Designing Hydrogels by ATRP - In-Situ Gelling Polymers: For Biomedical Applications - page 87

Gelation via overlap/packing

Micellar aggregates

AB diblockcopolymers

hydrophilic stimuli-responsive

Low concentration Moderate concentration

Stimulus

Intermicellarbridge

Injection

BAB triblock copolymers

Dangling blocks

stimuli-responsive hydrophilic stimuli-responsive

Dangling blocks

Micellar aggregates with dangling blocks Gelation via overlap/packing

and intermicellarbridging

Fig. 6 Illustration of in situ gelation of well-defined thermoresponsive block copolymers

diblock copolymers, which have a critical gelation concentration of approximately
20 wt% in solution [ 205 ]. Alternatively, stimuli-responsive triblock copolymers
such as ABA or BAB triblock copolymers, where the A block is hydrophilic
and B block hydrophobic can be used to reduce the critical gelation concentra-
tion. Gelation of ABA triblock copolymers is also caused by an overlap of micel-
lar coronas, although a lower polymer concentration may be used as the micellar
aggregates formed are typically larger than those from AB diblock copolymers.
BAB triblock copolymers however, can undergo gelation via an additional inter-
micelle bridging mechanism. Micellar aggregates formed from BAB triblocks
require folding of two B hydrophobic blocks into one micelle core, which can be
energetically unfavorable and, some B blocks can exist as dangling blocks in solu-
tion, which can form bridges when incorporated into other micelles (Fig. 6 ).
A series of BAB triblock copolymers, utilizing 2-methacryloyloxyethyl phos-
phorylcholine (MPC) as the central hydrophilic block, have been studied for pro-
duction of in situ formed hydrogels [ 206 - 209 ]. MPC contains a phosphorylcholine
functional group, which when incorporated into coatings makes the surface resist-
ant to protein adsorption and cellular adhesion without negatively impacting cell
viability [ 210 - 212 ]. The central MPC block was synthesized from a difunctional
ATRP initiator, and then subsequently chain extended with pendant amine-con-
taining methacylates, for example 2-(diethylamino)ethyl methacrylate (DEA) a
class of pH and temperature responsive monomers. These MPC-containing tri-
block solutions with approximately 10 wt% polymer formed physical gels at body
temperature and neutral pH. Release of encapsulated molecules could be enhanced
at acidic pH's due to dissolution of the gel as the polymer becomes protonated
[ 206 , 207 ]. Alternatively, MPC was copolymerized with NIPAM, a well-known
thermo-responsive monomer with a LCST transition ≈ 32 °C. The P(NIPAM-
b-MPC-b-NIPAM) copolymers underwent gelation at a lower polymer content