Moreira Teixeira L.S. - Enzyme-catalyzed crosslinkable hydrogels: Emerging strategies for tissue engineering

Liliana S. Moreira Teixeira, Jan Feijen, Clemens A. van Blitterswijk,
Pieter J. Dijkstra, Marcel Karperien

Biomaterials 2011


State-of-the-art bioactive hydrogels can easily and efficiently be formed by enzyme-catalyzed mildcrosslinking
reactions in situ. Yet this cell-friendly and substrate-specific method remains under
explored. Hydrogels prepared by using enzyme systems like tyrosinases, transferases and lysyl oxidases
show interesting characteristics as dynamic scaffolds and as systems for controlled release. Increased
attention is currently paid to hydrogels obtained via crosslinking of precursors by transferases or
peroxidases as catalysts. Enzyme-mediated crosslinking has proven its efficiency and attention has now
shifted to the development of enzymatically crosslinked hydrogels with higher degrees of complexity,
mimicking extracellular matrices. Moreover, bottom-up approaches combining biocatalysts and selfassembly
are being explored for the development of complex nano-scale architectures. In this review,
the use of enzymatic crosslinking for the preparation of hydrogels as an innovative alternative to other
crosslinking methods, such as the commonly used UV-mediated photo-crosslinking or physical crosslinking,
will be discussed. Photo-initiator-based crosslinking may induce cytotoxicity in the formed gels,
whereas physical crosslinking may lead to gels which do not have sufficient mechanical strength and
stability. These limitations can be overcome using enzymes to form covalently crosslinked hydrogels.
Herewith, we report the mechanisms involved and current applications, focusing on emerging strategies
for tissue engineering and regenerative medicine.