Synthesis and fabrication of a degradable poly(N‐isopropyl acrylamide) scaffold for tissue engineering applications

Abstract

Biodegradable poly(N-isopropyl acrylamide) (poly-NIPAM) hydrogels with controlled molecular weight of the parent polymer and its degradation products were synthesized by atom transfer radical polymerization in the presence of a polycaprolactone-based di-chlorinated macroinitiator and polycaprolactone dimethacrylate. The phase transition temperature, swelling, hydrolytic degradability, and mechanical properties at 25 and 37°C were explored. A cytocompatibility study showed good NIH3T3 cell response over 5 days culture on the surface of the hydrogels, demonstrated by a consistent increase in cell proliferation detected by an Alamar Blue assay. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo-lium bromide] results suggested that the hydrogels and their degradation products in the concentration range of 1–25 mg/ mL were not cytotoxic to NIH3T3 cells. A sphere-templating technique was utilized to fabricate biodegradable polyNIPAM scaffolds with monodisperse, pore size. Scaffolds with pore diameter of 48 ± 6 μm were loaded with A-10 smooth muscle cells and then warmed to 37°C entrapping cells in pores approximately 40 μm in diameter, a size we have found to be optimal for angiogenesis and biointegration. Due to their degradable nature, tunable molecular weight, highly interconnected morphology, thermally controlled monodisperse pore size, and temperature-induced volume expansion–contraction, the polyNIPAM-based scaffolds developed in this work will be valuable in tissue engineering.

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“…Therefore, when the polymer cleaves at the PCL linker, the polymer molecular weight should be roughly halved. This was shown for a 2.29 x 10 4 g/mol PNIPAM that had degradation products of 1.38 x 10 4 g/mol [99]. This linear PNIPAM also demonstrated an LCST of 30.8 °C, ideal for our application of a room temperature microspheres suspension to an adherent layer at physiological temperature and will be used in the work presented here.…”

“…The synthesis of the di-functional macroinitiator, ligand, and PNIPAM were characterized by NMR, comparing detected peaks to reported values [99]. In the case of PNIPAM, the 1 H-NMR spectra showed the disappearance of the peaks related to the vinyl protons (at 5.5 ppm and 6.2 ppm) of the NIPAM monomer and showed the characteristic PNIPAM peaks at 1.14, 1.4-2.4, and 4.03 ppm.…”

“…However, for the synthesis of a biodegradable PNIPAM, there are only limited reports [98,99]. In one study, a degradable PNIPAM hydrogel was synthesized using UV polymerization of the monomer NIPAM with a benzo-2-methylene-1,3-dioxepen in the presence of poly(ethylene glycol-co-glycolic acid) diacrylate.…”

“…In one study, a degradable PNIPAM hydrogel was synthesized using UV polymerization of the monomer NIPAM with a benzo-2-methylene-1,3-dioxepen in the presence of poly(ethylene glycol-co-glycolic acid) diacrylate. This created a hydrogel with degradable ester bonds in both the backbone of the PNIPAM and crosslinking sites [98,99].…”

“…Thermoresponsive PNIPAM has been used in many different applications ranging from scaffolding for tissue engineering [99], cell release from surfaces using low temperature lift-off [114], as a thermo-sensitive glue for retinal implants [115], microgels for biosensing [116],and vehicles for drug delivery including hydrogels, liposomes, and nanoparticles [117][118][119]. To the best of our knowledge, PNIPAM has not been applied in an aerosolized form as a vehicle for drug delivery.…”