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BACKGROUND: Brain plasticity evoked by environmental enrichment through early mobilization may improve sensorimotor functions of patients with moderate-to-severe traumatic brain injury (TBI). Increasing evidence also suggests that early... more
BACKGROUND: Brain plasticity evoked by environmental enrichment through early mobilization may improve sensorimotor functions of patients with moderate-to-severe traumatic brain injury (TBI). Increasing evidence also suggests that early mobilization increases verticalization, which is beneficial to TBI patients in critical care. However, there are limited data on early mobilization interventions provided to patients with moderate-to-severe TBI. OBJECTIVE: We investigated the possible enhancing effects of revised progressive early mobilization on functional mobility and the rate of out-of-bed mobility attained by patients with moderate-to-severe TBI. METHODS: This is a quantitative study with a retrospective and prospective pre–post intervention design. We implemented a revised progressive early mobilization protocol for patients with moderate-to-severe TBI admitted to the trauma intensive care unit (ICU) within the previous seven days. The outcome parameters were the rate of patient...
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Accumulating evidence has shown transcranial low-intensity ultrasound can be potentially a non-invasive neural modulation tool to treat brain diseases. However, the underlying mechanism remains elusive and the majority of studies on... more
Accumulating evidence has shown transcranial low-intensity ultrasound can be potentially a non-invasive neural modulation tool to treat brain diseases. However, the underlying mechanism remains elusive and the majority of studies on animal models applying rather high-intensity ultrasound that cannot be safely used in humans. Here, we showed low-intensity ultrasound was able to activate neurons in the mouse brain and repeated ultrasound stimulation resulted in adult neurogenesis in specific brain regions. In vitro calcium imaging studies showed that a specific ultrasound stimulation mode, which combined with both ultrasound-induced pressure and acoustic streaming mechanotransduction, is required to activate cultured cortical neurons. ASIC1a and cytoskeletal proteins were involved in the low-intensity ultrasound-mediated mechanotransduction and cultured neuron activation, which was inhibited by ASIC1a blockade and cytoskeleton-modified agents. In contrast, the inhibition of mechanical...
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Abstract Background: Early out-of-bed mobilization may improve acute post-intracerebral hemorrhage (ICH) outcomes, but hemodynamic instability may be a concern. Some recent studies have showed that an increase in mean systolic blood... more
Abstract Background: Early out-of-bed mobilization may improve acute post-intracerebral hemorrhage (ICH) outcomes, but hemodynamic instability may be a concern. Some recent studies have showed that an increase in mean systolic blood pressure (SBP) and high blood pressure variability (BPV), high standard deviation of SBP, may lead to negative ICH outcomes. Therefore, we investigated the impact of an early mobilization (EM) protocol on mean SBP and BPV during the acute phase. Methods: The study was an assessor-blinded, randomized controlled non-inferiority study. The participants were in An Early Mobilization for Acute Cerebral Hemorrhage trial and were randomly assigned to undergo EM or a standard early rehabilitation (SER) protocol within 24 to 72 hour after ICH onset at the stroke center. The EM and SER groups each had 30 patients. 24-measurement SBP were recorded on days 2 and 3 after onset, and SBP were recorded three times daily and during rehabilitation on days 4 through 7. The two groups’ mean SBP and BPV under three different time frames (days 2 and 3 during the acute phase, and days 4 through 7 during the late acute phase) were calculated and compared. Results: At baseline, the two groups’ results were similar, with the exception being that the mean time to first out-of-bed mobilization after symptom onset was 51.60 hours (SD 14.15) and 135.02 hours (SD 33.05) for the EM group and SER group, respectively (P < .001). There were no significant differences in mean SBP and BPV during the acute and late acute phase between the two groups for the three analyses (days 2, 3, and 4 through 7) (P > .05). Conclusions: It is safe to implement the EM protocol within 24 to 72 hour of onset for mild-moderate ICH patients during the acute phase.
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Research Interests: Computer Science, Biomedical Engineering, Bioelectrochemistry, Usability, Gene Therapy, and 14 moreMedicine, Mice, Electroporation, Animals, Gene transfer techniques, Gene Delivery, Genomic Medicine, Zebrafish, Transfection, Electrodes, Electrode, Concentric, Needles, and Biochemistry and cell biology
The study aim was to assess sympathetic vasomotor response (SVR) by using pulsed wave Doppler (PWD) ultrasound in patients with multiple system atrophy (MSA) and correlate with the tilt table study. We recruited 18 male patients and 10... more
The study aim was to assess sympathetic vasomotor response (SVR) by using pulsed wave Doppler (PWD) ultrasound in patients with multiple system atrophy (MSA) and correlate with the tilt table study. We recruited 18 male patients and 10 healthy men as controls. The SVR of the radial artery was evaluated by PWD, using inspiratory cough as a provocative maneuver. The response to head-up tilt was studied by a tilt table with simultaneous heart rate and blood pressure recording. The hemodynamic variables were compared between groups, and were examined by correlation analysis. Regarding SVR, MSA patients exhibited a prolonged latency and less heart rate acceleration following inspiratory cough. Compared with the tilt table test, the elevation of heart rate upon SVR was positively correlated to the increase of heart rate after head-up tilt. The correlation analysis indicated that the magnitude of blood pressure drop from supine to upright was positively associated with the SVR latency but ...
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Research Interests: Biology, Gene Therapy, Cancer Research, Medicine, Humans, and 15 moreGenetic Enhancement, Mice, Animals, Gene transfer techniques, Male, Cancer Gene Therapy, Doxorubicin, Amino Acid Sequence, ADJUVANT THERAPY, Gene Transfer, Combined Modality Therapy, Cell Membrane, calreticulin, Combination Therapy, and Genetic Therapy
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ABSTRACT Hands play a very important role in human daily activities. Hand robotic exoskeletons for rehabilitation have been and continuously are developed by many research institutions. Generally, the information on finger length is... more
ABSTRACT Hands play a very important role in human daily activities. Hand robotic exoskeletons for rehabilitation have been and continuously are developed by many research institutions. Generally, the information on finger length is required while using such device and assessing part of hand function. In this paper, we propose a hand joint localizer and a related hand model to measure the individual finger length by marking every key joint location on the plane. One can further translate these points into the line segments connecting them, and all these data will be stored into the computer database afterwards. The hereby developed device actually provides a simple and intuitive solution to finger length acquisition.
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Research Interests: Quality of life, Treatment Outcome, Dysphagia, Medicine, Functional Electrical Stimulation, and 14 moreHumans, Swallowing, Female, Male, Aged, Middle Aged, Questionnaires, Adult, Radiation Injuries, Hyoid bone, Home Care Services, Psychology and Cognitive Sciences, Deglutition disorders, and Medical and Health Sciences
In recent years, high intensity focused ultrasound (HIFU) was shown to have promising effect on ablating both malignant and benign tumors. Despite its unique advantages such as minimal invasiveness and radiation free, the size of the... more
In recent years, high intensity focused ultrasound (HIFU) was shown to have promising effect on ablating both malignant and benign tumors. Despite its unique advantages such as minimal invasiveness and radiation free, the size of the ablation lesion is small and thus the duration for complete tumor ablation is usually too long. In this study, the effect of using ultrasound contrast agent (UCA) to enhance the ultrasound thermal effect, and thus enlarge the lesion size, was studied. Different concentration of UCA ranging from 0% (control), 0.001% to 0.1% (v/v) was mixed evenly with polyacrylamide gel phantoms containing egg white as a temperature indicator. A 1.85-MHz HIFU transducer was used to form thermal lesions inside the 2 cm*2 cm*4 cm phantoms. For the electric power of 50W and 70W, 'cigar' and 'tadpole’ shaped lesions were formed inside the control phantoms, respectively. The volume enlargement ratio (VER), defined as the ratio of volume formed in experimental groups (adding UCA or increasing power) to the volume of controlled the sample, was used to evaluate the effect of UCA on thermal ablation. When the concentrations of UCA were 0.001%, 0.005%, 0.01% and 0.015%, the VER were 10.58, 39.11, 55.08, 64.65 at 50W, and 2.27, 5.29, 12.09, 10.61 at 70W, respectively. The administration of UCA significantly increased the lesion size up to 65 times! UCA also reduced the necessary power to form a lesion of a certain size. For example, 0.001% of UCA at 50W produced a lesion close to controls at 70W in size. Same concentration of UCA at 70W formed lesions equivalent in size for phantoms without UCA at 100W. 30% reduction of the power level was achieved. However, the shift of the most heating position also increased with the concentration of UCA. investigated. For example, at UCA concentration of 0.015%, the shift could be 2.16 cm from the geometric focus. For concentration higher than 0.1%, the lesion was basically formed at the surface of the phantom. The mechanism of lesion formation and transformation was also investigated. For samples without UCA insonified by high intensity ultrasound, the tadpole-shaped lesion was formed due to boiling effect. The larger lesion formed in samples with UCA was because of the generation of inertial cavitation and bubbles which scattered sound waves and evenly distributed energy absorption in a larger volume. In conclusion, UCA could increase the size of lesion by enhancing scattering. However, the most heating center also moved toward the transducer when UCA concentration increased. A lower concentration (0.001%) of UCA and lower power (50 W) were enough to produce a lesion 39 times larger, and produced a minimal lesion movement (0.65 cm). *Corresponding author: wen
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Abstract The use of physical agent modalities dates back to the early days in the development of the field of physical and rehabilitation medicine. The term physiatrist is derived from the Greek words physis, pertaining to physical... more
Abstract The use of physical agent modalities dates back to the early days in the development of the field of physical and rehabilitation medicine. The term physiatrist is derived from the Greek words physis, pertaining to physical phenomena, and iatreia, referring to healer or physician. Thus a physiatrist is a physician who uses physical agents to relieve a patient's discomfort. Modalities are physical agents used to produce desired therapeutic effect. They include cold, heat, sound, electromagnetic waves, electricity, and mechanical forces. In this chapter, their physiologic effects, indications, techniques, and precautions are reviewed and discussed. Acupuncture and moxibustion, which use needling and heat to produce therapeutic effect, are also included. Physical agent modalities, although generally considered adjunctive rather than curative treatments, are widely used and important in the daily practices of most physiatrists.
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Background The blood-cerebrospinal fluid (CSF) barrier (BCSFB) is critically important to the pathophysiology of the central nervous system (CNS). However, this barrier prevents the safe transmission of beneficial drugs from the blood to... more
Background The blood-cerebrospinal fluid (CSF) barrier (BCSFB) is critically important to the pathophysiology of the central nervous system (CNS). However, this barrier prevents the safe transmission of beneficial drugs from the blood to the CSF and thus the spinal cord and brain, limiting their effectiveness in treating a variety of CNS diseases. Methods This study demonstrates a method on SD rats for reversible and site-specific opening of the BCSFB via a noninvasive, low-energy focused shockwave (FSW) pulse (energy flux density 0.03 mJ/mm2) with SonoVue microbubbles (2 × 106 MBs/kg), posing a low risk of injury. Results By opening the BCSFB, the concentrations of certain CNS-impermeable indicators (70 kDa Evans blue and 500 kDa FITC-dextran) and drugs (penicillin G, doxorubicin, and bevacizumab) could be significantly elevated in the CSF around both the brain and the spinal cord. Moreover, glioblastoma model rats treated by doxorubicin with this FSW-induced BCSFB (FSW-BCSFB) open...
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Entrapment neuropathy (EN) is a prevalent and debilitative condition caused by a complex pathogenesis that involves a chronic compression–edema–ischemia cascade and perineural adhesion that results in excessive shear stress during motion.... more
Entrapment neuropathy (EN) is a prevalent and debilitative condition caused by a complex pathogenesis that involves a chronic compression–edema–ischemia cascade and perineural adhesion that results in excessive shear stress during motion. Despite decades of research, an easily accessible and surgery-free animal model mimicking the mixed etiology is currently lacking, thus limiting our understanding of the disease and the development of effective therapies. In this proof-of-concept study, we used ultrasound-guided perineural injection of a methoxy poly(ethylene glycol)-b-Poly(lactide-co-glycoilide) carboxylic acid (mPEG-PLGA-BOX) hydrogel near the rat’s sciatic nerve to induce EN, as confirmed sonographically, electrophysiologically, and histologically. The nerve that was injected with hydrogel appeared unevenly contoured and swollen proximally with slowed nerve conduction velocities across the injected segments, thus showing the compressive features of EN. Histology showed perineura...
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Extracorporeal shockwave therapy (ESWT) is proposed to be effective in reducing pain and improving functional outcome in chronic plantar fasciitis. However, no long-term reports exist on the changes in plantar fascia (PF) elasticity after... more
Extracorporeal shockwave therapy (ESWT) is proposed to be effective in reducing pain and improving functional outcome in chronic plantar fasciitis. However, no long-term reports exist on the changes in plantar fascia (PF) elasticity after ESWT. We aimed to evaluate the changes in PF stiffness in patients with plantar fasciitis undergoing ESWT. The visual analogue scale (VAS, 0–100) was used for evaluating heel pain severity. B-mode sonography and strain sonoelastography were used for evaluating the PF thickness and stiffness. The sonoelastogram was analyzed using hue histogram analysis (value: 0–255, from stiffer to softer). All evaluations were recorded before ESWT, and 1 week, 1 month, 3 months, 6 months, and 12 months after ESWT. Repeated measures ANOVA was used to compare pain VAS, PF thickness, and PF hue value at different follow-up time-points. Twenty-two participants (8 men, 14 women) completed all measurements for 12 months. The VAS of heel pain, PF thickness, and PF hue va...
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BackgroundGlenohumeral idiopathic adhesive capsulitis is a common shoulder condition that hinders functionality. Addressing the pathology has been extensively researched. Ultrasound (US)‐guided injections have shown their efficacy.... more
BackgroundGlenohumeral idiopathic adhesive capsulitis is a common shoulder condition that hinders functionality. Addressing the pathology has been extensively researched. Ultrasound (US)‐guided injections have shown their efficacy. However, no study has been conducted to compare anatomical accuracy between different approaches in targeting the coracohumeral ligament (CHL).ObjectiveTo investigate whether US‐guided injection of the CHL can be performed accurately using either the rotator interval (RI) or the coracoidal (CO) approach.MethodsAn experimental cadaveric case series.SettingAnatomy laboratory.SpecimensBoth shoulders of 13 Thiel‐embalmed cadavers.InterventionsThree physiatrists each injected a 0.1 mL bolus of colored dye in both shoulders of each cadaver using either the RI or the CO approach under US guidance. Each cadaver received a total of six injections (three injections per shoulder). The accuracy of the injection was determined following shoulder dissection by an anato...
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Imaging of the nerves in the cervical region is more complicated than those of the extremities. Although high-resolution ultrasound enables the depiction of peripheral nerves' morphology and their associations with the adjacent soft... more
Imaging of the nerves in the cervical region is more complicated than those of the extremities. Although high-resolution ultrasound enables the depiction of peripheral nerves' morphology and their associations with the adjacent soft tissues, precise identification of the nerves in the neck is still challenging. Familiarization with the cervical nerve tracking techniques can help interventional physiatrists explore/treat relevant entrapment syndromes, so does guiding proper electrode placement during nerve conduction studies. The present article integrates serial ultrasound images and videos to demonstrate how to scan brachial plexus, superficial cervical plexus, cranial nerves in the neck region, and certain branches of the major cervical nerves.
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It is well known that acoustic cavitation can facilitate the inward transport of genetic materials across cell membranes (sonoporation). However, partially due to the unstationary behavior of the initiation and leveling of cavitation, the... more
It is well known that acoustic cavitation can facilitate the inward transport of genetic materials across cell membranes (sonoporation). However, partially due to the unstationary behavior of the initiation and leveling of cavitation, the sonoporation effect is usually unstable, especially in low intensity conditions. A system which is able to regulate the cavitation level during sonication by modulating the applied acoustic intensity with a feedback loop is implemented and its effect on in vitro gene transfection is tested. The regulated system provided better time stability and reproducibility of the cavitation levels than the unregulated conditions. Cultured hepatoma cells (BNL) mixed with 10 μg luciferase plasmids are exposed to 1-MHz pulsed ultrasound with or without cavitation regulation, and the gene transfection efficiency and cell viability are subsequently assessed. Experimental results show that for all exposure intensities (low, medium, and high), stable and intensity dependent, although not higher, gene expression could be achieved in the regulated cavitation system than the unregulated conditions. The cavitation regulation system provides a better control of cavitation and its bioeffect which are crucial important for clinical applications of ultrasound-mediated gene transfection.
Research Interests: Biophysics, Chemistry, Medicine, DNA, Cell line, and 5 moreCavitation, Ultrasonics, Transfection, Sonication, and Sonoporation
Biological response against foreign implants often leads to encapsulation, possibly resulting in malfunction of implants devices. The aim of this study was to reduce the foreign body reaction by surface modification of biomaterials... more
Biological response against foreign implants often leads to encapsulation, possibly resulting in malfunction of implants devices. The aim of this study was to reduce the foreign body reaction by surface modification of biomaterials through layer-by-layer deposition of type I collagen (COL)/hyaluronic acid (HA) multilayer films. Polydimethylsiloxane (PDMS) samples were coated with alternative COL and HA layers with different layers. We found that the in vitro adhesion, proliferation, and activation of macrophage-like cells were greatly decreased by COL/HA multilayered deposition. The PDMS samples modified with 20 bilayers of COL/HA were implanted in rats for 3 weeks, and the thickness of encapsulation surrounding the samples was decreased by 29–57% compared to the control unmodified PDMS. This study demonstrates the potential of COL/HA multilayer films to reduce foreign body reaction.
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Research Interests: Algorithms, Materials Science, Skeletal muscle biology, Thermography, Ultrasound, and 15 moreMedicine, Multidisciplinary, Ultrasonography, Calibration, Animals, Behavioral Animal Models, Body Temperature, Time Factors, Swine, Reproducibility of Results, Rabbits, Thermocouple, Transducer, Predictive value of tests, and Reference standards
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Despite extensive efforts in recent years, the blood-brain barrier (BBB) remains a significant obstacle for drug delivery. This study proposes using a clinical extracorporeal shockwave instrument to open the BBB, combined with a laser... more
Despite extensive efforts in recent years, the blood-brain barrier (BBB) remains a significant obstacle for drug delivery. This study proposes using a clinical extracorporeal shockwave instrument to open the BBB, combined with a laser assisted bi-axial locating platform to achieve non-invasive, controllable-focus and reversible BBB opening in the brains of rats. Under shockwave treatment with an intensity level of 5 (P9.79 MPa, energy flux density (EFD) 0.21 mJ/mm) and a pulse repetition frequency of 5 Hz, the BBB could be opened after 50 shocks without the use of an ultrasound contrast agent. With the proposed method, the BBB opening can be precisely controlled in terms of depth, size and location. Moreover, a shockwave based gene transfection was demonstrated using a luciferase gene.
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Discrepancies between hyperecho-predicted necrosed volume in ultrasound (US) images and the actual size of a thermal lesion might cause incomplete ablation or damage normal structures during high intensity focused US (HIFU) ablations. A... more
Discrepancies between hyperecho-predicted necrosed volume in ultrasound (US) images and the actual size of a thermal lesion might cause incomplete ablation or damage normal structures during high intensity focused US (HIFU) ablations. A novel dual-frequency sonication procedure is proposed to reduce this discrepancy. HIFU transducers of either 1 or 3.5 MHz were applied to transparent tissue-mimicking phantoms and ex vivo bovine liver samples. A diagnostic probe and a charge-coupled device (CCD) camera were used to record lesion formation in real time, allowing for comparison of the sizes of the hyperechoes in US images and the protein denaturing area on optical images. Bovine liver specimens were segmented to reveal the lesion&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s terminal sizes. Differences between actual lesion volume and hyperechoes in US images were demonstrated to be dependent on acoustic frequency and intensity. At a low frequency (1 MHz), the hyperechoes appeared to be larger than the actual volume, but the difference decreased with the duration of ablation. In contrast, at a high frequency (3.5 MHz), the hyperechoes were smaller for ablations lasting longer than 10 s. Moreover, given certain low-intensity conditions, lesions were formed without detectable hyperechoes (3.5 MHz), or hyperechoes appeared before a visible lesion was formed (1 MHz). Dual frequency sonications (low frequency followed by high frequency) produce more stable and larger lesions, and with less position shift, which might be useful for designing future ablation strategies.
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Previous studies developed ultrasound temperature-imaging methods based on changes in backscattered energy (CBE) to monitor variations in temperature during hyperthermia. In conventional CBE imaging, tracking and compensation of the echo... more
Previous studies developed ultrasound temperature-imaging methods based on changes in backscattered energy (CBE) to monitor variations in temperature during hyperthermia. In conventional CBE imaging, tracking and compensation of the echo shift due to temperature increase need to be done. Moreover, the CBE image does not enable visualization of the temperature distribution in tissues during nonuniform heating, which limits its clinical application in guidance of tissue ablation treatment. In this study, we investigated a CBE imaging method based on the sliding window technique and the polynomial approximation of the integrated CBE (ICBEpaimage) to overcome the difficulties of conventional CBE imaging. We conducted experiments with tissue samples of pork tenderloin ablated by microwave irradiation to validate the feasibility of the proposed method. During ablation, the raw backscattered signals were acquired using an ultrasound scanner for B-mode andICBEpaimaging. The experimental res...
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This paper presents an assistive control system with a special kinematic structure of an upper limb rehabilitation robot embedded with force/torque sensors. A dynamic human model integrated with sensing torque is used to simulate human... more
This paper presents an assistive control system with a special kinematic structure of an upper limb rehabilitation robot embedded with force/torque sensors. A dynamic human model integrated with sensing torque is used to simulate human interaction under three rehabilitation modes: active mode, assistive mode, and passive mode. The hereby proposed rehabilitation robot, called NTUH-ARM, provides 7 degree-offreedom (DOF) motion and runs subject to an inherent mapping between the 7 DOFs of the robot arm and the 4 DOFs of the human arm. The Lyapunov theory is used to analyze the stability of the proposed controller design. Clinical trials have been conducted with 6 patients, one of which acts as a control. The results of these experiments are positive and STREAM assessment by physical therapists also reveals promising results.
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In this study, we describe the development of surface-modified chitosan substrates to examine topographically related Neuro-2a cell behaviors. Different functional groups can be modified on chitosan surfaces to probe Neuro-2a cell... more
In this study, we describe the development of surface-modified chitosan substrates to examine topographically related Neuro-2a cell behaviors. Different functional groups can be modified on chitosan surfaces to probe Neuro-2a cell morphology. To prepare chitosan substrates with micro/nano-scaled features, we demonstrated an easy-to-handle method that combined photolithography, inductively coupled plasma reactive ion etching, Ag nanoparticle-assisted etching, and solution casting. The results show that Neuro-2a cells preferred to adhere to a flat chitosan surface rather than a nanotextured chitosan surface as evidenced by greater immobilization and differentiation, suggesting that surface topography is crucial for neural patterning. In addition, we developed chitosan substrates with different geometric patterns and flat region depth; this allowed us to re-arrange or re-pattern Neuro-2a cell colonies at desired locations. We found that a polarity-induced micropattern provided the most suitable surface pattern for promoting neural network formation on a chitosan substrate. The cellular polarity of single Neuro-2a cell spreading correlated to a diamond-like geometry and neurite outgrowth was induced from the corners toward the grooves of the structures. This study provide greater insight into neurobiology, including neurotransmitter screening, electrophysiological stimulation platforms, and biomedical engineering.