Bi-layered Vascular Grafts Promote Vascular Regeneration

Cardiovascular disease is a serious threat to human health.Common vascular diseases are usually associated with stenosis or blockage of vascular.The preferred choice for the treatment of long-term vascular congestion is surgery using vascular graft.More and more researchers are working to develop an artificial blood vessel that can replace autologous blood vessels whose donor source is limited.Although satisfied results have been acquired in remodeling and repair of vascular grafts in the short-time study,some problems are uncertain.This appears to be particularly important for the long-term studies of vascular grafts.We can optimize the design of vascular graft to promote vascular regeneration based on the long-term results.In previous study,we fabricated a poly(?-caprolactone)(PCL)bi-layered vascular graft consisting of an internal layer with circumferentially aligned microfibers and an external layer with random nanofibers.We had confirmed that the vascular smooth muscle cells(VSMCs)with circumferentially oriented arrangement were successfully regenerated after the grafts were implanted in rat abdominal aorta for 3 months.Based on this result,we further explore the long-term(18 months)performance of the graft in the same model.All the grafts were patent and endothelialization was complete.No thrombosis,aneurysm,or stenosis happened.However,the number of vascular smooth muscle cells in the wall decreased and the function of the neoartery was lost.Additionally,the extracellular matrix showed high density in neointima layer while with low density in the grafts wall due to the incomplete degradation of PCL.A small part of calcification also observed in the graft.We speculated that it is the rigidity and slow degradation of the PCL material that lead to the above problems.Based on the above results,we further optimized the characteristics of vascular scaffolds.We used biodegradable elastic polymer,poly(L-lactide-co-?-caprolactone)(PLCL),to develop a vascular graft with aligned microfibers,which guided neoartery regeneration in rat abdominal aorta by prompting a positive remodeling.The grafts possess excellent handling properties and it can resist deformation.After implantation,rapid cell infiltration,alignment and complete endothelialization were achieved at 1 month.At 12 months,most of the materials degraded,a well-integrated neoartery was observed with the following characteristics comparable to native arteries: transparent appearance;synchronous pulsation;dense and orderly ECM arrangement;strong and compliant mechanical properties;vasomotor response to pharmacologic agents.In summary,our strategy that prepared the vascular grafts by well-designed the structure,degradation and mechanical properties of biomaterials can also be applied for designing and fabricating a wider range of tissue engineering scaffolds.It also provides a basis for the clinical transformation of small-diameter vascular grafts.