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.

Emerging Bioactive Agent Delivery-Based Regenerative Therapies for Lower Genitourinary Tissues

“…Advantages such as high availability, biocompatibility, and bioactivity have facilitated the use of bioderived materials as delivery systems for therapeutic substance release and tissue repair [49,50]. Among them, proteins (including, fibroin, collagen, and keratin), polysaccharides (such as, glycosaminoglycans, alginate, chitosan, plant origin natural gum, cellulose, and gellan gum), lipids (such as liposomes and saturated fatty acids), extracellular vesicles (EVs), and extracellular matrix (ECM) have been extensively investigated and are reviewed in detail elsewhere [51][52][53][54][55][56][57][58][59].…”

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.…”

Conductive extracellular matrix derived/chitosan methacrylate/ graphene oxide-pegylated hybrid hydrogel for cell expansion

“…Hydrogels have played an important role in advancing the fields of tissue engineering and regenerative medicine, owing to their pivotal role in developing accurate tissue models and facilitating drug testing ( Cascone and Lamberti, 2020 ). Their unique structure, hydrophilic properties, and versatile composition render them an ideal platform for designing and manufacturing cell-friendly and multifunctional microenvironments ( Ahadian et al, 2016 ; Serna et al, 2021 ). Hydrogels composed of naturally derived polymers such as fibrin, hyaluronic acid, and collagen offer biocompatibility and biochemical similarities to natural tissue microenvironments.…”