Collagen-chondroitin sulfate-based PLLA-SAIB-coated rhBMP-2 delivery system for bone repair.
Bone morphogenetic proteins (BMPs) are osteoinductive proteins used intensively in clinical investigations involving various bone-related treatments. Owing to their high potential in new bone formation they require local application at the treatment site. For this purpose various controlled delivery systems with BMPs as the excipients have been prepared in recent years. Focusing on this clinical need a disc-shaped BMP carrier was designed as a local delivery system using soluble collagen and chondroitin sulfate. In situ release studies carried out with a model protein (FITC-labeled Protein A) presented a very high rate of release; with most of the protein content being released within 24 h. This rate could be decreased by providing a poly(L-lactide) (PLLA) and sucrose acetate isobutyrate-based (SAIB-based) coat around the release system, applied after BMP loading. In this way, it was possible to extend the release period from 24 h to about 12 days. In situ release of BMP from the same carriers, as quantitated using an ELISA kit, was even slower, with 50% of the protein being released in 15 days. In order to be able to secure the BMP delivery system at the bone defect site and to provide support a mesh knitted using Vicryl sutures and bonded with poly(L-lactide-co-glycolide) (PLGA) was tested in in vivo. Two time periods, 1 and 3 weeks, were used to evaluate the healing process. Osteoinduction by the BMP carrier system was assessed by histology-based bone scoring and X-ray examinations. PLLA-SAIB-coated collagen discs containing BMP presented good biocompatibility and optimum osteogenic stimulation. Structural changes in histological micrographs at week 1 indicated dose-dependent periosteal ossification. At the end of week 3 histological findings with both BMP (1 and 2 microg) doses were almost the same.
Keskin
Dilek Sendil
DS
Department of Engineering Sciences, Middle East Technical University, 06531 Ankara, Turkey.
Tezcaner
Aysen
A
Korkusuz
Petek
P
Korkusuz
Feza
F
Hasirci
Vasif
V
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000737:chemistry; D001861:Bone Regeneration / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000737:chemistry*; D020099:Coated Materials, Biocompatible / Q000008:administration & dosage / Q000737:chemistry; D024042:Collagen Type I / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D004058:Diffusion; D004548:Elasticity; D005264:Femoral Fractures / Q000175:diagnosis / Q000188:drug therapy*; D017102:Fracture Healing / Q000187:drug effects*; D006244:Hardness; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008422:Materials Testing; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000031:analogs & derivatives* / Q000737:chemistry*; D013718:Tensile Strength; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome
C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D020099:Coated Materials, Biocompatible; D024042:Collagen Type I; D003692:Delayed-Action Preparations; D011091:Polyesters; D011108:Polymers; D016212:Transforming Growth Factor beta; D019344:Lactic Acid; C033616:poly(lactide); D013395:Sucrose; D002809:Chondroitin Sulfates; C002885:sucrose acetate isobutyrate