Soft bioelectronics for diagnostic and therapeutic applications in neurological diseases.

Physical and chemical signals in the central nervous system yield crucial information that is clinically relevant under both physiological and pathological conditions. The emerging field of bioelectronics focuses on the monitoring and manipulation of neurophysiological signals with high spatiotemporal resolution and minimal invasiveness. Significant advances have been realized through innovations in materials and structural design, which have markedly enhanced mechanical and electrical properties, biocompatibility, and overall device performance. The diagnostic and therapeutic potential of soft bioelectronics has been corroborated across a diverse array of pre-clinical settings. This review summarizes recent studies that underscore the developments and applications of soft bioelectronics in neurological disorders, including neuromonitoring, neuromodulation, tumor treatment, and biosensing. Limitations and outlooks of soft devices are also discussed in terms of power supply, wireless control, biocompatibility, and the integration of artificial intelligence. This review highlights the potential of soft bioelectronics as a future platform to promote deciphering brain functions and clinical outcomes of neurological diseases.

Clinically Translatable Solid-State Dye for NIR-II Imaging of Medical Devices.

Medical devices are commonly implanted underneath the skin, but how to real-time noninvasively monitor their migration, integrity, and biodegradation in human body is still a formidable challenge. Here, the study demonstrates that benzyl violet 4B (BV-4B), a main component in the FDA-approved surgical suture, is found to produce fluorescence signal in the first near-infrared window (NIR-I, 700-900 nm) in polar solutions, whereas BV-4B self-assembles into highly crystalline aggregates upon a formation of ultrasmall nanodots and can emit strong fluorescence in the second near-infrared window (NIR-II, 1000-1700 nm) with a dramatic bathochromic shift in the absorption spectrum of ≈200 nm. Intriguingly, BV-4B-involved suture knots underneath the skin can be facilely monitored during the whole degradation process in vivo, and the rupture of the customized BV-4B-coated silicone catheter is noninvasively diagnosed by NIR-II imaging. Furthermore, BV-4B suspended in embolization glue achieves hybrid fluorescence-guided surgery (hybrid FGS) for arteriovenous malformation. As a proof-of-concept study, the solid-state BV-4B is successfully used for NIR-II imaging of surgical sutures in operations of patients. Overall, as a clinically translatable solid-state dye, BV-4B can be applied for in vivo monitoring the fate of medical devices by NIR-II imaging.

Soft and stretchable organic bioelectronics for continuous intraoperative neurophysiological monitoring during microsurgery.

In microneurosurgery, it is crucial to maintain the structural and functional integrity of the nerve through continuous intraoperative identification of neural anatomy. To this end, here we report the development of a translatable system leveraging soft and stretchable organic-electronic materials for continuous intraoperative neurophysiological monitoring. The system uses conducting polymer electrodes with low impedance and low modulus to record near-field action potentials continuously during microsurgeries, offers higher signal-to-noise ratios and reduced invasiveness when compared with handheld clinical probes for intraoperative neurophysiological monitoring and can be multiplexed, allowing for the precise localization of the target nerve in the absence of anatomical landmarks. Compared with commercial metal electrodes, the neurophysiological monitoring system allowed for enhanced post-operative prognoses after tumour-resection surgeries in rats. Continuous recording of near-field action potentials during microsurgeries may allow for the precise identification of neural anatomy through the entire procedure.

Nanowired human cardiac organoid transplantation enables highly efficient and effective recovery of infarcted hearts.

Human cardiac organoids hold remarkable potential for cardiovascular disease modeling and human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) transplantation. Here, we show cardiac organoids engineered with electrically conductive silicon nanowires (e-SiNWs) significantly enhance the therapeutic efficacy of hPSC-CMs to treat infarcted hearts. We first demonstrated the biocompatibility of e-SiNWs and their capacity to improve cardiac microtissue engraftment in healthy rat myocardium. Nanowired human cardiac organoids were then engineered with hPSC-CMs, nonmyocyte supporting cells, and e-SiNWs. Nonmyocyte supporting cells promoted greater ischemia tolerance of cardiac organoids, and e-SiNWs significantly improved electrical pacing capacity. After transplantation into ischemia/reperfusion-injured rat hearts, nanowired cardiac organoids significantly improved contractile development of engrafted hPSC-CMs, induced potent cardiac functional recovery, and reduced maladaptive left ventricular remodeling. Compared to contemporary studies with an identical injury model, greater functional recovery was achieved with a 20-fold lower dose of hPSC-CMs, revealing therapeutic synergy between conductive nanomaterials and human cardiac organoids for efficient heart repair.

Periplasmic biomineralization for semi-artificial photosynthesis.

Semiconductor-based biointerfaces are typically established either on the surface of the plasma membrane or within the cytoplasm. In Gram-negative bacteria, the periplasmic space, characterized by its confinement and the presence of numerous enzymes and peptidoglycans, offers additional opportunities for biomineralization, allowing for nongenetic modulation interfaces. We demonstrate semiconductor nanocluster precipitation containing single- and multiple-metal elements within the periplasm, as observed through various electron- and x-ray-based imaging techniques. The periplasmic semiconductors are metastable and display defect-dominant fluorescent properties. Unexpectedly, the defect-rich (i.e., the low-grade) semiconductor nanoclusters produced in situ can still increase adenosine triphosphate levels and malate production when coupled with photosensitization. We expand the sustainability levels of the biohybrid system to include reducing heavy metals at the primary level, building living bioreactors at the secondary level, and creating semi-artificial photosynthesis at the tertiary level. The biomineralization-enabled periplasmic biohybrids have the potential to serve as defect-tolerant platforms for diverse sustainable applications.

Study on the Correlation between Morphology and Distribution of Common Psoriasis Lesions.

Objective: Through the analysis of the morphological distribution of psoriasis lesions, we can study the relationship between psoriasis lesions and age, gender, and course of disease and dialectically look at the location of lesion morphology and the impact of course of disease on it, so as to provide more basis for the treatment of psoriasis. Method: Through a questionnaire survey of 512 patients in the dermatology clinic of a well-known traditional Chinese medicine hospital in Jiangsu Province, their symptoms met the diagnostic criteria of psoriasis in Chinese clinical dermatology. The current situation of psoriasis was analyzed by literature analysis, and the collected data were analyzed by general mean analysis, analysis of variance, and descriptive analysis. Result: There were some differences in the proportion of male to female in 512 patients. It is possible to conclude that male incidence rate is higher than that of women. It can be deduced from bad habits such as heavy drinking and smoking in male life. Bad habits can reduce male immunity and cause disease. The distribution of skin lesions in different parts shows that the skin is more affected by the outside world, which leads to the repeated attack of psoriasis. The incidence of chest, scalp, and upper arm is also relatively high. There have been similar demonstrations in relevant medical data, which may be related to the vascular density in them. Some substances that induce psoriasis in the dense blood vessels are easy to accumulate here, leading to the pathogenic bacteria to induce the onset of psoriasis. Conclusion: By studying the distribution of psoriasis lesions and the correlation between lesions, gender, and disease course, we can improve the dialectical treatment of psoriasis, which has reference significance, and provide a new thinking direction for the treatment system theory of psoriasis.

Inhibiting Fibroblast Mechanotransduction Modulates Severity of Idiopathic Pulmonary Fibrosis.

Objective: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that affects 63 in every 100,000 Americans. Its etiology remains unknown, although inflammatory pathways appear to be important. Given the dynamic environment of the lung, we examined the significance of mechanotransduction on both inflammatory and fibrotic signaling during IPF. Innovation: Mechanotransduction pathways have not been thoroughly examined in the context of lung disease, and pharmacologic approaches for IPF do not currently target these pathways. The interplay between mechanical strain and inflammation in pulmonary fibrosis remains incompletely understood. Approach: In this study, we used conditional KO mice to block mechanotransduction by knocking out Focal Adhesion Kinase (FAK) expression in fibroblasts, followed by induction of pulmonary fibrosis using bleomycin. We examined both normal human and human IPF fibroblasts and used immunohistochemistry, quantitative real-time polymerase chain reaction, and Western Blot to evaluate the effects of FAK inhibitor (FAK-I) on modulating fibrotic and inflammatory genes. Results: Our data indicate that the deletion of FAK in mice reduces expression of fibrotic and inflammatory genes in lungs. Similarly, mechanical straining in normal human lung fibroblasts activates inflammatory and fibrotic pathways. The FAK inhibition decreases these signals but has a less effect on IPF fibroblasts as compared with normal human fibroblasts. Conclusion: Administering FAK-I at early stages of fibrosis may attenuate the FAK-mediated fibrotic response pathway in IPF, potentially mediating disease progression.

Adipose-Derived Stromal Cells Seeded in Pullulan-Collagen Hydrogels Improve Healing in Murine Burns.

Burn scars and scar contractures cause significant morbidity for patients. Recently, cell-based therapies have been proposed as an option for improving healing and reducing scarring after burn injury, through their known proangiogenic and immunomodulatory paracrine effects. Our laboratory has developed a pullulan-collagen hydrogel that, when seeded with mesenchymal stem cells (MSCs), improves cell viability and augments their proangiogenic capacity in vivo. Concurrently, recent research suggests that prospective isolation of cell subpopulations with desirable transcriptional profiles can be used to further improve cell-based therapies. In this study, we examined whether adipose-derived stem cell (ASC)-seeded hydrogels could improve wound healing following thermal injury using a murine contact burn model. Partial thickness contact burns were created on the dorsum of mice. On days 5 and 10 following injury, burns were debrided and received either ASC hydrogel, ASC injection alone, hydrogel alone, or no treatment. On days 10 and 25, burns were harvested for histologic and molecular analysis. This experiment was repeated using CD26+/CD55+ FACS-enriched ASCs to further evaluate the regenerative potential of ASCs in wound healing. ASC hydrogel-treated burns demonstrated accelerated time to reepithelialization, greater vascularity, and increased expression of the proangiogenic genes MCP-1, VEGF, and SDF-1 at both the mRNA and protein level. Expression of the profibrotic gene Timp1 and proinflammatory gene Tnfa was downregulated in ASC hydrogel-treated burns. ASC hydrogel-treated burns exhibited reduced scar area compared to hydrogel-treated and control wounds, with equivalent scar density. CD26+/CD55+ ASC hydrogel treatment resulted in accelerated healing, increased dermal appendage count, and improved scar quality with a more reticular collagen pattern. Here we find that ASC hydrogel therapy is effective for treating burns, with demonstrated proangiogenic, fibromodulatory, and immunomodulatory effects. Enrichment for CD26+/CD55+ ASCs has additive benefits for tissue architecture and collagen remodeling postburn injury. Research is ongoing to further facilitate clinical translation of this promising therapeutic approach. Impact statement Burns remain a significant public health burden. Stem cell therapy has gained attention as a promising approach for treating burns. We have developed a pullulan-collagen biomimetic hydrogel scaffold that can be seeded with adipose-derived stem cells (ASCs). We assessed the delivery and activity of our scaffold in a murine contact burn model. Our results suggest that localized delivery of ASC hydrogel treatment is a promising approach for the treatment of burn wounds, with the potential for rapid clinical translation. We believe our work will have broad implications for both hydrogel therapeutics and regenerative medicine and will be of interest to the general scientific community.

Texturing Silicon Nanowires for Highly Localized Optical Modulation of Cellular Dynamics.

Engineered silicon-based materials can display photoelectric and photothermal responses under light illumination, which may lead to further innovations at the silicon-biology interfaces. Silicon nanowires have small radial dimensions, promising as highly localized cellular modulators, however the single crystalline form typically has limited photothermal efficacy due to the poor light absorption and fast heat dissipation. In this work, we report strategies to improve the photothermal response from silicon nanowires by introducing nanoscale textures on the surface and in the bulk. We next demonstrate high-resolution extracellular modulation of calcium dynamics in a number of mammalian cells including glial cells, neurons, and cancer cells. The new materials may be broadly used in probing and modulating electrical and chemical signals at the subcellular length scale, which is currently a challenge in the field of electrophysiology or cellular engineering.

Lupus Panniculitis as an Initial Manifestation of Systemic Lupus Erythematosus: A Case Report.

Lupus erythematosus panniculitis (LEP) is a variant of chronic cutaneous lupus erythematosus (CCLE). Reported cases of LEP lesions before the diagnosis of systemic lupus erythematosus (SLE) were very rare; only 9 cases have been reported, to the best of our knowledge. We now describe the case of a 19-year-old male patient, with an overall review of the English literature. In the earliest stage of the present case, nodules and ulcers involved his left leg and face, with no other accompanied symptoms. The skin lesions disappeared after treatment with methylprednisolone, 16 mg/d for 1 month. Seven months after discontinuing methylprednisolone, the cutaneous nodules and ulcers on his back recurred and were accompanied by fever, hair loss, and polyarthritis. Blood tests revealed leucopenia, positive antinuclear antibody and Smith antibody, and proteinuria. Histopathological findings were most consistent with LEP. This was followed sequentially by the diagnosis of SLE. The patient improved again after treatment with methylprednisolone and cyclophosphamide.Patients with LEP should have regular follow-ups because the development of SLE is possible. Early diagnosis and proper treatment is pivotal to improve the prognosis of such patients.

[Connexin 43 gene in the in vivo treatment of cerebral glioma in C6 rats].

OBJECTIVE: To study the role of connexin gene (Cx43) in the suppression of C6 glioma. METHODS: Cx43 gene depleted parental C6 rats (control group) and C6 cells transfected with Cx43 cDNA (transfection group) were implanted into the right caudate nucleus of SD rats. Rats bearing cerebral C6 gliomas were treated with Cx43 cDNA (treatment group) with another group treated with empty vector (empty vector group) serving as control. The general manifestation, survival time, MRI dynamic scanning and histopathological changes in all rats were observed. Cx43 mRNA and its protein were examined by in situ hybridization and immunohistochemistry. Proliferation activity was monitored by the average number of AgNOR stain. Cell apoptosis was examined by the Tolt-mediated x-duTP nick end labeling (TUNEL) method. RESULTS: All rats in the control and empty vector groups died of cerebral glioma within 3 weeks after implantation of C6 cells. Six in the transfection group and 8 in the treatment group were alive beyond 120 days with complete disappearance of the tumor foci, except one in this group having some residue of tumor. In the glioma of transfection and treatment groups, Cx43 gene expression was up-regulated, proliferation activity reduced while the apoptotic cells did not increase. CONCLUSION: The development of glioma is greatly suppressed by the transfection of Cx43 gene, which has great effectiveness in rats bearing cerebral malignant gliomas. This could become a target of choice in the gene treatment of malignant gliomas.