Promoting Cell Migration and Neurite Extension along Uniaxially Aligned Nanofibers with Biomacromolecular Particles in a Density Gradient

Abstract

A simple method based upon masked electrospray is reported for directly generating both unidirectional and bidirectional density gradients of biomacromolecular particles on uniaxially aligned nanofibers. The method has been successfully applied to different types of biomacromolecules, including collagen and a mixture of collagen and fibronectin or laminin, to suit different types of applications. Collagen particles in a unidirectional or bidirectional gradient are able to promote the linear migration of bone marrow stem cells or NIH-3T3 fibroblasts along the direction of increasing particle density. In the case of particles made of a mixture of collagen and fibronectin, their deposition in a bidirectional gradient promotes the migration of Schwann cells from two opposite sides toward the center, matching the scenario in peripheral nerve repair. As for a mixture of collagen and laminin, the particles in a unidirectional gradient promote the extension of neurites from embryonic chick dorsal root ganglion in the direction of increasing particle density. Taken together, the scaffolds featuring a combination of uniaxially aligned nanofibers and biomacromolecular particles in density gradient can be applied to a range of biological studies and biomedical applications.

Programmable Building of Radially Gradient Nanofibrous Patches Enables Deployment, Bursting Bearing Capability, and Stem Cell Recruitment

“…These results indicated that the SDF1α gradient release induced MSC migration along the aligned nanofibers and the gradient pattern could affect MSC migration. As displayed in Figure 5d, the satisfactory migration outcome could be attributed to two factors: (1) the nanoscale dimensions of the electrospun fibers facilitated cell adhesion and the aligned nanofibers promoted cell migration through a process called contact guidance; [ 40 ] (2) the gradient chemokine cues directed cell migration potently through SDF1α and its receptor CXCR4 pathway. [ 41 ] These observations supported that integrated aligned nanofiber topography and gradient chemokine cues directed MSCs from the cell pool at the periphery to the central region synergistically.…”

Augmenting Tendon‐to‐Bone Repair with Functionally Graded Scaffolds

“…Graded Distribution of Particles by Masked Electrospray Deposition : To create a microenvironment that mimics the natural ECM proteins at the tendon enthesis and thus promotes cell migration and differentiation, we developed a method to deposit particles of natural biomacromolecules (e.g., collagen) on uniaxially aligned nanofiber mats (Figure 2C). [ 56,57 ] In this approach, electrospray, a variant form of electrospinning, was used to coat the surface of a nanofiber mat with a uniform distribution of protein‐based particles. [ 58 ] To generate a gradient in particle density, we modulated electrospray deposition with a physical mask that moved at a constant rate.…”

“…To this end, we combined electrospinning and masked electrospray to fabricate uniaxially aligned nanofibers with graded collagen particles, providing a topological pattern together with a graded biochemical cue. [ 56 ] The SEM images in Figure a (i, ii) indicated that the pristine PCL nanofibers had smooth surfaces. As the collection time was prolonged, an increasing number of collagen particles were found on the nanofibers (Figure 5A, iii–vi).…”

“…The actin cytoskeleton and vinculin are shown in red and green, respectively, in which the yellow color corresponds to the overlay of red and green. A-C) Adapted with permission [56]. Copyright 2020, Wiley-VCH GmbH.…”

Accelerating Cell Migration along Radially Aligned Nanofibers through the Addition of Electrosprayed Nanoparticles in a Radial Density Gradient

“…In a previous study, we combined electrospray with masking to deposit biomacromolecular nanoparticles on uniaxially aligned electrospun nanofibers in a linear density gradient. [ 29 ] It was shown that collagen nanoparticles in a unidirectional gradient on the uniaxially aligned nanofibers promoted the migration of bone marrow stem cells in the direction of increasing particle density. On the uniaxially aligned nanofibers functionalized with collagen nanoparticles in a bidirectional gradient, fibroblasts migrated from two opposite sides toward the center of the scaffold in the direction of increasing particle density.…”