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The decellularized extracellular matrix (dECM) in various forms represents a promising class of naturally derived biomaterials extracted from harvested organs and tissues. In general, decellularized extracellular matrix (dECM) contains the components of tissue specific microenvironment i.e. fibrous proteins, glycosaminoglycans (GAGs), growth factors and many of the cell adhesion ligands that are not possible to create synthetically. This makes decellularized tissue materials an excellent platform to help direct seeded and infiltrating cells toward a target phenotype. Progress in the this area over the past decades has led to significant translational advances such as 3D- bio-printed dECM patches, scaffolds, injectable hydrogels for surgical constructions and drug delivery systems , regeneration of complex vascularized 3D organs such as heart , lung and liver 8 in preclinical models, and recently emerging microfluidic organ-on-a-chip for the construction of in vitro disease models and drug screening devices ,

       Despite these significant translational advances, a key challenge to the clinical implementation of (dECM)-based tissue engineering is to identify the minimal tissue-specific compositional requirement that functionally distinguish the different tissue sources. It is currently unknown what specific molecules are essential for neo-tissue formation. In response to this ignorance, a large push to more quantitatively describe what remains within a decellularized tissue, represented by both desired and undesired components, is frequently urged.

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         Presently, most of the researchers have focused extensively on the biomedical applications of decellularized extracellular matrix without giving the importance of detail tissue specific dECM cellular components.  In addition, few reports were also published on decellularized tissue directing stem cell differentiation into specific cell phenotypes where matrix stiffness has been demonstrated to control differentiation ( modify the text). However, there is no detailed description about tissue specific dECM components role toward stem cell differentiation into specific phenotypes. Thus, ECM components are attracting attention to characterized tissue-specific ECM proteins which can provide a high accuracy mechanistic evidence to correlate recruited cell phenotypes and ultimately regenerative tissue-specific behaviours.

       Nonetheless, It is notoriously analytical challenge to characterize the large number of ECM -associated proteins (>1000 proteins) because of their covalent crosslinking and numerous modifications. A proteomic analysis can address this challenge by characterizing the important tissue-specific dECMs remnant components in decellularized extracellular matrix (dECM) biomaterials. Mass spectrometry (MS) is a key analytical method which offers the opportunity to characterize protein identity and abundance at the whole-proteome level due to its large-scale protein detection capability with a single experiment.

The decellularized extracellular matrixes (dECM) retain organ-specific cues that can support and direct the cell growth and regulating organ function. Although, it is not yet well understood what minimal tissue specific dECM components are essential for neo-tissue formation (change). There is still a huge debate regarding the importance of spatial relationships between tissue-specific ECM components and complete ECM composition to determine how they recruit host cells in vivo to generate tissue-specific responses. This interest stems predominantly large push to more quantitatively describe what tissue-specific unproven components remains within a decellularized tissue. Here, we first optimized novel decellularization process for various tissues such as heart, liver, trachea and skin, cornea on the basis of biochemical assay and proteomics analysis, and in-depth differential proteomics analyses of the various respective dECMs were performed. Differential tissue specific components of heart, liver and trachea dECMs have preserved high value as compared to skin and cornea in elucidating tissue-specific response mechanisms that drive their functional capacity. Furthermore, mechanisms of tissue specificity of the differential tissue specific dECM components were again justified by comparing stem cell differentiation ability in particular tissue-specific context. We observed the role of differential dECM compositional variations derived from different tissue types have significance to directed stem cell phenotypic behaviors in tissue-specific context. On the basis of above results, Tissue specificity ability of decellularized heart, liver and trachea were higher compared to cornea and skin, due to less tissue specific components preserved as evident in proteomics analysis. This study sheds new light on systematic in-depth differential proteomics analysis of various optimized decellularized tissues to provide what specific dECM components and its crucial role in tissue-specific remodeling, and will further readily applicable for future tissue/ organ replacement therapies.

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