{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T13:47:48Z","timestamp":1784123268247,"version":"3.55.0"},"reference-count":195,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:p>Platelet-mimicking therapeutic systems have expanded well beyond hemostasis, yet clinical translation is increasingly constrained by controllability and safety-bounded deployability rather than proof-of-function. Here, we propose an engineering framework that maps design choices onto four coupled layers-structure, membrane, function, and gating-to decouple efficacy from systemic thrombotic and immunological risks. Central to this framework is a minimal platelet interface (MPI), defined as a bounded, low-gain basal state in circulation that permits lesion engagement while resisting systemic amplification. We render this interface measurable through membrane critical quality attributes (CQAs) (QC-linked membrane features), including receptor retention\/orientation, shear-capture thresholds under flow, and baseline procoagulant leakage in the OFF state. We further elevate gating from simple stimulus triggering to permission-based gating (stimulus is necessary but not sufficient) by requiring risk-stratified logic, predefined activation thresholds and dynamic ranges, and validated deactivation or fail-safe constraints under worst-case conditions such as high shear and systemic inflammation. Finally, we organize applications along a risk gradient-execution for hemostasis and reversal, navigation for vascular inflammation and ischemia-reperfusion, and multilayer-gated de-risking for cancer and infection-explicitly linking biomimetic design to falsifiable safety boundaries, release criteria, chemistry, manufacturing, and controls (CMC), and regulatory requirements.<\/jats:p>","DOI":"10.3389\/fbioe.2026.1787749","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:53:37Z","timestamp":1778651617000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Engineering design of platelet-mimicking therapeutic systems: multilevel biomimicry, gating strategies, and translational boundaries"],"prefix":"10.3389","volume":"14","author":[{"given":"Jiali","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Zigong Fourth People\u2019s Hospital","place":["Zigong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Zigong Fourth People\u2019s Hospital","place":["Zigong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine, Zigong First People\u2019s Hospital","place":["Zigong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.2174\/1389201024666230804140926","article-title":"Engineering platelet membrane imitating nanoparticles for targeted therapeutic delivery","volume":"25","author":"Adhalrao","year":"2024","journal-title":"Curr. 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