Optimizing the alignment of thermoresponsive poly(N-isopropyl acrylamide) electrospun nanofibers for tissue engineering applications: A factorial design of experiments approach

• Published in: PloS one 2019-07, Vol.14 (7), p.e0219254
• Main Authors: Young, Rachel E, Graf, Jodi, Miserocchi, Isabella, Van Horn, Ryan M, Gordon, Melissa B, Anderson, Christopher R, Sefcik, Lauren S
• Format: Article
• Language: English
• Subjects: Acrylamide; Acrylamides - chemistry; Acrylic Resins - chemistry; Alignment; Amides; Binding sites; Biochemistry; Biocompatibility; Biocompatible Materials - chemistry; Biocompatible polymers; Biology and Life Sciences; Biomedical materials; Biotechnology; Cell adhesion & migration; Cell culture; Chemical stimuli; Crosslinking; Design of experiments; Dynamic mechanical analysis; EDTA; Electrospinning; Engineering and Technology; Enzymes; Extracellular Matrix; Factorial design; Genotype & phenotype; Hydrogels; Innovations; Mats; Mechanical analysis; Mechanical properties; Medicine and Health Sciences; Molecular weight; Nanofibers; Nanofibers - chemistry; Nanotechnology; Organic chemistry; Phenotypes; Physical Sciences; Polymer industry; Polymers; Polymers - chemistry; Process parameters; Production processes; Research and Analysis Methods; Scaffolds; Storage modulus; Substrates; Technology; Thermal properties; Tissue engineering; Tissue Engineering - methods; Tissue Scaffolds - chemistry
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0219254

Thermoresponsive polymers, such as poly(N-isopropyl acrylamide) (PNIPAM), have been identified and used as cell culture substrates, taking advantage of the polymer's lower critical solution temperature (LCST) to mechanically harvest cells. This technology bypasses the use of biochemical enzymes that cleave important cell-cell and cell-matrix interactions. In this study, the process of electrospinning is used to fabricate and characterize aligned PNIPAM nanofiber scaffolds that are biocompatible and thermoresponsive. Nanofiber scaffolds produced by electrospinning possess a 3D architecture that mimics native extracellular matrix, providing physical and chemical cues to drive cell function and phenotype. We present a factorial design of experiments (DOE) approach to systematically determine the effects of different electrospinning process parameters on PNIPAM nanofiber diameter and alignment. Results show that high molecular weight PNIPAM can be successfully electrospun into both random and uniaxially aligned nanofiber mats with similar fiber diameters by simply altering the speed of the rotating mandrel collector from 10,000 to 33,000 RPM. PNIPAM nanofibers were crosslinked with OpePOSS, which was verified using FTIR. The mechanical properties of the scaffolds were characterized using dynamic mechanical analysis, revealing an order of magnitude difference in storage modulus (MPa) between cured and uncured samples. In summary, cross-linked PNIPAM nanofiber scaffolds were determined to be stable in aqueous culture, biocompatible, and thermoresponsive, enabling their use in diverse cell culture applications.