The hydrogels of natural extracellular matrix (ECM) are excellent biomaterials with promising applications in the physiological manufacture of three-dimensional (3D) constructs that replicate native tissue-like architectures and function as cargo-delivery, 3D bioprinting, or injectable systems. ECM hydrogels retain the bioactivity to trigger key cellular processes in the tissue engineering and regenerative medicine (TERM) strategies. However, they lack suitable physicochemical properties, which restricts their applications . This demand that mechanical and degradation properties of the ECM hydrogels must be balanced against biological properties. By incorporating poly(ethylene glycol) (PEG) into mammalian type I collagen-rich ECM substrates, this task can be accomplished. This review is focused on the use of PEG derivatives, widely used in formulations of pharmaceutical products or in synthesis of biomedical polyurethanes, as a strategy to modulate both physical and biological properties of natural ECM hydrogels. The processing-property relationship in decellularized ECM hydrogels, as well as the main results when used in TERM, are discussed. A comparison of the characteristics of PEG-ECM hydrogels is provided in terms of the improvement of structure, mechanics, and degradation behavior. Finally, the benefits of producing PEG-ECM hydrogels according to and performance in different proofs-of-concept of emergent biomedical technologies are overviewed.
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