Click Hydrogels, Microgels and Nanogels: Emerging Platforms for Drug Delivery and Tissue Engineering

Hydrogels, microgels and nanogels have emerged as versatile and viable
platforms for sustained protein release, targeted drug delivery, and
tissue engineering due to excellent biocompatibility, a microporous
structure with tunable porosity and pore size, and dimensions spanning
from human organs, cells to viruses. In the past decade, remarkable
advances in hydrogels, microgels and nanogels have been achieved with
click chemistry. It is a most promising strategy to prepare gels with
varying dimensions owing to its high reactivity, superb selectivity, and
mild reaction conditions. In particular, the recent development of
copper-free click chemistry such as strain-promoted azide-alkyne
cycloaddition, radical mediated thiol-ene chemistry, Diels-Alder
reaction, tetrazole-alkene photo-click chemistry, and oxime reaction
renders it possible to form hydrogels, microgels and nanogels without
the use of potentially toxic catalysts or immunogenic enzymes that are
commonly required. Notably, unlike other chemical approaches, click
chemistry owing to its unique bioorthogonal feature does not interfere
with encapsulated bioactives such as living cells, proteins and drugs
and furthermore allows versatile preparation of micropatterned
biomimetic hydrogels, functional microgels and nanogels. In this review,
recent exciting developments in click hydrogels, microgels and
nanogels, as well as their biomedical applications such as controlled
protein and drug release, tissue engineering, and regenerative medicine
are presented and discussed.