Fast Thermoresponsive Poly(oligoethylene glycol methacrylate) (POEGMA)-Based Nanostructured Hydrogels for Reversible Tuning of Cell Interactions

Abstract

Reactive electrospinning is demonstrated as a viable method to create fast-responsive and degradable macroporous thermoresponsive hydrogels based on poly(oligoethylene glycol methacrylate) (POEGMA). Hydrazide-and aldehyde-functionalized POEGMA precursor polymers were coelectrospun to create hydrazone cross-linked nanostructured hydrogels in a single processing step that avoids the need for porogens, phase separation-driving additives, or scaffold postprocessing. The resulting nanostructured hydrogels can respond reversibly and repeatedly to changes in external temperature within seconds, in contrast to the minutes-tohours response time observed with bulk hydrogels. Furthermore, nearly quantitative cell delamination can be achieved within 2 min of incubation at 4 °C, resulting in the recovery of as many or more (as well as more proliferatively active) cells from the substrate relative to the conventional trypsinization protocol. The combined macroporosity, nanoscale feature size, and interfacial switching potential of these nanostructured hydrogels thus offer promise for manipulating cell−hydrogel interactions as well as other applications in which rapid responses to external stimuli are desirable.

Editorial: Special Issue on Advanced Biomedical Hydrogels

“…Also, the rapid control of cell-to-hydrogel interactions is important for desirable 2D or 3D cell engineering without affecting cellular behavior. Hoare and co-workers demonstrated cell delamination within 2 min from thermoresponsive hydrogel nanofibrous mats fabricated by co-electrospinning of aldehyde-/hydrazide-tethered poly­(oligoethylene glycol methacrylate) …”

“…Hoare and co-workers demonstrated cell delamination within 2 min from thermoresponsive hydrogel nanofibrous mats fabricated by co-electrospinning of aldehyde-/hydrazidetethered poly(oligoethylene glycol methacrylate). 15 Attracting personalized medicine on the basis of patients' genetic information, health status, size and shape of organs, and tissue defects, the precise fabrication of tissue constructs using 3D bioprinting techniques has grown in the field and the development of hydrogel inks is a crucial component in this area. A summary of advanced bioink materials is introduced in this special issue.…”

Hydrogels for Tissue Engineering: Addressing Key Design Needs Toward Clinical Translation

“…POEGMA offers an attractive alternative to PNIPAM and PEG because of its non-toxic degradation products and facile functionalizability, respectively ( Smeets et al, 2014 ; Bakaic et al, 2015 ). In situ gelling thermosensitive POEGMA hydrogels that can undergo phase transitions at a range of physiologically relevant temperatures can be obtained by mixing di(ethylene glycol) methyl ether methacrylate (M(EO) 2 MA) with longer chain ( n = 7–8 ethylene oxide repeat units) OEGMA monomers, with the transition temperature varying linearly with the mole percentage of each monomer ( Lutz et al, 2006 ) while preserving a relatively sharp temperature response (unlike with PNIPAM, in which transitions become much broader when hydrophilic comonomers are incorporated) ( Smeets et al, 2014 ; Xu et al, 2021 ). In addition, although POEGMA does not contain inherent binding cell binding domains, the thermo-reversible natural of POEGMA smart gels enables cell adhesion at temperatures above the volume phase transition temperature of the hydrogel ( Xu et al, 2021 ).…”

“…Of note, conducting the process in a biosafety cabinet can also directly produce sterile scaffolds without any additional sterilization requirement. Both protein-repellent and thermo-responsive electrospun POEGMA scaffolds were prepared by varying the polymer component ratios, with the latter found to expand and contract reversibly to facilitate cell adhesion (at physiological temperature) but rapid cell delamination within 2 min upon swelling of the scaffold at 4°C that could serve as a replacement for typical trypsin-based cell delamination methods ( Xu et al, 2021 ).…”

Construction of tissue-customized hydrogels from cross-linkable materials for effective tissue regeneration

“…8 For instance, poly(hydroxyethyl methacrylate) (PHEMA), poly(vinyl alcohol) (PVA), poly(ethylene glycol) (PEG), poly(ethylene glycol)-diacrylate (PEGDA), polycaprolactone (PCL), poly(acryl amide)/ poly(acrylic acid), gelatin methacryloyl (GelMA), poly(propylene fumarate) (PPF), poly(oligo ethylene glycol methacrylate) (POEGMA), and poly(N-isopropylacrylamide) (PNIPAM) are the typical synthesized materials that have been widely adopted to produce tissue-engineering hydrogels. 7,8,65,69,72,75,76,134,181 These synthetic materials are often modified macromers that present elongated degradation rates and make tissue engineering more tunable. 182,183 For example, thio-b ester-modified PEGDA hydrogels provide tunable degradation rates without changing the network of the PEGDA hydrogel.…”