Alginate-g-PNIPAM-Based Thermo/Shear-Responsive Injectable Hydrogels: Tailoring the Rheological Properties by Adjusting the LCST of the Grafting Chains

Abstract

Graft copolymers of alginate backbone and N-isopropylacrylamide/N-tert-butylacrylamide random copolymer, P(NIPAMx-co-NtBAMy), side chains (stickers) with various NtBAM content were designed and explored in aqueous media. Self-assembling thermoresponsive hydrogels are formed upon heating, in all cases, through the hydrophobic association of the P(NIPAMx-co-NtBAMy) sticky pendant chains. The rheological properties of the formulations depend remarkably on the NtBAM hydrophobic content, which regulates the lower critical solution temperature (LCST) and, in turn, the stickers’ thermo-responsiveness. The gelation point, Tgel, was shifted to lower temperatures from 38 to 20 °C by enriching the PNIPAM chains with 20 mol % NtBAM, shifting accordingly to the gelation temperature window. The consequences of the Tgel shift to the hydrogels’ rheological properties are significant at room and body temperature. For instance, at 37 °C, the storage modulus increases about two orders of magnitude and the terminal relaxation time increase about 10 orders of magnitude by enriching the stickers with 20 mol % hydrophobic moieties. Two main thermo-induced behaviors were revealed, characterized by a sol–gel and a weak gel–stiff gel transition for the copolymer with stickers of low (0.6 mol %) and high (14, 20 mol %) NtBAM content, respectively. The first type of hydrogels is easily injectable, while for the second one, the injectability is provided by shear-thinning effects. The influence of the type of media (phosphate buffer (PB), phosphate-buffered saline (PBS), Dulbecco’s modified Eagle’s medium (DMEM)) on the hydrogel properties was also explored and discussed. The 4 wt % NaALG-g-P(NIPAM80-co-NtBAM20)/DMEM formulation showed excellent shear-induced injectability at room temperature and instantaneous thermo-induced gel stiffening at body temperature, rendering it a good candidate for cell transplantation potential applications.

Poly(N-isopropylacrylamide-co-N-tert-butylacrylamide)-graph-polydopamine as a Thermoresponsive Surface with Adjustable Transformation Temperature for Efficient Microalgal Cell Adhesion and Detachment

“…The wettability of thermoresponsive copolymers was linked to the competition between hydrophilic and hydrophobic groups in the copolymer molecule . The presence of hydrophobic groups (-(CH 3 ) 2 CH- and -C­(CH 3 ) 2 -) in the polymer molecule could make it easier for the polymer surface to transition from hydrophilic to hydrophobic . As shown in Table S5, the relative contents of C–C/C–H are 49.2%, 55.3%, 68.9%, and 56.6%, corresponding to the coatings of DOP-dopamine, NI:Nt = 100:0, NI:Nt = 90:10, and NI:Nt = 80:20, respectively.…”

Poly(N-isopropylacrylamide)-Based Hydrogels for Biomedical Applications: A Review of the State-of-the-Art

“…Accordingly, systems such as, PNIPAM@ magnetic NPs (Fe 3 O 4 )/5-fluorouracil (5FU) and oxaliplatin (OXA)- acrylic acid (AA), 3-butenoic acid (3BA) or allylamine (AL) (pNIPAM@ Fe 3 O 4 /5FU/OXA-AA, 3BA, AL) [ 181 ], doxorubicin(DOX)-gold nanorods (GNRs)-PNIPAM@poly (d, l-lactide)-poly (ethylene glycol) (PLA-PEG) (DAPP)micelles (DOX-GNRs-PNIPAM@PEG-PLA,DAPP) [ 182 ], vancomycin (VANCO)/SF-Na Alg NPs/PNIPAM@epidermal growth factor (EGF) (VANCO/SF-Na Alg NPs/PNIPAM@EGF) [ 183 ], PNIPAM- superparamagnetic iron oxide nanoparticles (SPION)- etoposide (SPION-PNIPAM-Etoposide) [ 184 ], NaALG-g-P(NIPAM 80 - co -NtBAM 20 )/Dulbecco’s modified Eagle’s medium (DMEM) (NaALG-g-P(NIPAM 80 - co -NtBAM 20 )/DMEM) [ 185 ] and many more have been designed by researchers in order to intensify the use of PNIPAM polymer in the field of drug delivery [ 186 , 187 ]. Table 1 depicts the latest investigations of PNIPAM-based hydrogels in drug delivery.…”

Comparison of Bulk- vs Layer-by-Layer-Cured Stimuli-Responsive PNIPAM–Alginate Hydrogel Dynamic Viscoelastic Property Response via Embedded Sensors

“…This trend agrees with previously reported temperature response data. 52,53 For example, Safakas et al found the thermo-induced response of alginate-g-PNIPAM hydrogels shifts according to the content of NIPAM. It is also well established that PNIPAM hydrogels exhibit relatively large changes in shape and properties upon temperature change, which is not the case for alginate.…”