Mechanical, topographical and chemical cues combined with physical therapy for peripheral nerve injuries.

Aim: The aim of this paper is to evaluate biomaterial cues combined with physical therapy (PT) on functional recovery in a rat sciatic nerve injury model. Materials & methods: Nerve growth conduits were filled with longitudinally aligned hyaluronic acid fibers and microspheres containing neurotrophic factor (growth factor [GF]). All animals received behavior and functional testing throughout the study, which concluded with measurement of compound muscle action potentials and contractile force of the gastrocnemius muscle. Results & conclusion: Including GF improved recovery of gross motor function and increased sensory pain sensation. During the 4 weeks that animals participated in PT, these groups showed higher static sciatic index scores. Including GF and PT has the potential to improve clinical outcomes following peripheral nerve injury.

Combining growth factor releasing microspheres within aligned nanofibers enhances neurite outgrowth.

Current treatments for peripheral nerve injuries include autografts, the gold standard, and commercially available nerve growth conduits (NGCs). Autografts have several drawbacks including donor site morbidity and nerve size mismatch, which lead to incomplete recovery. However, even with these drawbacks, autografts work better then commercially available NGCs that lack sufficient cues to promote complete regeneration. This study evaluated a combination of biomaterial components that can be added to the hollow internal space of a NGC to promote and direct nerve regeneration; specifically, mechanical, chemical, and topographical cues. Methacrylated hyaluronic acid (MeHA, mechanical cue) is electrospun into aligned fibers (topographical cue), with poly-lactic-co-glycolic acid microspheres to deliver nerve growth factor (NGF, chemical cue). The properties of the scaffold were evaluated under physiological conditions using environmental scanning electron microscopy and mechanical testing. The resulting scaffolds have hydrated porosities of 35-55% and Young's modulus in the range of 0.43-2.86 MPa. Enzyme-linked immunosorbent assay showed that NGF is released from the microspheres for up to 4 weeks. Dorsal root ganglia (DRG) neurons showed that the released NGF is bioactive. DRG testing on the scaffolds also showed that the combination of NGF released from the microspheres and the aligned nanofibers significantly enhanced neurite outgrowth. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 17-25, 2018.

Electrospinning growth factor releasing microspheres into fibrous scaffolds.

This procedure describes a method to fabricate a multifaceted substrate to direct nerve cell growth. This system incorporates mechanical, topographical, adhesive and chemical signals. Mechanical properties are controlled by the type of material used to fabricate the electrospun fibers. In this protocol we use 30% methacrylated Hyaluronic Acid (HA), which has a tensile modulus of ~500 Pa, to produce a soft fibrous scaffold. Electrospinning on to a rotating mandrel produces aligned fibers to create a topographical cue. Adhesion is achieved by coating the scaffold with fibronectin. The primary challenge addressed herein is providing a chemical signal throughout the depth of the scaffold for extended periods. This procedure describes fabricating poly(lactic-co-glycolic acid) (PLGA) microspheres that contain Nerve Growth Factor (NGF) and directly impregnating the scaffold with these microspheres during the electrospinning process. Due to the harsh production environment, including high sheer forces and electrical charges, protein viability is measured after production. The system provides protein release for over 60 days and has been shown to promote primary nerve cell growth.