Practical applications of teledentistry during the Covid-19 pandemic in ASEAN member states - a systematic review.

OBJECTIVE: The objective of this review is to determine the utilisation and adoption of teledentistry based solutions and technologies during the Covid-19 Pandemic in the Asean region. BACKGROUND: Teledentistry is a branch of telemedicine that has rapidly advanced in the last few years and has the potential to provide solutions to oral health problems of patients and locations that do not have prompt and immediate access to a dentist or dental services. The Covid-19 has increased the adaption of all digital health technologies and teledentistry is no exception. METHODOLOGY: The study utilized online databases such as Pubmed (Medline), Scopus (Embase) and CINAHL for the purpose of document search. Newcastle Ottawa (NOS) scale was used to determine the quality of the studies included in our systematic review. PRISMA guidelines were used as the criteria for reporting items in the systematic review. RESULTS: A total of 1297 documents were found after applying the search criteria and the keywords for the selected study. After applying the Prisma guidelines, removal of duplicates and irrelevant entries, 10 studies that were conducted during the Covid-19 pandemic were selected, fitting the inclusion criteria. All the studies included were evaluated for quality and risk of bias through the Newcastle Ottawa scale. Only high-quality studies were included for the final review. CONCLUSION: Teledentistry is a cost-effective solution to screen, diagnose and treat dental patients from a distance. Teledentistry also has the potential to continue seamless continuation of dental education to dental students, during disruptive and non-disruptive periods. ASEAN countries should fully utilise the potential of teledentistry, however sound and effective legislation would be the key first step to achieving that potential.

Reciprocal relationship between cancer stem cells and myeloid-derived suppressor cells: implications for tumor progression and therapeutic strategies.

Recently, there has been an increased focus on cancer stem cells (CSCs) due to their resilience, making them difficult to eradicate. This resilience often leads to tumor recurrence and metastasis. CSCs adeptly manipulate their surroundings to create an environment conducive to their survival. In this environment, myeloid-derived suppressor cells (MDSCs) play a crucial role in promoting epithelial-mesenchymal transition and bolstering CSCs' stemness. In response, CSCs attract MDSCs, enhancing their infiltration, expansion and immunosuppressive capabilities. This interaction between CSCs and MDSCs increases the difficulty of antitumor therapy. In this paper, we discuss the interplay between CSCs and MDSCs based on current research and highlight recent therapeutic strategies targeting either CSCs or MDSCs that show promise in achieving effective antitumor outcomes.

Cancer stem cells (CSCs) are a kind of tumor cell. These cells are hard to kill but contribute to tumor progression and metastasis. Myeloid-derived suppressor cells (MDSCs) exist in the tumor tissue and are unfriendly to the antitumor immune response. The interaction between CSCs and MDSCs has a protective effect on tumor progression. Therapeutic strategies targeting CSCs or MDSCs present potential to weaken the complex interaction between the two cell types. This review summarizes the current knowledge of CSCs­MDSCs interaction and offers fresh perspectives on the future development of antitumor therapies targeting CSCs or MDSCs.

Phasic dopamine signals are reduced in the spontaneously hypertensive rat and increased by methylphenidate.

The spontaneously hypertensive rat (SHR) is a selectively bred animal strain that is frequently used to model attention-deficit hyperactivity disorder (ADHD) because of certain genetically determined behavioural characteristics. To test the hypothesis that the characteristically altered response to positive reinforcement in SHRs may be due to altered phasic dopamine response to reward, we measured phasic dopamine signals in the SHRs and Sprague Dawley (SD) rats using in vivo fast-scan cyclic voltammetry. The effects of the dopamine reuptake inhibitor, methylphenidate, on these signals were also studied. Phasic dopamine signals during the pairing of a sensory cue with electrical stimulation of midbrain dopamine neurons were significantly smaller in the SHRs than in the SD rats. Over repeated pairings, the dopamine response to the sensory cue increased, whereas the response to the electrical stimulation of dopamine neurons decreased, similarly in both strains. However, the final amplitude of the response to the sensory cue after pairing was significantly smaller in SHRs than in the SD rats. Methylphenidate increased responses to sensory cues to a significantly greater extent in the SHRs than in the SD rats, due largely to differences in the low dose effect. At a higher dose, methylphenidate increased responses to sensory cues and electrical stimulation similarly in SHRs and SD rats. The smaller dopamine responses may explain the reduced salience of reward-predicting cues previously reported in the SHR, whereas the action of methylphenidate on the cue response suggests a potential mechanism for the therapeutic effects of low-dose methylphenidate in ADHD.

Evaluating interhemispheric synchronization and cortical activity in acute stroke patients using optical hemodynamic oscillations.

Objective.An understanding of functional interhemispheric asymmetry in ischemic stroke patients is a crucial factor in the designs of efficient programs for post-stroke rehabilitation. This study evaluates interhemispheric synchronization and cortical activities in acute stroke patients with various degrees of severity and at different post-stroke stages.Approach.Twenty-three patients were recruited to participate in the experiments, including resting-state and speed finger-tapping tasks at week-1 and week-3 post-stroke. Multichannel near-infrared spectroscopy (NIRS) was used to measure the changes in hemodynamics in the bilateral prefrontal cortex (PFC), the supplementary motor area (SMA), and the sensorimotor cortex (SMC). The interhemispheric correlation coefficient (IHCC) measuring the synchronized activities in time and the wavelet phase coherence (WPCO) measuring the phasic activity in time-frequency were used to reflect the symmetry between the two hemispheres within a region. The changes in oxyhemoglobin during the finger-tapping tasks were used to present cortical activation.Main results.IHCC and WPCO values in the severe-stroke were significantly lower than those in the minor-stroke at low frequency bands during week-3 post-stroke. Cortical activation in all regions in the affected hemisphere was significantly lower than that in the unaffected hemisphere in the moderate-severe stroke measured in week-1, however, the SMC activation on the affected hemisphere was significantly enhanced in week-3 post-stroke.Significance.In this study, non-invasive NIRS was used to observe dynamic synchronization in the resting-state based on the IHCC and WPCO results as well as hemodynamic changes in a motor task in acute stroke patients. The findings suggest that NIRS could be used as a tool for early stroke assessment and evaluation of the efficacy of post-stroke rehabilitation.

Designing and pilot testing a novel high-definition transcranial burst electrostimulation device for neurorehabilitation.

Objective.Non-invasive brain stimulation has been promoted to facilitate neuromodulation in treating neurological diseases. Recently, high-definition (HD) transcranial electrical stimulation and a novel electrical waveform combining a direct current (DC) and theta burst stimulation (TBS)-like protocol were proposed and demonstrated high potential to enhance neuroplastic effects in a more-efficient manner. In this study, we designed a novel HD transcranial burst electrostimulation device and to preliminarily examined its therapeutic potential in neurorehabilitation.Approach.A prototype of the transcranial burst electrostimulation device was developed, which can flexibly output a waveform that combined a DC and TBS-like protocol and can equally distribute the current into 4 × 1 HD electrical stimulation by automatic impedance adjustments. The safety and accuracy of the device were then validated in a series ofin vitroexperiments. Finally, a pilot clinical trial was conducted to assess its clinical safety and therapeutic potential on upper-extremity rehabilitation in six patients with chronic stroke, where patients received either active or sham HD transcranial burst electrostimulation combined with occupational therapy three times per week for four weeks.Main results.The prototype was tested, and it was found to comply with all safety requirements. The output parameters were accurate and met the clinical study needs. The pilot clinical study demonstrated that the active HD transcranial burst electrostimulation group had greater improvement in voluntary motor function and coordination of the upper extremity than the sham control group. Additionally, no severe adverse events were noted, but slight skin redness under the stimulus electrode immediately after stimulation was seen.Conclusions.The results demonstrated the feasibility of incorporating the HD electrical DC and TBS-like protocol in our device; and the novel neuromodulatory device produced positive neurorehabilitation outcomes in a safe fashion, which could be the basis for the future clinical implementation for treating neurological diseases.Trial registration:ClinicalTrials.gov Identifier: NCT04278105. Registered on 20 February 2020.

An Improved Sensing Method of a Robotic Ultrasound System for Real-Time Force and Angle Calibration.

An ultrasonic examination is a clinically universal and safe examination method, and with the development of telemedicine and precision medicine, the robotic ultrasound system (RUS) integrated with a robotic arm and ultrasound imaging system receives increasing attention. As the RUS requires precision and reproducibility, it is important to monitor the real-time calibration of the RUS during examination, especially the angle of the probe for image detection and its force on the surface. Additionally, to speed up the integration of the RUS and the current medical ultrasound system (US), the current RUSs mostly use a self-designed fixture to connect the probe to the arm. If the fixture has inconsistencies, it may cause an operating error. In order to improve its resilience, this study proposed an improved sensing method for real-time force and angle calibration. Based on multichannel pressure sensors, an inertial measurement unit (IMU), and a novel sensing structure, the ultrasonic probe and robotic arm could be simply and rapidly combined, which rendered real-time force and angle calibration at a low cost. The experimental results show that the average success rate of the downforce position identification achieved was 88.2%. The phantom experiment indicated that the method could assist the RUS in the real-time calibration of both force and angle during an examination.

A Novel Method Enables General Pathologists to Create Web Dynamic Forms for Synoptic Tumor Reporting.

CONTEXT.­: Tumor reporting constitutes a significant daily task of pathologists. An efficient tumor-reporting methodology is thus vitally important. The Web dynamic form (WbDF) method offers a multitude of advantages over the prevailing transcription-mediated reporting method based on static-text checklists. However, its adaptation has been severely hampered for 2 decades by its costly needs to maintain a complex back-end system and to change the system for frequent updates of reporting content. OBJECTIVE.­: To overcome these 2 obstacles with a serverless Web platform that enables users to create, customize, use, and download WbDFs as synoptic templates for structured tumor reporting. DESIGN.­: Deploy ReactJS as a Web platform. Create form components in JavaScript Object Notation files. Use JavaScript Object Notation files to make WbDFs on the Web platform. Use the WbDFs to generate final pathology reports. RESULTS.­: Ordinary users (pathologists) can create/customize reporting templates as WbDFs on the Web platform. The WbDF can be used to make a pathology report and stored/shared like ordinary document files. There is no back-end system to change, nor a requirement for computer programming skills. CONCLUSIONS.­: This strategy eliminates the need for a complex back-end system and the associated cost when updating tumor-reporting standards, making it possible to adopt the WbDF method without the technological drawbacks associated with content updates. It also opens a new field of how the tumor-reporting system should be organized, updated, and implemented.

Enhancement of PVDF Sensing Characteristics by Retooling the Near-Field Direct-Write Electrospinning System.

This research aimed to develop a direct-write near-field electrospinning system (DW-NFES) with three-axis positioning of controllable speed, torque and position to produce sizable and high-quality piezoelectric fibers for sensing purposes. Sensor devices with high electrical response signals were developed and tested. To achieve DW-NFES purpose, a servo motor controller was designed to develop a high response rate, accurate positioning, and stable mobile device through the calculation of bandwidth and system time delay. With this retooled system of DW-NFES, controllable and uniform size fibers in terms of diameters, stretching force, and interspaces can be obtained. Sensor devices can be made selectively without a complicated lithography process. The characteristics of this DW-NFES platform were featured by high response rate, accurate positioning, and stable movement to make fibers with high piezoelectric property. In this study, polyvinylidene fluoride (PVDF) was used to explore and enhance their sensing quality through the platform. The parametric study of the process factors on piezoelectric sensing signals mainly included the concentration of electrospinning PVDF solution, high voltage electric field, and collection speed. Finally, the surface morphology and piezoelectric properties of the as-electrospun PVDF fibers were examined by scanning electron microscopy (SEM) and characterized by electrical response measurement techniques. The results showed that the fiber spinning speed of the DW-NFES system could be increased to ~125 from ~20 mm/s and the accuracy precision was improved to ~1 from ~50 µm, compared to conventional step motor system. The fiber diameter reached ~10 µm, and the electrospinning pitch reached to as small as ~10 µm. The piezoelectric output voltage of the electrospun fibers was increased ~28.6% from ~97.2 to ~125 mV; the current was increased ~27.6% from ~163 to ~208 nA, suggesting that the piezoelectric signals can be enhanced significantly by using this retooled system. Finally, an external control module (Arduino-MAGE) was introduced to control the PVDF piezoelectric fiber sensors integrated as a sensing array. The behavior of long-term sedentary patients can be successfully detected by this module system to prevent the patients from the bedsores.

Modulation of motor excitability by cortical optogenetic theta burst stimulation.

Intermittent theta burst stimulation (iTBS) and continuous theta burst stimulation (cTBS) are protocols used in repetitive transcranial magnetic stimulation (rTMS) or cortical electrical stimulation (CES) to facilitate or suppress corticospinal excitability. However, rTMS and CES excite all types of neuron in the target cortex probed by the coil or electrode, making it difficult to differentiate the effect of TBS on specific neural circuits involved in motor plasticity. In this study, TBS protocols were converted into an optogenetic model to achieve focalized and cell-type-specific cortical modulation. Light-sensitive channelrhodopsin-2 (ChR2) was expressed in the glutamatergic neuron in the primary motor cortex (M1) driven by the CaMKIIα promoter. A custom-made optrode comprising an optical fiber and a metal cannula electrode was fabricated to achieve optogenetic stimulation and simultaneous local field potential (LFP) recording. Single-pulse CES was delivered into M1 to elicit motor-evoked potential (MEP), which served as an indicator of motor excitability, before and after TBS intervention. Results show that both CES-iTBS and optogenetic iTBS (Opto-iTBS) can potentiate MEP activity. However, CES-cTBS suppressed MEP activity whereas Opto-cTBS enhanced it. This discrepancy may have resulted from the different neural networks targeted by the two TBS modalities, with CES-cTBS exciting all types of neuron and Opto-cTBS targeting excitatory neuron specifically. The results support the idea that intra-cortical networks determine the variation of TBS-induced neuroplasticity. This study shows that focalized and cell-type-specific brain stimulation using the optogenetic approach is viable and can be extended for further exploration of neuroplasticity.

Bilateral changes in afterhyperpolarization duration of spinal motoneurones in post-stroke patients.

This paper extends the observations presented in the previously published work on the afterhyperpolarization (AHP) duration changes in motoneurones (MNs) on the paretic (more affected) side of 11 post-stroke patients by the same analysis on the non-paretic (less-affected) side. The estimated AHP duration for patients' MNs supplying more-affected muscles was significantly longer than control values and the elongation decreased with patient age and disorder duration. For MNs supplying less-affected muscles, dependency of AHP duration on age was closer to the control data, but the scatter was substantially bigger. However, the AHP duration estimate of less-affected MNs tended to be longer than that of controls in the short time elapsed since the stroke, and shorter than controls in the long time. Our results thus suggest that the spinal MNs on both sides respond to the cerebral stroke rapidly with prolongation of AHP duration, which tends to normalize with time, in line with functional recovery. This suggestion is in concert with the published research on post-stroke changes in brain hemispheres. To our knowledge, these dependencies have never been investigated before. Since the number of our data was limited, the observed trends should be verified in a larger sample of patients and such a verification could take into account the suggestions for data analysis that we provide in this paper. Our data are in line with the earlier published research on MN firing characteristics post-stroke and support the conclusion that the MUs of the muscles at the non-paretic side are also affected and cannot be considered a suitable control for the MUs on the paretic side.

Extracellular Vesicles: A Brief Overview and Its Role in Precision Medicine.

Precision medicine has emerged as an approach to tailor therapies for an individual at the time of diagnosis and/or treatment. This emergence has been fueled by the ability to profile nucleic acids, along with proteins and lipids isolated from biofluids, a method called "liquid biopsy ," either by or in combination of one of the following components: circulating tumor cells (CTCs), cell-free DNA (cfDNA), and/or extracellular vesicles (EVs) . EVs are membrane-surrounded structures released by cells in an evolutionarily conserved manner. EVs have gained much attention from both the basic and clinical research areas, as EVs appear to play a role in many diseases; however, the well-known case is cancer. The hallmark of EVs in cancer is their role as mediators of communication between cells both at physiological and pathophysiological levels; hence, EVs are thought to contribute to the creation of a microenvironmental niche that promotes cancer cell survival, as well as reprogramming distant tissue for invasion. It is important to understand the mechanistic and functional aspects at the basic science level of EVs to get a better grasp on their role in healthy and disease states. EVs range from 30-1000 nm membrane-enclosed vesicles that are released by many mammalian cell types and present in a variety of biofluids. EVs have emerged as an area of clinical interest in the era of Precision Medicine, from their role in liquid biopsy (tissue biopsy free) approach for screening, assessing tumor heterogeneity, monitoring therapeutic responses, and minimal residual disease detection to EV-based therapeutics . EVs' diagnostic and therapeutic exploitation is under intense investigation in various indications. This chapter highlights EV biogenesis , composition of EVs, and their potential role in liquid biopsy diagnostics and therapeutics in the area of cancer.

Cancer Liquid Biopsy: Is It Ready for Clinic?

The management of cancer relies on a combination of imaging and tissue biopsy for diagnosis, monitoring, and molecular classification-based patient stratification to ensure appropriate treatment. Conventional tissue biopsy harvests tumor samples with invasive procedures, which are often difficult for patients with advanced disease. Given the well-recognized intratumor genetic heterogeneity [1], the biopsy of small tumor fragments does not necessarily represent all the genetic aberrations in the tumor, but sampling the entire tumor in each patient is not realistic. Moreover, tumors evolve all the time from local to advanced disease and by adapting to selective pressure from treatment.

Distinct Somatic Discrimination Reflected by Laser-Evoked Potentials Using Scalp EEG Leads.

Discrimination is an important function in pain processing of the somatic cortex. The involvement of the somatic cortex has been studied using equivalent dipole analysis and neuroimaging, but the results are inconsistent. Scalp electroencephalography (EEG) can reflect functional changes of particular brain regions underneath a lead. However, the responses of EEG leads close to the somatic cortex in response to pain have not been systematically evaluated. The present study applied CO2 laser stimulation to the dorsum of the left hand. Laser-evoked potentials (LEPs) of C4, T3, and T4 leads and pain ratings in response to four stimulus intensities were analyzed. LEPs started earlier at the C4 and T4 leads. The onset latency and peak latency of LEPs for C4 and T4 leads were the same. Only 10 of 22 subjects (45 %) presented equivalent current dipoles within the primary somatosensory or motor cortices. LEP amplitudes of these leads increased as stimulation intensity increased. The stimulus-response pattern of the C4 lead was highly correlated with pain rating. In contrast, an S-shaped stimulus-response curve was obtained for the T3 and T4 leads. The present study provides supporting evidence that particular scalp channels are able to reflect the functional characteristics of their underlying cortical areas. Our data strengthen the clinical application of somatic-cortex-related leads for pain discrimination.

Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes.

Gastric cancer, a leading cause of cancer-related deaths, is a heterogeneous disease. We aim to establish clinically relevant molecular subtypes that would encompass this heterogeneity and provide useful clinical information. We use gene expression data to describe four molecular subtypes linked to distinct patterns of molecular alterations, disease progression and prognosis. The mesenchymal-like type includes diffuse-subtype tumors with the worst prognosis, the tendency to occur at an earlier age and the highest recurrence frequency (63%) of the four subtypes. Microsatellite-unstable tumors are hyper-mutated intestinal-subtype tumors occurring in the antrum; these have the best overall prognosis and the lowest frequency of recurrence (22%) of the four subtypes. The tumor protein 53 (TP53)-active and TP53-inactive types include patients with intermediate prognosis and recurrence rates (with respect to the other two subtypes), with the TP53-active group showing better prognosis. We describe key molecular alterations in each of the four subtypes using targeted sequencing and genome-wide copy number microarrays. We validate these subtypes in independent cohorts in order to provide a consistent and unified framework for further clinical and preclinical translational research.

Genomic landscape and genetic heterogeneity in gastric adenocarcinoma revealed by whole-genome sequencing.

Gastric cancer (GC) is the second most common cause of cancer-related deaths. It is known to be a heterogeneous disease with several molecular and histological subtypes. Here we perform whole-genome sequencing of 49 GCs with diffuse (N=31) and intestinal (N=18) histological subtypes and identify three mutational signatures, impacting TpT, CpG and TpCp[A/T] nucleotides. The diffuse-type GCs show significantly lower clonality and smaller numbers of somatic and structural variants compared with intestinal subtype. We further divide the diffuse subtype into one with infrequent genetic changes/low clonality and another with relatively higher clonality and mutations impacting TpT dinucleotide. Notably, we discover frequent and exclusive mutations in Ephrins and SLIT/ROBO signalling pathway genes. Overall, this study delivers new insights into the mutational heterogeneity underlying distinct histologic subtypes of GC that could have important implications for future research in the diagnosis and treatment of GC.

The draft genome of the large yellow croaker reveals well-developed innate immunity.

The large yellow croaker, Larimichthys crocea, is one of the most economically important marine fish species endemic to China. Its wild stocks have severely suffered from overfishing, and the aquacultured species are vulnerable to various marine pathogens. Here we report the creation of a draft genome of a wild large yellow croaker using a whole-genome sequencing strategy. We estimate the genome size to be 728 Mb with 19,362 protein-coding genes. Phylogenetic analysis shows that the stickleback is most closely related to the large yellow croaker. Rapidly evolving genes under positive selection are significantly enriched in pathways related to innate immunity. We also confirm the existence of several genes and identify the expansion of gene families that are important for innate immunity. Our results may reflect a well-developed innate immune system in the large yellow croaker, which could aid in the development of wild resource preservation and mariculture strategies.

Real-time electrochemical recording of dopamine release under optogenetic stimulation.

Dopaminergic PC12 cells can synthesize and release dopamine, providing a good cellular model for investigating dopamine regulation. Optogenetic stimulation of channelrhodopsin-2 provides high spatial and temporal precision for selective stimulation as a powerful neuromodulation tool for neuroscience studies. The aim of this study is to measure dopamine release from dopaminergic PC12 cells under optogenetic stimulation using electrochemical recording of self-assembled monolayers modified microelectrode with amperometric measurement in real time. The activation of PC12 cells under various optogenetic stimulation schemes are characterized by measuring single-cell Ca(2+) imaging. After 10 seconds of optogenetic stimulation, the evoked intracellular Ca(2+) level and dopamine current of channelrhodopsin-2-transfected PC12 cells were 1.6- and 3.5-fold higher than those of the control cells. The optogenetic stimulation effects on Ca(2+) influx and dopamine release were 81% and 63% inhibition by using a Ca(2+) channel antagonist Nifedipine. The results indicate that optogenetic stimulation can evoke voltage-gated Ca(2+) channel-dependent dopamine exocytosis from PC12 cells in a cell specific, temporally precise and dose-dependent manner. This proposed dopamine recording system can be developed to be a good cell model for dopamine regulation and drug screening in vitro, or dopaminergic cell implantation therapy in vivo using optogenetic stimulation in a precise and convenient way.

Impaired baroreflex sensitivity in subjects with impaired glucose tolerance, but not isolated impaired fasting glucose.

Impaired baroreflex sensitivity (BRS) is associated with adverse cardiovascular outcomes. There are currently no studies on BRS changes in subjects with different glycemic statuses, including normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and newly diagnosed diabetes (NDD). The aim of this study was to investigate the effects of NDD, IGT and isolated IFG on BRS, based on a community-based data. A total of 768 subjects were classified as NGT (n = 498), isolated IFG (n = 61), IGT (n = 126) and NDD (n = 83). Spontaneous BRS was determined by the spectral α coefficient method, i.e., the square root of the ratio between the power of the RR interval and the power of systolic blood pressure in the LF frequency region (0.04-0.15 Hz) after the subjects had rested in a supine position for 5 min. Valsalva ratio was calculated as the longest RR interval after release of the Valsalva maneuver, divided by the shortest RR interval during the maneuver. As compared with NGT subjects, NDD (p = 0.039) and IGT (p = 0.041) subjects had a reduced spontaneous BRS in multivariate analysis based on analysis of covariance. NDD subjects exhibited a lower Valsalva ratio than NGT subjects (p = 0.043). However, there were no significant differences in spontaneous BRS and Valsalva ratio between subjects with isolated IFG and NGT. In conclusion, NDD and IGT subjects had an impaired BRS as compared to NGT subjects. However, reduced BRS was not apparent in subjects with isolated IFG.

The effect of tenocyte/hyaluronic acid therapy on the early recovery of healing Achilles tendon in rats.

The aim of this study was to explore the potential for a better recovery outcome for the Achilles tendon at an early healing stage when a mixed biomaterial-tenocyte injection is used. The experimental animals underwent single limb Achilles tendon transection followed by suturing repair. A solution of either hyaluronic acid with or without tenocytes or normal saline was randomly chosen to be injected around the injury site after surgery. To obtain the comprehensive recovery condition of the rats on different management protocols, the animals were evaluated histologically, mechanically, and functionally. A significant difference in the recovery condition was found in the injured tendon injected with the hyaluronic acid solution with tenocytes compared with the other groups. Tendon stiffness and the locomotion abilities of the rats with healing Achilles tendons were improved in the hyaluronic acid with tenocyte transplantation group. The acceleration of the inflammatory phase in rats with the hyaluronic acid with tenocyte injections might be the major reason for the better functional outcomes.

Functional recoveries of sciatic nerve regeneration by combining chitosan-coated conduit and neurosphere cells induced from adipose-derived stem cells.

Suboptimal repair occurs in a peripheral nerve gap, which can be partially restored by bridging the gap with various biosynthetic conduits or cell-based therapy. In this study, we developed a combination of chitosan coating approach to induce neurosphere cells from human adipose-derived stem cells (ASCs) on chitosan-coated plate and then applied these cells to the interior of a chitosan-coated silicone tube to bridge a 10-mm gap in a rat sciatic nerve. Myelin sheath degeneration and glial scar formation were discovered in the nerve bridged by the silicone conduit. By using a single treatment of chitosan-coated conduit or neurosphere cell therapy, the nerve gap was partially recovered after 6 weeks of surgery. Substantial improvements in nerve regeneration were achieved by combining neurosphere cells and chitosan-coated conduit based on the increase of myelinated axons density and myelin thickness, gastrocnemius muscle weight and muscle fiber diameter, and step and stride lengths from gait analysis. High expressions of interleukin-1ß and leukotriene B4 receptor 1 in the intra-neural scarring caused by using silicone conduits revealed that the inflammatory mechanism can be inhibited when the conduit is coated with chitosan. This study demonstrated that the chitosan-coated surface performs multiple functions that can be used to induce neurosphere cells from ASCs and to facilitate nerve regeneration in combination with a cells-assisted coated conduit.