PLGA microsphere/calcium phosphate cement composites for tissue engineering: in vitro release and degradation characteristics.
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.
Habraken
W J E M
WJ
Department of Periodontology and Biomaterials, College of Dental Science, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Wolke
J G C
JG
Mikos
A G
AG
Jansen
J A
JA
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D001843:Bone Cements / Q000737:chemistry / Q000378:metabolism; D002130:Calcium Phosphates / Q000737:chemistry / Q000378:metabolism; D002417:Cattle; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism; D008422:Materials Testing; D008863:Microspheres; D008970:Molecular Weight; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D023822:Tissue Engineering / Q000295:instrumentation*
D001672:Biocompatible Materials; D001843:Bone Cements; D002130:Calcium Phosphates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C020243:calcium phosphate