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The Experimental Study Of Constructing Functionalizable Tissue Engineering Blood Vessels Using Biodegradable Materials

Posted on:2018-10-28Degree:MasterType:Thesis
Country:ChinaCandidate:J L ZhangFull Text:PDF
GTID:2404330596491282Subject:Academy of Pediatrics
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Purpose:Preparing small diameter vascular grafts make use of functionalized biodegradable polyurethane elastomers,acquire the performance of anticoagulant and endothelialization by functional modification.In addition,for the clinical use of the reconstruction of right ventricular outflow tract,fabricate a novel valve integrated scaffold with suitable mechanical and hydrodynamic performance,which having morphology similar to pulmonary artery.Methods:A novel biodegradable polyurethane containing pendant cyclic disulfide groups and amino groups(PUSN)was developed,then nanofiber scaffolds with an 2 mm inner diameter were constructed using an electrospinning technique.Heparin was conjugated onto the amino groups,and TPS was clicked on the cyclic disulfide groups.Platelet adhesion tests and cell proliferation tests were implemented in vitro,and the modified grafts were transplanted in rabbit common carotid artery defect model ultimately.Continuous monitoring were achieved by Doppler ultrasonography.The grafts were estimated with histological staining method after 8 weeks.40:60 weight ratios of the PLLA/ PLCL mixture as the materials,a TIPS-based strategy combining with a 3D printing mold was utilized to rapidly fabricate PLLA/PLCL valve integrated scaffolds.After mechanical properties and biodegradability tests,the techniques of CFD and CSD were employed for the investigation of hemodynamics,valve deformation and stress analysis.The valve scaffolds were implanted subcutaneous into mice ultimately.Results : PUSN nanofibrous small-diameter grafts had great morphology and cell compatibility after modification,and also could anti-platelet adhesion and promote the growth and proliferation of EPCs.Doppler imaging showed that patency rate of the grafts was significantly improved after modified by heparin.The histological results indicated there were lots of cells and abundant collagen were produced in grafts,endothelial cells and smooth muscle cells were distributed in the inner and middle layer of the grafts respectively.The assembled mold produced by 3D printer was accurate.PLLA/PLCL valve integrated scaffold had a bionic,stable and microporous structure and satisfied mechanical properties,which also showed suitable elasticity and toughness.The valves could block the reflow effectively in the simulated fluid system.The materials were degraded controllably and had good biocompatibility.Conclusion:Functionalized biodegradable polyurethane could be used for preparing porous small-diameter vascular grafts.The modification of heparin and TPS could improve the patency of grafts and promote the infiltration of host cells and formation of extracellular matrix,which will beneficial to vascular remodeling and regeneration.A novel PLLA/PLCL valve integrated scaffold could be prepared by TIPS combined with3 D printing,and had great mechanical properties.The structure and function of the valves were desirable,The materials were biodegraded and had good biocompatibility,which were expected to achieve the regeneration process after degradation in vivo.
Keywords/Search Tags:Tissue engineering in vivo, Small diameter blood vessels, Polyurethane, Vascular Transplan-tation in situ, valve integrated scaffold, Poly(L-lactic acid)
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