{"doi":"10.1016/j.addr.2025.115765","title":"Engineering tissue patterning in human stem cell-based embryo models","abstract":"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. • Human stem-cell-based embryo models (SCBEMs) of the blastocyst, through to early organogenesis, have revealed previously inaccessible developmental mechanisms. • Engineering approaches represent a new frontier, supporting patterned spatial fields at native physiological scales. • Micropatterning technologies can define starting conditions for morpho-and-histogenetic fields; biomaterials provide architectural and mechanical programming; microwells control aggregate geometry at scale; microfluidics enables orthogonal morphogen control; dynamic systems overcome diffusion limits. • Standardised engineering-anchored taxonomy enables direct comparison of technological platforms and biological outcome. • Metabolic constraints remain a critical bottleneck in SCBEM development; engineered vascular-like perfusion systems offer promising solutions for more complex, physiologically relevant models. • “Moral status by design” framework establishes technical boundaries for responsible SCBEM engineering.","journal":"Advanced Drug Delivery Reviews","year":2025,"id":585915,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":900438,"name":"Sara Romanazzo","orcid":"0000-0002-7074-1248","position":1,"is_corresponding":false},{"id":417888,"name":"Peter Newman","orcid":"0000-0002-5202-4819","position":2,"is_corresponding":false},{"id":686534,"name":"K. Kilian","orcid":"0000-0002-8963-9796","position":3,"is_corresponding":false},{"id":1500083,"name":"Ella G. Lambert","orcid":null,"position":0,"is_corresponding":true}],"reference_count":106,"raw_metadata":null,"created_at":"2026-07-19T02:59:24.273134Z","pmid":"41429358","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}