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Cholesteryl group- and acryloyl group-bearing pullulan nanogel to deliver BMP2 and FGF18 for bone tissue engineering.

Abstract
To create a drug delivery system that allows the controlled release of proteins, such as growth factors, over a long-term period, cholesteryl group- and acryloyl group-bearing pullulan (CHPOA) nanogels were aggregated to form fast-degradable hydrogels (CHPOA/hydrogels) by cross-linking with thiol-bearing polyethylene glycol. The gold standard of clinical bone reconstruction therapy with a physiologically active material is treatment with recombinant human bone morphogenetic protein 2 (BMP2); however, this approach has limitations, such as inflammation, poor cost-efficiency, and varying interindividual susceptibility. In this study, two distinct growth factors, BMP2 and recombinant human fibroblast growth factor 18 (FGF18), were applied to a critical-size skull bone defect for bone repair by the CHPOA/hydrogel system. The CHPOA-FGF18/hydrogel displayed identical results to the control CHPOA-PBS/hydrogel, and the CHPOA-BMP2/hydrogel treatment imperfectly induced bone repair. By contrast, the CHPOA-FGF18 + BMP2/hydrogel treatment strongly enhanced and stabilized the BMP2-dependent bone repair, inducing osteoprogenitor cell infiltration inside and around the hydrogel. This report indicates that the CHPOA/hydrogel system can successfully deliver two different proteins to the bone defect to induce effective bone repair. The combination of the CHPOA/hydrogel system with the growth factors FGF18 and BMP2 might be a step towards efficient bone tissue engineering.
AuthorsMasako Fujioka-Kobayashi, Masato S Ota, Asako Shimoda, Ken-ichi Nakahama, Kazunari Akiyoshi, Youji Miyamoto, Sachiko Iseki
JournalBiomaterials (Biomaterials) Vol. 33 Issue 30 Pg. 7613-20 (Oct 2012) ISSN: 1878-5905 [Electronic] Netherlands
PMID22800537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier Ltd. All rights reserved.
Chemical References
  • Acrylates
  • Bone Morphogenetic Protein 2
  • Glucans
  • Nanogels
  • Recombinant Proteins
  • Rhodamines
  • Transforming Growth Factor beta
  • fibroblast growth factor 18
  • polyethylene glycol polyethyleneimine nanogel
  • recombinant human bone morphogenetic protein-2
  • Polyethylene Glycols
  • Fibroblast Growth Factors
  • pullulan
  • Polyethyleneimine
  • Cholesterol
  • acrylic acid
Topics
  • Acrylates (chemistry)
  • Animals
  • Bone Morphogenetic Protein 2 (pharmacology)
  • Bone Regeneration (drug effects)
  • Bone and Bones (diagnostic imaging, drug effects, pathology)
  • Cell Lineage (drug effects)
  • Cholesterol (chemistry)
  • Drug Delivery Systems
  • Fibroblast Growth Factors (pharmacology)
  • Glucans (chemistry)
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Nanogels
  • Osteoblasts (drug effects, pathology)
  • Polyethylene Glycols (chemistry)
  • Polyethyleneimine (chemistry)
  • Recombinant Proteins (pharmacology)
  • Rhodamines (metabolism)
  • Tissue Engineering (methods)
  • Tomography, X-Ray Computed
  • Transforming Growth Factor beta (pharmacology)
  • Wound Healing (drug effects)

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