A tissue engineered renovascular graft composed of proteins, polymers, smooth muscle and endothelial cells for renal artery stenosis.
Endarterectomy and bypass surgery to treat renal artery stenosis are increasingly shunned these days due to high risks of complications during and after the surgery. Striving to find a sound alternative solution, we pioneered the construction of a tissue engineered renovascular graft that could immediately restore the normal blood flow to kidneys and sustain renal functions without suffering restenosis after the surgery. A highly porous scaffold was first constructed by electrospinning polycaprolactone, poliglecaprone, gelatin and elastin, giving the vast majority of non-woven fibers in the scaffold a diameter below 1200 nm. To recapitulate the anatomical and functional signatures of renal arteries, a bi-layer vasculature comprising a smooth muscle layer topped by an endothelial layer was built on the scaffold. The vasculature witnessed a sustained proliferation for up to 10 days in vitro and robustly secreted prostacyclin and endothelin-1, evidencing that the vasculature was functionally comparable to native renal arteries. After 30 days as a renovascular graft in mice, the luminal diameter of the graft remained clear without a restenosis and an increased confluence of the endothelial layer was observed. The tensile test confirmed that the renovascular graft was mechanically superior to native renal arteries and retained this advantage within 30 days in vivo. Also, this renovascular graft sustained renal functions as evidenced by normal levels of serum creatinine, urine creatinine and serum urea nitrogen and the lack of edema in the kidney cortex. These results demonstrate that this renovascular graft holds a great therapeutic promise for renal artery stenosis.
Department of Surgery, Transplant Section, Shanghai Changzheng Hospital, Shanghai Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
Hao
H
Yin
Xiao-Hui
XH
Wang
Xiang-Dong
XD
Zhu
Huifang
H
Han
Wen-Yuan
WY
Guo
Zhi-Ren
ZR
Ful
D000818:Animals; D001807:Blood Vessel Prosthesis; D002478:Cells, Cultured; D003404:Creatinine / Q000737:chemistry / Q000494:pharmacology; D004146:Dioxanes / Q000737:chemistry; D004549:Elastin / Q000737:chemistry / Q000494:pharmacology; D004691:Endarterectomy / Q000295:instrumentation / Q000379:methods; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology / Q000637:transplantation; D019332:Endothelin-1 / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005780:Gelatin / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000502:physiology / Q000637:transplantation; D011091:Polyesters / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D012077:Renal Artery / Q000601:surgery; D012078:Renal Artery Obstruction / Q000601:surgery*; D054457:Tissue Scaffolds / Q000737:chemistry
D004146:Dioxanes; D019332:Endothelin-1; D011091:Polyesters; D011108:Polymers; D011506:Proteins; C016240:polycaprolactone; C095495:glycolide E-caprolactone copolymer; D005780:Gelatin; D004549:Elastin; D003404:Creatinine