Synergistic Effects of Electrical Stimulation and Aligned Nanofibrous Microenvironment on Growth Behavior of Mesenchymal Stem Cells

Incontrollable cellular growth behavior is a significant issue, which severely affects the functional tissue formation and cellular protein expression. Development of natural extracellular matrix (ECM) like biomaterials to present microenvironment cues for regulation of cell responses can effectively overcome this problem. The external simulation and topological characteristics as typical guiding cues are capable of providing diverse influences on cellular growth. Herein, we fabricated two-dimensional aligned conductive nanofibers (2D-ACNFs) by an electrospinning process and surface polymerization, and the obtained 2D-ACNFs provided the effects of both alignment and electrical stimulation (ES) on cellular response of human mesenchymal cells (hMSCs). The results of cellular responses implied that the obtained 2D-ACNFs could offer a synergistic effect of both ES and aligned nanopattern on hMSC growth behavior. The effects could not only promote hMSCs to contact each other and maintain cellular activity but also provide positive promotion to regulate cellular proliferation. Thus, we believe that the obtained 2D-ACNFs will have a broad application in the biomedical field, such as cell culture with ES, directional induction for cell growth, and damaged tissue repair, etc

Celastrol-based nanomedicine hydrogels eliminate posterior capsule opacification - Supplementary table

Aim: To formulate an injectable thermosensitive micelle–hydrogel hybrid system loaded with celastrol (celastrol-loaded micelle hydrogel: CMG) to prevent posterior capsule opacification (PCO). Materials & methods: Celastrol-loaded micelles were embedded in a thermosensitive hydrogel matrix to enable controlled on-demand celastrol delivery into the residual capsule. The efficacy and mechanisms of the system for eliminating PCO were evaluated in rabbits. Results: Celastrol-loaded micelles inhibited the migration and proliferation of lens epithelial cells induced by TGF-β1. Celastrol prevents epithelial– mesenchymal transition in lens epithelial cells induced by TGF-β1 through the TGF-β1/Smad2/3/TEAD1 signaling pathway. In vivo efficiency evaluations showed that CMG demonstrated an excellent inhibitory effect on PCO in rabbits and had no obvious tissue toxicity. Conclusion: Injectable CMG may represent a promising ophthalmic platform for preventing PCO. This versatile injectable micelle–hydrogel hybrid represents a clinically relevant platform to achieve localized therapy and controlled release of drugs in other disease therapies.</p

M2 macrophages promote subconjunctival fibrosis through YAP/TAZ signalling

To evaluate the role of M2 macrophages in subconjunctival fibrosis after silicone implantation (SI) and investigate the underlying mechanisms. A model of subconjunctival fibrosis was established by SI surgery in rabbit eyes. M2 distribution and collagen deposition were evaluated by histopathology. The effects of M2 cells on the migration (using wound-scratch assay) and activation (by immunofluorescence and western blotting) of human Tenon’s fibroblasts (HTFs) were investigated. There were more M2 macrophages (CD68+/CD206+ cells) occurring in tissue samples around silicone implant at 2 weeks postoperatively. Dense collagen deposition was observed at 8 weeks after SI. In vitro experiment showed M2 expressed high level of CD206 and transforming growth factor-β1 (TGF-β1). The M2-conditioned medium promoted HTFs migration and the synthesis of collagen I and fibronectin. Meanwhile, M2-conditioned medium increased the protein levels of TGF-β1, TGF-βR II, p-Smad2/3, yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ). Verteporfin, a YAP inhibitor, suppressedTGF-β1/Smad2/3-YAP/TAZ pathway and attenuated M2-induced extracellular matrix deposition by HTFs. TGF-β1/Smad2/3-YAP/TAZ signalling may be involved in M2-induced fibrotic activities in HTFs. M2 plays a key role in promoting subconjunctival fibrosis and can serve as an attractive target for anti-fibrotic therapeutics.</p

Antibiotic-free Self-assembled Polypeptide Nanomicelles for Bacterial Keratitis

Drug resistance of bacteria limits the effectiveness of traditional antibiotics for bacterial keratitis. Antimicrobial peptides with a broad-spectrum antibacterial activity and bactericidal mechanism of membrane disruption provide an alternative for the treatment of bacterial keratitis. In the present study, an antimicrobial peptide polymer was developed and self-assembled into polypeptide nanomicelles (PPNMs) for treatment of bacterial keratitis. The self-assembly process led to spherical shapes with a diameter of around 45 nm and a relatively narrow size distribution. The nanomicelles also exhibited a positive charge and excellent biocompatibility. Antimicrobial tests have shown that PPNMs possessed a mechanism of action to destroy bacterial membranes and were superior to tobramycin in the treatment of bacterial keratitis. Therefore, we expect PPNMs to have good potential as an antimicrobial drug