Material-related effects of BMP-2 delivery systems on bone regeneration.
Material-related effects of a brushite and a PLGA controlled release system loaded with two distinct doses of bone morphogenetic protein-2 (BMP-2) (3.5 and 17.5 μg), pre-encapsulated in poly(lactic-co-glycolic acid) (PLGA), were investigated in an intramedullary femur defect model in rabbits. The systems were characterized in vitro and in vivo over 12 weeks in terms of morphology, release kinetics, porosity, molecular weight, and composition using scanning electron microscopy, mercury porosimetry, radioactivity counting, X-ray diffractometry, differential scanning calorimetry, and gel permeation chromatography. During the experimental period the investigated systems underwent significant changes in vitro as well as in vivo. It should be stressed that the two in vitro release patterns were similar, however in vivo parallel profiles were observed with a higher burst effect for BMP-2 in the PLGA system. The PLGA system degraded and disintegrated significantly faster than the brushite system, which suffered slowly progressing external erosion and, additionally, material resorption by osteoclasts in vivo. The consequences of this were reflected in the degree of bone regeneration. Although a sustained delivery of BMP-2 was achieved with both systems, the brushite construct, independent of the loaded growth factor dose, failed to consistently induce defect repair, a result attributed to its slow resorption rate. In contrast, the PLGA system resulted in complete regeneration with mature trabecular bone formation 8 weeks after implantation.
Department of Chemical Engineering and Pharmaceutical Technology, Universidad de La Laguna, San Cristóbal de La Laguna, Spain.
Antonio
A
Hernández
Esther
E
Sánchez
Isabel
I
Soriano
Ricardo
R
Reyes
Araceli
A
Delgado
Carmen
C
Évora
D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage* / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002130:Calcium Phosphates / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005269:Femur / Q000187:drug effects / Q000473:pathology; D020007:Implants, Experimental; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity / Q000187:drug effects; D011817:Rabbits; D014961:X-Ray Diffraction
D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D015675:Osteocalcin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C494366:calcium phosphate, dibasic, dihydrate