Emerging Nanofibrous Polycaprolactone Vascular Grafts in Small and Large Animal Models: in vivo and in vitro Analyses

Document Type : Review Paper


Department of Textile Engineering, Isfahan University of Technology Isfahan, Iran


Over the last decade, engineering the polymeric vascular grafts has been extensively studied. Various types of polymers have been used in this field such as synthetic polymers, natural polymers, and polymer blends. Synthetic polymers, such as Polycaprolactone (PCL), have displayed improved mechanical specifications compared to natural polymers. Polycaprolactone is biodegradable polyester that can be blended with another synthetic polymer or a natural polymer to yield even greater enhanced mechanical properties. The mechanical properties of artificial blood vessels play an important role while the vessels are attached to the native vessels in the animal body. Furthermore, the artificial blood vessels must be adequately strong to resist frequent blood circulation and related pressure. The most significant advantage of engineered vascular tissue implants is their ability to grow, remodel, rebuild, and respond to injury. This article serves as a review of the fabrication, specifications, and benefits of various kinds of polycaprolactone grafts. The primary focus is on the in vivo implantation of nanofibrous ones for vascular regeneration in large and small animals. First, the subject of the study was thoroughly investigated, then the search was conducted with a combination of index and text terms. Finally, a number of articles, scientific books, patents, manuals, and university theses were selected and studied, and the obtained data were analyzed, categorized, and edited. PCL polymer has been the most sought-after biodegradable polymer for use as a vascular tissue engineering material.



Polycaprolactone (PCL)

Polycaprolactone is a biodegradable polyester having a low melting point of about 60 °C and a glass transition temperature of about −60 °C[1-3]. The most widespread public usage of PCL is in the manufacture of specialty polyurethanes (Table 1) [4-6].


Vascular Tissue Engineering

Vascular tissue damages resulting from defects, accidents, wounds or other kinds of injuries poses a significant challenge to human health [10].

However, in current years, the use of tissue engineering methods has become increasingly important in advancing the field of cardio-vascular biology and improving patient care [11-15]. The objective of vascular tissue engineering is to produce neo-vessels and neo-organ tissue using autologous cells through a biodegradable polymer like polycaprolactone (PCL) as a scaffold [16-18]. Fabrication of scaffolds with improved mechanical properties and promising cellular compatibility is essential for many tissue engineering applications [8,19-20]. Favorable scaffolds can be prepared via reinforcement with nanoparticles and hydrogels [21-23].

A proper vascular graft must reproduce the biomechanical specifications of blood vessels, as serving like a platform for cell attachment and proliferation [24-26]. It must exhibit nonthrombogenic, nonimmunogenic, biocompatible, and hemocompatible properties; biodegradability, suitable pore size, and elasticity are also important factors [27-29]. Therefore, this graft must aid the in vivo regeneration of a tissue-engineered vascular material after being implanted in a suitable location (Fig. 1 )[30-32].


Application of PCL Nanofibrous Grafts in the Vascular Regeneration

PCL nano-fibrous scaffolds possess substantial surface area–to-volume ratios and porosity that resemble the structure of protein fibers in native ECM [33-35]. The versatilities of polymer components, fiber structures, and functionalization have made feasible the fabrication of PCL nanofibrous scaffolds with appropriate mechanical strength, transparency, and biological specifications for vascular tissue engineering [17, 36].


Implantation of PCL Vascular Grafts

The fabrication of PCL nanofibrous scaffolds for cell cultivating serves as an important process for vascular tissue engineering method. Subsequently, implanting the PCL scaffold-cell matrix in an animal body is a main stage for vascular regeneration. One of the primary benefits of vascular engineered implants is that these tissues can grow, remodel, rebuild, and respond to damage [14, 37].


Implantation of PCL Scaffolds in the Blood Vessels

A blood vessel consists of three covers: intima (internal layer), media (central layer), and adventitia (external layer) (Fig. 2).

In the process of blood vessel tissue engineering, effective phases include cell sources, cell culture, scaffolds, vessel bio‑reactors, and implantation. Non immunogenic autologous endothelium cells and smooth muscle cells (tunica media area) are isolated from patients. These cells are optimal choices for vessel tissue engineering [15, 38].

Table 2 presents the results of PCL vascular implantation surgery in the blood vessels (abdominal aorta, carotid artery) of various animals (Rat, Rabbit, Sheep, Canine).



Scanning electron microscopy (SEM), an easily acquired and widely applied image acquisition and analysis method [52, 53], has rarely been used to study the structure of PCL scaffolds after cell culture process. Fig. 3 exhibits the SEM images of cultured cells on PCL scaffolds for vascular regeneration.



In recent years, adapting tissue engineering methods is crucial for advancing the field of cardio-vascular biology and providing better patient care. PCL polymer has drawn significant attention amongst the biodegradable polymers as an appropriate vascular tissue engineering material.The authors propose an alternative strategy, namely “Ultraviolet/O3 Irradiation,” on the PCL nanofibers (for increasing of cell adhesion on the scaffolds). This strategy is expected to improve the success of scaffold implantation.



The authors declare no conflicts of interest.



This study was supported by the Applied Textile Research Center.

  1. Jin Q, Fu Y, Zhang G, Xu L, Jin G, Tang L, et al. Nanofiber electrospinning combined with rotary bioprinting for fabricating small-diameter vessels with endothelium and smooth muscle. Composites Part B: Engineering. 2022;234:109691. https://doi.org/10.1016/j.compositesb.2022.109691
  2. Fang Z, Xiao Y, Geng X, Jia L, Xing Y, Ye L, et al. Fabrication of heparinized small diameter TPU/PCL bi-layered artificial blood vessels and in vivo assessment in a rabbit carotid artery replacement model. Biomaterials Advances. 2022;133:112628. https://doi.org/10.1016/j.msec.2021.112628
  3. Eom S, Jo J, Kim DS. Investigation of Effects of Electrospinning Parameters on Transcription Quality of Nanofibrous Bifurcated-Tubular Scaffold. Macromolecular Materials and Engineering. 2022;307(8):2200030. https://doi.org/10.1002/mame.202200030
  4. Cao Y, Jiang J, Jiang Y, Li Z, Hou J, Li Q. Biodegradable highly porous interconnected poly(ε-caprolactone)/poly(L-lactide-co-ε-caprolactone) scaffolds by supercritical foaming for small-diameter vascular tissue engineering. Polymers for Advanced Technologies. 2022;33(1):440-51. https://doi.org/10.1002/pat.5528
  5. Sun Q, Si J, Zhao L, Wei T, Wang T, Li F, et al. Direct thrombin inhibitor-bivalirudin improved the hemocompatibility of electrospun polycaprolactone vascular grafts. Composites Part B: Engineering. 2022;234:109702. https://doi.org/10.1016/j.compositesb.2022.109702
  6. Wan X, Zhao Y, Li Z, Li L. Emerging polymeric electrospun fibers: From structural diversity to application in flexible bioelectronics and tissue engineering. Exploration. 2022;2(1):20210029. https://doi.org/10.1002/EXP.20210029
  7. Yuan Z, Sheng D, Jiang L, Shafiq M, Khan AuR, Hashim R, et al. Vascular Endothelial Growth Factor-Capturing Aligned Electrospun Polycaprolactone/Gelatin Nanofibers Promote Patellar Ligament Regeneration. Acta Biomaterialia. 2022;140:233-46. https://doi.org/10.1016/j.actbio.2021.11.040
  8. Fattahi F. Poly (Lactic Acid) Nano-structures for Cartilage Regeneration and Joint Repair: Strategies and Ideas. 2020.
  9. Fadaie M, Mirzaei E. Nanofibrillated chitosan/polycaprolactone bionanocomposite scaffold with improved tensile strength and cellular behavior. 2018:77-89. 10.22038/nmj.2018.005.004
  10. Aghazadeh Y, Khan ST, Nkennor B, Nunes SS. Cell-based therapies for vascular regeneration: Past, present and future. Pharmacology & Therapeutics. 2022;231:107976. https://doi.org/10.1016/j.pharmthera.2021.107976
  11. Fattahi F, Khoddami A, Avinc O. Nano-Fibrous and Tubular Poly (Lactic Acid) Scaffolds for Vascular Tissue Engineering. Nanomedicine Research Journal. 2019;4:141-56. 10.22034/nmrj.2019.03.003
  12. Hu G, Chen L, Zhao S, Hong FF. Mercerization of tubular bacterial nanocellulose for control of the size and performance of small-caliber vascular grafts. Chemical Engineering Journal. 2022;428:131104. https://doi.org/10.1016/j.cej.2021.131104
  13. Hosseinzadeh S, Zarei-Behjani Z, Bohlouli M, Khojasteh A, Ghasemi N, Salehi-Nik N. Fabrication and optimization of bioactive cylindrical scaffold prepared by electrospinning for vascular tissue engineering. Iranian Polymer Journal. 2022;31(2):127-41. 10.1007/s13726-021-00983-0
  14. Fattahi F-S. Nanoscience and nanotechnology in fabrication of scaffolds for tissue regeneration. International Nano Letters. 2021;11(1):1-23. 10.1007/s40089-020-00318-6
  15. Ebhodaghe S, Fattahi F, Ndibe H, Imanah O. Emerging Fabrication Techniques for Engineering Extracellular Matrix Biomimetic Materials2021. 10.20944/preprints202111.0389.v1
  16. Boys AJ, Barron SL, Tilev D, Owens RM. Building Scaffolds for Tubular Tissue Engineering. 2020;8. 10.3389/fbioe.2020.589960
  17. Fathi-Karkan S, Banimohamad-Shotorbani B, Saghati S, Rahbarghazi R, Davaran S. A critical review of fibrous polyurethane-based vascular tissue engineering scaffolds. Journal of Biological Engineering. 2022;16(1):6. 10.1186/s13036-022-00286-9
  18. Khandan A, Esmaeili S. Fabrication of polycaprolactone and polylactic acid shapeless scaffolds via fused deposition modelling technology. Journal of Advanced Materials Processing. 2019;7(4):16-29.
  19. Moarrefzadeh A, Morovvati MR, Angili SN, Smaisim GF, Khandan A, Toghraie D. Fabrication and finite element simulation of 3D printed poly L-lactic acid scaffolds coated with alginate/carbon nanotubes for bone engineering applications. Int J Biol Macromol. 2023;224:1496-508. 10.1016/j.ijbiomac.2022.10.238
  20. Fattahi F-s, Khoddami A, Avinc O. Poly(lactic acid) (PLA) Nanofibers for Bone Tissue Engineering. Journal of Textiles and Polymers. 2019;7(2):47-64.
  21. Rajaei A, Kazemian M, Khandan A. Investigation of mechanical stability of lithium disilicate ceramic reinforced with titanium nanoparticles. Nanomedicine Research Journal. 2022;7(4):350-9. 10.22034/nmrj.2022.04.005
  22. Heydary HA, Karamian E, Poorazizi E, Khandan A, Heydaripour J. A Novel Nano-Fiber of Iranian Gum Tragacanth-Polyvinyl Alcohol/Nanoclay Composite for Wound Healing Applications. Procedia Materials Science. 2015;11:176-82. https://doi.org/10.1016/j.mspro.2015.11.079
  23. Khandan A, Jazayeri H, Fahmy MD, Razavi M. Hydrogels: Types, structure, properties, and applications. Biomat Tiss Eng. 2017;4(27):143-69.
  24. Saidy NT, Fernández-Colino A, Heidari BS, Kent R, Vernon M, Bas O, et al. Spatially Heterogeneous Tubular Scaffolds for In Situ Heart Valve Tissue Engineering Using Melt Electrowriting. Advanced Functional Materials. 2022;32(21):2110716. https://doi.org/10.1002/adfm.202110716
  25. Gupta P, Mandal BB. Fabrication of Small-Diameter Tubular Grafts for Vascular Tissue EngineeringTissue engineering Applications Using Mulberry and Non-mulberry Silk Proteins. In: Zhao F, Leong KW, editors. Vascular Tissue Engineering: Methods and Protocols. New York, NY: Springer US; 2022. p. 125-39. 10.1007/978-1-0716-1708-3_11
  26. Fattahi F-s. Evaluation of the Application of Polylactic Acid Bioactive Scafolds in Reconsructive Medicine. Basparesh. 2022;11(4):16-30. 10.22063/basparesh.2021.2773.1534
  27. Yao W, Gu H, Hong T, Wang Y, Chen S, Mo X, et al. A bi-layered tubular scaffold for effective anti-coagulant in vascular tissue engineering. Materials & Design. 2020;194:108943. https://doi.org/10.1016/j.matdes.2020.108943
  28. Kopeć K, Wojasiński M, Eichler M, Genç H, Friedrich RP, Stein R, et al. Polydopamine and gelatin coating for rapid endothelialization of vascular scaffolds. Biomaterials Advances. 2022;134:112544. https://doi.org/10.1016/j.msec.2021.112544
  29. Liu X, Sun Y, Chen B, Li Y, Zhu P, Wang P, et al. Novel magnetic silk fibroin scaffolds with delayed degradation for potential long-distance vascular repair. Bioactive Materials. 2022;7:126-43. https://doi.org/10.1016/j.bioactmat.2021.04.036
  30. Rabionet M, Guerra AJ, Puig T, Ciurana J. 3D-printed Tubular Scaffolds for Vascular Tissue Engineering. Procedia CIRP. 2018;68:352-7. https://doi.org/10.1016/j.procir.2017.12.094
  31. Maleki S, Shamloo A, Kalantarnia F. Tubular TPU/SF nanofibers covered with chitosan-based hydrogels as small-diameter vascular grafts with enhanced mechanical properties. Scientific Reports. 2022;12. 10.1038/s41598-022-10264-2
  32. Brooks-Richards TL, Paxton NC, Allenby MC, Woodruff MA. Dissolvable 3D printed PVA moulds for melt electrowriting tubular scaffolds with patient-specific geometry. Materials & Design. 2022;215:110466. https://doi.org/10.1016/j.matdes.2022.110466
  33. Rodrigues ICP, Lopes ÉSN, Pereira KD, Huber SC, Jardini AL, Annichino-Bizzacchi JM, et al. Extracellular matrix-derived and low-cost proteins to improve polyurethane-based scaffolds for vascular grafts. Scientific Reports. 2022;12(1):5230. 10.1038/s41598-022-09040-z
  34. Doersam A, Tsigkou O, Jones C. A Review: Textile Technologies for Single and Multi-Layer Tubular Soft Tissue Engineering. 2022;7(11):2101720. https://doi.org/10.1002/admt.202101720
  35. Wang H, Xing M, Deng W, Qian M, Wang F, Wang K, et al. Anti-Sca-1 antibody-functionalized vascular grafts improve vascular regeneration via selective capture of endogenous vascular stem/progenitor cells. Bioactive Materials. 2022;16:433-50. https://doi.org/10.1016/j.bioactmat.2022.03.007
  36. Cuenca JP, Kang H-J, Fahad MAA, Park M, Choi M, Lee H-Y, et al. Physico-mechanical and biological evaluation of heparin/VEGF-loaded electrospun polycaprolactone/decellularized rat aorta extracellular matrix for small-diameter vascular grafts. Journal of Biomaterials Science, Polymer Edition. 2022;33(13):1664-84. 10.1080/09205063.2022.2069398
  37. Liu L, Ji X, Mao L, Wang L, Chen K, Shi Z, et al. Hierarchical-structured bacterial cellulose/potato starch tubes as potential small-diameter vascular grafts. Carbohydrate Polymers. 2022;281:119034. https://doi.org/10.1016/j.carbpol.2021.119034
  38. Fattahi F, Zamani T. Hemocompatibility Poly (lactic acid) Nanostructures: A Bird’s Eye View. 2020;7:263-71.
  39. Zhao L, Li X, Yang L, Sun L, Mu S, Zong H, et al. Evaluation of remodeling and regeneration of electrospun PCL/fibrin vascular grafts in vivo. Materials Science and Engineering: C. 2021;118:111441. https://doi.org/10.1016/j.msec.2020.111441
  40. Fang S, Ahlmann AH, Langhorn L, Hussein K, Sørensen JA, Guan X, et al. Small diameter polycaprolactone vascular grafts are patent in sheep carotid bypass but require antithrombotic therapy. Regenerative Medicine. 2021;16(2):117-30. 10.2217/rme-2020-0171
  41. Li P, Jin D, Dou J, Wang L, Wang Y, Jin X, et al. Nitric oxide-releasing poly(ε-caprolactone)/S-nitrosylated keratin biocomposite scaffolds for potential small-diameter vascular grafts. Int J Biol Macromol. 2021;189:516-27. https://doi.org/10.1016/j.ijbiomac.2021.08.147
  42. Fu J, Wang M, De Vlaminck I, Wang Y. Thick PCL Fibers Improving Host Remodeling of PGS-PCL Composite Grafts Implanted in Rat Common Carotid Arteries. Small. 2020;16(52):2004133. https://doi.org/10.1002/smll.202004133
  43. Ye L, Takagi T, Tu C, Hagiwara A, Geng X, Feng Z. The performance of heparin modified poly(ε-caprolactone) small diameter tissue engineering vascular graft in canine—A long-term pilot experiment in vivo. Journal of Biomedical Materials Research Part A. 2021;109(12):2493-505. https://doi.org/10.1002/jbm.a.37243
  44. Jin X, Geng X, Jia L, Xu Z, Ye L, Gu Y, et al. Preparation of Small-Diameter Tissue-Engineered Vascular Grafts Electrospun from Heparin End-Capped PCL and Evaluation in a Rabbit Carotid Artery Replacement Model. Macromolecular Bioscience. 2019;19(8):1900114. https://doi.org/10.1002/mabi.201900114
  45. Abdal-hay A, Sheikh FA, Gómez-Cerezo N, Alneairi A, Luqman M, Pant HR, et al. A review of protein adsorption and bioactivity characteristics of poly ε-caprolactone scaffolds in regenerative medicine. European Polymer Journal. 2022;162:110892. https://doi.org/10.1016/j.eurpolymj.2021.110892
  46. Wang Z, Zheng W, Wu Y, Wang J, Zhang X, Wang K, et al. Differences in the performance of PCL-based vascular grafts as abdominal aorta substitutes in healthy and diabetic rats. Biomaterials Science. 2016;4(10):1485-92. 10.1039/C6BM00178E
  47. Fukunishi T, Best CA, Sugiura T, Shoji T, Yi T, Udelsman B, et al. Tissue-Engineered Small Diameter Arterial Vascular Grafts from Cell-Free Nanofiber PCL/Chitosan Scaffolds in a Sheep Model. PLOS ONE. 2016;11(7):e0158555. 10.1371/journal.pone.0158555
  48. de Valence S, Tille J-C, Mugnai D, Mrowczynski W, Gurny R, Möller M, et al. Long term performance of polycaprolactone vascular grafts in a rat abdominal aorta replacement model. Biomaterials. 2012;33(1):38-47. https://doi.org/10.1016/j.biomaterials.2011.09.024
  49. Raeisdasteh Hokmabad V, Davaran S, Ramazani A, Salehi R. Design and fabrication of porous biodegradable scaffolds: a strategy for tissue engineering. Journal of Biomaterials Science, Polymer Edition. 2017;28(16):1797-825. 10.1080/09205063.2017.1354674
  50. saghebasl S, Davaran S, Rahbarghazi R, Montaseri A, Salehi R, Ramazani A. Synthesis and in vitro evaluation of thermosensitive hydrogel scaffolds based on (PNIPAAm-PCL-PEG-PCL-PNIPAAm)/Gelatin and (PCL-PEG-PCL)/Gelatin for use in cartilage tissue engineering. Journal of Biomaterials Science, Polymer Edition. 2018;29(10):1185-206. 10.1080/09205063.2018.1447627
  51. Hokmabad VR, Davaran S, Aghazadeh M, Rahbarghazi R, Salehi R, Ramazani A. Fabrication and characterization of novel ethyl cellulose-grafted-poly (ɛ-caprolactone)/alginate nanofibrous/macroporous scaffolds incorporated with nano-hydroxyapatite for bone tissue engineering. Journal of Biomaterials Applications. 2019;33(8):1128-44. 10.1177/0885328218822641
  52. Fattahi FS. Nano-dimension pore structure analysis of poly(ethylene terephthalate) knitted materials: An insight combining SEM images. Nanochemistry Research. 2021;6(2):143-8. 10.22036/ncr.2021.02.002
  53. Fattahi F, Khodami A, Avinc O. Nano-Structure Roughening on Poly(Lactic Acid)PLA Substrates: Scanning Electron Microscopy (SEM) Surface Morphology Characterization. Journal of Nanostructures. 2020;10(2):206-16. 10.22052/JNS.2020.02.002