Tracheal stenosis is one of major challenging issues in clinical medicine because of the poor intrinsic ability of tracheal cartilage for repair. Tissue engineering provides an alternative method for the treatment of tracheal defects by generating replacement tracheal structures. In this study, we fabricated coaxial electrospun fibers using poly(L-lactic acid-co-caprolactone) and collagen solution as shell fluid and kartogenin solution as core fluid. Scanning electron microscope and transmission electron microscope images demonstrated that nanofibers had uniform and smooth structure. The kartogenin released from the scaffolds in a sustained and stable manner for about 2 months. The bioactivity of released kartogenin was evaluated by its effect on maintain the synthesis of type II collagen and glycosaminoglycans by chondrocytes. The proliferation and morphology analyses of mesenchymal stems cells derived from bone marrow of rabbits indicated the good biocompatibility of the fabricated nanofibrous scaffold. Meanwhile, the chondrogenic differentiation of bone marrow mesenchymal stem cells cultured on core-shell nanofibrous scaffold was evaluated by real-time polymerase chain reaction. The results suggested that the core-shell nanofibrous scaffold with kartogenin could promote the chondrogenic differentiation ability of bone marrow mesenchymal stem cells. Overall, the core-shell nanofibrous scaffold could be an effective delivery system for kartogenin and served as a promising tissue engineered scaffold for tracheal cartilage regeneration.
This study explored
a new rosuvastatin calcium- and heparin-loaded
poly(l-lactide-co-caprolactone) (PLCL) scaffold
for covered stents for treating aneurysms. The mechanism of rosuvastatin-induced
endothelialization via vascular endothelial growth factor (VEGF)-A
elevation was further explored. Rosu50, Rosu75, Rosu100, and phosphate-buffered
saline (PBS) nanofibrous scaffolds were fabricated by coaxial electrospinning
and observed by electron microscopy. Anticoagulation and pro-endothelialization
properties were tested. Sixteen rabbits were selected for an in vivo
assay and underwent microsurgery to establish a carotid aneurysm model.
The animals were treated with covered stents and followed for 4 months
using digital subtraction angiography (DSA), electron microscopy,
and histology. Rosuvastatin-treated human umbilical vein endothelial
cell (HUVEC) viability, function, and VEGF-A modulation were further
studied to elucidate the pro-endothelialization mechanism of rosuvastatin.
Our study demonstrates that rosuvastatin and heparin can be incorporated
into PLCL nanofibers via electrospinning. Rosu100 nanofiber scaffolds
exhibited significant anticoagulation properties. The viability of
HUVECs transferred to Rosu100 nanofiber scaffolds was increased significantly.
In vivo, DSA revealed that the Rosu100 group had better outcomes than
the PBS group. In addition, the Rosu100 stents induced more integrated
endothelialization. Further study demonstrated that rosuvastatin promoted
HUVEC viability and function in vitro. The effects of rosuvastatin
may be attributed to an elevation in VEGF-A. We demonstrated that
rosuvastatin- and heparin-loaded PLCL-covered stents show favorable
anticoagulation and pro-endothelialization properties in vitro and
in vivo in a rabbit aneurysm model. VEGF-A elevation played a crucial
role in rosuvastatin-promoted endothelialization. This work provides
an additional option for treating cerebral aneurysms with covered
stents.
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