Adv Drug Deliv Rev. 2025 Dec 20;229:115765. doi: 10.1016/j.addr.2025.115765. Online ahead of print.
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.
PMID:41429358 | DOI:10.1016/j.addr.2025.115765