In situ blood vessel regeneration through host stem/progenitor cell mobilization may hold great promise for vascular reconstruction. Neuropeptide substance P (SP) has been shown to accelerate tissue repair by endogenous cell mobilization and recruitment. This study was aimed to evaluate the vascular regeneration potential of SP and heparin co-tethered vascular grafts. Polycaprolactone (PCL), PCL/SP-conjugated poly(L-lactide-co-ε-caprolactone) (PLCL-SP) (SP), and PCL/PLCL-SP/heparin-conjugated PLCL (Hep/SP) vascular grafts were implanted as rat abdominal aorta substitutes for up to 2 weeks and 4 weeks. Ex vivo results delineate that heparin can improve the hemocompatibility and SP can recruit mesenchymal stem cells. Histological and immunohistochemical staining reveal higher cellular infiltration and homogeneous cell distribution in SP and Hep/SP grafts than that of the control grafts. At 4 weeks, SP and Hep/SP grafts show the presence of cobblestone-like cells on the luminal side, whereas the surface of PCL grafts remains bare. Immunoflourescence staining using von Willibrand factor (vWF) antibody shows improved endothelialization in SP and Hep/SP grafts compared with the PCL grafts. SP and Hep/SP grafts also exhibit more numbers of α-smooth muscle actin-positive cells and laminin+ blood vessels than that of the control group. Evaluation of inflammatory response reveals that three groups did not differ in terms of the numbers of CD68+ macrophages, whereas SP and Hep/SP grafts show higher numbers of CD206+ macrophages. These results indicate that SP can induce endogenous tissue regeneration in cell-free grafts, which may be of great interest for regenerative medicine and tissue engineering applications.
|Number of pages||15|
|Journal||Journal of Biomedical Materials Research - Part B Applied Biomaterials|
|Publication status||Published - 2019 Jul|
Bibliographical noteFunding Information:
Additional Supporting Information may be found in the online version of this article. †These authors contributed equally to this work. Correspondence to: S. H. Kim; e-mail: firstname.lastname@example.org and L. Wang; e-mail: email@example.com Contract grant sponsor: KIST Institutional Program and KU-KIST Graduate School of Converging Science and Technology Program Contract grant sponsor: KU-KIST Graduate School Contract grant sponsor: KIST Contract grant sponsor: National Nature Science Foundation of China; contract grant number: 31670990, 81530059, 81772000
This work was supported by the National Nature Science Foundation of China (Grant number 31670990, 81530059, 81772000), KIST Institutional Program, and by the KU-KIST Graduate School of Converging Science and Technology Program.
© 2018 Wiley Periodicals, Inc.
- bioactive material
- stem cells
- tissue engineering
- vascular graft
ASJC Scopus subject areas
- Biomedical Engineering