title: Covalent immobilization of stem cell inducing/recruiting factor and heparin on cell-free small-diameter vascular graft for accelerated in situ tissue regeneration.
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-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.
authors.affiliation: Department of Biomedical Engineering, Korea University of Science and Technology (UST) (305-350), Gajeong-Ro, Yuseong-Gu, Daejeon, Korea.|Center for Biomaterials 5, Hwarang-Ro 14-Gil, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seongbuk-Gu, Seoul, 136-791, Republic of Korea.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Shafiq
authors.affiliation: Department of Biomedical Engineering, Korea University of Science and Technology (UST) (305-350), Gajeong-Ro, Yuseong-Gu, Daejeon, Korea.|Center for Biomaterials 5, Hwarang-Ro 14-Gil, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seongbuk-Gu, Seoul, 136-791, Republic of Korea.
authors.forename: Youngmee
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Department of Biomedical Engineering, Korea University of Science and Technology (UST) (305-350), Gajeong-Ro, Yuseong-Gu, Daejeon, Korea.|Center for Biomaterials 5, Hwarang-Ro 14-Gil, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seongbuk-Gu, Seoul, 136-791, Republic of Korea.|NBIT, KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001807:Blood Vessel Prosthesis; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D018914:Cells, Immobilized / Q000166:cytology / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D020007:Implants, Experimental; D007249:Inflammation / Q000473:pathology; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects; D011091:Polyesters / Q000737:chemistry; D051381:Rats; D012038:Regeneration / Q000187:drug effects*; D013194:Staining and Labeling; D013373:Substance P / Q000494:pharmacology; D054457:Tissue Scaffolds / Q000737:chemistry; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D006493:Heparin; D011091:Polyesters; D013373:Substance P; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C016240:polycaprolactone; C033616:poly(lactide)
keywords: electrospinning; in situ tissue regeneration; neovascularization/angiogenesis; stem cell; vascular graft