No abstract

The utility and efficacy of thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels as smart materials is limited by their physical properties. In this study, we sought to design PNIPAAm nanocomposite hydrogels which displayed enhanced mechanical properties as well as deswelling–reswelling kinetics but without reducing equilibrium swelling or altering the convenient volume phase transition temperature (VPTT) of PNIPAAm. PNIPAAm hydrogels were formed as double networks (DN) comprised of a tightly crosslinked 1st network and a loosely crosslinked 2nd network. In addition, polysiloxane nanoparticles of two different average diameters (~50 nm and ~200 nm) were incorporated during formation of the 1st or 2nd network. The influence of the hydrogel composition on VPTT, morphology, equilibrium swelling, deswelling–reswelling kinetics and mechanical properties was evaluated. We observed that DN hydrogels formed with ~200 nm polysiloxane nanoparticles introduced during formation of the 1st network achieved the best combination of the desired properties.

Inorganic-organic hydrogels based on methacrylated star polydimethylsiloxane (PDMS(star)-MA) and diacrylated poly(ethylene glycol) (PEG-DA) macromers were prepared via solvent-induced phase separation (SIPS). The macromers were combined in a dichloromethane precursor solution and sequentially photopolymerized, dried and hydrated. The chemical and physical properties of the hydrogels were further tailored by varying the number average molecular weight (M(n)) of PEG-DA (M(n)=3.4k and 6k gmol(-1)) as well as the weight percent ratio of PDMS(star)-MA (M(n)=7k gmol(-1)) to PEG-DA from 0:100 to 20:80. Compared to analogous hydrogels fabricated from aqueous precursor solutions, SIPS produced hydrogels with a macroporous morphology, a more even distribution of PDMS(star)-MA, increased modulus and enhanced degradation rates. The morphology, swelling ratio, mechanical properties, bioactivity, non-specific protein adhesion, controlled introduction of cell adhesion, and cytocompatibility of the hydrogels were characterized. As a result of their tunable properties, this library of hydrogels is useful to study material-guided cell behavior and ultimate tissue regeneration.

The lifetime and efficacy of a subcutaneously implanted glucose biosensor could be greatly improved by a self-cleaning membrane capable of periodic physical removal of adhered cells associated with the foreign body reaction. Previously, we reported thermoresponsive double network nanocomposite (DNNC) membrane comprised of poly(N-isopropylacrylamide) (PNIPAAm) and embedded polysiloxane nanoparticles. When the membrane was thermally cycled above and below its volume phase transition temperature (VPTT, ~33–35 °C), the associated deswelling and reswelling, respectively, led to in vitro cell release. Herein, this membrane design was tailored to meet the specific demands of a subcutaneously implanted glucose biosensor and critical functional properties were assessed. First, N-vinylpyrrolidone (NVP) comonomer increased the VPTT to ~38 °C so that the membrane would be swollen and thus more permeable to glucose in the “off-state” (i.e. no heating) while residing in the subcutaneous tissue (~35 °C). Second, glucose diffusion kinetics though the DNNC membrane was experimentally measured in its deswollen and reswollen states. A cylindrical DNNC membrane with dimensions considered suitable for implantation (1.5×5 mm, diameter × length) was used to model the glucose diffusion lag time. In addition, the DNNC cylinder was used to observe dimensional changes associated with deswelling and reswelling. Non-cytotoxicity was confirmed and self-cleaning was assessed in vitro in terms of thermally-driven cell release to confirm the potential of the DNNC membrane to control biofouling.

A self-cleaning membrane that periodically rids itself of attached cells to maintain glucose diffusion could extend the lifetime of implanted glucose biosensors. Herein, we evaluate the functionality of thermoresponsive double network (DN) hydrogel membranes based on poly(N-isopropylacrylamide) (PNIPAAm) and an electrostatic co-monomer, 2-acrylamido-2-methylpropane sulfonic acid (AMPS). DN hydrogels are comprised of a tightly crosslinked, ionized first network [P(NIPAAm-co-AMPS)] containing variable levels of AMPS (100:0–25:75 wt% ratio of NIPAAm:AMPS) and a loosely crosslinked, interpenetrating second network [PNIPAAm]. To meet the specific requirements of a subcutaneously implanted glucose biosensor, the volume phase transition temperature is tuned and essential properties, such as glucose diffusion kinetics, thermosensitivity, and cytocompatibility are evaluated. In addition, the self-cleaning functionality is demonstrated through thermally driven cell detachment from the membranes in vitro.