Abstract
Background Engineered heart tissues (EHTs) present a promising alternative to current materials for surgical ventricular restoration (SVR); however, the clinical application remains limited by inadequate vascularization postimplantation. Moreover, a suitable and economic animal model for primary screening is another important issue. Methods Recently, we used 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride chemistry (EDC) to initiate a strengthened, cytokine-conjugated collagenous platform with a controlled degradation speed. In vitro, the biomaterial exhibited an enhanced mechanical strength maintaining a porous ultrastructure, and the constant release of cytokines promoted the proliferation of seeded human mesenchymal stem cells (hMSCs). In vivo, with the hMSC-seeded, cytokine-immobilized patch (MSCs + GF patch), we performed modified SVR for rats with left ventricular aneurysm postmyocardial infarction (MI). Overall, the rats that underwent modified SVR lost less blood and had lower mortality. After 4 weeks, the rats repaired with this cell-seeded, cytokine-immobilized patch presented preserved cardiac function, beneficial morphology, enhanced cell infiltration, and functional vessel formation compared with the cytokine-free (MSC patch), cell-free (GF patch), or blank controls (EDC patch). Furthermore, the degradable period of the collagen patch in vivo extended up to 3 months after EDC treatment. Conclusions EDC may substantially modify collagen scaffold and provide a promising and practical biomaterial for SVR.
Highlights
Acute myocardial infarction (AMI) remains a leading “killer” in humans [1]
We aimed to demonstrate that this modified biomaterial may be used for surgical ventricular restoration (SVR) to restore the cardiac function of rats with ventricular aneurysm
We evaluated whether the modification may minimize the injury to weak rats, decrease the mortality of SVR, and provide an economic and effective small animal model for the primary screening of Engineered heart tissues (EHTs)
Summary
Acute myocardial infarction (AMI) remains a leading “killer” in humans [1]. The current materials for SVR are typically stiff and synthetic, which render the patch and the adjacent regions scarred and nonelastic, resulting in chronic stresses and contributing to ventricular redilatation and dysfunction. Engineered heart tissues (EHTs) present a promising alternative to current materials for surgical ventricular restoration (SVR); the clinical application remains limited by inadequate vascularization postimplantation. With the hMSC-seeded, cytokine-immobilized patch (MSCs + GF patch), we performed modified SVR for rats with left ventricular aneurysm postmyocardial infarction (MI). After 4 weeks, the rats repaired with this cell-seeded, cytokine-immobilized patch presented preserved cardiac function, beneficial morphology, enhanced cell infiltration, and functional vessel formation compared with the cytokine-free (MSC patch), cell-free (GF patch), or blank controls (EDC patch). EDC may substantially modify collagen scaffold and provide a promising and practical biomaterial for SVR
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