College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA.
Regenerative Medicine Research, Texas Heart Institute, Houston, TX, USA.
Adv Exp Med Biol. 2018;1098:85-114. doi: 10.1007/978-3-319-97421-7_5.
Bioscaffolds serve as structures for cells in building complex tissues and full organs including heart. Decellularizing cardiac tissue results in cell-free extracellular matrix (ECM) that can be used as a cardiac tissue bioscaffold. The field of whole-heart tissue engineering has been revolutionized since the 2008 publication of the first perfusion-decellularized whole heart, and since then, studies have shown how decellularized cardiac tissue retains its native architecture and biochemistry following recellularization. Chemical, enzymatic, and physical decellularization methods preserve the ECM to varying degrees with the widely accepted standard of less than 50 ng/mg of double-stranded DNA present in decellularized ECM. Following decellularization, replacement of cells occurs via recellularization: seeding cells into the decellularized ECM structure either via perfusion of cells into the vascular conduits, injection into parenchyma, or a combination of perfusion and injection. Endothelial cells are often perfused through existing vessel conduits to provide an endothelial lining of the vasculature, with cardiomyocytes and other parenchymal cells injected into the myocardium of decellularized ECM bioscaffolds. Uniform cell density and cell retention throughout the bioscaffold still needs to be addressed in larger animal models of the whole heart. Generating the necessary cell numbers and types remains a challenge. Still, recellularized cardiac tissue bioscaffolds offer therapeutic solutions to heart failure, heart valve replacement, and acute myocardial infarction. New technologies allow for decellularized ECM to be bioprinted into cardiac bioscaffolds or formed into a cardiac hydrogel patch. This chapter reviews the advances made in decellularization and recellularization of cardiac ECM bioscaffolds with a discussion of the potential clinical applications of ECM bioscaffolds.
生物支架为细胞构建复杂组织和完整器官（包括心脏）提供了结构。脱细胞化的心脏组织产生无细胞的细胞外基质（ECM），可作为心脏组织生物支架。自 2008 年首次发布灌注脱细胞化全心脏以来，整个心脏组织工程领域发生了革命性变化，此后的研究表明，脱细胞化的心脏组织在再细胞化后如何保留其固有结构和生物化学特性。化学、酶和物理脱细胞方法在不同程度上保留了 ECM，广泛接受的标准是脱细胞 ECM 中存在的双链 DNA 少于 50ng/mg。脱细胞化后，通过再细胞化来替代细胞：将细胞接种到脱细胞 ECM 结构中，方法是通过将细胞灌注到血管导管中、注入实质中，或灌注和注射的组合。内皮细胞通常通过现有的血管导管进行灌注，以提供血管的内皮衬里，将心肌细胞和其他实质细胞注射到脱细胞 ECM 生物支架的心肌中。在整个生物支架中均匀的细胞密度和细胞保留仍需要在更大的全心脏动物模型中解决。在更大的动物模型中仍需要解决整个生物支架中均匀的细胞密度和细胞保留问题。生成必要的细胞数量和类型仍然是一个挑战。然而，再细胞化的心脏组织生物支架为心力衰竭、心脏瓣膜置换和急性心肌梗死提供了治疗解决方案。新技术允许将脱细胞 ECM 生物打印到心脏生物支架中，或形成心脏水凝胶贴片。本章综述了心脏 ECM 生物支架脱细胞化和再细胞化的进展，并讨论了 ECM 生物支架的潜在临床应用。
