In Vitro and In Vivo Correlation of Bone Morphogenetic Protein-2 Release Profiles from Complex Delivery Vehicles

Maurits G.L. Olthof, Marianna A. Tryfonidou, Mahrokh Dadsetan, Wouter J.A. Dhert, Michael J Yaszemski, Diederik H.R. Kempen, Lichun Lu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)379-390
Number of pages12
JournalTissue Engineering - Part C: Methods
Volume24
Issue number7
DOIs
StatePublished - Jul 1 2018
Externally publishedYes

Fingerprint

Bone Morphogenetic Protein 2
Bone
Proteins
Bone Regeneration
Buffers
Composite materials
Biocompatible Materials
Surface chemistry
Cell culture
Desorption
Intercellular Signaling Peptides and Proteins
United States Food and Drug Administration
Phosphates
In Vitro Techniques
Osteogenesis
Molecules
Cell Culture Techniques
Biomaterials
Pharmaceutical Preparations

Keywords

  • bone morphogenetic protein-2 release
  • bone regeneration
  • in vitro-in vivo correlation
  • oligo(polyethelene glycol) fumarate

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering

Cite this

In Vitro and In Vivo Correlation of Bone Morphogenetic Protein-2 Release Profiles from Complex Delivery Vehicles. / Olthof, Maurits G.L.; Tryfonidou, Marianna A.; Dadsetan, Mahrokh; Dhert, Wouter J.A.; Yaszemski, Michael J; Kempen, Diederik H.R.; Lu, Lichun.

In: Tissue Engineering - Part C: Methods, Vol. 24, No. 7, 01.07.2018, p. 379-390.

Research output: Contribution to journalArticle

Olthof, Maurits G.L. ; Tryfonidou, Marianna A. ; Dadsetan, Mahrokh ; Dhert, Wouter J.A. ; Yaszemski, Michael J ; Kempen, Diederik H.R. ; Lu, Lichun. / In Vitro and In Vivo Correlation of Bone Morphogenetic Protein-2 Release Profiles from Complex Delivery Vehicles. In: Tissue Engineering - Part C: Methods. 2018 ; Vol. 24, No. 7. pp. 379-390.
@article{cfc5fe034d704fcd9607bb9358dc5ed7,
title = "In Vitro and In Vivo Correlation of Bone Morphogenetic Protein-2 Release Profiles from Complex Delivery Vehicles",
abstract = "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.",
keywords = "bone morphogenetic protein-2 release, bone regeneration, in vitro-in vivo correlation, oligo(polyethelene glycol) fumarate",
author = "Olthof, {Maurits G.L.} and Tryfonidou, {Marianna A.} and Mahrokh Dadsetan and Dhert, {Wouter J.A.} and Yaszemski, {Michael J} and Kempen, {Diederik H.R.} and Lichun Lu",
year = "2018",
month = "7",
day = "1",
doi = "10.1089/ten.tec.2018.0024",
language = "English (US)",
volume = "24",
pages = "379--390",
journal = "Tissue Engineering - Part C: Methods",
issn = "1937-3384",
publisher = "Mary Ann Liebert Inc.",
number = "7",

}

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

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

VL - 24

SP - 379

EP - 390

JO - Tissue Engineering - Part C: Methods

JF - Tissue Engineering - Part C: Methods

SN - 1937-3384

IS - 7

ER -