Three aligned, electrospun fiber scaffolds with unique surface features were created from poly-L-lactic acid (PLLA). Fibers without surface nanotopography (smooth fibers), fibers with surface divots (shallow pits), and fibers with surface pits (deeper pits) were fabricated, and fiber alignment, diameter, and density were characterized using scanning electron microscopy (SEM). Whole dorsal root ganglia (DRG) were isolated from rats and placed onto uncoated fibers or fibers coated with laminin. On uncoated fibers, neurite outgrowth was restricted by fibers displaying divoted or pitted nanotopography when compared to neurite outgrowth on smooth fibers. However, neurites extending from whole DRG cultured on laminin-coated fibers were not restricted by divoted or pitted surface nanotopography. Thus, neurites extending on laminin-coated fibers were able to extend long neurites even in the presence of surface divots or pits. To further explore this result, individual neurons isolated from dissociated DRG were seeded onto laminin-coated smooth, pitted, or divoted fibers. Interestingly, neurons on pitted or divoted fibers exhibited a 1.5-fold increase in total neurite length, and a 2.3 or 2.7-fold increase in neurite branching compared to neurons on smooth fibers, respectively. Based on these findings, we conclude that fiber roughness in the form of pits or divots can promote extension and branching of long neurites along aligned electrospun fibers in the presence of an extracellular matrix protein coating. Thus, aligned, electrospun fibers can be crafted to not only direct the extension of axons but to induce unique branching morphologies.

Objective Generator site pain is a relatively common phenomenon in patients undergoing spinal cord stimulation (SCS) that complicates management and effective pain relief. This pain may be managed conservatively, with repositioning of the battery and in some cases with explant. Here we explore our experience with management of generator site pain (‘pocket pain’) in a large single-center study. Methods All SCS permanent implants and implantable pulse generator (IPG) placements over 9 years were reviewed. Of 785 cases, we identified 43 patients with pocket pain (5.5%). Demographics and treatments of the pocket pain cohort were analyzed. Results The mean age (± SEM) of the pocket pain cohort was 46.86 ± 1.06 and there were 10/33 males/females. Females were overrepresented in pocket pain cohort (76.7%) when compared to the total SCS cohort (59.0%) (X2 = 5.93, p = 0.015). Diagnosis included failed back surgery syndrome (51.2%), complex regional pain syndrome (23.3%), and chronic neuropathic pain (25.5%). No patients improved with conservative therapy. All patients either went on to revision (n = 23) or explant (n = 20). Time from initial surgery to development of pocket pain was 7.5 months (range: 0.3-88) and from pocket pain to revision surgery was 4.5 months (range: 0.4-26). In addition, significantly more pocket pain patients (65.1%) had workers’ compensation (WC) insurance compared to patients without pocket pain (24.9%) (X2 = 33.3, p < 0.001). Conclusion In our institutional experience, pocket pain was inadequately managed with conservative treatments. Being female and having SCS filed under WC increased risk of pocket pain. Future work will explore the nuances in device placement based on body shape and manual activity responsibilities.

Fingolimod-Releasing Biomaterial Fibers fingolimod-loaded fibers enhanced neurite outgrowth from whole and dissociated DRG neurons, increased Schwann cell migration, and reduced the Schwann cell expression of promyelinating factors. The in vitro findings show the potential of the aligned fingolimod-releasing electrospun fibers to enhance peripheral nerve regeneration and serve as a basis for future in vivo studies.

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Intracortical microelectrodes are used with brain–computer interfaces to restore lost limb function following nervous system injury. While promising, recording ability of intracortical microelectrodes diminishes over time due, in part, to neuroinflammation. As curcumin has demonstrated neuroprotection through anti-inflammatory activity, we fabricated a 300 nm-thick intracortical microelectrode coating consisting of a polyurethane copolymer of curcumin and polyethylene glycol (PEG), denoted as poly­(curcumin-PEG1000 carbamate) (PCPC). The uniform PCPC coating reduced silicon wafer hardness by two orders of magnitude and readily absorbed water within minutes, demonstrating that the coating is soft and hydrophilic in nature. Using an in vitro release model, curcumin eluted from the PCPC coating into the supernatant over 1 week; the majority of the coating was intact after an 8-week incubation in buffer, demonstrating potential for longer term curcumin release and softness. Assessing the efficacy of PCPC within a rat intracortical microelectrode model in vivo, there were no significant differences in tissue inflammation, scarring, neuron viability, and myelin damage between the uncoated and PCPC-coated probes. As the first study to implant nonfunctional probes with a polymerized curcumin coating, we have demonstrated the biocompatibility of a PCPC coating and presented a starting point in the design of poly­(pro-curcumin) polymers as coating materials for intracortical electrodes.

Neuropathic pain is a rampant disease exacting a significant toll on patients, providers, and health care systems around the globe. Neuromodulation has been successfully employed to treat many indications including failed back surgery syndrome (FBSS), complex regional pain syndrome (CRPS), phantom limb pain (PLP), radiculopathies, and intractable pelvic pain, among many others. Recent studies have also demonstrated efficacy for cancer-related pain and chemotherapy induced neuropathy with these techniques. Spinal cord stimulation (SCS) is the most commonly employed technique and involves implantation of percutaneous or paddle leads targeting the dorsal columns of the spinal cord with the goal of disrupting the pain signals traveling to the brain. Tonic, high frequency, and burst waveforms have all been shown to reduce pain and disability in chronic pain patients. Closed-loop SCS systems that automatically adjust stimulation parameters based on feedback (such as evoked compound action potentials) are becoming increasingly used to help ease the burden placed on patients to adjust their programming to their pain and position. Additionally, dorsal root ganglion stimulation (DRGS) is a newer technique that allows for dermatomal coverage especially in patients with pain in up to two dermatomes. Regardless of the technique chosen, neuromodulation has been shown to be cost-effective and efficacious and should be given full consideration in patients with chronic pain conditions.

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