title: Mineralized poly(lactic acid) scaffolds loading vascular endothelial growth factor and the in vivo performance in rat subcutaneous model.
abstract: The functionalization of degradable polymeric scaffolds with therapeutic molecules such as vascular endothelial growth factor (VEGF) is a key strategy to gain better regenerative ability of damaged bone tissue by stimulating vascularization and tissue perfusion. Here, we combined VEGF with poly(lactic acid) (PLA) porous scaffold, after modifying the PLA surface with calcium phosphate (CaP) mineral. The mineralized PLA scaffold (mPLA) showed more effective loading capacity of VEGF than the PLA without mineralization as well as profiled sustainable release of VEGF for up to a couple of weeks. The VEGF-loaded mPLA scaffold presented significantly improved proliferation of primary endothelial cells for up to 7 days, with respect to the scaffold without the VEGF loading. The performance of the engineered scaffold was assessed after subcutaneous implantation in rats for 4 weeks. Histological results showed favorable tissue compatibility of both the mPLA scaffolds (with and without VEGF loading), as characterized by infiltration of inflammatory cells, formation of fibrous capsule, and ingrowth of fibroblasts into the matrices. Immunohistochemical staining of the von Willebrand Factor revealed significantly improved formation of neo-capillaries in the VEGF-loaded mPLA. Based on this study, the strategy of VEGF loading onto mineralized PLA scaffold is considered beneficial for gaining improved vascularization of the polymeric scaffolds, suggesting potential applications for bone tissue engineering.
authors.affiliation: Institute of Tissue Regeneration Engineering (ITREN), Dankook University, South Korea.
authors.forename: Joong-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Tae-Hyun
authors.initials: TH
authors.lastname: Kim
authors.forename: Guang-Zhen
authors.initials: GZ
authors.lastname: Jin
authors.forename: Jeong-Hui
authors.initials: JH
authors.lastname: Park
authors.forename: Ye-Rang
authors.initials: YR
authors.lastname: Yun
authors.forename: Jun-Hyeog
authors.initials: JH
authors.lastname: Jang
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Kim
mesh_terms: D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D042783:Endothelial Cells / Q000166:cytology; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D002130:Calcium Phosphates; D020099:Coated Materials, Biocompatible; D011091:Polyesters; D011108:Polymers; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D019344:Lactic Acid; C033616:poly(lactide); C020243:calcium phosphate