Superporous hydrogels with Oriented pores having relatively Large elasticity and Thermoresponsive near human body Temperature

R.E. RIVERO; M.A. MOLINA; C.R. RIVAROLA; CRISTINA MIRAS; C.A. BARBERO

Berlin

Conferencia; 12th International PAT Conference; 2013

Smart hydrogels have been used in a wide range of biomedicalapplications including contact lenses, cornealimplants, drug delivery, artificial menisci [1] and substitutesfor skin, ligament, tendon, cartilage and bone. Thechoice of using an implanted material to replace a biologicaltissue-like the particular cartilage depends onthe materials ability to behave in a similar way to thetissue it is replacing. A critical barrier to their use asload-bearing tissue replacements is a lack of sufficientmechanical properties.Thermosensitive hydrogels based on N-isopropylacrylamideoffer another advantage: their phase transitionallows the controlled release of pharmaceuticaldrugs such as vitamins, antibiotics or anti-inflammatory.Our group has synthesized, by copolymerization orsemi-interpenetration with conductive polymers [2],macroporous thermosensitive hydrogels [3], whichphysicochemical properties are tailored to severalapplications. These thermosensitive hydrogels haveshown both ability to drug release and changes onthe topography before and after phase transition.While the phase transition temperature of PNIPAM(32?33 °C) is close to basal human body temperature,still remains below it.. Therefore, the gel will changeafter insertion into the body, making it less useful. Fordrug delivery applications in-situ, the gel should havethe phase transition temperature just above thehuman body temperature to be triggered by changesin temperature. In this work, it is shown that hydrogelswith phase transition temperatures (TPT) close tohuman body temperature can be synthesized by copolymerizationof N-isopropylacrylamide and a hydrophilicmonomer (N-acryloyl-tris-(hydroxymethyl) aminomethane,HMA) (Figure1). This monomer unit is hydrophilicbut not charged, avoiding ionic strength effects. However,also it is possible to use an ionic monomer as 2-acrylamido-2-methylpropanesulfonic acid (AMPS) toincrease TPT.In this work thermosensitive hydrogels based oncrosslinked N-isopropylacrylamide (NIPAM) were synthesizedby free radical polymerization. The goal is toobtain porous thermosensitive hydrogels with phasetransition around basal human temperatures for in-situdrug delivery and scaffold to growth biological cells.Porous hydrogel were synthesized using two methodsof pore formation: cryogelation and in-situ gas as porogenicagent. A novel method to form the porogenicgas is proposed Size and shape of the hydrogel poreswere investigated by scanning electronic microscopy(SEM). The physicochemical and mechanical propertiessuch as swelling capacity, porosity and elastic modulusare clearly affected by monomeric composition andthe method of pores formation. Although the hydrogelssynthesized have soft viscoelastic structure (from2 to 7 kPa), we can obtain by cryogelation a materialwith relatively higher rigidity (20-30 kPa) by incorporationof interconnected and oriented macropores withoutlosing its sensitivity to basal temperature. Themechanical properties depend on the direction offorce application, being larger in the parallel than intransversal direction, confirming the effect of pore orientation(Figure 2). The materials are potential candidatesfor applications in biomedicine and tissueengineering.