The alphabeta and gammadelta T lineages are thought to arise from a common precursor; however, the regulation of separation and development of these lineages is not fully understood. We report here that development of alphabeta and gammadelta precursors was differentially affected by elimination of ribosomal protein L22 (Rpl22), which is ubiquitously expressed but not essential for translation. Rpl22 deficiency selectively arrested development of alphabeta-lineage T cells at the beta-selection checkpoint by inducing their death. The death was caused by induction of p53 expression, because p53 deficiency blocked death and restored development of Rpl22-deficient thymocytes. Importantly, Rpl22 deficiency led to selective upregulation of p53 in alphabeta-lineage thymocytes, at least in part by increasing p53 synthesis. Taken together, these data indicate that Rpl22 deficiency activated a p53-dependent checkpoint that produced a remarkably selective block in alphabeta T cell development but spared gammadelta-lineage cells, suggesting that some ribosomal proteins may perform cell-type-specific or stage-specific functions.

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.

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.

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