TY - JOUR
T1 - Retention of in vitro and in vivo BMP-2 bioactivities in sustained delivery vehicles for bone tissue engineering
AU - Kempen, Diederik H.R.
AU - Lu, Lichun
AU - Hefferan, Teresa E.
AU - Creemers, Laura B.
AU - Maran, Avudaiappan
AU - Classic, Kelly L.
AU - Dhert, Wouter J.A.
AU - Yaszemski, Michael J.
N1 - Funding Information:
The authors gratefully acknowledge the National Institutes of Health (R01 AR45871 and R01 EB03060) and The Netherlands Organization for Health Research and The Netherlands Organization for Health Research and Development ZonMW (Agiko 920-03-325) for financial support. The authors thank Dr. Andras Heijink, Dr. Shanfeng Wang, Mr. James Greutzmacher, Mr. James Herrick, and Mrs. Julie Burgess from the Tissue Engineering and Biomaterials laboratory at Mayo Clinic for their contributions to this work.
PY - 2008/8
Y1 - 2008/8
N2 - In this study, we investigated the in vitro and in vivo biological activities of bone morphogenetic protein 2 (BMP-2) released from four sustained delivery vehicles for bone regeneration. BMP-2 was incorporated into (1) a gelatin hydrogel, (2) poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in a gelatin hydrogel, (3) microspheres embedded in a poly(propylene fumarate) (PPF) scaffold and (4) microspheres embedded in a PPF scaffold surrounded by a gelatin hydrogel. A fraction of the incorporated BMP-2 was radiolabeled with 125I to determine its in vitro and in vivo release profiles. The release and bioactivity of BMP-2 were tested weekly over a period of 12 weeks in preosteoblast W20-17 cell line culture and in a rat subcutaneous implantation model. Outcome parameters for in vitro and in vivo bioactivities of the released BMP-2 were alkaline phosphatase (AP) induction and bone formation, respectively. The four implant types showed different in vitro release profiles over the 12-week period, which changed significantly upon implantation. The AP induction by BMP-2 released from gelatin implants showed a loss in bioactivity after 6 weeks in culture, while the BMP-2 released from the other implants continued to show bioactivity over the full 12-week period. Micro-CT and histological analysis of the delivery vehicles after 6 weeks of implantation showed significantly more bone in the microsphere/PPF scaffold composites (Implant 3, p < 0.02). After 12 weeks, the amount of newly formed bone in the microsphere/PPF scaffolds remained significantly higher than that in the gelatin and microsphere/gelatin hydrogels (p < 0.001), however, there was no statistical difference compared to the microsphere/PPF/gelatin composite. Overall, the results from this study show that BMP-2 could be incorporated into various bone tissue engineering composites for sustained release over a prolonged period of time with retention of bioactivity.
AB - In this study, we investigated the in vitro and in vivo biological activities of bone morphogenetic protein 2 (BMP-2) released from four sustained delivery vehicles for bone regeneration. BMP-2 was incorporated into (1) a gelatin hydrogel, (2) poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in a gelatin hydrogel, (3) microspheres embedded in a poly(propylene fumarate) (PPF) scaffold and (4) microspheres embedded in a PPF scaffold surrounded by a gelatin hydrogel. A fraction of the incorporated BMP-2 was radiolabeled with 125I to determine its in vitro and in vivo release profiles. The release and bioactivity of BMP-2 were tested weekly over a period of 12 weeks in preosteoblast W20-17 cell line culture and in a rat subcutaneous implantation model. Outcome parameters for in vitro and in vivo bioactivities of the released BMP-2 were alkaline phosphatase (AP) induction and bone formation, respectively. The four implant types showed different in vitro release profiles over the 12-week period, which changed significantly upon implantation. The AP induction by BMP-2 released from gelatin implants showed a loss in bioactivity after 6 weeks in culture, while the BMP-2 released from the other implants continued to show bioactivity over the full 12-week period. Micro-CT and histological analysis of the delivery vehicles after 6 weeks of implantation showed significantly more bone in the microsphere/PPF scaffold composites (Implant 3, p < 0.02). After 12 weeks, the amount of newly formed bone in the microsphere/PPF scaffolds remained significantly higher than that in the gelatin and microsphere/gelatin hydrogels (p < 0.001), however, there was no statistical difference compared to the microsphere/PPF/gelatin composite. Overall, the results from this study show that BMP-2 could be incorporated into various bone tissue engineering composites for sustained release over a prolonged period of time with retention of bioactivity.
KW - Bioactivity
KW - Bone morphogenetic protein
KW - Controlled drug release
KW - Ectopic bone formation
KW - Gelatin
KW - Poly(lactic-co-glycolic acid) microspheres
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UR - http://www.scopus.com/inward/citedby.url?scp=43749120033&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2008.04.031
DO - 10.1016/j.biomaterials.2008.04.031
M3 - Article
C2 - 18472153
AN - SCOPUS:43749120033
SN - 0142-9612
VL - 29
SP - 3245
EP - 3252
JO - Biomaterials
JF - Biomaterials
IS - 22
ER -