TABLE 2.
Experimental contexts and their implications for interpreting ROS-interacting cardiovascular biomaterials.
| Experimental context | Primary question | Strength | Main limitation | Representative refs |
|---|---|---|---|---|
| Pretreatment/prevention | Can the platform prevent oxidative injury before or around onset? | Mechanistically useful for prophylactic protection | Limited applicability to unplanned acute MI or reperfusion therapy | (Bei et al., 2020; Boarescu et al., 2019; Shi et al., 2024) |
| Acute transient ischemia-reperfusion | Can rapid redox intervention limit reperfusion injury? | Directly relevant to MIRI biology | Sensitive to ischemia duration and dosing window | (Ai et al., 2021; Huang et al., 2022; Ikeda et al., 2016; Ma et al., 2025b; Wang et al., 2025c; Wang et al., 2024c; Zhen et al., 2025) |
| Established MI/permanent ligation | Can treatment improve infarct repair after injury is established? | Relevant to repair, angiogenesis, and remodeling | Not equivalent to reperfused MI | (Liao et al., 2025; Mahmood et al., 2020; Maranhao et al., 2017; Pan et al., 2025) |
| Chronic remodeling follow-up | Are structural and functional benefits durable? | Captures fibrosis, dilation, and long-term function | Often lacks parallel chronic material-safety data | (Song L. et al., 2025; Wang et al., 2025b; Wang et al., 2022; Wang et al., 2024b; Yang et al., 2025a; Zheng et al., 2024) |
| Cellular stress assays | Which molecular pathways are affected? | Mechanistic resolution | H/R, H2O2, OGD, and immune assays are not equivalent | (Altshuler et al., 2021; Dai et al., 2026; Hu et al., 2024; Li et al., 2026; Qin et al., 2026; Wang et al., 2025c; Zhang et al., 2025) |
| Ex vivo heart | Does cardioprotection occur in intact cardiac tissue without systemic confounding? | Intermediate between cells and in vivo models | No systemic PK, immunity, or clearance | (Liu et al., 2016) |
| Direct route comparison | How much does administration route alter efficacy? | Controls material and payload while changing route | Rarely performed | (Tan et al., 2024) |
| Mixed-organ ischemic models | Are redox/material principles transferable across tissues? | Useful mechanistic context | Cannot establish cardiac delivery or safety | (Lee et al., 2015; Wang et al., 2024d) |