Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, 44106, USA.
Department of Chemical and Biomedical Engineering, Cleveland State University, Cleveland, OH, 44115, USA.
Adv Healthc Mater. 2022 Apr;11(8):e2102265. doi: 10.1002/adhm.202102265. Epub 2022 Feb 18.
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.
缺血性心脏损伤会导致永久性心肌细胞损失和纤维化,从而损害心脏功能。组织衍生的生物材料已被证明是一种有前途的可注射治疗缺血性心脏的方法。具体来说,去细胞细胞外基质 (dECM) 是一种富含蛋白质的悬浮液,一旦注射就会形成治疗性水凝胶,可改善啮齿动物和猪模型的心脏损伤后反应。目前,dECM 衍生的生物材料以液体 dECM 水凝胶前体或胶体悬浮液的形式递送到心脏,在数分钟内凝胶化。为了提高 dECM 治疗的功能,开发了一种源自心脏组织的可注射固体 dECM 微颗粒制剂,以控制粒径并延长在水相中的稳定性。当递送到梗死的小鼠心脏中时,这些 dECM 微颗粒通过持续输送生物分子来保护心脏功能、促进血管密度并减少左心室重构。与液体 dECM 水凝胶前体相比,dECM 微颗粒具有更长的保留时间、更高的硬度和更慢的蛋白质释放。此外,dECM 微颗粒可被开发为大分子递药平台。总之,这些结果表明,dECM 微颗粒可被开发为心脏损伤的模块化治疗方法。