# The Long and Winding Road to Cardiac Regeneration
## 4 Biomaterials
### Natural Biomaterials
#### 4.2.8. Decellularized Extracellular Matrix  
Decellularized extracellular matrix (d-ECM) has emerged as a groundbreaking natural biomaterial for cardiac regeneration. This procedure involves the removal of cells from a donor heart, leaving a scaffold composed of extracellular matrix. Decellularization relies on a combination of chemical, physical, and enzymatic processes to achieve cell removal while preserving the structural and functional integrity of the scaffold. Recent studies have demonstrated the effectiveness of decellularization in removing cells from donor hearts. These studies employed a variety of methods, including chemical agents, physical forces such as sonication and pressure, and enzymatic treatments like proteolytic digestion, which proved particularly efficient [253; 254]. The choice of a decellularization procedure over other cell removal methods lies in its ability to minimize damage to the heart's ECM [255; 256]. This matrix plays a crucial role in providing a supportive environment for the growth and differentiation of newcells [257]. By obtaining a cell-free matrix, decellularization creates optimal conditions for the proliferation of new cells [258]. Moreover, this technique offers advantages in terms of speed and cost-effectiveness compared to alternative cell removal methods. What makes d-ECM truly remarkable is its ability to mimic the native cardiac tissue, offering a nurturing environment for cell growth and differentiation. The preserved three-dimensional architecture of d-ECM plays a pivotal role in promoting the organization of cells and facilitating tissue regeneration within the damaged heart. Moreover, it houses a rich assortment of bioactive molecules, including growth factors and cytokines, which orchestrate cellular activities such as migration, angiogenesis, and tissue repair [259; 260]. Customization is a key advantage of d-ECM, as its composition and mechanical properties can be tailored to suit individual patient needs. By serving as a scaffold, it aids in the integration of endogenous or exogenous cells into the damaged tissue, facilitating their regeneration and functional recovery [261]. Studies have demonstrated the remarkable potential of d-ECM in promoting the differentiation of stem cells into cardiomyocytes, thus bolstering the heart contractile capacity. Additionally, its immunomodulatory properties dampen inflammation and reduce the risk of immune rejection, enhancing the acceptance and survival of transplanted cells or tissue grafts [262; 263]. Remarkably, d-ECM has already exhibited promising results in clinical settings [264]. Its safety and efficacy in improving cardiac function and reducing scar tissue formation after myocardial infarction have been established, igniting hope for a brighter future in cardiac regeneration [265]. In conclusion, d-ECM stands at the forefront of natural biomaterials for cardiac regeneration. Its ability to closely replicate the native cardiac tissue, facilitate cell integration, and stimulate tissue repair processes has opened new avenues for innovative therapies. With further advancements, this remarkable biomaterial holds the potential to restore heart function and offer renewed hope to patients grappling with heart disease. The effectiveness of decellularization has been documented through several notable published examples. One standout study conducted by [PERSON] et al. (2008) delved into the regeneration of functional myocardial tissue using decellularization. The researchers achieved success by decellularizing rat hearts through detergent-based methods, resulting in acellular scaffolds. These scaffolds were then repopulated with cardiac cells, which exhibited the remarkable ability to contract and generate electrical signals, indicating the successful regeneration of functional cardiac tissue [266]. Another significant publication by [PERSON] et al. (2022) shed light on the immense potential of decellularization in human cardiac tissue engineering.