(194ag) Dopant-Free Hydrogels with Intrinsic Photoluminescent, Injectable and Biodegradable Properties

Yung-Hao Tsou, Xiaoyang Xu

Department of Chemical and Material
Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA

Email: xiaoyang@njit.edu

Abstract: Photoluminescent hydrogels that
function as both injectable scaffolds and fluorescent imaging probes hold great
promise for many biomedical applications. Current photoluminescent hydrogels
are fabricated by either conjugating or doping a fluorescent dye, fluorescent
protein, lanthanide chelate, or quantum dot into the hydrogel matrix. A
dopant-free hydrogel with intrinsic photolumincescent and degradable properties
is yet to be demonstrated. Here, we report a successful development of
dopant-free photoluminescent hydrogels in situ formed by crosslinking of
polymer precursors, which can be synthesized by incorporating an amino acid to
a citric acid based polyester oligomer followed by functionalization of multivalent
crosslinking group through an enzyme-catalyzed transesterification reaction.
The hydrogels possess tunable degradation, intrinsic photoluminescence, sustained
release properties, and exhibit excellent biocompatibility in vitro and in vivo. Their
in vivo degradation profiles can be
depicted by non-invasively monitoring fluorescence intensity without
sacrificing animals, making them an attractive implant biomaterial for
bioimaging, therapeutics delivery, and tissue engineering.

Method: A series of polyester oligomers with tunable
intrinsically fluorescent properties have been successfully synthesized from
biocompatible monomers including citric acid, poly (ethylene glycol) (PEG)-diol
and various amino acids via a facile polycondensation reaction. A 6-membered
ring chromophore can be formed through the amidation reaction between the
unreacted carboxylic acid on the citrate and the N terminus of an amino acid,
followed by an esterification reaction between the free carboxylic acid of the
amino acid molecule and the hydroxyl group remaining on citrate. The ring
contributes strong photoluminescent emitting due to the electrons
hyperconjugation over the ring. The synthesized oligomers were further modified
by introducing multiple thiol functional groups using a high efficient enzyme
assisted transesterification reaction. A library of hydrogels with diverse
physiochemical properties can be formed by combining thiol group functionalized
polymers with different molecular weight multi-armed PEG acrylates or PEG
maleimides through a convenient Michael addition reaction.

Results: The results show that the hydrogels can be
formed in situ (Figure 1a and c) and illustrate strong fluorescence (Figure 1b
and d) with an emission wavelength from around 360 nm to 620 nm with quantum
yields up to 36%. The gelation time (ranging from 20 seconds to several
minutes) and mechanic properties can be tuned by controlling crosslinking
conditions and selection of monomers. The hydrogel is degradable both in vitro
and in vivo from 4 days to a few weeks. The in vivo animal experiment shows that
the injectable photoluminescent hydrogels can be non-invasively injected under
the skin of nude mice (Figure 1e and f) and show strong fluorescence when
imaged by a small animal imaging system. In addition, the hydrogel possesses great
biocompatibility property demonstrated by H&E and Immunohistochemical staining. Importantly, the in vivo
degradation of the implanted hydrogel can be tracked without sacrificing the
animal.

 Figure
1: Photo images of hydrogels containing cysteine (a) and serine (c)
moieties and after UV light excitation of 360 (b) and 450 (d) nm.
Photoluminescent hydrogel before (e) and after (f) inject into nude mice.

 Conclusions:
A series of polyester based hydrogels have been fabricated. The hydrogels show
unique photoluminescent, tunable mechanical and degradation properties. The
development of the photoluminescent hydrogel provides a solid basis for
subsequently study materials structure-function relationship and has potential
applications as tissue engineering, drug delivery and imaging biomaterials.

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