PLGA microsphere/calcium phosphate cement composites for tissue engineering: in vitro release and degradation characteristics

Authors: Habraken, W.J.E.M.1; Wolke, J.G.C.1; Mikos, A.G.2; Jansen, J.A.1

Source: Journal of Biomaterials Science, Polymer Edition, Volume 19, Number 9, 2008 , pp. 1171-1188(18)

Publisher: VSP, an imprint of Brill

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Abstract:

Bone cements with biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres have already been proven to provide a macroporous calcium phosphate cement (CPC) during in situ microsphere degradation. Furthermore, in vitro/in vivo release studies with these PLGA microsphere/CPC composites (PLGA/CPCs) showed a sustained release of osteo-inductive growth factor when drug was distributed inside/onto the microspheres. The goal of this study was to elucidate the mechanism behind drug release from PLGA/CPC. For this, in vitro release and degradation characteristics of a low-molecular-weight PLGA/CPC (Mw = 5 kg/mol) were determined using bovine serum albumin (BSA) as a model protein. Two loading mechanisms were applied; BSA was either adsorbed onto the microspheres or incorporated inside the microspheres during double-emulsion. BSA release from PLGA microspheres and CPC was also measured and used as reference. Results show fast degrading polymer microspheres which produced a macroporous scaffold within 4 weeks, but also showed a concomitant release of acidic degradation products. BSA release from the PLGA/CPC was similar to the CPC samples and showed a pattern consisting of a small initial release, followed by a period of almost no sustained release. Separate PLGA microspheres exhibited a high burst release and release efficiency that was higher with the adsorbed samples. Combining degradation and release data we can conclude that for the PLGA/CPC samples BSA re-adsorbed to the cement surface after being released from the microspheres, which was mediated by the pH decrease during microsphere degradation.

Keywords: PLGA MICROSPHERES; CALCIUM PHOSPHATE CEMENT; BSA RELEASE; DEGRADATION

Document Type: Research article

DOI: http://dx.doi.org/10.1163/156856208785540136

Affiliations: 1: Department of Periodontology and Biomaterials, College of Dental Science, Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands 2: Department of Bioengineering, Rice University, Houston, TX, USA

Publication date: 2008-09-01

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