Recent advancements in enzyme-mediated crosslinkable hydrogels: In vivo-mimicking strategies

Abstract

Enzymes play a central role in fundamental biological processes and have been traditionally used to trigger various processes. In recent years, enzymes have been used to tune biomaterial responses and modify the chemical structures at desired sites. These chemical modifications have allowed the fabrication of various hydrogels for tissue engineering and therapeutic applications. This review provides a comprehensive overview of recent advancements in the use of enzymes for hydrogel fabrication. Strategies to enhance the enzyme function and improve biocompatibility are described. In addition, we describe future opportunities and challenges for the production of enzyme-mediated crosslinkable hydrogels.

Interrelation between swelling, mechanical constraints and reaction–diffusion processes in molecular responsive hydrogels

“…Examples of this include cas12 digestion of DNA strands in hydrogels 12 thus inducing decreased crosslink density, or enzyme catalyzed increased crosslinking. 50 It should also be noted that similar strategies can be applied also for the coupled phenomena when enzyme induced degradation of the extracellular matrix by cell secreted enzymes are integrated in a model. 51,52 In these examples, the representation of the molecular mechanism of the molecular specie triggering the network structural changes can be different from the present work, and need to be changed accordingly in their modeling representation.…”

Advances in Injectable In Situ-Forming Hydrogels for Intratumoral Treatment

“…Further, the products of these reactions tend to be highly biocompatible and are especially well suited to the preparation of injectable hydrogels. Nevertheless, several physicochemical factors such as the pH, temperature, and steric hindrance caused by the substrate structure can significantly affect the catalytic activity of enzymes [74].…”

Tyrosinase‐mediated hydrogel crosslinking for tissue engineering

“…There is another minor reaction in the oxidation of ortho-quinones. 7 However, as the main focus in the field of tissue engineering is recapitulating biomimetic and biocompatible chemistry, further discussion in mechanism is beyond our scope.…”

“…As the harsh organic solvents and radical species essential in a broad range of chemical crosslinking are not necessary for enzymatic reactions, the mild crosslinking strategy provides biocompatibility, cellfriendly, and biomimetic environments to native cells, proteins, and tissues. 7 Across the enzymes, tyrosinase has been particularly investigated as important in melanin and other pigment syntheses. 8 In mammals, tyrosinase can be found in melanosome where melanin particle is synthesized.…”

“…As phenolic moieties (e.g., tyrosine, catechol, and polyphenols) are universally expressed in human protein and can be easily conjugated to hydrogel, tyrosinase has been devoted to enzyme-mediated protein and hydrogel crosslinking for tissue engineering and regenerative medicine. 7,11 On the other hand, the oxidative reaction of tyrosinase ensembles the process of mussel adhesion on the sea rock induced by DOPA in mussel foot protein (Mfp). 12,13 Thanks to the development of mussel-inspired chemistry, the tyrosinase-mediated reaction have been broadened from hydrogel crosslinking to a tissue adhesive.…”