Many procedures in modern clinical medicine rely on the use of electronic implants in treating conditions that range from acute coronary events to traumatic injury. However, standard permanent electronic hardware acts as a nidus for infection: bacteria form biofilms along percutaneous wires, or seed haematogenously, with the potential to migrate within the body and to provoke immune-mediated pathological tissue reactions. The associated surgical retrieval procedures, meanwhile, subject patients to the distress associated with re-operation and expose them to additional complications. Here, we report materials, device architectures, integration strategies, and in vivo demonstrations in rats of implantable, multifunctional silicon sensors for the brain, for which all of the constituent materials naturally resorb via hydrolysis and/or metabolic action, eliminating the need for extraction. Continuous monitoring of intracranial pressure and temperature illustrates functionality essential to the treatment of traumatic brain injury; the measurement performance of our resorbable devices compares favourably with that of non-resorbable clinical standards. In our experiments, insulated percutaneous wires connect to an externally mounted, miniaturized wireless potentiostat for data transmission. In a separate set-up, we connect a sensor to an implanted (but only partially resorbable) data-communication system, proving the principle that there is no need for any percutaneous wiring. The devices can be adapted to sense fluid flow, motion, pH or thermal characteristics, in formats that are compatible with the body's abdomen and extremities, as well as the deep brain, suggesting that the sensors might meet many needs in clinical medicine.
SUMMARY
In vivo pharmacology and optogenetics hold tremendous promise for dissection of neural circuits, cellular signaling and manipulating neurophysiological systems in awake, behaving animals. Existing neural interface technologies, such as metal cannulas connected to external drug supplies for pharmacological infusions and tethered fiber optics for optogenetics, are not ideal for minimally-invasive, untethered studies on freely behaving animals. Here we introduce wireless optofluidic neural probes that combine ultrathin, soft microfluidic drug delivery with cellular-scale inorganic light-emitting diode (μ-ILED) arrays. These probes are orders of magnitude smaller than cannulas and allow wireless, programmed spatiotemporal control of fluid delivery and photostimulation. We demonstrate these devices in freely moving animals to modify gene expression, deliver peptide ligands, and provide concurrent photostimulation with antagonist drug delivery to manipulate mesoaccumbens reward-related behavior. The minimally-invasive operation of these probes forecasts utility in other organ systems and species, with potential for broad application in biomedical science, engineering, and medicine.
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.
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