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Bioresorbable Intracranial Sensors: A New Frontier for Neurosurgeons
Bioresorbable Intracranial Sensors: A New Frontier for Neurosurgeons Roshan Panchanathan1,2, Rami James N. Aoun2, Andrew R. Pines2, Mithun G. Sattur2, Matthew E. Welz2, Kristin Swanson2, Bernard R. Bendok2
INTRODUCTION The management of brain, spinal cord, and peripheral nerve disorders and injury may benefit from more robust continuous monitoring. Implantation of biosensors is limited by the risk of infection and the need for a second procedure to extract the sensor.1,2 Bioresorbable sensors are electronic sensors that can run the required functional course in the body but eliminate via absorption over a reasonable period of time. If properly designed, bioresorbable sensors promise to overcome the limitations of current sensors and reduce the threshold for continuous monitoring.
To ensure safety and accuracy of transmitted data, they electrically insulated the molybdenum wires with narrow strips of PLGA. With all these components in place, the group implanted the fully absorbable system into the intracranial space of male Lewis rats through a craniectomy. To assess the device’s ability to monitor intracranial temperature and pressure, device measurements were recorded while rats were heated, cooled, held upside down, and had their flanks squeezed. The efficacy of the implanted near-fieldcommunication wireless system also was evaluated. RESULTS
METHODS In a recent issue of NATURE, Kang et al.3 discuss important advances their group has made in developing bioresorbable sensors. They began by constructing a piezoresistive pressure sensor, a device that measures the change in the electrical resistance of a metal or semiconductor when mechanical strain is applied. A poly(lactic-co-glycolic acid) (PLGA) membrane was built into the cavity of a nanoporous silicon or magnesium foil substrate. A smaller silicon membrane served as the piezoresistive pressure sensor and was located on the outer edge of the cavity, where the response of the PLGA membrane to pressure changes would be most acute (Figure 1). Three-dimensional finite element analysis was used to refine device development. The pressure sensor was tested in an environment that mimicked the intracranial space. This allowed for direct performance comparisons to a current standard monitoring device and calibration for absolute intracranial pressure measurements. In addition to performance comparisons, the research group examined the rates of hydrolysis of the sensors in artificial cerebrospinal fluid to understand their probable lifespan in vivo. Furthermore, the authors also examined the ability to make the proposed system compatible with wireless communications. They used biodegradable molybdenum wires as a wireless interface for the simultaneous sensing and transmission of pressure and temperature information.
WORLD NEUROSURGERY 93: 421-422, SEPTEMBER 2016
Compared with an industry-standard implantable electronic sensor (NeuLog; Fisher Scientific, Waltham, Massachusetts, USA), the absorbable sensors performed at a comparable level in monitoring pressure, acceleration, and temperature in the environment that resembled the intracranial cavity. In rat models, the results from the bioresorbable device were comparable with those from the standard monitoring device in every tested category: heating, cooling, and monitoring of pressure changes. Hydrolysis of the device components occurred at a rate between 4 mm and 23 nm per day. Although the device was going through normal dissolution in vivo, the accuracy of the system was reported to lose only a few percentage points of accuracy when operated over several days. This falls even within the acceptable standards as set by the Association for the Advancement of Medical Instrumentation. It was determined that the device allowed for stable and continuous operation for 3 days before the physiological fluids caused marked dissolution of the system. This timeframe is more than within reasonable on for monitoring parameters after a traumatic brain injury or other acute neurologic conditions. Several studies of the immunohistochemistry of brain tissue and confocal fluorescence images after implantation suggest that the device and its dissolution products are biocompatible with brain glial cells. Astrocytosis and microglial activity were both within normal limits as well. The group showed that the results measured by their wireless communication system were equivalent to
www.WORLDNEUROSURGERY.org
421
CONCLUSIONS/IMPACT
Figure 1. Representation of sensor. PLGA, poly(lactic-co-glycolic acid).
measurements made by standard commercial devices. Preliminary biocompatibility studies also appeared favorable.
REFERENCES 1. Chamis AL, Peterson GE, Cabell CH, Corey GR, Sorrentino RA, Greenfield RA, et al. Staphylococcus aureus bacteremia in patients with permanent pacemakers or implantable cardioverter-defibrillators. Circulation. 2001;104:1029-1033.
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www.SCIENCEDIRECT.com
Kang et al.3 present a remarkable breakthrough in the field of biosensor monitoring. Self-resorbing monitoring devices promise to decrease the risks of invasive monitoring. Moreover, the range of operation can be manipulated by altering the sensor’s dimensions and characteristics to apply the appropriate timeline for any specific disease process. The potential of such devices to track biochemical and hemodynamic parameters open new avenues for patient monitoring. Devices could be implanted during surgery to monitor patients in the postoperative period. For example, one could envision a bioresorbable sensor in a fusion bed to monitor a patient following spinal surgery. Another tantalizing possibility is leaving a device near a surgical clip to monitor for spasm after subarachnoid hemorrhage or in a glioma surgical bed to monitor for recurrence. Delivering these devices stereotactically or endovascularly raises additional exciting possibilities that may only be limited by the imagination of neurosurgeons. Future direction of similar devices should be catered towards encompassing more health parameters, a longer lifetime catered towards chronic diseases, and wireless connection capabilities. The work of Kang et al.3 is a valuable advancement over the current technological standard.
2. Hall-Stoodley L, Costerton JW, Stoodley P. Bacterial biofilms: from the natural environment to infectious diseases. Nature Rev Microbiol. 2004;2: 95-108. 3. Kang SK, Murphy RK, Hwang SW, Lee SM, Harburg DV, Krueger NA, et al. Bioresorbable silicon electronic sensors for the brain. Nature. 2016; 530:71-76.
From the 1University of Arizona College of Medicine; and 2 Department of Neurological Surgery, Mayo Clinic, Phoenix, Arizona, USA 1878-8750/$ - see front matter ª 2016 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.wneu.2016.06.076
93: 421-422, SEPTEMBER 2016 WORLD NEUROSURGERY
INTRODUCTION The management of brain, spinal cord, and peripheral nerve disorders and injury may benefit from more robust continuous monitoring. Implantation of biosensors is limited by the risk of infection and the need for a second procedure to extract the sensor.1,2 Bioresorbable sensors are electronic sensors that can run the required functional course in the body but eliminate via absorption over a reasonable period of time. If properly designed, bioresorbable sensors promise to overcome the limitations of current sensors and reduce the threshold for continuous monitoring.
To ensure safety and accuracy of transmitted data, they electrically insulated the molybdenum wires with narrow strips of PLGA. With all these components in place, the group implanted the fully absorbable system into the intracranial space of male Lewis rats through a craniectomy. To assess the device’s ability to monitor intracranial temperature and pressure, device measurements were recorded while rats were heated, cooled, held upside down, and had their flanks squeezed. The efficacy of the implanted near-fieldcommunication wireless system also was evaluated. RESULTS
METHODS In a recent issue of NATURE, Kang et al.3 discuss important advances their group has made in developing bioresorbable sensors. They began by constructing a piezoresistive pressure sensor, a device that measures the change in the electrical resistance of a metal or semiconductor when mechanical strain is applied. A poly(lactic-co-glycolic acid) (PLGA) membrane was built into the cavity of a nanoporous silicon or magnesium foil substrate. A smaller silicon membrane served as the piezoresistive pressure sensor and was located on the outer edge of the cavity, where the response of the PLGA membrane to pressure changes would be most acute (Figure 1). Three-dimensional finite element analysis was used to refine device development. The pressure sensor was tested in an environment that mimicked the intracranial space. This allowed for direct performance comparisons to a current standard monitoring device and calibration for absolute intracranial pressure measurements. In addition to performance comparisons, the research group examined the rates of hydrolysis of the sensors in artificial cerebrospinal fluid to understand their probable lifespan in vivo. Furthermore, the authors also examined the ability to make the proposed system compatible with wireless communications. They used biodegradable molybdenum wires as a wireless interface for the simultaneous sensing and transmission of pressure and temperature information.
WORLD NEUROSURGERY 93: 421-422, SEPTEMBER 2016
Compared with an industry-standard implantable electronic sensor (NeuLog; Fisher Scientific, Waltham, Massachusetts, USA), the absorbable sensors performed at a comparable level in monitoring pressure, acceleration, and temperature in the environment that resembled the intracranial cavity. In rat models, the results from the bioresorbable device were comparable with those from the standard monitoring device in every tested category: heating, cooling, and monitoring of pressure changes. Hydrolysis of the device components occurred at a rate between 4 mm and 23 nm per day. Although the device was going through normal dissolution in vivo, the accuracy of the system was reported to lose only a few percentage points of accuracy when operated over several days. This falls even within the acceptable standards as set by the Association for the Advancement of Medical Instrumentation. It was determined that the device allowed for stable and continuous operation for 3 days before the physiological fluids caused marked dissolution of the system. This timeframe is more than within reasonable on for monitoring parameters after a traumatic brain injury or other acute neurologic conditions. Several studies of the immunohistochemistry of brain tissue and confocal fluorescence images after implantation suggest that the device and its dissolution products are biocompatible with brain glial cells. Astrocytosis and microglial activity were both within normal limits as well. The group showed that the results measured by their wireless communication system were equivalent to
www.WORLDNEUROSURGERY.org
421
CONCLUSIONS/IMPACT
Figure 1. Representation of sensor. PLGA, poly(lactic-co-glycolic acid).
measurements made by standard commercial devices. Preliminary biocompatibility studies also appeared favorable.
REFERENCES 1. Chamis AL, Peterson GE, Cabell CH, Corey GR, Sorrentino RA, Greenfield RA, et al. Staphylococcus aureus bacteremia in patients with permanent pacemakers or implantable cardioverter-defibrillators. Circulation. 2001;104:1029-1033.
422
www.SCIENCEDIRECT.com
Kang et al.3 present a remarkable breakthrough in the field of biosensor monitoring. Self-resorbing monitoring devices promise to decrease the risks of invasive monitoring. Moreover, the range of operation can be manipulated by altering the sensor’s dimensions and characteristics to apply the appropriate timeline for any specific disease process. The potential of such devices to track biochemical and hemodynamic parameters open new avenues for patient monitoring. Devices could be implanted during surgery to monitor patients in the postoperative period. For example, one could envision a bioresorbable sensor in a fusion bed to monitor a patient following spinal surgery. Another tantalizing possibility is leaving a device near a surgical clip to monitor for spasm after subarachnoid hemorrhage or in a glioma surgical bed to monitor for recurrence. Delivering these devices stereotactically or endovascularly raises additional exciting possibilities that may only be limited by the imagination of neurosurgeons. Future direction of similar devices should be catered towards encompassing more health parameters, a longer lifetime catered towards chronic diseases, and wireless connection capabilities. The work of Kang et al.3 is a valuable advancement over the current technological standard.
2. Hall-Stoodley L, Costerton JW, Stoodley P. Bacterial biofilms: from the natural environment to infectious diseases. Nature Rev Microbiol. 2004;2: 95-108. 3. Kang SK, Murphy RK, Hwang SW, Lee SM, Harburg DV, Krueger NA, et al. Bioresorbable silicon electronic sensors for the brain. Nature. 2016; 530:71-76.
From the 1University of Arizona College of Medicine; and 2 Department of Neurological Surgery, Mayo Clinic, Phoenix, Arizona, USA 1878-8750/$ - see front matter ª 2016 Published by Elsevier Inc. http://dx.doi.org/10.1016/j.wneu.2016.06.076
93: 421-422, SEPTEMBER 2016 WORLD NEUROSURGERY