Construction of a biomimetic three-layered PLLA/PCL large-diameter vessel via electrospinning and ultrasonic pore-forming: Preliminary animal evaluation_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

WANG Wenjun ¹ , GAO Yang ¹ , GAO Feng ¹ , SHI Lei ¹ , LIU Wei ¹ , FAN Weiwang ¹ , XU Chang ² , ZHENG Hong ³ ,  DONG Xufeng ⁴ ,  ZHUANG Xijing ¹

1. Department of Cardiovascular Surgery, Dalian University of Technology Affiliated Central Hospital (Dalian Municipal Central Hospital), Dalian, 116000, Liaoning, P. R. China;
2. Institute of Cardiovascular and Cerebrovascular Medicine, Dalian University of Technology, Dalian, 116000, Liaoning, P. R. China;
3. The First Operating Room, Dalian University of Technology Affiliated Central Hospital (Dalian Municipal Central Hospital), Dalian, 116000, Liaoning, P. R. China;
4. School of Materials Science and Engineering, Dalian University of Technology, Dalian, 116000, Liaoning, P. R. China;

Corresponding?author：

DONG Xufeng, Email: dongxf@dlut.edu.cn; ZHUANG Xijing, Email: dlmchcsd@126.com

Keywords：

Large-diameter artificial blood vessels; poly-L-lactic acid; polycaprolactone; three-layer artificial blood vessels; animal evaluation

DOI：

10.7507/1007-4848.202408006

Video：

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Objective To fabricate a large-diameter vascular graft with a pore size gradient structure mimicking that of natural blood vessels, using poly-L-lactic acid (PLLA) and polycaprolactone (PCL) as base materials through electrospinning and ultrasonic pore-forming techniques, and to evaluate its application potential. Methods A three-layered tubular graft was fabricated from a PCL/PLLA blend (mass ratio 6 : 4) via electrospinning, followed by an ultrasonic pore-forming process to create a gradient porosity. The resulting graft (diameter: 2 cm, length: 4 cm) was implanted into the descending thoracic aorta of an experimental pig using an end-to-end anastomosis. Graft patency and anastomotic sites were monitored by computed tomography angiography (CTA) at 1 and 6 weeks post-surgery. After 2 months, the graft was explanted for systematic evaluation of vascular regeneration and repair through gross examination, histopathology (H&E and elastic fiber staining), immunohistochemistry [for ETS-related gene (ERG), Actin, and Vimentin], and scanning electron microscopy (SEM). Results Postoperative CTA confirmed excellent graft patency at both 1 and 6 weeks, with no evidence of thrombosis or anastomotic stenosis. Gross examination of the 2-month explant revealed a smooth luminal surface covered by neotissue. Histopathological analysis demonstrated that the graft successfully induced the formation of a three-layered structure resembling a native vessel wall, comprising endothelial cells, smooth muscle cells, and fibroblasts. Immunohistochemistry further verified coverage of the luminal surface by endothelial cells (ERG-positive), along with the presence of neosmooth muscle (Actin-positive) and fibroblasts (Vimentin-positive). Endothelial cells were observed adhering to the inner surface of the artificial vessel under SEM. Conclusion The biomimetic, three-layered PLLA/PCL large-diameter vascular graft, constructed via electrospinning and ultrasonic pore-forming, exhibits excellent short-term patency and biocompatibility in a large animal model. More importantly, it demonstrates a significant potential to promote host cell infiltration and achieve in situ regeneration of a three-layered vascular wall structure, providing a promising experimental basis for the development of next-generation functional vascular substitutes.

Citation： WANG Wenjun, GAO Yang, GAO Feng, SHI Lei, LIU Wei, FAN Weiwang, XU Chang, ZHENG Hong, DONG Xufeng, ZHUANG Xijing. Construction of a biomimetic three-layered PLLA/PCL large-diameter vessel via electrospinning and ultrasonic pore-forming: Preliminary animal evaluation. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2026, 33(7): 1093-1100. doi: 10.7507/1007-4848.202408006 Copy

1.	Sirota DA, Zhulkov MO, Khvan DS, et al. Predictors of lethality, remodeling, and aorta-related events in different types of proximal aortic dissection surgery. Sovrem Tekhnologii Med, 2023, 15(1): 38-50.
2.	Li Q, Li B, Xi S, et al. Experience with aortic arch inclusion technique using artificial blood vessel for type A aortic dissection: an application study. J Cardiothorac Surg, 2024, 19(1): 189.
3.	Czerny M, Grabenw?ger M, Berger T, et al. EACTS/STS guidelines for diagnosing and treating acute and chronic syndromes of the aortic organ. Eur J Cardiothorac Surg, 2024, 65(2): ezad426.
4.	Isselbacher EM, Preventza O, Hamilton Black J, et al. 2022 ACC/AHA guideline for the diagnosis and management of aortic disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation, 2022, 146(24): e334-e482.
5.	Natanov R, Shrestha ML, Martens A, et al. Acute aortic dissection type A in younger patients (<60 years old): does full arch replacement provide benefits compared to limited approach? Braz J Cardiovasc Surg, 2023, 39(1): e20220434.
6.	Chen Y, Feng Y, Wang T, et al. In vivo endothelialization and neointimal hyperplasia assessment after rabbit carotid endarterectomy with bovine pericardium. Ann Transl Med, 2021, 9(6): 471.
7.	Rovas G, Bikia V, Stergiopulos N. Design and computational optimization of compliance-matching aortic grafts. Front Bioeng Biotechnol, 2023, 11: 1179174.
8.	Wang W, Gao F, He X, et al. Efficacy of tolvaptan in postoperative volume therapy for acute Stanford type A aortic dissection. BMC Cardiovasc Disord, 2023, 23(1): 95.
9.	何學志, 高峰, 高洋, 等. 擴大主動脈外膜內翻并人工血管端翻轉吻合處理急性A型主動脈夾層根部的近期效果. 中國胸心血管外科臨床雜志, 2022, 29(3): 371-376.He XZ, Gao F, Gao Y, et al. Short-term effects of extended adventitial inversion with graft eversion anastomosis technique in the root treatment of acute type A aortic dissection. Chin J Clin Thorac Cardiovasc Surg, 2022, 29(3): 371-376.
10.	Jalaie H, Steitz J, Afify M, et al. In vivo endothelialization and neointimal hyperplasia assessment after angioplasty of sheep carotid artery with a novel polycarbonate polyurethane patch. J Biomater Appl, 2019, 34(2): 208-218.
11.	Gaudino M, Benedetto U, Fremes S, et al. Association of radial artery graft vs saphenous vein graft with long-term cardiovascular outcomes among patients undergoing coronary artery bypass grafting: a systematic review and meta-analysis. JAMA, 2020, 324(2): 179-187.
12.	Agrafiotis E, Mayer C, Grabenw?ger M, et al. Global and local stiffening of ex vivo-perfused stented human thoracic aortas: a mock circulation study. Acta Biomater, 2023, 161: 170-183.
13.	馬金輝, 張嵐林, 陽晟, 等. 升主動脈包裹聯合Ⅰ型雜交全主動脈弓修復術治療主動脈弓部病變的臨床療效分析. 中國胸心血管外科臨床雜志, 2024, 31(9): 1313-1318.Ma JH, Zhang LL, Yang S, et al. Clinical effect of ascending aorta banding combined with typeⅠ hybrid aortic arch repair on aortic arch diseases. Chin J Clin Thorac Cardiovasc Surg, 2024, 31(9): 1313-1318.
14.	周曉輝, 關強, 劉睿, 等. 主動脈瓣置換術+升主動脈成形術后升主動脈直徑變化及中遠期臨床結果分析. 中國胸心血管外科臨床雜志, 2023, 30(3): 381-388.Zhou XH, Guan Q, Liu R, et al. Reduction ascending aortoplasty in adult patients undergoing aortic valve replacement: aorta diameter change, mid- and long-term clinical results. Chin J Clin Thorac Cardiovasc Surg, 2023, 30(3): 381-388.
15.	Gu Y, Tian C, Qin Y, et al. The novel hybrid polycarbonate polyurethane/polyester three-layered large-diameter artificial blood vessel. J Biomater Appl, 2022, 36(6): 965-975.
16.	Liu D, Meng Q, Hu J. Bacterial nanocellulose hydrogel: a promising alternative material for the fabrication of engineered vascular grafts. Polymers (Basel), 2023, 15(18): 3812.
17.	Naegeli KM, Kural MH, Li Y, et al. Bioengineering human tissues and the future of vascular replacement. Circ Res, 2022, 131(1): 109-126.
18.	Turner ME, Blum KM, Watanabe T, et al. Tissue engineered vascular grafts are resistant to the formation of dystrophic calcification. Nat Commun, 2024, 15(1): 2187.
19.	Di Francesco D, Pigliafreddo A, Casarella S, et al. Biological materials for tissue-engineered vascular grafts: overview of recent advancements. Biomolecules, 2023, 13(9): 1389.
20.	Li Z, Giarto J, Zhang J, et al. Design and synthesis of P (AAm-co-NaAMPS)-alginate-xanthan hydrogels and the study of their mechanical and rheological properties in artificial vascular graft applications. Gels, 2024, 10(5): 319.
21.	Jeong HJ, Nam H, Kim JS, et al. Dragging 3D printing technique controls pore sizes of tissue engineered blood vessels to induce spontaneous cellular assembly. Bioact Mater, 2023, 31: 590-602.
22.	Bellani CF, Yue K, Flaig F, et al. Suturable elastomeric tubular grafts with patterned porosity for rapid vascularization of 3D constructs. Biofabrication, 2021, 13(3): 035020.
23.	Uehara H, Uchiyama M, Imazuru T. Placement of stent grafts with different calibers into the true and false lumens of anastomotic aneurysms after descending aortic replacement for aortic dissection. J Cardiothorac Surg, 2024, 19(1): 9.
24.	Liu D, Han J, Zhuang X, et al. Evaluation of mechanical properties and biocompatibility of three-layer PCL/PLLA small-diameter vascular graft with pore diameter gradient. Eur Poly J, 2023, 186: 111864.
25.	Fernandes A, Miéville A, Grob F, et al. Endothelial-smooth muscle cell interactions in a shear-exposed intimal hyperplasia on-a-dish model to evaluate therapeutic strategies. Adv Sci (Weinh), 2022, 9(28): e2202317.
26.	D'Alessio A. Role of Endothelial cell metabolism in normal and tumor vasculature. Cancers (Basel), 2023, 15(7): 1921.
27.	Weber J, Weber M, Feile A, et al. Development of an in vitro blood vessel model using autologous endothelial cells generated from footprint-free hiPSCs to analyze interactions of the endothelium with blood cell components and vascular implants. Cells, 2023, 12(9): 1217.
28.	Kole GE, Hasirci V, Yucel D. Development of a tri-layered vascular construct and in vitro evaluation of endothelization. Macromol Biosci, 2024, 24(5): e2300369.
29.	Zhao D, Yuan W, Fang C, et al. Biomimetic vascular grafts with circumferentially and axially oriented microporous structures for native blood vessel regeneration. Adv Funct Mater, 2024, 34(1): 2308888.

1. Sirota DA, Zhulkov MO, Khvan DS, et al. Predictors of lethality, remodeling, and aorta-related events in different types of proximal aortic dissection surgery. Sovrem Tekhnologii Med, 2023, 15(1): 38-50.
2. Li Q, Li B, Xi S, et al. Experience with aortic arch inclusion technique using artificial blood vessel for type A aortic dissection: an application study. J Cardiothorac Surg, 2024, 19(1): 189.
3. Czerny M, Grabenw?ger M, Berger T, et al. EACTS/STS guidelines for diagnosing and treating acute and chronic syndromes of the aortic organ. Eur J Cardiothorac Surg, 2024, 65(2): ezad426.
4. Isselbacher EM, Preventza O, Hamilton Black J, et al. 2022 ACC/AHA guideline for the diagnosis and management of aortic disease: a report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation, 2022, 146(24): e334-e482.
5. Natanov R, Shrestha ML, Martens A, et al. Acute aortic dissection type A in younger patients (<60 years old): does full arch replacement provide benefits compared to limited approach? Braz J Cardiovasc Surg, 2023, 39(1): e20220434.
6. Chen Y, Feng Y, Wang T, et al. In vivo endothelialization and neointimal hyperplasia assessment after rabbit carotid endarterectomy with bovine pericardium. Ann Transl Med, 2021, 9(6): 471.
7. Rovas G, Bikia V, Stergiopulos N. Design and computational optimization of compliance-matching aortic grafts. Front Bioeng Biotechnol, 2023, 11: 1179174.
8. Wang W, Gao F, He X, et al. Efficacy of tolvaptan in postoperative volume therapy for acute Stanford type A aortic dissection. BMC Cardiovasc Disord, 2023, 23(1): 95.
9. 何學志, 高峰, 高洋, 等. 擴大主動脈外膜內翻并人工血管端翻轉吻合處理急性A型主動脈夾層根部的近期效果. 中國胸心血管外科臨床雜志, 2022, 29(3): 371-376.He XZ, Gao F, Gao Y, et al. Short-term effects of extended adventitial inversion with graft eversion anastomosis technique in the root treatment of acute type A aortic dissection. Chin J Clin Thorac Cardiovasc Surg, 2022, 29(3): 371-376.
10. Jalaie H, Steitz J, Afify M, et al. In vivo endothelialization and neointimal hyperplasia assessment after angioplasty of sheep carotid artery with a novel polycarbonate polyurethane patch. J Biomater Appl, 2019, 34(2): 208-218.
11. Gaudino M, Benedetto U, Fremes S, et al. Association of radial artery graft vs saphenous vein graft with long-term cardiovascular outcomes among patients undergoing coronary artery bypass grafting: a systematic review and meta-analysis. JAMA, 2020, 324(2): 179-187.
12. Agrafiotis E, Mayer C, Grabenw?ger M, et al. Global and local stiffening of ex vivo-perfused stented human thoracic aortas: a mock circulation study. Acta Biomater, 2023, 161: 170-183.
13. 馬金輝, 張嵐林, 陽晟, 等. 升主動脈包裹聯合Ⅰ型雜交全主動脈弓修復術治療主動脈弓部病變的臨床療效分析. 中國胸心血管外科臨床雜志, 2024, 31(9): 1313-1318.Ma JH, Zhang LL, Yang S, et al. Clinical effect of ascending aorta banding combined with typeⅠ hybrid aortic arch repair on aortic arch diseases. Chin J Clin Thorac Cardiovasc Surg, 2024, 31(9): 1313-1318.
14. 周曉輝, 關強, 劉睿, 等. 主動脈瓣置換術+升主動脈成形術后升主動脈直徑變化及中遠期臨床結果分析. 中國胸心血管外科臨床雜志, 2023, 30(3): 381-388.Zhou XH, Guan Q, Liu R, et al. Reduction ascending aortoplasty in adult patients undergoing aortic valve replacement: aorta diameter change, mid- and long-term clinical results. Chin J Clin Thorac Cardiovasc Surg, 2023, 30(3): 381-388.
15. Gu Y, Tian C, Qin Y, et al. The novel hybrid polycarbonate polyurethane/polyester three-layered large-diameter artificial blood vessel. J Biomater Appl, 2022, 36(6): 965-975.
16. Liu D, Meng Q, Hu J. Bacterial nanocellulose hydrogel: a promising alternative material for the fabrication of engineered vascular grafts. Polymers (Basel), 2023, 15(18): 3812.
17. Naegeli KM, Kural MH, Li Y, et al. Bioengineering human tissues and the future of vascular replacement. Circ Res, 2022, 131(1): 109-126.
18. Turner ME, Blum KM, Watanabe T, et al. Tissue engineered vascular grafts are resistant to the formation of dystrophic calcification. Nat Commun, 2024, 15(1): 2187.
19. Di Francesco D, Pigliafreddo A, Casarella S, et al. Biological materials for tissue-engineered vascular grafts: overview of recent advancements. Biomolecules, 2023, 13(9): 1389.
20. Li Z, Giarto J, Zhang J, et al. Design and synthesis of P (AAm-co-NaAMPS)-alginate-xanthan hydrogels and the study of their mechanical and rheological properties in artificial vascular graft applications. Gels, 2024, 10(5): 319.
21. Jeong HJ, Nam H, Kim JS, et al. Dragging 3D printing technique controls pore sizes of tissue engineered blood vessels to induce spontaneous cellular assembly. Bioact Mater, 2023, 31: 590-602.
22. Bellani CF, Yue K, Flaig F, et al. Suturable elastomeric tubular grafts with patterned porosity for rapid vascularization of 3D constructs. Biofabrication, 2021, 13(3): 035020.
23. Uehara H, Uchiyama M, Imazuru T. Placement of stent grafts with different calibers into the true and false lumens of anastomotic aneurysms after descending aortic replacement for aortic dissection. J Cardiothorac Surg, 2024, 19(1): 9.
24. Liu D, Han J, Zhuang X, et al. Evaluation of mechanical properties and biocompatibility of three-layer PCL/PLLA small-diameter vascular graft with pore diameter gradient. Eur Poly J, 2023, 186: 111864.
25. Fernandes A, Miéville A, Grob F, et al. Endothelial-smooth muscle cell interactions in a shear-exposed intimal hyperplasia on-a-dish model to evaluate therapeutic strategies. Adv Sci (Weinh), 2022, 9(28): e2202317.
26. D'Alessio A. Role of Endothelial cell metabolism in normal and tumor vasculature. Cancers (Basel), 2023, 15(7): 1921.
27. Weber J, Weber M, Feile A, et al. Development of an in vitro blood vessel model using autologous endothelial cells generated from footprint-free hiPSCs to analyze interactions of the endothelium with blood cell components and vascular implants. Cells, 2023, 12(9): 1217.
28. Kole GE, Hasirci V, Yucel D. Development of a tri-layered vascular construct and in vitro evaluation of endothelization. Macromol Biosci, 2024, 24(5): e2300369.
29. Zhao D, Yuan W, Fang C, et al. Biomimetic vascular grafts with circumferentially and axially oriented microporous structures for native blood vessel regeneration. Adv Funct Mater, 2024, 34(1): 2308888.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Construction of a biomimetic three-layered PLLA/PCL large-diameter vessel via electrospinning and ultrasonic pore-forming: Preliminary animal evaluation

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