Cell‐mediated BMP‐2 release from a novel dual‐drug delivery system promotes bone formation. Issue 12 (29th October 2013)

• Record Type: Journal Article
• Authors: Liu, Tie; Wu, Gang; Zheng, Yuanna; Wismeijer, Daniel; Everts, Vincent; Liu, Yuelian
• Is Part Of: Clinical oral implants research. Volume 25:Issue 12(2014:Dec.)
• Page Start: 1412
• Page End: 1421
• Publication Date: 2013-10-29
• Subjects: Dental implants -- Research -- Periodicals; 617.69
• DOI: 10.1111/clr.12283
• Languages: English
• ISSNs: 0905-7161

Abstract

<abstract abstract-type="main" id="clr12283-abs-0001"> <title>Abstract</title> <sec id="clr12283-sec-0001" sec-type="section"> <title>Objectives</title> <p>In this study, a novel biomimetic calcium phosphate bone substitute (BioCaP) is introduced as a dual‐drug release system with two drug/protein delivery modes: protein is incorporated into (i) the interior of BioCaP (an internal depot); and (ii) a superficial calcium phosphate coating on BioCaP (a surface‐coated depot). Our aim is to investigate each of the two delivery modes of BioCaP. Our hypotheses are that (i) both of the drug delivery modes, in <italic>in vitro</italic> as well as <italic>in vivo</italic> environment, can achieve a sustained cell‐mediated protein release; and (ii) BioCaP with these two delivery modes with incorporated bone morphogenetic protein‐2 (BMP‐2) promotes bone formation.</p> </sec> <sec id="clr12283-sec-0002" sec-type="section"> <title>Materials and Methods</title> <p>Tablets of BioCaP were prepared with different carrying modes using bovine serum albumin (BSA) as model protein. The release of this protein was analysed (<italic>n</italic> = 6 per group). Granules of BioCaP with different carrying modes of BMP‐2 were implanted subcutaneously in rats (<italic>n</italic> = 6 animals per group). Samples were collected after 5 weeks for histomorphometric analysis.</p> </sec> <sec id="clr12283-sec-0003" sec-type="section"> <title>Results</title> <p> <italic>In vitro</italic> data showed that the internal and surface‐coated depots of BSA resulted in a sustained osteoclast‐mediated release, while the adsorbed BSA was rapidly released, and this release was not affected by osteoclasts. <italic>In vivo</italic> data showed that the volume densities of bone, bone marrow, and blood vessels were significantly higher in samples where BMP‐2 was incorporated internally or in the coating compared with granules with adsorbed growth factor. Osteoclast‐like cells were associated with the granules, and resorption lacunae were frequently observed.</p> </sec> <sec id="clr12283-sec-0004" sec-type="section"> <title>Conclusion</title> <p>It is shown that different modes of incorporation of BMP‐2 on and in BioCaP granules have a beneficial effect on the formation of ectopic bone. This dual‐drug release system makes BioCaP granule a promising tool for delivering multiple therapeutic agents for different clinical applications.</p> </sec> </abstract>