Electrospun Chitosan/Polyethylene Oxide Nanofibrous Scaffolds with Potential Antibacterial Wound Dressing Applications

Electrospinning is a simple and versatile technique for the fabrication of nonwoven fibrous materials for biomedical applications. In the present study, chitosan (CS) and polyethylene oxide (PEO) nanofibrous scaffolds were successfully prepared using three different CS/PEO mass ratios and then evaluated for their physical, chemical, and biological characteristics. Scaffold morphologies were observed by scanning electron microscopy, which showed decreasing fiber diameters with increasing CS content. Higher CS concentrations also correlated with increased tensile strength and decreased elasticity of the scaffold. Degradation studies demonstrated that PEO was solubilized from the scaffold within the first six hours, followed by CS. This profile was unaffected by changes in the CS/PEO ratio or the pH of the media. Only the 2 : 1 CS/PEO scaffold demonstrated superior inhibition of both growth and attachment of Staphylococcus aureus. Finally, all scaffolds exhibited little impact on the proliferation of murine fibroblast monolayers. These data demonstrate that the 2 : 1 CS/PEO scaffold is a promising candidate for wound dressing applications due to its excellent antibacterial characteristics and biocompatibility

Development of Electrospun Chitosan-Polyethylene Oxide/Fibrinogen Biocomposite for Potential Wound Healing Applications

Abstract Normal wound healing is a highly complex process that requires the interplay of various growth factors and cell types. Despite advancements in biomaterials, only a few bioactive wound dressings reach the clinical setting. The purpose of this research was to explore the feasibility of electrospinning a novel nanofibrous chitosan (CS)-fibrinogen (Fb) scaffold capable of sustained release of platelet-derived growth factor (PDGF) for the promotion of fibroblast migration and wound healing. CS-Fb scaffolds were successfully electrospun using a dual-spinneret electrospinner and directly evaluated for their physical, chemical, and biological characteristics. CS-polyethylene/Fb scaffolds exhibited thinner fiber diameters than nanofibers electrospun from the individual components while demonstrating adequate mechanical properties and homogeneous polymer distribution. In addition, the scaffold demonstrated acceptable water transfer rates for wound healing applications. PDGF was successfully incorporated in the scaffold and maintained functional activity throughout the electrospinning process. Furthermore, released PDGF was effective at promoting fibroblast migration equivalent to a single 50 ng/mL dose of PDGF. The current study demonstrates that PDGF-loaded CS-Fb nanofibrous scaffolds possess characteristics that would be highly beneficial as novel bioactive dressings for enhancement of wound healing

Heat Shock Protein 96 Is Elevated in Rheumatoid Arthritis and Activates Macrophages Primarily via TLR2 Signaling

Macrophages are important mediators of chronic inflammation and are prominent in the synovial lining and sublining of patients with rheumatoid arthritis (RA). Recently, we demonstrated increased TLR2 and TILR4 expression and increased response to microbial TLR2 and TLR4 ligands in macrophages from the joints of RA. The current study characterized the expression of the 96-kDa heat shock glycoprotein (gp96) in the joints of RA and its role as an endogenous TLR ligand to promote innate immunity in RA. gp96 was increased in RA compared with osteoarthritis and arthritis-free control synovial tissues. The expression of gp96 strongly correlated with inflammation and synovial lining thickness. gp96 was increased in synovial fluid from the joints of RA compared with disease controls. Recombinant gp96 was a potent activator of macrophages and the activation was mediated primarily through TLR2 signaling. The cellular response to gp96 was significantly stronger with RA synovial macrophages compared with peripheral blood monocytes from RA or healthy controls. The transcription of TLR2, TNF-alpha, and IL-8, but not TLR4, was significantly induced by gp96, and the induction was significantly greater in purified RA synovial macrophages. The expression of TLR2, but not TLR4, on synovial fluid macrophages strongly correlated with the level of gp96 in the synovial fluid. The present study documents the potential role of gp96 as an endogenous TLR2 ligand in, RA and provides insight into the mechanism by which gp96 promotes the chronic inflammation of RA, identifying gp96 as a potential new therapeutic target. The Journal of Immunology, 2009, 182: 4965-497