title: Promoting angiogenesis with mesoporous microcarriers through a synergistic action of delivered silicon ion and VEGF.
abstract: Angiogenic capacity of biomaterials is a key asset to drive vascular ingrowth during tissue repair and regeneration. Here we design a unique angiogenic microcarrier based on sol-gel derived mesoporous silica. The microspheres offer a potential angiogenic stimulator, Si ion, 'intrinsically' within the chemical structure. Furthermore, the highly mesoporous nature allows the loading and release of angiogenic growth factor 'extrinsically'. The Si ion is released from the microcarriers at therapeutic ranges (over a few ppm per day), which indeed up-regulates the expression of hypoxia inducing factor 1α (HIF1α) and stabilizes it by blocking HIF-prolyl hydroxylase 2 (PHD2) in HUVECs. This in turn activates the expression of a series of proangiogenic molecules, including bFGF, VEGF, and eNOS. VEGF is incorporated effectively within the mesopores of microcarriers and is then released continuously over a couple of weeks. The Si ion and VEGF released from the microcarriers synergistically stimulate endothelial cell functions, such as cell migration, chemotactic homing, and tubular networking. Furthermore, in vivo neo-blood vessel sprouting in chicken chorioallantoic membrane model is significantly promoted by the Si/VEGF releasing microcarriers. The current study demonstrates the synergized effects of Si ion and angiogenic growth factor through a biocompatible mesoporous microsphere delivery platform, and the concept provided here may open the door to a new co-delivery system of utilizing ions with growth factors for tissue repair and regeneration.
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea; Department of Nanobiomedical Science & BK21 PLUS Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Khandmaa
authors.initials: K
authors.lastname: Dashnyam
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea; Department of Nanobiomedical Science & BK21 PLUS Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Guang-Zhen
authors.initials: GZ
authors.lastname: Jin
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea; Department of Nanobiomedical Science & BK21 PLUS Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Joong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea; Department of Nanobiomedical Science & BK21 PLUS Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; UIC Regenerative Medicine Research Institute, Universitat Internacional de Catalunya, Barcelona, Spain.
authors.forename: Roman
authors.initials: R
authors.lastname: Perez
authors.affiliation: Department of Biochemistry, College of Medicine, Inha University, Incheon, Republic of Korea.
authors.forename: Jun-Hyeog
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea; Department of Nanobiomedical Science & BK21 PLUS Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan 330-714, Republic of Korea; Department of Biochemical Engineering, University College London, London, WC1H 0AH, United Kingdom. Electronic address: kimhw@dku.edu.
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Kim
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage; D002214:Capsules / Q000008:administration & dosage / Q000737:chemistry*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D004338:Drug Combinations; D004357:Drug Synergism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007477:Ions / Q000008:administration & dosage* / Q000737:chemistry; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology*; D016062:Porosity; D012825:Silicon / Q000008:administration & dosage* / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000097:blood
chemical_list: D043925:Angiogenesis Inducing Agents; D002214:Capsules; D004338:Drug Combinations; D007477:Ions; D042461:Vascular Endothelial Growth Factor A; D012825:Silicon
keywords: Angiogenesis; Co-delivery; Mesoporous; Microsphere; Silicon ion; VEGF