RT Journal Article
SR Electronic
T1 Meso-scale multi-material fabrication of a Synthetic ECM Mimic for In vivo-like Peripheral Nerve Regeneration
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 842906
DO 10.1101/842906
A1 Paul Wieringa
A1 Ana Rita Gonçalves de Pinho
A1 Roman Truckenmüller
A1 Silvestro Micera
A1 Richard van Wezel
A1 Lorenzo Moroni
YR 2019
UL http://biorxiv.org/content/early/2019/11/15/842906.abstract
AB A growing focus and continuing challenge for biological sciences is creating representative in vitro environments to study and influence cell behavior. Here, we describe the synthetic recreation of the highly ordered extracellular matrix (ECM) of the peripheral nervous system (PNS) in terms of structure and scale, providing a versatile 3D culturing platform that achieves some of the highest in vitro neurite growth rates so far reported. By combining electrospinning technology with a unique multi-material processing sequence that harnesses intrinsic material properties, a hydrogel construct is realized that incorporates oriented 6 μm-diameter microchannels decorated with topographical nanofibers. We show that this mimics the native PNS ECM architecture and promotes extensive growth from primary neurons; through controlled variation in design, we show that the open lumens of the microchannels directing rapid axon invasion of the hydrogel while the nanofibers provide essential cues for cell adhesion and topographical guidance. Furthermore, these microstructural and nanofibrillar elements enabled a typically bioinert hydrogel (PEGDA) to achieve similar neurite extension when compared to a biocompatible collagen hydrogel, with PEGDA-based devices approaching neurite growth rates similar to what is observed in vivo. Through the accessible fabrication approach developed here, multi-material scaffolds were designed with cell-relevant architectures ranging from meso-to nanoscale and shown to support nerve growth to mimic PNS regeneration, with potential for regenerative medicine and neural engineering applications.