Chemical cross-linking methods for cell encapsulation in hydrogels

Abstract

Cell-encapsulating hydrogels are of tremendous interest in regenerative medicine. Tissue engineering relies on biomaterials able to act as artificial extracellular matrices to guide cells towards the development of new tissues. Therefore, considerable efforts have been made to design biomaterials which mimic cells' native environment, thus encouraging natural behavior. The choice of biomaterial in which cells are embedded is crucial for their survival, proliferation and differentiation. Being more stable, chemical hydrogels are preferred over physical hydrogels as cell-laden substrates. When designing chemical hydrogels, scientists must choose not only the nature of the network (synthetic and/or biopolymers) but also the type of cross-link bridging hydrogel constituents. For that purpose, numerous chemistries have been used (i) to introduce reactive functions on the hydrogel precursors and (ii) to form covalent bonds in the presence of living cells. The review will discuss the advantages and limitations of each strategy.

Natural biopolymer‐based hydrogels for use in food and agriculture

“…) . Polymers with functional groups such as primary amines, alcohols, thiols, carbonyls, and carboxylic acids can covalently link to these crosslinker molecules …”

Controlled release fertilizer encapsulated by a κ-carrageenan hydrogel

“…These modifications require the integration of more inner charges to the non covalent spatial networks by cross-linking through covalent chemical bonds, which stabilizes the hydrogel and improves the nutrients retention properties. To integrate more inner charges it is suggested to increase the concentration of any of the following: calcium salts (from 2 to 5% w / v), glycerol (from 5 to 10% w / v) or self-assembling peptides [56] . Additionally, the hydrogel synthesis pH could be modified to guarantee the reduction of hydrolysis and thus ensure the formation of stronger networks.…”

Impact of the Type of Crosslinking Agents on the Properties of Modified Sodium Alginate/Poly(vinyl Alcohol) Hydrogels

“…Generally, bio-based hydrogels can be prepared using several chemical and ionic crosslinking methods and also in different ways, e.g., photopolymerization and exposure to radiation (e.g., gamma rays or microwaves) [29]. The chemical method is based on the formation of covalent bridges during the reaction between the polymer or monomer with the crosslinking agent (N, N'-methylenebisacrylamine (NMBA) and poly(ethylene glycol) diacrylate (PEGDA) in the presence of an initiator (ammonium, potassium or sodium persulfates [30][31][32]. Meanwhile, the method of crosslinking by ionic interaction takes place in the presence of bivalent or multivalent ions, such as Ca 2+ , Cu 2+ , Fe 2+ or Al 3+ .…”