Recent Advances on Stimuli-Responsive Hydrogels Based on Tissue-Derived ECMs and Their Components: Towards Improving Functionality for Tissue Engineering and Controlled Drug Delivery

Abstract

Due to their highly hydrophilic nature and compositional versatility, hydrogels have assumed a protagonic role in the development of physiologically relevant tissues for several biomedical applications, such as in vivo tissue replacement or regeneration and in vitro disease modeling. By forming interconnected polymeric networks, hydrogels can be loaded with therapeutic agents, small molecules, or cells to deliver them locally to specific tissues or act as scaffolds for hosting cellular development. Hydrogels derived from decellularized extracellular matrices (dECMs), in particular, have gained significant attention in the fields of tissue engineering and regenerative medicine due to their inherently high biomimetic capabilities and endowment of a wide variety of bioactive cues capable of directing cellular behavior. However, these hydrogels often exhibit poor mechanical stability, and their biological properties alone are not enough to direct the development of tissue constructs with functional phenotypes. This review highlights the different ways in which external stimuli (e.g., light, thermal, mechanical, electric, magnetic, and acoustic) have been employed to improve the performance of dECM-based hydrogels for tissue engineering and regenerative medicine applications. Specifically, we outline how these stimuli have been implemented to improve their mechanical stability, tune their microarchitectural characteristics, facilitate tissue morphogenesis and enable precise control of drug release profiles. The strategic coupling of the bioactive features of dECM-based hydrogels with these stimulation schemes grants considerable advances in the development of functional hydrogels for a wide variety of applications within these fields.

Tissue-specific gelatin bioink as a rheology modifier for high printability and adjustable tissue properties

“…1,7 However, dECM's principal thermal crosslinking mechanism is considerably restricted by the heat transport rate within the gel environment, resulting in inadequate structural stability of the printed constructs with unique geometries (e.g., tubular, curved, spherical). 8 These limitations pose challenges in printing flexible tissue constructs with high resolution; to date, tissue engineering of hollow organs with dECM bioinks mostly relies on polymer scaffolds to ensure tissue geometry and mechanical stability. 9,10 Alternatively, exogenous additions and modifications of dECM have been tried in various ways to improve their mechanical rigidity.…”

pH-Responsive Gallol-Functionalized Hyaluronic Acid-Based Tissue Adhesive Hydrogels for Injection and Three-Dimensional Bioprinting

“…Stimuli-responsive hydrogels have also been investigated as candidates for bioinks and can be induced by exposing the ink to various environmental changes, including pH, temperature, light, and ions . These properties provide versatility to bioinks, as they harness the on-demand tunability of bioinks and can be used for various applications .…”

“…25−27 Stimuli-responsive hydrogels have also been investigated as candidates for bioinks and can be induced by exposing the ink to various environmental changes, including pH, temperature, light, and ions. 28 and can be used for various applications. 29 The pH-responsive hydrogels have gained wide interest because of their excellent adaptation in physiological conditions for in situ bioprinting applications.…”