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

• Published in: Journal of biomaterials science. Polymer ed. 2008-01, Vol.19 (9), p.1171-1188
• Main Authors: Habraken, W. J. E. M., Wolke, J. G. C., Mikos, A. G., Jansen, J. A.
• Format: Article
• Language: English
• Subjects: Animals; Biocompatible Materials - chemistry; Biocompatible Materials - metabolism; Bone Cements - chemistry; Bone Cements - metabolism; BSA RELEASE; CALCIUM PHOSPHATE CEMENT; Calcium Phosphates - chemistry; Calcium Phosphates - metabolism; Cattle; DEGRADATION; Hydrogen-Ion Concentration; Lactic Acid - chemistry; Lactic Acid - metabolism; Materials Testing; Microspheres; Molecular Weight; Particle Size; PLGA MICROSPHERES; Polyglycolic Acid - chemistry; Polyglycolic Acid - metabolism; Tissue Engineering - instrumentation
• ISSN: 0920-5063; 1568-5624
• DOI: 10.1163/156856208785540136

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 (M w = 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.