Crosslinking strategies of decellularized extracellular matrix in tissue regeneration

By removing the immunogenic cellular components through various decellularization methods, decellularized extracellular matrix (dECM) is considered a promising material in the field of tissue engineering and regenerative medicine with highly preserved physicochemical properties and superior biocompatibility. However, decellularization treatment can lead to some loss of structural integrity, mechanical strength, degradation stability, and biological performance of dECM biomaterials. Therefore, physical and chemical crosslinking methods are preferred to restore or even improve the biomechanical properties, stability, and bioactivity, and to achieve a delicate balance between degradation of the implanted biomaterial and regeneration of the host tissue. This review provides an overview of dECM biomaterials, and describes and compares the mechanisms and characteristics of commonly used crosslinking methods for dECM, with a focus on the potential applications of versatile dECM-based biomaterials derived from skin, cardiac tissues (pericardium, heart valves, myocardial tissue), blood vessels, liver, and kidney, modified with different chemical crosslinking reagents, in tissue and organ regeneration.