Table 2.

Common chemical and biological agents used for tissue/organ decellularization and their immunological impact on derived scaffolds

Method	Typical decellularization agents	Advantages	Disadvantages	Ref.
Acids	PAA	Favorable ECM preservation ↓ pathogen-related immunogenicity due to simultaneous sterilization	Weak antigen removal	[48, 55]
Bases	NAOH	High potency in removing DNA and other immunogens Cytocompatibility	↑ ECM alteration and DAMP release ↓ growth factor	[81, 82]
Non-ionic detergents	TX100	↑ removal of DNA and membrane immunogens	↑ ECM alteration and DAMP release Low efficiency in dense tissues Cytotoxicity	[51, 56, 75, 83–85]
Ionic detergents	SDS SDC	High potency in removing protein antigens, especially in dense tissues	↑ ECM alteration and DAMP release Exposing hidden antigenic sites ↓ GAG and growth factor Cytotoxicity Necessitating robust washing methods	[48, 55, 56, 87–89]
Zwitterionic detergents	CHAPS Sulfobetaines	Effective agents for solubilizing both hydrophobic and hydrophilic immunogens	↓ GAG and elastin ↑ DAMP release Exposing hidden antigenic sites	[51, 75, 82, 88]
Chelating agents	EDTA	↑ cell-ECM dissociation ↑ nuclear material removal	Weak cell and antigen removal efficacy	[48, 93–95]
Enzymes	Proteases Nucleases	↑ cell-ECM dissociation Eliminating nuclear antigens	Disrupting the structure of collagen, laminin, GAG, and elastin ↑ DAMP release Exposing hidden antigenic sites ↓ recellularization due to retention of enzymes within dECM	[69, 72, 84, 97, 98]