title: Therapeutic foam scaffolds incorporating biopolymer-shelled mesoporous nanospheres with growth factors.
abstract: A novel therapeutic scaffolding system of engineered nanocarriers within a foam matrix for the long-term and sequential delivery of growth factors is reported. Mesoporous silica nanospheres were first functionalized to have an enlarged mesopore size (12.2nm) and aminated surface, which was then shelled by a biopolymer, poly(lactic acid) (PLA) or poly(ethylene glycol) (PEG), via electrospraying. The hybrid nanocarrier was subsequently combined with collagen to produce foam scaffolds. Bovine serum albumin (BSA), used as a model protein, was effectively loaded within the enlarged nanospheres. The biopolymer shell substantially prolonged the release period of BSA (2-3weeks from shelled nanospheres vs. within 1week from bare nanospheres), and the release rate was highly dependent on the shell composition (PEG>PLA). Collagen foam scaffolding of the shelled nanocarrier further slowed down the protein release, while enabling the incorporation of a rapidly releasing protein, which is effective for sequential protein delivery. Acidic fibroblast growth factor (aFGF), loaded onto the shelled-nanocarrier scaffolds, was released over a month at a highly sustainable rate, profiling a release pattern similar to that of BSA. The biological activity of the aFGF was evidenced by the significant proliferation of osteoblastic precursor cells in the aFGF-releasing scaffolds. Furthermore, the aFGF-delivering scaffolds implanted in rat subcutaneous tissue for 2weeks showed a substantially enhanced invasion of fibroblasts with a homogeneous population. Taken together, it is concluded that the biopolymer encapsulation of mesoporous nanospheres effectively prolongs the release of growth factors over weeks to a month, providing a nanocarrier platform for a long-term growth factor delivery. Moreover, the foam scaffolding of the nanocarrier system is a potential therapeutic three-dimensional matrix for cell culture and tissue engineering.
authors: Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea.
authors: Tae-Hyun
authors: TH
authors: Kim
authors: Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea.
authors: Mohamed
authors: M
authors: Eltohamy
authors: Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea.
authors: Meeju
authors: M
authors: Kim
authors: Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea.
authors: Roman A
authors: RA
authors: Perez
authors: Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea.
authors: Joong-Hyun
authors: JH
authors: Kim
authors: Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea.
authors: Ye-Rang
authors: YR
authors: Yun
authors: Department of Biochemistry, Inha University Medical College, Incheon, Republic of Korea.
authors: Jun-Hyeog
authors: JH
authors: Jang
authors: Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea.
authors: Eun-Jung
authors: EJ
authors: Lee
authors: Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, University College London, 256 Gray's Inn Road, London WC1X 8LD, UK.
authors: Jonathan C
authors: JC
authors: Knowles
authors: Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan 330-714, Republic of Korea. Electronic address: kimhw@dku.edu.
authors: Hae-Won
authors: HW
authors: Kim
mesh_terms: D001704:Biopolymers / Q000737:chemistry*; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D054457:Tissue Scaffolds
chemical_list: D001704:Biopolymers; D016220:Fibroblast Growth Factor 1
keywords: Growth factors; Mesoporous nanospheres; Protein delivery; Therapeutic system; Tissue regeneration