Glycosaminoglycan-Based Cryogels as Scaffolds for Cell Cultivation and Tissue Regeneration

Abstract

Cryogels are a class of macroporous, interconnective hydrogels polymerized at sub-zero temperatures forming mechanically robust, elastic networks. In this review, latest advances of cryogels containing mainly glycosaminoglycans (GAGs) or composites of GAGs and other natural or synthetic polymers are presented. Cryogels produced in this way correspond to the native extracellular matrix (ECM) in terms of both composition and molecular structure. Due to their specific structural feature and in addition to an excellent biocompatibility, GAG-based cryogels have several advantages over traditional GAG-hydrogels. This includes macroporous, interconnective pore structure, robust, elastic, and shape-memory-like mechanical behavior, as well as injectability for many GAG-based cryogels. After addressing the cryogelation process, the fabrication of GAG-based cryogels and known principles of GAG monomer crosslinking are discussed. Finally, an overview of specific GAG-based cryogels in biomedicine, mainly as polymeric scaffold material in tissue regeneration and tissue engineering-related controlled release of bioactive molecules and cells, is provided.

Sponge-like Scaffolds for Colorectal Cancer 3D Models: Substrate-Driven Difference in Micro-Tumors Morphology

“…Diglycidyl ethers of glycols (DGE) are commonly used in biomedicine for scaffolds and fillers fabrication to control their stiffness and in-body enzymatic degradation rate [ 25 , 26 ], although the cytotoxicity of this type of cross-linkers is still an issue [ 25 , 27 ]. Cross-linking with DGE can be performed via amino-, hydroxyl-, and carboxyl groups [ 28 ] that covers most important classes of polymers used as matrices in cell culturing and tissue engineering [ 20 , 26 , 29 , 30 ]. However, efficient cross-linking with DGE occurs only at pH > 10 [ 27 , 31 ], when chitosan is not soluble.…”

“…At lower temperature (−15 °C and −20 °C), the loss of reactivity did not result in cross-linking at an equimolar BDDGE:polymer ratio during 14 days. Another reason for cryogel fabrication at higher temperature is the observation that a lower cryogelation temperature leads to the smaller pore size [ 20 , 26 ] that is not desirable for scaffolds for 3D tumor models development. Moreover, the fabrication of macroporous scaffolds from CMC hydrogels reported earlier was possible only via freeze-drying.…”

“…Although high stiffness promotes adherent cell proliferation in 2D culture, the development of 3D cancer models is challenging, since a high cross-linking degree or high polymer concentration in stiff hydrogels result in spatial constraints and low permeability for nutrients that negatively affect the size, morphology and density of the growing spheroids [ 13 , 17 ]. Therefore, the fabrication of macroporous scaffolds is promising for providing simultaneously required scaffold stiffness, efficient transport of nutrients and cell metabolites, and sufficient inner space for 3D cell growth [ 2 , 17 , 18 , 19 , 20 ]. Among different methods of porous materials fabrication, including salt/particle leaching, freeze drying, phase separation, and gas foaming, cryogelation, i.e., the polymerization of monomers or cross-linking of polymers at subzero temperature with the subsequent removal of porogenic ice crystals by thawing, is a simple, green and efficient approach.…”

Cryogenically structured gelatin-based hydrogel as a resorbable macroporous matrix for biomedical technologies

“…Одним из технологических подходов к формированию 3D-носителей в виде губок является крио генное структурирование полимерных систем [18][19][20][21]. Когда в замороженном образце происходит формирование ковалентных или нековалентных узлов трехмерной сетки, сам такой процесс называют криотропным гелеобразованием, а получающиеся полимерные объекты -криогелями, если же гелеобразование отсутствует, то конечными продуктами (обычно после удаления замороженного растворителя) являются полимерные объекты, называемые криоструктуратами [22].…”

Studying the Effect of Chondroitin Sulfate on the Physicochemical Properties of Novel Gelatin/Chitosan Biopolymer-Based Cryogels

“…Chondroitin sulfate (CS) is a sulfated polysaccharide in C4 or C6 of its repeating unit, containing GAG and galactosamine [35]. CS attaches to proteins as part of proteoglycan, an important component of cartilage, and its inclusion in a scaffold allows for the secretion of proteoglycans and type II collagen [36]. Due to its physicochemical, mechanical, and biological properties, CS is used as a polymer network for tissue engineering [37][38][39].…”