Decellularized extracellular matrix and silk fibroin-based hybrid biomaterials: A comprehensive review on fabrication techniques and tissue-specific applications

Biomaterials play a fundamental role in tissue engineering by providing biochemical and physical cues that influence cellular fate and matrix development. Decellularized extracellular matrix (dECM) as a biomaterial is distinguished by its abundant composition of matrix proteins, such as collagen, elastin, fibronectin, and laminin, as well as glycosaminoglycans and proteoglycans. However, the mechanical properties of only dECM-based constructs may not always meet tissue-specific requirements. Recent advancements address this challenge by utilizing hybrid biomaterials that harness the strengths of silk fibroin (SF), which contributes the necessary mechanical properties, while dECM provides essential cellular cues for in vitro studies and tissue regeneration. This review discusses emerging trends in developing such biopolymer blends, aiming to synergistically combine the advantages of SF and dECM through optimal concentrations and desired cross-linking density. We focus on different fabrication techniques and cross-linking methods that have been utilized to fabricate various tissue-engineered hybrid constructs. Furthermore, we survey recent applications of such biomaterials for the regeneration of various tissues, including bone, cartilage, trachea, bladder, vascular graft, heart, skin, liver, and other soft tissues. Finally, the trajectory and prospects of the constructs derived from this blend in the tissue engineering field have been summarized, highlighting their potential for clinical translation.