Lambert
article en

Abstract

Human embryonic development is challenging to study in vitro as animal models inadequately represent human biology, while use of natural human embryos is both ethically and technically limited. Stem cell-based embryo models (SCBEMs) have emerged as a powerful alternative, enabling faithful recapitulation of early human development. However, current approaches predominantly rely on stochastic self-organisation with globally delivered signals, producing variable and often non-recapitulative structures. This review addresses this gap by introducing the first engineering-anchored taxonomy of human SCBEMs, systematically organizing the literature by their underlying technical platform rather than biological outcome alone. We demonstrate how five key engineering approaches - micropatterning, biomaterials, microwells, microfluidics, and dynamic culture - constrain morpho-and-histogenic patterning to determine developmental fidelity. We identify metabolic constraints limiting current models to ∼1 mm diameter as the primary bottleneck and demonstrate how vascular engineering and perfusion systems offer solutions. Finally, we propose standardisation metrics linking technical parameters to biological outcomes and establish an ethical framework defined by engineering choices.

Advanced Drug Delivery ReviewsVol. 229
Garvan Institute of Medical Research (AU), UNSW Sydney (AU), Division of Materials Science and Engineering (AU)
Openalex Percentile: Top 59%
3D Printing in Biomedical Research
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