PMID- 15626448 OWN - NLM STAT- MEDLINE DCOM- 20050712 LR - 20161124 IS - 0142-9612 (Print) IS - 0142-9612 (Linking) VI - 26 IP - 18 DP - 2005 Jun TI - Collagen-chondroitin sulfate-based PLLA-SAIB-coated rhBMP-2 delivery system for bone repair. PG - 4023-34 AB - 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. FAU - Keskin, Dilek Sendil AU - Keskin DS AD - Department of Engineering Sciences, Middle East Technical University, 06531 Ankara, Turkey. FAU - Tezcaner, Aysen AU - Tezcaner A FAU - Korkusuz, Petek AU - Korkusuz P FAU - Korkusuz, Feza AU - Korkusuz F FAU - Hasirci, Vasif AU - Hasirci V LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 RN - 0 (Bmp2 protein, rat) RN - 0 (Bone Morphogenetic Protein 2) RN - 0 (Bone Morphogenetic Proteins) RN - 0 (Coated Materials, Biocompatible) RN - 0 (Collagen Type I) RN - 0 (Delayed-Action Preparations) RN - 0 (Polyesters) RN - 0 (Polymers) RN - 0 (Transforming Growth Factor beta) RN - 33X04XA5AT (Lactic Acid) RN - 459TN2L5F5 (poly(lactide)) RN - 57-50-1 (Sucrose) RN - 9007-28-7 (Chondroitin Sulfates) RN - H5KI1C3YTV (sucrose acetate isobutyrate) SB - IM MH - Animals MH - Bone Morphogenetic Protein 2 MH - Bone Morphogenetic Proteins/*administration & dosage/chemistry MH - Bone Regeneration/drug effects MH - Chondroitin Sulfates/*chemistry MH - Coated Materials, Biocompatible/administration & dosage/chemistry MH - Collagen Type I/*chemistry MH - Delayed-Action Preparations/*administration & dosage/chemistry MH - Diffusion MH - Elasticity MH - Femoral Fractures/diagnosis/*drug therapy MH - Fracture Healing/*drug effects MH - Hardness MH - Lactic Acid/*chemistry MH - Male MH - Materials Testing MH - Polyesters MH - Polymers/*chemistry MH - Rats MH - Rats, Sprague-Dawley MH - Sucrose/*analogs & derivatives/*chemistry MH - Tensile Strength MH - Transforming Growth Factor beta/*administration & dosage/chemistry MH - Treatment Outcome EDAT- 2005/01/01 09:00 MHDA- 2005/07/13 09:00 CRDT- 2005/01/01 09:00 PHST- 2004/07/15 00:00 [received] PHST- 2004/09/28 00:00 [accepted] PHST- 2005/01/01 09:00 [pubmed] PHST- 2005/07/13 09:00 [medline] PHST- 2005/01/01 09:00 [entrez] AID - S0142-9612(04)00902-0 [pii] AID - 10.1016/j.biomaterials.2004.09.063 [doi] PST - ppublish SO - Biomaterials. 2005 Jun;26(18):4023-34. doi: 10.1016/j.biomaterials.2004.09.063.