Synthesis of Photodegradable Macromers for Conjugation
and Release of Bioactive Molecules
Donald
R. Griffin
Jessica L. Schlosser
Sandra
F. Lam
Thi H. Nguyen
Heather D. Maynard
Andrea M. Kasko
10.1021/bm400169d.s001
https://acs.figshare.com/articles/journal_contribution/Synthesis_of_Photodegradable_Macromers_for_Conjugation_and_Release_of_Bioactive_Molecules/2426176
Hydrogel scaffolds are used in biomedicine
to study cell differentiation
and tissue evolution, where it is critical to control the delivery
of chemical cues both spatially and temporally. While large molecules
can be physically entrapped in a hydrogel, moderate molecular weight
therapeutics must be tethered to the hydrogel network through a labile
linkage to allow controlled release. We synthesized and characterized
a library of polymerizable <i>ortho</i>-nitrobenzyl (<i>o</i>-NB) macromers with different functionalities at the benzylic
position (alcohol, amine, BOC-amine, halide, acrylate, carboxylic
acid, activated disulfide, <i>N</i>-hydroxysuccinyl ester,
biotin). This library of polymerizable macromers containing <i>o</i>-NB groups should allow direct conjugation of nearly any
type of therapeutic agent and its subsequent controlled photorelease
from a hydrogel network. As proof-of-concept, we incorporated the <i>N</i>-hydroxysuccinyl ester macromer into hydrogels and then
reacted phenylalanine with the NHS ester. Upon exposure to light (λ
= 365 nm; 10 mW/cm<sup>2</sup>, 10 min), 81.3% of the phenylalanine
was released from the gel. Utilizing the photodegradable macromer
incorporating an activated disulfide, we conjugated a cell-adhesive
peptide (G<b>C</b>GYG<b>RGDS</b>PG), a protein that exhibits
enzymatic activity (bovine serum albumin (BSA)), and a growth factor
(transforming growth factor-β1 (TGF-β1)) into hydrogels,
controlled their release with light (λ = 365 nm; 10 mW/cm<sup>2</sup>, 0–20 min), and verified the bioactivity of the photoreleased
molecules. The photoreleasable peptide allows real-time control over
cell adhesion. BSA maintains full enzymatic activity upon sequestration
and release from the hydrogel. Photoreleased TGF-β1 is able
to induce chondrogenic differentiation of human mesenchymal stem cells
comparable to native TGF-β1. Through this approach, we have
demonstrated that photodegradable tethers can be used to sequester
peptides and proteins into hydrogel depots and release them in an
externally controlled, predictable manner without compromising biological
function.
2016-02-19 12:59:26
peptide
hydrogel network
release
365 nm
Bioactive MoleculesHydrogel scaffolds
macromer
GCGYGRGDSPG
BSA
TGF
NHS
ester
study cell differentiation