TY - JOUR
T1 - In Vitro and In Vivo Correlation of Bone Morphogenetic Protein-2 Release Profiles from Complex Delivery Vehicles
AU - Olthof, Maurits G.L.
AU - Tryfonidou, Marianna A.
AU - Dadsetan, Mahrokh
AU - Dhert, Wouter J.A.
AU - Yaszemski, Michael J.
AU - Kempen, Diederik H.R.
AU - Lu, Lichun
N1 - Funding Information:
We thank James L. Herrick and Carl T. Gustafson of Mayo Clinic for technical support. The authors wish to acknowledge the National Institutes of Health (R01 AR45871 and R01 EB03060), AO Foundation (AO startup grant S-15-46K), Dutch Arthritis Foundation (LLP22), and Anna-NOREF foundation for their financial support.
Publisher Copyright:
© Copyright 2018, Mary Ann Liebert, Inc.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - Local sustained delivery of bioactive molecules from biomaterials is a promising strategy to enhance bone regeneration. To optimize delivery vehicles for bone formation, the design characteristics are tailored with consequential effect on bone morphogenetic protein-2 (BMP-2) release and bone regeneration. Complying with the 3R principles (Replacement, Reduction, and Refinement), the growth factor release is often investigated in vitro using several buffers to mimic the in vivo physiological environment. However, this remains an unmet need. Therefore, this study investigates the in vitro-in vivo correlation (IVIVC) of BMP-2 release from complex delivery vehicles in several commonly used in vitro buffers: cell culture model, phosphate buffered saline, and a strong desorption buffer. The results from this study showed that the release environment affected the BMP-2 release profiles, creating distinct relationships between release versus time and differences in extent of release. According to the guidance set by the U.S. Food and Drug Administration (FDA), IVIVC resulted in level A internal predictability for individual composites. Since the IVIVC was influenced by the BMP-2 loading method and composite surface chemistry, the external predictive value of the IVIVCs was limited. These results show that the IVIVCs can be used for predicting the release of an individual composite. However, the models cannot be used for predicting in vivo release for different composite formulations since they lack external predictability. Potential confounding effects of drug type, delivery vehicle formulations, and application site should be added to the equation to develop one single IVIVC applicable for complex delivery vehicles. Altogether, these results imply that more sophisticated in vitro systems should be used in bone regeneration to accurately discriminate and predict in vivo BMP-2 release from different complex delivery vehicles.
AB - Local sustained delivery of bioactive molecules from biomaterials is a promising strategy to enhance bone regeneration. To optimize delivery vehicles for bone formation, the design characteristics are tailored with consequential effect on bone morphogenetic protein-2 (BMP-2) release and bone regeneration. Complying with the 3R principles (Replacement, Reduction, and Refinement), the growth factor release is often investigated in vitro using several buffers to mimic the in vivo physiological environment. However, this remains an unmet need. Therefore, this study investigates the in vitro-in vivo correlation (IVIVC) of BMP-2 release from complex delivery vehicles in several commonly used in vitro buffers: cell culture model, phosphate buffered saline, and a strong desorption buffer. The results from this study showed that the release environment affected the BMP-2 release profiles, creating distinct relationships between release versus time and differences in extent of release. According to the guidance set by the U.S. Food and Drug Administration (FDA), IVIVC resulted in level A internal predictability for individual composites. Since the IVIVC was influenced by the BMP-2 loading method and composite surface chemistry, the external predictive value of the IVIVCs was limited. These results show that the IVIVCs can be used for predicting the release of an individual composite. However, the models cannot be used for predicting in vivo release for different composite formulations since they lack external predictability. Potential confounding effects of drug type, delivery vehicle formulations, and application site should be added to the equation to develop one single IVIVC applicable for complex delivery vehicles. Altogether, these results imply that more sophisticated in vitro systems should be used in bone regeneration to accurately discriminate and predict in vivo BMP-2 release from different complex delivery vehicles.
KW - bone morphogenetic protein-2 release
KW - bone regeneration
KW - in vitro-in vivo correlation
KW - oligo(polyethelene glycol) fumarate
UR - http://www.scopus.com/inward/record.url?scp=85050030453&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050030453&partnerID=8YFLogxK
U2 - 10.1089/ten.tec.2018.0024
DO - 10.1089/ten.tec.2018.0024
M3 - Article
C2 - 29756545
AN - SCOPUS:85050030453
SN - 1937-3384
VL - 24
SP - 379
EP - 390
JO - Tissue Engineering - Part C: Methods
JF - Tissue Engineering - Part C: Methods
IS - 7
ER -