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Covalent immobilization of stem cell inducing/recruiting factor and heparin on cell‐free small‐diameter vascular graft for accelerated in situ tissue regeneration
Author(s) -
Shafiq Muhammad,
Jung Youngmee,
Kim Soo Hyun
Publication year - 2016
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.35666
Subject(s) - mesenchymal stem cell , tissue engineering , transplantation , biomedical engineering , materials science , regeneration (biology) , decellularization , microbiology and biotechnology , biocompatibility , elastin , pathology , medicine , biology , surgery , metallurgy
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‐ɛ‐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. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1352–1371, 2016.