<p>Heart failure or myocardial infarction (MI) is among the leading causes of death worldwide. However, current therapeutic procedures, including pharmacological interventions and ventricular assist devices, are unable to reverse the pathological changes and regenerate the injured cardiac tissue. Here, tailored recombinant humanized collagen type I (rhCol I) with high bioactivity for myocardial tissue-related cells was loaded into injectable hydrogels to construct a microenvironment favorable for angiogenesis, myocardial tissue repair and the restoration of heart function after MI. rhCol I-loaded hydrogels (gel@rhCol I) had a good response to the MI microenvironment, which indicated that they can release rhCol I for MI treatment. In vitro and in vivo results showed that the gel@rhCol I is able to effectively promote myocardial tissue repair and restore cardiac function after MI by inhibiting cell apoptosis, downregulating pro-inflammatory factors and promoting angiogenesis. In conclusion, injectable hydrogel based on tailored rhCol I exhibited great potential in the repair of damaged myocardial tissue. More importantly, the discovery of the mechanism of rhCol I promoting the repair of damaged myocardial tissue will broaden the clinical application of rhCol I for MI or heart failure treatment.</p> Graphic Abstract <p></p>