Biophysical Electrical and Mechanical Stimulations for Promoting Chondrogenesis of Stem Cells on PEDOT:PSS Conductive Polymer Scaffolds.

The investigation of the effects of electrical and mechanical stimulations on chondrogenesis in tissue engineering scaffolds is essential for realizing successful cartilage repair and regeneration. The aim of articular cartilage tissue engineering is to enhance the function of damaged or diseased articular cartilage, which has limited regenerative capacity. Studies have shown that electrical stimulation (ES) promotes mesenchymal stem cell (MSC) chondrogenesis, while mechanical stimulation (MS) enhances the chondrogenic differentiation capacity of MSCs. Therefore, understanding the impact of these stimuli on chondrogenesis is crucial for researchers to develop more effective tissue engineering strategies for cartilage repair and regeneration. This study focuses on the preparation of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) conductive polymer (CP) scaffolds using the freeze-drying method. The scaffolds were fabricated with varying concentrations (0, 1, 3, and 10 wt %) of (3-glycidyloxypropyl) trimethoxysilane (GOPS) as a crosslinker and an additive to tailor the scaffold properties. To gain a comprehensive understanding of the material characteristics and the phase aggregation phenomenon of PEDOT:PSS scaffolds, the researchers performed theoretical calculations of solubility parameters and surface energies of PSS, PSS-GOPS, and PEDOT polymers, as well as conducted material analyses. Additionally, the study investigated the potential of promoting chondrogenic differentiation of human adipose stem cells by applying external ES or MS on a PEDOT:PSS CP scaffold. Compared to the group without stimulation, the group that underwent stimulation exhibited significantly up-regulated expression levels of chondrogenic characteristic genes, such as SOX9 and COL2A1. Moreover, the immunofluorescence staining images exhibited a more vigorous fluorescence intensity of SOX9 and COL II proteins that was consistent with the trend of the gene expression results. In the MS experiment, the strain excitation exerted on the scaffold was simulated and transformed into stress. The simulated stress response showed that the peak gradually decreased with time and approached a constant value, with the negative value of stress representing the generation of tensile stress. This stress response quantification could aid researchers in determining specific MS conditions for various materials in tissue engineering, and the applied stress conditions could be further optimized. Overall, these findings are significant contributions to future research on cartilage repair and biophysical ES/MS in tissue engineering.

Treatment Effect of Platelet Gel on Reconstructing Bone Defects and Nonunions: A Review of In Vivo Human Studies.

In ideal circumstances, a fractured bone can heal properly by itself or with the aid of clinical interventions. However, around 5% to 10% of bone fractures fail to heal properly within the expected time even with the aid of clinical interventions, resulting in nonunions. Platelet gel is a blood-derived biomaterial used in regenerative medicine aiming to promote wound healing and regeneration of damaged tissues. The purpose of this paper is to review relevant articles in an attempt to explore the current consensus on the treatment effect of platelet gel on reconstructing bone defects and nonunions, hoping to provide a valuable reference for clinicians to make treatment decisions in clinical practice. Based on the present review, most of the studies applied the combination of platelet gel and bone graft to reconstruct bone defects and nonunions, and most of the results were positive, suggesting that this treatment strategy could promote successful reconstruction of bone defects and nonunions. Only two studies tried to apply platelet gel alone to reconstruct bone defects and nonunions, therefore a convincing conclusion could not be made yet regarding the treatment effect of platelet gel alone on reconstructing bone defects and nonunions. Only one study applied platelet gel combined with extracorporeal shock wave therapy to reconstruct nonunions, and the results were positive; the hypothetical mechanism of this treatment strategy is reasonable and sound, and more future clinical studies are encouraged to further justify the effectiveness of this promising treatment strategy. In conclusion, the application of platelet gel could be a promising and useful treatment method for reconstructing bone defects and nonunions, and more future clinical studies are encouraged to further investigate the effectiveness of this promising treatment method.

Change of Eyelid Parameters in Patients With Marin-Amat Syndrome.

PURPOSE: Marin-Amat syndrome is an acquired facial synkinesis manifesting as involuntary eyelid closure on jaw movement. The authors investigate the clinical features, especially the quantitative changes in eyelid parameters of patients with Marin-Amat syndrome. METHODS: Patients with Marin-Amat syndrome between 2015 and 2017 in a medical center were collected. Clinical features and the change of eyelid parameters, including margin reflex distance 1 (MRD-1), margin reflex distance 2 (MRD-2), and palpebral fissure height, were evaluated. RESULTS: There were 5 men and 3 women with a mean age of 76 years. All had a history of facial palsy. The mean time to onset of Marin-Amat syndrome was 4.4 years after facial palsy. Seven patients (87.5%) developed subsequent ipsilateral facial spasm after facial palsy. Most patient complaints were ptosis (62.5%) and ptosis on eating (37.5%). The mean palpebral fissure height of involved eyes decreased from 5.88 to 2 mm on jaw opening (p = 0.011), which resulted from decrease in MRD-1 (from 2.06 to 0.06 mm, p = 0.012) and MRD-2 (from 3.81 to 1.94 mm; p = 0.012). Botulinum toxin A (Botox) injection into the periorbital orbicularis muscle in 6 patients significantly relieved the change of palpebral fissure height on jaw opening compared with that before injection (9.9% vs. 68.6 %, p = 0.027). CONCLUSIONS: Most patients with Marin-Amat syndrome present with ptosis and might be overlooked or underestimated. The reduction in palpebral fissure height in our patients with Marin-Amat syndrome was due to involuntary orbicularis oculi muscle contraction, resulting in decrease of both the MRD-1 and MRD-2 on jaw opening.

Targeting TGFß receptor-mediated snail and twist: WSG, a polysaccharide from Ganoderma lucidum, and it-based dissolvable microneedle patch suppress melanoma cells.

Cutaneous melanoma is a lethal skin cancer variant with pronounced aggressiveness and metastatic potential. However, few targeted medications inhibit the progression of melanoma. Ganoderma lucidum, which is a type of mushroom, is widely used as a non-toxic alternative adjunct therapy for cancer patients. This study determines the effect of WSG, which is a water-soluble glucan that is derived from G. lucidum, on melanoma cells. The results show that WSG inhibits cell viability and the mobility of melanoma cells. WSG induces changes in the expression of epithelial-to-mesenchymal transition (EMT)-related markers. WSG also downregulates EMT-related transcription factors, Snail and Twist. Signal transduction assays show that WSG reduces the protein levels in transforming growth factor ß receptors (TGFßRs) and consequently inhibits the phosphorylation of intracellular signaling molecules, such as FAK, ERK1/2 and Smad2. An In vivo study shows that WSG suppresses melanoma growth in B16F10-bearing mice. To enhance transdermal drug delivery and prevent oxidation, two highly biocompatible compounds, polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), are used to synthesize a dissolvable microneedle patch that is loaded with WSG (MN-WSG). A functional assay shows that MN-WSG has an effect that is comparable to that of WSG alone. These results show that WSG has significant potential as a therapeutic agent for melanoma treatment. MN-WSG may allow groundbreaking therapeutic approaches and offers a novel method for delivering this potent compound effectively.

Rational design of a highly porous electronic scaffold with concurrent enhancement in cell behaviors and differentiation under electrical stimulation.

Conductive polymers (CPs) have received increasing attention as promising materials for studying electrophysiological signals in cell and tissue engineering. The combination of CPs with electrical stimulation (ES) could possibly enhance neurogenesis, osteogenesis, and myogenesis. To date, research has been prioritized on capitalizing CPs as two-dimensional (2D) structures for guiding the differentiation. In contrast, relatively little is conducted on the implementation of 3D conductive scaffolds. In this research, we report the synergic assembly of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and multi-walled carbon nanotubes (MWCNTs) as a biocompatible, electrically conductive, mechanically robust and structurally porous 3D scaffold. To showcase the bioelectronic utilization, a proof-of-concept demonstration of electrically stimulated cell culture under ES is conducted. The ES effects coupled with the 3D scaffold are promising on pheochromocytoma 12 (PC12), a neuronal cell line, and the ES effect on osteogenesis of human adipose-derived stem cells (hASC) was further studied. PC12 cultured on this PEDOT:PSS/MWCNT 3D scaffolds was induced to differentiate toward a more mature neuronal phenotype with the ES treatment. Furthermore, hASC osteogenesis could be highly promoted in this conductive scaffold with ES. Calcium deposition concentration and osteo-differentiated gene markers were significantly higher with ES. The facile assembly of 3D conductive scaffolds sheds light on both platforms for investigating the 3D microenvironment for electrophysiological simulation of cells and tissues under the ES treatment of in vivo tissue engineering.

Wheat germ agglutinin-conjugated liposomes incorporated with cardiolipin to improve neuronal survival in Alzheimer's disease treatment.

Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with surface wheat germ agglutinin (WGA) to downregulate the phosphorylation of kinases in Alzheimer's disease (AD) therapy. Cardiolipin (CL)-conjugated LIP carrying CRM (CRM-CL/LIP) and also carrying NGF (NGF-CL/LIP) were used with AD models of SK-N-MC cells and Wistar rats after an insult with ß-amyloid peptide (Aß). We found that CRM-CL/LIP inhibited the expression of phosphorylated p38 (p-p38), phosphorylated c-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 and prevented neurodegeneration of SK-N-MC cells. In addition, NGF-CL/LIP could enhance the quantities of p-neurotrophic tyrosine kinase receptor type 1 and p-extracellular signal-regulated kinase 5 for neuronal rescue. Moreover, WGA-grafted CRM-CL/LIP and WGA-grafted NGF-CL/LIP significantly improved the permeation of CRM and NGF across the blood-brain barrier, reduced Aß plaque deposition and the malondialdehyde level, and increased the percentage of normal neurons and cholinergic activity in the hippocampus of AD rats. Based on the marker expressions and in vivo evidence, current LIP carriers can be promising drug delivery systems to protect nervous tissue against Aß-induced apoptosis in the brain during the clinical management of AD.

Targeting delivery of liposomes with conjugated p-aminophenyl-α-d-manno-pyranoside and apolipoprotein E for inhibiting neuronal degeneration insulted with ß-amyloid peptide.

Liposomes with conjugated p-aminophenyl-α-d-manno-pyranoside (APMP) and apolipoprotein E (ApoE) (APMP-ApoE-liposomes) were employed to carry neuron growth factor (NGF) across the blood-brain barrier (BBB) and enhance the survival of degenerated neurons. APMP-ApoE-liposomes were used to deliver NGF across a monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by human astrocytes (HAs) for rescuing SK-N-MC cells from an insult of ß-amyloid peptide 1-42 (Aß1-42). An increase in the APMP concentration enhanced the particle size, HBMEC and HA viability, permeability for propidium iodide (PI), and permeability for NGF, however, reduced the absolute value of zeta potential, APMP conjugation efficiency and transendothelial electrical resistance (TEER). In addition, an increase in the ApoE concentration increased the particle size, absolute value of zeta potential, HBMEC and HA viability, permeability for PI, permeability for NGF and SK-N-MC cell viability, however, decreased the ApoE conjugation efficiency and TEER. APMP and ApoE on liposomes can be promising surface moieties to carry NGF across the BBB, target degenerated neurons and inhibit Aß1-42-induced neurotoxicity in Alzheimer's disease.