This thesis describes work on the development of several novel stimuli-responsive
porous hydrogels prepared from oil-in-water (o/w) high internal phase emulsion
(HIPE) as injectable scaffolds for soft tissue engineering. Firstly, by copolymerising
glycidyl methacrylate (GMA) derivatised dextran and N-isopropylacrylamide
(NIPAAm) in the aqueous phase of a toluene-in-water HIPE, thermo-responsive
polyHIPE hydrogels were obtained. The temperature depended modulus of these
porous hydrogels, as revealed by oscillatory mechanical measurements, indicated
improvements of the mechanical properties of these hydrogels when heated from
room temperature to human body temperature, as the polyNIPAAm copolymer
segments starts to phase separate from the aqueous phase and causes the hydrogel to
form a more compact structure within the aqueous phase of the polyHIPE. Secondly
ion responsive methacrylate modified alginate polyHIPE hydrogels were prepared.
The physical dimensions, pore and pore throat sizes as well as water uptakes of these
ion responsive hydrogels can be controllably decreased in the presence of Ca2+ ions
and are fully recovered after disruption of the ionic crosslinking using a chelating
agent (sodium citrate). These ion-responsive polyHIPE hydrogels also possess good
mechanical properties (modulus up to 20 kPa). Both of these polyHIPE hydrogels
could be easily extruded through a hypodermic needle while breaking into small
fragments (about 0.5 to 3.0 mm in diameter), but the interconnected porous morphology was maintained after injection as revealed by SEM characterisation.
Furthermore, the hydrogel fragments produced during injection can be crosslinked
into a coherent scaffold under very mild condition using Ca2+ salts and alginate
aqueous solution as the ionically crosslinkable adhesive.
In order to increase the pore size of these covalently crosslinked polyHIPE hydrogels
and also find a biocompatible nontoxic emulsifier as substitution to traditional
surfactants, methyl myristate-in-water and soybean oil-in-water HIPEs solely
stabilised by hydroxyapatite (HAp) nanoparticle were prepared. These Pickering-
HIPEs were used as template to prepare polyHIPE hydrogels. Dextran-GMA, a water
soluble monomer, was polymerised in the continuous phase of the HAp Pickering
HIPEs leading to porous hydrogels with a tunable pore size varying from 1.5 μm to
41.0 μm. HAp is a nontoxic biocompatible emulsifier, which potentially provides
extra functions, such as promoting hard tissue cell proliferation.
HIPE-templated materials whose porous structure is maintained solely by the
reversible physical aggregation between thermo-responsive dextran-b-polyNIPAAm
block polymer chains in an aqueous environment (for this type of HIPE templated
material we coined the name thermo-HIPEs) were prepared. No chemical reaction is
required for the solidification of this porous material. This particular feature should
provide a safer route to injectable scaffolds as issues of polymerisation/crosslinking
chemistry or residual initiator fragments or monomers potentially being cytotoxic do not arise in our case, as all components are purified polymers prior to HIPE formation.
Thermo-HIPEs with soybean oil or squalene as dispersed oil phase were prepared.
Also in this HIPE system it was possible to replace the original surfactant Triton
X405 with colloidal HAp nanoparticles or pH/thermo-responsive polyNIPAAm-co-
AA microgel particles. The pore sizes and the mechanical properties of colloidal
particles stabilised thermo-HIPEs showed improvement compared with thermo-HIPEs
stabilised by Triton X405.
In summary new injectable polyHIPEs have been prepared which retain their pore
morphology during injection and can be solidified by either a thermal or ion (Ca2+) or
chelating ion (Ca2+) stimulus. The materials used are intrinsically biocompatible and
thus makes these porous injectable scaffolds excellent candidates for soft tissue
engineering.