Promoting Neurite Growth and Schwann Cell Migration by the Harnessing Decellularized Nerve Matrix onto Nanofibrous Guidance

Abstract

Synergistic intercellular interactions have been widely acknowledged in tuning functional cell behaviors in vivo, and these interactions have inspired the development of a variety of scaffolds for regenerative medicine. In this paper, the promotion of Schwann cell (SC)−neurite interactions through the use of a nerve extracellular matrix-coated nanofiber composite in vitro was demonstrated using a cell culturing platform consisting of either random or aligned electrospun poly(L-lactic acid) nanofibers and decellularized peripheral nerve matrix gel (pDNM gel) from porcine peripheral nervous tissue. The pDNMcoated nanofiber platform served as a superior substrate for dorsal root ganglion culturing. Furthermore, SC migration was facilitated by pDNM gel coating on the nanofibers, accompanied with much faster axonal extension, in comparison with the effect of topographical guidance from the aligned electrospun fibers only. Finally, the decellularized nerve matrix promoted the ability of SCs to wrap around bundled neurites, triggering axonal remyelination toward nerve fiber functionalization.

Electrospun Fiber Scaffolds for Engineering Glial Cell Behavior to Promote Neural Regeneration

“…Similar to in vitro findings [120,121,[146][147][148][149][150], functionalizing electrospun fibers with biochemical cues can significantly enhance their ability to improve peripheral nerve regeneration in vivo [175,176]. Cheong et al fabricated aligned PLGA electrospun fibers loaded with mussel adhesive proteins fused to bifunctional peptides derived from two different regions of the laminin (IKVAV or YIGSR) protein or the fibronectin protein (GRGDS).…”

“…This gel was rich with ECM proteins and growth factors and, when coated onto random and aligned electrospun fibers, increased Schwann cell migration. Further, this decellularized matrix gel also facilitated nerve fiber remyelination by Schwann cells in vitro, indicating that the gel supported the maturation of the Schwann cells [150]. In addition to using native ECM proteins and their peptide derivatives to functionalize electrospun fibers, researchers have employed biochemical cues not native to the PNS ECM to enhance Schwann cell adhesion, proliferation, elongation, and migration [151][152][153].…”

“…Similarly, Rajabi et al found that laminin-functionalized electrospun silk fibroin (SF)/poly (ethylene oxide) (PEO) nanofibrous scaffolds improved Schwann cell attachment, growth, and proliferation compared to control fibers and tissue culture polystyrene [147]. The incorporation of these cues can also promote the migration of Schwann cells along the electrospun fibers [148][149][150]. Bockelmann et al found that aligned electrospun PCL/star-shaped NCO-poly (ethylene glycol)-stat-poly (propylene glycol) (PCL/sPEG) fibers functionalized with GRGDS (PCL/sPEG-GRGDS) increased the rate and distance of Schwann cell migration compared to PCL or PCL/sPEG control fibers [149].…”

Electrospun poly(l‐lactide) nanofibers coated with mineral trioxide aggregate enhance odontogenic differentiation of dental pulp stem cells

“…9 The biological properties of polymeric nanofibrous scaffolds can be improved by modifying their surface with biocompatible and bioactive materials. [10][11][12] Several works have used bioceramics to cover the surface of nanofibers to simultaneously benefit from their advantageous. These bioceramic-coated nanofibers have been shown to improve the process of osteogenesis in vitro and in vivo.…”

Regeneration of the peripheral nerve via multifunctional electrospun scaffolds

“…Coating decellularized peripheral nerve matrix gel (pDNM‐gel) on aligned electrospun nanofibers significantly enlarged the distance of SCs migration almost three‐fold more than on only aligned nanofibers. It also increased neurite growth 150 . Presenting ECM biomolecules such as laminin on the surface of guidance channels induced axon density, thermal sensitivity recovery, and neurofilament regeneration 39 .…”