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The extracellular matrix (ECM), which is ubiquitously present in tissues and organs, is an intricate network composed of multi-domain macromolecules, such as proteins, proteoglycans, and glycoproteins. These molecules assemble in varied proportions, structures, and orientations in different tissues, providing unique biochemical cues and biophysical signals to regulate tissue-specific cellular behaviors. Decellularized ECM (dECM) refers to a category of biomaterials acquired from natural tissues subjected to a combination of decellularization treatments that preserve ECM components and inherent structures eliminating cellular substances. dECM has been considered as one of the most promising biomaterials for recreating functional 3D tissue models because of its superior capacity to comprehensively mimic the original tissue microenvironment. In this chapter, we introduce the structural and functional role of natural ECMs and summarize the representative decellularization and evaluation methods. We also focus on recent applications of dECM in tissue engineering using traditional approaches (e.g., implantable sheets and injectable hydrogels) and 3D cell printing technology.

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