Conspectus
Bioadhesives are important for
the future of medicine in their
roles in wound closure and as measures to enhance wound healing. These
adhesives are more effective and less invasive than conventional wound
closure methods, such as surgical sutures or staples. Adhesive substances
based on naturally occurring biological materials from living organisms
harness phenolic compounds for their attachment to wet surfaces. For
example, plants, such as Boston ivy, or animals, such as mussels,
have evolved tissues that create optimal adhesion under a variety
of challenging conditions, including in aqueous and saline environments.
Current research aims at using biomimetic strategies to create a new
generation of bioadhesives that will be better suited for medical
use. Biomaterials design has evolved around integration of phenols
with protein backbones among which gelatin has received particular
attention due to its excellent bioactivity, biocompatibility, biodegradability,
low cost, facile chemical tunability, and tissue-mimetic properties.
Bioadhesion performance in these biomaterials is a strong function
of polyphenolic functionality and the processing approach for their
integration into hydrogel networks. A number of studies have used
phenolic small molecules to modify biomacromolecules chemically for
bioadhesion. One of the major hurdles in these studies is insufficient
phenolic uptake due to low-yield modification chemistries and inherently
limited functionalization capacity of proteins. Polyphenols are an
attractive toolbox for bioadhesive design, as they not only enable
stronger interactions with various substrates but also act as cross-linking
points, strengthening polymer network cohesion. In addition, the cross-linking
mechanism used for gelation of bioadhesives should be compatible with
polyphenolic moieties, as, for instance, free-radical polymerization
in the presence of phenolic compounds is compromised by their free-radical
scavenging effects. Polyphenolic compounds derived synthetically from
phenolic small molecules as well as those occurring naturally, such
as tannins, have added a large library of additional functionality,
such as antimicrobial and photothermal responsiveness, calling for
further developments for applications in wound management.
In
this Account, we review several recent breakthroughs in polyphenol-integrated
gelatin that have been analyzed in the context of their use as bioadhesives.
Polyphenols play important roles in covalent and noncovalent interactions
with functional groups in biological substrates, including keratins,
connective tissue, or soft internal tissues. We consider different
polyphenol-carrying compounds for modification including catecholamines,
phenolic amino acids, tannins, and lignins. We then discuss how these
polyphenolic materials can be fabricated to mimic naturally derived
bioadhesives through infusion, physical mixing, and copolymerization.
We discuss the implications of using these bioadhesives, questioning
their viability and prospects. Finally, we highl...
