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.
This paper reports the fabrication of scaffolds consisting of radially aligned poly(ε-caprolactone) nanofibers by utilizing a collector comprised of a central point electrode and a peripheral ring electrode. This novel class of scaffolds was able to present nanoscale topographic cues to cultured cells, directing and enhancing their migration from the periphery to the center. We also established that such scaffolds could induce faster cellular migration and population than nonwoven mats consisting of random nanofibers. Dural fibroblast cells cultured on these two types of scaffolds were found to express type I collagen, the main extracellular matrix component in dural mater. The type I collagen exhibited a high degree of organization on the scaffolds of radially aligned fibers and a haphazard distribution on the scaffolds of random fibers. Taken together, the scaffolds based on radially aligned, electrospun nanofibers show great potential as artificial dural substitutes and may be particularly useful as biomedical patches or grafts to induce wound closure and/or tissue regeneration. Keywordselectrospinning; aligned nanofibers; dural substitutes; wound closure Dura mater is a membranous connective tissue located at the outermost of the three layers of the meninges surrounding the brain and spinal cord, which covers and supports the dural sinuses and carries blood from the brain towards the heart. 1 Dural substitutes are often needed after a neurosurgical procedure to expand or replace the resected dura mater. 2 Although a lot of efforts have been made, the challenge to develop a suitable dural substitute has been met with limited success. 3 Autografts (e.g., fascia lata, temporalis fascia, and pericranium) are preferred because they do not provoke severe inflammatory or immunologic reactions, but they are limited by potential drawbacks such as difficulty in achieving a watertight closure, formation of scar tissue, insufficiently accessible graft materials to close large dural defects, and additional incisions for harvesting the graft. 4,5 Allografts and xenografts are often associated with adverse effects such as graft dissolution, encapsulation, foreign body reaction, scarring, and adhesion formation. Lyophilized human * Address correspondence to: xia@biomed.wustl.edu. † These two authors contributed equally to this work. NIH Public AccessAuthor Manuscript ACS Nano. Author manuscript; available in PMC 2011 September 28.Published in final edited form as: ACS Nano. 2010 September 28; 4(9): 5027-5036. doi:10.1021/nn101554u. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript dura mater as a dural substitute has also been clarified as a source of Creutzfeldt-Jakob disease. 6,7 In terms of materials, nonabsorbable synthetic polymers, such as silicone and expanded polytetrafluoroethylene (ePTFE), often cause serious complications. These may include induction of granulation tissue formation due to their chronic stimulation of the surrounding tissues and long-term foreign body reactions. [8]...
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