title: A dual delivery of substance P and bone morphogenetic protein-2 for mesenchymal stem cell recruitment and bone regeneration.
abstract: Implantation of ex vivo expanded and osteogenically differentiated mesenchymal stem cells (MSCs) for bone regeneration has drawbacks for clinical applications, such as poor survival of implanted cells and increased treatment expenses. As a new approach for bone regeneration that can circumvent these limitations, we propose dual delivery of substance P (SP) and bone morphogenetic protein-2 (BMP-2) to facilitate endogenous stem cell recruitment to bone defects by SP and subsequent in situ osteogenic differentiation of those cells by BMP-2. A heparin-conjugated fibrin (HCF) gel enabled dual delivery with fast release of SP and slow release of BMP-2, which would be ideal for prompt recruitment of endogenous stem cells in the first stage and time-consuming osteogenic differentiation of the recruited stem cells in the second stage. The HCF gels with SP and/or BMP-2 were implanted into mouse calvarial defects for 8 weeks. Local delivery of SP to the calvarial defects using HCF gel was more effective in recruiting MSCs to the calvarial defects than intraperitoneal or intravenous administration of SP. Many of the cells recruited by SP underwent osteogenic differentiation through local delivery of BMP-2. The efficacy of in vivo bone regeneration was significantly higher in the SP/BMP-2 dual delivery group. The dual delivery of SP and BMP-2 using the HCF gel therefore has potential as an effective bone regeneration strategy.
authors.affiliation: 1 School of Chemical and Biological Engineering, Seoul National University , Seoul, Republic of Korea.
authors.forename: Seong-Seo
authors.initials: SS
authors.lastname: Noh
authors.forename: Suk Ho
authors.initials: SH
authors.lastname: Bhang
authors.forename: Wan-Geun
authors.initials: WG
authors.lastname: La
authors.forename: Seahyoung
authors.initials: S
authors.lastname: Lee
authors.forename: Jung-Youn
authors.initials: JY
authors.lastname: Shin
authors.forename: Yoon-Ji
authors.initials: YJ
authors.lastname: Ma
authors.forename: Hyeon-Ki
authors.initials: HK
authors.lastname: Jang
authors.forename: Seokyung
authors.initials: S
authors.lastname: Kang
authors.forename: Min
authors.initials: M
authors.lastname: Jin
authors.forename: Jooyeon
authors.initials: J
authors.lastname: Park
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D005337:Fibrin / Q000494:pharmacology; D005434:Flow Cytometry; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D012886:Skull / Q000187:drug effects / Q000473:pathology; D013373:Substance P / Q000494:pharmacology*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D055396:Bone Morphogenetic Protein 2; D013373:Substance P; D005337:Fibrin; D006493:Heparin