Long‐term cell‐mediated protein release from calcium phosphate ceramics

Abstract

Efficient delivery of growth factors from carrier biomaterials depends critically on the release kinetics of the proteins that constitute the carrier. Immobilizing growth factors to calcium phosphate ceramics has been attempted by direct adsorption and usually resulted in a rapid and passive release of the superficially adherent proteins. The insufficient retention of growth factors limited their bioavailability and their efficacy in the treatment of bone regeneration. In this study, a coprecipitation technique of proteins and calcium phosphate was employed to modify the delivery of proteins from biphasic calcium phosphate (BCP) ceramics. To this end, tritium-labeled bovine serum albumin ([(3)H]BSA) was utilized as a model protein to analyze the coprecipitation efficacy and the release kinetics of the protein from the carrier material. Conventional adsorption of [(3)H]BSA resulted in a rapid and passive release of the protein from BCP ceramics, whereas the coprecipitation technique effectively prevented the burst release of [(3)H]BSA. Further analysis of the in vitro kinetics demonstrated a sustained, cell-mediated release of coprecipitated [(3)H]BSA from BCP ceramics induced by resorbing osteoclasts. The coprecipitation technique described herein, achieved a physiologic-like protein release, by incorporating [(3)H]BSA into its respective carriers, rendering it a promising tool in growth factor delivery for bone healing.

Biomimetic coatings for bone tissue engineering of critical-sized defects

“…By the fifth week, the mild acute inflammatory response was almost completely quelled, but the resorption of coatings by FBGCs and osteoclasts continued. The release of coating-incorporated proteins mediated by osteoclasts was corroborated by our previous study (Wernike et al 2009) Although the cell-mediated release of coating-incorporated proteins by osteoclasts was proved by others' and our studies, whether such a release mode can also be mediated by FBGCs remains unclear. Although FBGCs are considered to originate from the fusion of monocyte -macrophage lineage cells and have been induced in vitro from human blood monocytes as Langhans giant cells and osteoclasts, molecular and cell biology studies have shown that the FBGC has distinctly different functional and phenotypic characteristics (Anderson 2000).…”

“…In contrast, a coating-incorporated depot of such an agent is liberated gradually (Liu et al 2005) and in a cell-mediated manner over a period of several weeks (Wernike et al 2009). Under these conditions, osteogenic activity can be efficaciously induced and sustained at both ectopic and orthotopic sites in animal models (Liu et al 2005(Liu et al , 2007a.…”

The BMP2 variant L51P restores the osteogenic differentiation of human mesenchymal stromal cells in the presence of intervertebral disc cells

“…Efficient and controlled delivery of growth factors from the carrier critically depends on their release kinetics. We propose L51P immobilised on β-tricalcium phosphate (β-TCP) ceramics with a calcium phosphate co-precipitation technique previously described (Choy et al, 2014;Wernike et al, 2010) for spinal fusion surgery, as well as for reconstruction of large bone defects. This modified form of local and sustained delivery system might allow a long-term release of the biologically active L51P into the surrounding extracellular matrix, possibly by cellmediated mechanism, such as the resorption activity of bone marrow cells differentiated into osteoclasts.…”

<i>In vitro</i> study on the osteogenesis enhancement effect of BMP-2 incorporated biomimetic apatite coating on titanium surfaces

“…The release behavior of the bioactive molecules is affected by the incorporation efficacy, degradation speed of the coating, as well as the site where the bioactive molecules are bound or absorbed. Generally, there are three release mechanisms: 1) nature diffusion resulted by the concentration gradient; 2) release along the dissolving of the coating; and 3) release along the degradation of the coating caused by various enzymes, osteoclast or lymphocyte 36) . In our study, the releasing profiles of all the groups consist of two stages: the initial burst release stage and the latter slow release stage.…”