Multiple sessions of therapeutic electrical stimulation using implantable thin-film wireless nerve stimulators improve functional recovery after sciatic nerve isograft repair.

INTRODUCTION/AIMS: Although therapeutic electrical stimulation (TES) of injured peripheral nerve promotes axon regeneration and functional recovery, clinical applications of this therapy are limited to the intraoperative timeframe. Implantable, thin-film wireless nerve stimulators offer a potential solution to this problem by enabling delivery of electrical stimuli to an injured nerve over a period of several days post-surgery. The aim of this study was to determine the optimal time course of stimulation for maximizing functional recovery in a rat sciatic nerve isograft repair model. METHODS: Adult male Lewis rats underwent thin-film wireless nerve stimulator implantation following sciatic nerve transection and 40 mm nerve isograft repair. Immediately after surgery, animals began a daily regimen of TES for up to 12 consecutive days. Functional recovery was assessed by compound muscle action potential (CMAP), evoked muscle force, wet muscle mass, and axon counting. RESULTS: Serial CMAP measurements increased in amplitude over the course of the study, yet no significant difference between cohorts for serial or terminal CMAPs was observed. Axon counts and wet muscle mass measurements were greatest in the 6-day stimulation group, which correlated with a significant increase in evoked muscle force for the 6-day stimulation group at the terminal time point. DISCUSSION: Six daily sessions of TES were found to be most effective for augmenting functional recovery compared to other time courses of stimulation. Future studies should incorporate additional subjects and track axonal sprouting or measure neurotrophin levels during the therapeutic window to further elucidate the mechanisms behind, and ideal amount of, TES.

Stretchable, dynamic covalent polymers for soft, long-lived bioresorbable electronic stimulators designed to facilitate neuromuscular regeneration.

Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery.

Vitamin D status in cervical spondylotic myelopathy: comparison of fusion rates and patient outcome measures.

BACKGROUND: Patients undergoing elective spinal fusion have an alarming rate of vitamin D deficiency, but its impact on bone fusion and patient outcomes is unclear. We investigated the association of perioperative vitamin D levels, fusion rates, and patient-reported outcome in patients undergoing spinal fusion for cervical spondylotic myelopathy. METHODS: In this one-year, prospective, single-center observational study, serum 25-OH vitamin D levels were measured perioperatively in adult patients. Serum vitamin D levels <30 ng/mL were considered abnormal. The primary outcome measures were postoperative patient-reported outcomes (Neck Disability Index, Visual Analog Scale, EuroQol EQ-5D-3L, EQ-VAS). Secondary outcome measures were the presence of and time to solid bony fusion, controlling for Body Mass Index (BMI), age, and number of motion segments. RESULTS: Forty-one of 58 patients (71%) had laboratory-confirmed abnormal vitamin D levels. Patients with low vitamin D were younger (P<0.05) and had a higher BMI (P<0.05) than patients with adequate vitamin D, but the groups were otherwise similar. There were no differences in mean time to fusion between the two groups, but patients with low vitamin D reported more postoperative disability (P<0.05). Multivariate model analysis demonstrated an independent, significant association between normal vitamin D and lower postoperative neck disability index (P=0.05) and EQ-5D-3L (P=0.03). CONCLUSIONS: Vitamin D deficiency (<30 ng/mL) is highly prevalent in patients undergoing elective spinal fusion for cervical myelopathy. Low vitamin D levels were associated with worse patient-reported outcomes and were an independent predictor of greater disability, which suggests vitamin D supplementation may offer some benefit in these patients.

Electrical Stimulation and Bone Healing: A Review of Current Technology and Clinical Applications.

Pseudarthrosis is an exceedingly common, costly, and morbid complication in the treatment of long bone fractures and after spinal fusion surgery. Electrical bone growth stimulation (EBGS) presents a unique approach to accelerate healing and promote fusion success rates. Over the past three decades, increased experience and widespread use of EBGS devices has led to significant improvements in stimulation paradigms and clinical outcomes. In this paper, we comprehensively review the literature and examine the history, scientific evidence, available technology, and clinical applications for EBGS. We summarize indications, limitations, and provide an overview of cost-effectiveness and future directions of EBGS technology. Various models of electrical stimulation have been proposed and marketed as adjuncts for spinal fusions and long bone fractures. Clinical studies show variable safety and efficacy of EBGS under different conditions and clinical scenarios. While the results of clinical trials do not support indiscriminate EBGS utilization for any bone injury, the evidence does suggest that EBGS is desirable and cost efficient for certain orthopedic indications, especially when used in combination with standard, first-line treatments. This review should serve as a reference to inform practicing clinicians of available treatment options, facilitate evidence-based decision making, and provide a platform for further research.

Serial assessment of functional recovery following nerve injury using implantable thin-film wireless nerve stimulators.

INTRODUCTION: Comprehensive assessment of the time course of functional recovery following peripheral nerve repair is critical for surgical management of peripheral nerve injuries. This study describes the design and implementation of a novel implantable wireless nerve stimulator capable of repeatedly interfacing peripheral nerve tissue and providing serial evaluation of functional recovery postoperatively. METHODS: Thin-film wireless implants were fabricated and subcutaneously implanted into Lewis rats. Wireless implants were used to serially stimulate rat sciatic nerve and assess functional recovery over 3 months following various nerve injuries. RESULTS: Wireless stimulators demonstrated consistent performances over 3 months in vivo and successfully facilitated serial assessment of nerve and muscle function following nerve crush and nerve transection injuries. CONCLUSIONS: This study highlights the ability of implantable wireless nerve stimulators to provide a unique view into the time course of functional recovery in multiple motor targets. Muscle Nerve 54: 1114-1119, 2016.

Prevalence of Vitamin D Deficiency in Patients Undergoing Elective Spine Surgery: A Cross-Sectional Analysis.

OBJECTIVE: Decreased bone density secondary to osteoporosis and osteomalacia represents a significant risk factor for bony fracture and spinal instrumentation failure. We evaluated the incidence of vitamin D deficiency in patients undergoing elective spinal instrumentation to investigate which patient-level risk factors are associated with deficient vitamin D levels. METHODS: Serum 25-OH vitamin D levels were evaluated postoperatively (<72 hours) in patients undergoing elective spinal fusion from 2011 through 2012. Patients >18 years with a diagnosis of degenerative spinal spondylosis or spinal instability treated with spinal fusion were included. Risk factors for vitamin D deficiency (<20 ng/mL) were analyzed using univariate and multiple logistic regression to identify independent predictors of deficiency. RESULTS: The mean preoperative neck and Oswestry disability indexes of the 230 consecutive patients (mean, 57 ± 13.9 years) were 21.0 ± 9.8 and 22.2 ± 8.5, respectively. Mean 25-OH vitamin D level was 25.9 ± 12.4 ng/mL (range, 6-77 ng/mL). Sixty-nine (30.0%) patients had laboratory-confirmed vitamin D deficiency and 89 (38.9%) had laboratory-confirmed vitamin D insufficiency (20-30 ng/mL). The risk of vitamin D deficiency was greater in men (odds ratio [OR] 2.53; P = 0.009), patients aged 40-60 years (OR 2.45; P = 0.018), and those who had body mass index >40 (OR 7.55; P = 0.004), an existing diagnosis of diabetes (OR 3.29; P = 0.019), or no vitamin D supplementation (OR 4.96; P = 0.043). CONCLUSIONS: Vitamin D deficiency was common in patients with degenerative spondylosis undergoing spinal fusion. Middle-aged patients, men, the morbidly obese, those with a history of diabetes, and those with no history of supplementation had a higher incidence of vitamin D deficiency.