Anisotropic scaffolds for peripheral nerve and spinal cord regeneration

Abstract

The treatment of long-gap (>10 mm) peripheral nerve injury (PNI) and spinal cord injury (SCI) remains a continuous challenge due to limited native tissue regeneration capabilities. The current clinical strategy of using autografts for PNI suffers from a source shortage, while the pharmacological treatment for SCI presents dissatisfactory results. Tissue engineering, as an alternative, is a promising approach for regenerating peripheral nerves and spinal cords. Through providing a beneficial environment, a scaffold is the primary element in tissue engineering. In particular, scaffolds with anisotropic structures resembling the native extracellular matrix (ECM) can effectively guide neural outgrowth and reconnection. In this review, the anatomy of peripheral nerves and spinal cords, as well as current clinical treatments for PNI and SCI, is first summarized. An overview of the critical components in peripheral nerve and spinal cord tissue engineering and the current status of regeneration approaches are also discussed. Recent advances in the fabrication of anisotropic surface patterns, aligned fibrous substrates, and 3D hydrogel scaffolds, as well as their in vitro and in vivo effects are highlighted. Finally, we summarize potential mechanisms underlying the anisotropic architectures in orienting axonal and glial cell growth, along with their challenges and prospects.

A conductive supramolecular hydrogel creates ideal endogenous niches to promote spinal cord injury repair

“…Consistent findings were observed in the current study in vitro, whereby neurons were more abundant in the AGP3 hydrogel compared with other hydrogels. Therefore, remodeling the endogenous electrical microenvironment of the lesion site can provide new strategies to promote endogenous neurogenesis to construct a neural bridging network [ 65 , 66 ]. Large populations of neurons were generated from endogenous NSCs after transplanting the AGP3 hydrogel into a rat hemisection SCI model, which further rebuild neuronal connectivity.…”

The Role of Biomaterials in Peripheral Nerve and Spinal Cord Injury: A Review

“…These filopodia consist of bundles of filamentous F actin. The F actin filaments align with external anisotropic cues to minimize cell cytoskeletal distortion [117]. The F actin alignment then affects the directionality of axonal growth via regulatory and structural interactions present between the growth cone's F actin and axonal microtubules.…”

Biomaterials-based strategies for in vitro neural models

“…Matrices that consist of fibers are particularly attractive for neural models due to the natural fibrous architecture of the nervous system. 187 Indisputably, electrospinning is the most prominent and well-established method for obtaining fibers of varying size and geometry for cell culture applications. The technique typically involves a polymer solution or melt being loaded into a syringe placed a set distance from an electrically grounded, conductive target called a collector and a high voltage is applied between the syringe nozzle and the collector.…”

“…These anisotropic meshes provide the neural population with a path of least resistance for growth in a general direction. 187,197 This concept is useful for matrix-assisted neurite guidance which makes it possible to model nerve fibers in vitro. 198 Besides being recruited as aligned 3D scaffolds or 2D substrates, they can be used as sacrificial fibers to imprint another substrate with the anisotropic fiber pattern to guide axonal growth.…”