Advances in abiotic tissue-based biomaterials: A focus on decellularization and devitalization techniques

This Review explores the growing and diversifying field of tissue-derived abiotic constructs for tissue engineering applications, with main focus on decellularization and devitalization techniques and principles. Acellular fractions derived from biological tissues, such as the extracellular matrix (ECM), have long been considered a valuable approach for the generation of numerous scaffolds and more complex constructs. The removal of the cellular content has been considered essential to prevent the development of adverse immunological reactions. Nevertheless, the discovery of promising features of certain cellular components has sparked interest in the use of inactivated or devitalized cellular fractions for several applications, particularly in regenerative medicine and inflammation control. Devitalization has been described for several clinical applications, but remains poorly explored in terms of in vitro constructs compared to decellularization methods currently available. In this review, we present and critically evaluate a spectrum of approaches for the decellularization of whole-organs and in vitro constructs, and the most prevalent devitalization techniques, with a discussion on their implications on scaffolds composition, structure, and potentially therapeutic properties. Processing methodologies to achieve optimal cell-based abiotic materials and approaches for their effective characterization are described and discussed. The application of these materials in healthcare, with most focus on regenerative approaches and including examples of commercially available products, is also addressed.