^* Calvarial Bone Regeneration Is Enhanced by Sequential Delivery of FGF-2 and BMP-2 from Layer-by-Layer Coatings with a Biomimetic Calcium Phosphate Barrier Layer.

Content Provider	Europe PMC
Author	Gronowicz, Gloria Jacobs, Emily Peng, Tao Zhu, Li Hurley, Marja Kuhn, Liisa T.
Copyright Year	2017
Abstract	A drug delivery coating for synthetic bone grafts has been developed to provide sequential delivery of multiple osteoinductive factors to better mimic aspects of the natural regenerative process. The coating is composed of a biomimetic calcium phosphate (bCaP) layer that is applied to a synthetic bone graft and then covered with a poly-l-Lysine/poly-l-Glutamic acid polyelectrolyte multilayer (PEM) film. Bone morphogenetic protein-2 (BMP-2) was applied before the coating process directly on the synthetic bone graft and then, bCaP-PEM was deposited followed by adsorption of fibroblast growth factor-2 (FGF-2) into the PEM layer. Cells access the FGF-2 immediately, while the bCaP-PEM temporally delays the cell access to BMP-2. In vitro studies with cells derived from mouse calvarial bones demonstrated that Sca-1 and CD-166 positive osteoblast progenitor cells proliferated in response to media dosing with FGF-2. Coated scaffolds with BMP-2 and FGF-2 were implanted in mouse calvarial bone defects and harvested at 1 and 3 weeks. After 1 week in vivo, proliferation of cells, including Sca-1+ progenitors, was observed with low dose FGF-2 and BMP-2 compared to BMP-2 alone, indicating that in vivo delivery of FGF-2 activated a similar population of cells as shown by in vitro testing. At 3 weeks, FGF-2 and BMP-2 delivery increased bone formation more than BMP-2 alone, particularly in the center of the defect, confirming that the proliferation of the Sca-1 positive osteoprogenitors by FGF-2 was associated with increased bone healing. Areas of bone mineralization were positive for double fluorochrome labeling of calcium and alkaline phosphatase staining of osteoblasts, along with increased TRAP+ osteoclasts, demonstrating active bone formation distinct from the bone-like collagen/hydroxyapatite scaffold. In conclusion, the addition of a bCaP layer to PEM delayed access to BMP-2 and allowed the FGF-2 stimulated progenitors to populate the scaffold before differentiating in response to BMP-2, leading to improved bone defect healing.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC5729881&blobtype=pdf
Page Count	12
ISSN	19373341
Volume Number	23
DOI	10.1089/ten.tea.2017.0111
PubMed Central reference number	PMC5729881
Issue Number	23-24
PubMed reference number	28946792
Journal	Tissue Engineering. Part A [Tissue Eng Part A]
e-ISSN	1937335X
Language	English
Publisher	Mary Ann Liebert, Inc.
Publisher Date	2017-11-13
Publisher Place	USA
Access Restriction	Open
Rights License	Copyright 2017, Mary Ann Liebert, Inc.
Subject Keyword	calcium phosphate fibroblast growth factor-2 bone morphogenetic protein-2 bone tissue engineering polyelectrolyte multilayer
Content Type	Text
Resource Type	Article
Subject	Biomaterials Biochemistry Bioengineering Biomedical Engineering