Direct reactive electrospinning of degradable hydrogel nanofibers for tissue engineering

Hydrogels have received considerable attention in the context of soft tissue engineering due to their as high water contents, (general) cell compatibility, and physicochemical and mechanical similarities to native soft tissues[1]. Most hydrogels used for such applications are either monolithic or macroporous with primarily spherical pore structures, despite the fact that it is known that native extracellular matrix (ECM) contains primarily fibrous structures that play key roles in regulating cell behavior[2],[3]. Consequently, to mimic these fibrous ECM gel structures using a single processing step, we aim to prepare crosslinked fibrous hydrogels in situ via electrospinning of reactive functional precursor polymers. Poly(oligoethylene glycol methacrylate) (POEGMA) was functionalized with hydrazide and aldehyde groups via copolymerization; when mixed, these functionalized polymers crosslink rapidly to form hydrazone bonds[4]. POEGMA precursors (Mw ~ 30 kDa, 15 wt% in deionized water) and PEO (Mw = 600,000 g/mol, 3-5 wt%) were loaded into separate barrels of a double-barrel syringe mounted on a syringe pump. A voltage of 8.5 kV was provided to a conductive needle (18G), with electrospinning conducted using a 10 cm falling distance between the needle and collector. POEGMA could not be effectively electrospun directly due to its low molecular weight (~30 kDa) and low entanglement; as such, PEO was used as an electrospinning aid. Continuous nanofibers with an average diameter of 340∓80 nm were obtained. By changing mass ratio of POEGMA to PEO from 3:1 to 10:1 or 15:1, the continuous nanofibrous structure was transformed to bead-on-fiber and finally to a bead-only structure. When any of these scaffolds was exposed to water, a clear increase in nanofiber diameter was observed; however, unlike PEO nanofibers that dissolve fully within minutes, the POEGMA scaffold remains stable. Differential scanning calorimetry data indicated that PEO could be removed nearly quantitative.