A Biomimetic Nonwoven-Reinforced Hydrogel for Spinal Cord Injury Repair

Abstract

In clinical trials, new scaffolds for regeneration after spinal cord injury (SCI) should reflect the importance of a mechanically optimised, hydrated environment. Composite scaffolds of nonwovens, self-assembling peptides (SAPs) and hydrogels offer the ability to mimic native spinal cord tissue, promote aligned tissue regeneration and tailor mechanical properties. This work studies the effects of an aligned electrospun nonwoven of P11-8—enriched poly(ε-caprolactone) (PCL) fibres, integrated with a photo-crosslinked hydrogel of glycidylmethacrylated collagen (collagen-GMA), on neurite extension. Mechanical properties of collagen-GMA hydrogel in compression and shear were recorded, along with cell viability. Collagen-GMA hydrogels showed J-shaped stress–strain curves in compression, mimicking native spinal cord tissue. For hydrogels prepared with a 0.8-1.1 wt.% collagen-GMA concentration, strain at break values were 68 ± 1–81 ± 1% (±SE); maximum stress values were 128 ± 9–311 ± 18 kPa (±SE); and maximum force values were 1.0 ± 0.1–2.5 ± 0.1 N (±SE). These values closely mimicked the compression values for feline and porcine tissue in the literature, especially those for 0.8 wt.%. Complex shear modulus values fell in the range 345–2588 Pa, with the lower modulus hydrogels in the range optimal for neural cell survival and growth. Collagen-GMA hydrogel provided an environment for homogenous and three-dimensional cell encapsulation, and high cell viability of 84 ± 2%. Combination of the aligned PCL/P11-8 electrospun nonwoven and collagen-GMA hydrogel retained fibre alignment and pore structure, respectively, and promoted aligned neurite extension of PC12 cells. Thus, it is possible to conclude that scaffolds with mechanical properties that both closely mimic native spinal cord tissue and are optimal for neural cells can be produced, which also promote aligned tissue regeneration when the benefits of hydrogels and electrospun nonwovens are combined.

Hydrogel and Nanomedicine‐Based Multimodal Therapeutic Strategies for Spinal Cord Injury

“…[ 108 ] These synthetic hydrogels have been designed to exhibit promising properties, including electroconductivity, macroporosity, and specific mechanical properties. [ 109 ] Synthetic hydrogels are capable of being customized prior to their creation to achieve specific properties. These properties may include tailored molecular weights, structural units, porosity, degradation times, and mechanical properties.…”

Stem Cell Scaffolds for the Treatment of Spinal Cord Injury—A Review

“…Furthermore, given the large One of the key purposes of a scaffold is to provide a mechanical support network for stem cells to reside within. This framework protects growing cells and axons from applied forces post-SCI [92,93]. The porosity or the percentage of pores per area of scaffold is a vital feature.…”