Injectable Extracellular Matrix Microparticles Promote Heart Regeneration in Mice with Post-ischemic Heart Injury

Document Type

Article

Publication Date

2-2022

Publication Title

Advanced Health Care Materials

Abstract

Ischemic heart injury causes permanent cardiomyocyte loss and fibrosis impairing cardiac function. Tissue derived biomaterials have shown promise as an injectable treatment for the post-ischemic heart. Specifically, decellularized extracellular matrix (dECM) is a protein rich suspension that forms a therapeutic hydrogel once injected and improves the heart post-injury response in rodents and pig models. Current dECM-derived biomaterials are delivered to the heart as a liquid dECM hydrogel precursor or colloidal suspension, which gels over several minutes. To increase the functionality of the dECM therapy, an injectable solid dECM microparticle formulation derived from heart tissue to control sizing and extend stability in aqueous conditions is developed. When delivered into the infarcted mouse heart, these dECM microparticles protect cardiac function promote vessel density and reduce left ventricular remodeling by sustained delivery of biomolecules. Longer retention, higher stiffness, and slower protein release of dECM microparticles are noted compared to liquid dECM hydrogel precursor. In addition, the dECM microparticle can be developed as a platform for macromolecule delivery. Together, the results suggest that dECM microparticles can be developed as a modular therapy for heart injury.

Comments

The authors would like to acknowledge the use of microscopes in the Light Microscopy Imaging Facility at CWRU, made available through NIH Grant S10-OD024996.

This work was supported by NIH R25-HL145817 (S.E.S.), NIH 1 C06 RR12463-01 (CWRU), and 5T32HL134622 (A.A.), NSF Award 1937968 (K.Y.), and NSF Award 1337859 (C.R.K.).

DOI

10.1002/adhm.202102265

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