Covalent immobilization of stem cell inducing/recruiting factor and heparin on cell-free small-diameter vascular graft for accelerated in situ tissue regeneration

Muhammad Shafiq, Youngmee Jung, Soo Hyun Kim

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The development of cell-free vascular grafts has tremendous potential for tissue engineering. However, thrombus formation, less-than-ideal cell infiltration, and a lack of growth potential limit the application of electrospun scaffolds for in situ tissue-engineered vasculature. To overcome these challenges, here we present development of an acellular tissue-engineered vessel based on electrospun poly(L-lactide-co-e-caprolactone) scaffolds. Heparin was conjugated to suppress thrombogenic responses, and substance P (SP) was immobilized to recruit host cells. SP was released in a sustained manner from scaffolds and recruited human bone marrow-derived mesenchymal stem cells. The biocompatibility and biological performance of the grafts were evaluated by in vivo experiments involving subcutaneous scaffold implantation in Sprague-Dawley rats (n=12) for up to 4 weeks. Histological analysis revealed a higher extent of accumulative host cell infiltration, neotissue formation, collagen deposition, and elastin deposition in scaffolds containing either SP or heparin/SP than in the control groups. We also observed the presence of a large number of laminin-positive blood vessels, von Willebrand factor (vWF+) cells, and alpha smooth muscle actin-positive cells in the explants containing SP and heparin/SP. Additionally, SP and heparin/SP grafts showed the existence of CD90+ and CD105+ MSCs and induced a large number of M2 macrophages to infiltrate the graft wall compared with that observed with the control group. Our cell-free grafts could enhance vascular regeneration by endogenous cell recruitment and by mediating macrophage polarization into the M2 phenotype, suggesting that these constructs may be a promising cell-free graft candidate and are worthy of further in vivo evaluation.

Original languageEnglish
JournalJournal of Biomedical Materials Research - Part A
DOIs
Publication statusAccepted/In press - 2016

    Fingerprint

Keywords

  • Electrospinning
  • in situ tissue regeneration
  • Neovascularization/angiogenesis
  • Stem cell
  • Vascular graft

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials
  • Ceramics and Composites
  • Metals and Alloys

Cite this