Abstract
Recently, the benefit of step-wise sequential delivery of fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 from a bioinspired apatite drug delivery system on mouse calvarial bone repair was demonstrated. The thicknesses of the nanostructured poly-l-Lysine/poly-l-Glutamic acid polyelectrolyte multilayer (PEM) and the bone-like apatite barrier layer that make up the delivery system, were varied. The effects of the structural variations of the coating on the kinetics of cell access to a cytotoxic factor delivered by the layered structure were evaluated. FGF-2 was adsorbed into the outer PEM, and cytotoxic antimycin-A (AntiA) was adsorbed to the substrate below the barrier layer to detect the timing of the cell access. While MC3T3-E1 osteoprogenitor cells accessed AntiA after three days, the RAW 264.7 macrophage access occurred within 4 h, unless the PEM layer was removed, in which case the results were reversed. Pits were created in the coating by the RAW 264.7 macrophages and initiated delivery, while the osteoprogenitor cell access to drugs occurred through a solution-mediated coating dissolution, at junctions between the islands of crystals. Macrophage-mediated degradation is therefore a mechanism that controls drug release from coatings containing bioinspired apatite.
Highlights
Bone is a unique organ that is in a state of constant remodeling, in order to maintain a strong structure capable of supporting the varied forces applied to it
The recruitment, proliferation, and differentiation of cells participating in bone injury repair and remodeling are controlled by multiple growth factors; such as, transforming growth factor beta 1 (TGFβ1) [4,5], insulin-like growth factor 1 (IGF-1) [6,7], bone morphogenetic protein-2 (BMP-2) [8], and fibroblast growth factor-2 (FGF-2) [9–12]
System is ideally suited to impact both osteoprogenitors and macrophages, given the long standing recognition of the osteopromotive effects of calcium phosphates on bone formation, and these effects on macrophages seen in the present studies during the first three days of culture, which would apply to modulating inflammation. These studies show that osteoprogenitor cell access rates to a cytotoxic compound embedded below a bone-like apatite coating were difficult to alter, despite increasing the biomimetic calcium phosphate (bCaP) coating thickness five times, from 5.8 ± 1.8 μm to 24.0 ± 2.4 μm
Summary
Bone is a unique organ that is in a state of constant remodeling, in order to maintain a strong structure capable of supporting the varied forces applied to it. The recruitment, proliferation, and differentiation of cells participating in bone injury repair and remodeling are controlled by multiple growth factors; such as, transforming growth factor beta 1 (TGFβ1) [4,5], insulin-like growth factor 1 (IGF-1) [6,7], bone morphogenetic protein-2 (BMP-2) [8], and fibroblast growth factor-2 (FGF-2) [9–12]. Some of these factors are produced and released from the cells participating in the repair, while others become entrapped within the extracellular matrix and are re-released by the actions of bone matrix resorbing cells like osteoclasts and macrophages.
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