Pathology-informed hydrogel design for myocardial infarction repair: engineering criteria, standardized evaluation, and clinical translation

Myocardial infarction (MI) produces coupled structural and biological injury that evolves across overlapping and spatially heterogeneous pathological contexts. Existing reviews have commonly summarized hydrogel material classes, therapeutic cargos, delivery routes, or individual mechanisms, but less attention has been given to translating post-MI pathology into measurable engineering criteria, explicit evidence boundaries, and structured translational requirements. This conceptual narrative review addresses this gap using a pathology-informed engineering framework supported by targeted literature searches in PubMed and the Web of Science Core Collection. The review links pathological and delivery-related challenges to hydrogel design requirements, measurable material properties, therapeutic strategies, and validation endpoints. It organizes the hydrogel design space using orthogonal descriptors of material origin, network behavior, functional attributes, and architecture; compares injectable, patch-based, cellular, extracellular-vesicle, protein, drug, and nucleic-acid delivery strategies; and defines engineering criteria for mechanics, viscoelasticity, injectability, adhesion, degradation, release, electrical function, responsiveness, and biological validation. Mechanistic plausibility, small-animal efficacy, large-animal evidence, first-in-human safety/feasibility, and demonstrated clinical benefit are treated as distinct evidence levels. Advanced multifunctional systems are evaluated through benefit–trade-off–validation relationships, while clinical translation is considered through manufacturing, CMC, device compatibility, safety, clinically meaningful endpoints, and sequential product-development gates. Future cardiac hydrogel development should be context-aware rather than assigned to fixed post-MI stages, quantitatively characterized using method-appropriate measurements, and advanced according to evidence appropriate to the intended use and development phase. Emphasis on minimum sufficient functionality, reproducible evaluation, clinically realistic delivery, manufacturing feasibility, and safety may improve comparison across platforms and help prioritize candidates for further translational development.