Engineering Decellularized Extracellular Matrix-Based Scaffolds Through Non-Enzymatic Processing Treatment

An ideal tissue engineering scaffold should recapitulate the native extracellular matrix (ECM) microenvironment, providing structural support and biochemical cues that regulate cellular behavior and promote tissue regeneration. Decellularized extracellular matrix (dECM) preserves the compositional and biological features of native ECM, but its limited processability restricts direct fabrication into scaffolds with defined structures and functions. To overcome these limitations, a variety of strategies have been developed for building dECM-based scaffolds including hydrogels, scaffolds, membranes and other formats for broader application. In this review, we begin with a brief overview of the decellularization strategies and the compositional characteristics of dECM, and then we focus on summarizing the recent developments in processing strategies including enzymatic and non-enzymatic processing of dECM materials. Next, this review focuses on the design and application of dECM-based scaffolds with different forms by non-enzymatic processing treatment. Finally, we discuss the current challenges and future perspectives for non-enzymatic engineering of dECM-based scaffolds.