Application of BMP-Bone Cement and FGF-Gel on Periodontal Tissue Regeneration in Nonhuman Primates
The ultimate challenge of tissue engineering research is the translation of experimental knowledge into clinical application. In the preclinical testing phase of any new therapy, animal models remain the gold standard. Therefore, the methodological choice of a suitable model is critical to meet the...
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Published in | Tissue engineering. Part C, Methods Vol. 25; no. 12; p. 748 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
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United States
01.12.2019
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Abstract | The ultimate challenge of tissue engineering research is the translation of experimental knowledge into clinical application. In the preclinical testing phase of any new therapy, animal models remain the gold standard. Therefore, the methodological choice of a suitable model is critical to meet the requirements for a safe clinical application of the developed treatment. For instance, we have shown in rats that the application of calcium phosphate cement (CPC)/propylene glycol alginate (PGA) with bone morphogenetic protein (BMP)-2 or fibroblast growth factor (FGF)-2 resulted in the regeneration of periodontal defects. However, it is debated whether using small models form a predictive method for translation to larger species. At the same time, the 3R framework is encouraged as guiding principles of the ethical use of animal testing. Therefore, based on the successful rat study, the objective of this study was to further investigate the periodontal regenerative efficacy of the CPC/BMP and PGA/FGF system in a periodontal defect model with a low number of nonhuman primates (NHPs). Three
-overstocked from breeding for other purposes-were used (reuse of animals and appropriateness of the experimental animal species according to 3R framework). Three-wall periodontal defects were surgically created in the mandible. In total, 10 defects were created and distributed over two groups: (1) control group: PGA+CPC (
= 5) and (2) experimental group: PGA/FGF+CPC/BMP (
= 5). After 3 months, tissue regeneration was evaluated by histomorphometry and radiographic measurements. Data showed that epithelial downgrowth, cementum, and ligament regeneration were significantly enhanced in the experimental group compared with the control group (
= 5;
= 0.013,
= 0.028, and
= 0.018, respectively). However, the amount of newly formed bone did not differ (
= 0.146). Overall, as a translational proof-of-principle study, the hybrid periodontal regenerative method of CPC/BMP+PGA/FGF promoted periodontal regeneration in NHPs. This study warrants the application of CPC/BMP/PGA/FGF in clinical trials. Impact Statement This study validated an earlier successful periodontal regeneration strategy from a rat model into a few spare nonhuman primates (NHPs). The hybrid periodontal regenerative method of calcium phosphate cement (CPC)/bone morphogenetic protein (BMP)-2/propylene glycol alginate (PGA)/fibroblast growth factor (FGF)-2 promoted periodontal regeneration in NHPs, which corroborated the previous rat results. This translational approach was a very practical option and thus reduced the number and species of experimental animals in translational research. These results found in NHPs indicate a consistent conclusion with the earlier findings in the rat model. It further warrants the application of CPC/BMP-2+PGA/FGF-2 in human clinical trials. |
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AbstractList | The ultimate challenge of tissue engineering research is the translation of experimental knowledge into clinical application. In the preclinical testing phase of any new therapy, animal models remain the gold standard. Therefore, the methodological choice of a suitable model is critical to meet the requirements for a safe clinical application of the developed treatment. For instance, we have shown in rats that the application of calcium phosphate cement (CPC)/propylene glycol alginate (PGA) with bone morphogenetic protein (BMP)-2 or fibroblast growth factor (FGF)-2 resulted in the regeneration of periodontal defects. However, it is debated whether using small models form a predictive method for translation to larger species. At the same time, the 3R framework is encouraged as guiding principles of the ethical use of animal testing. Therefore, based on the successful rat study, the objective of this study was to further investigate the periodontal regenerative efficacy of the CPC/BMP and PGA/FGF system in a periodontal defect model with a low number of nonhuman primates (NHPs). Three
-overstocked from breeding for other purposes-were used (reuse of animals and appropriateness of the experimental animal species according to 3R framework). Three-wall periodontal defects were surgically created in the mandible. In total, 10 defects were created and distributed over two groups: (1) control group: PGA+CPC (
= 5) and (2) experimental group: PGA/FGF+CPC/BMP (
= 5). After 3 months, tissue regeneration was evaluated by histomorphometry and radiographic measurements. Data showed that epithelial downgrowth, cementum, and ligament regeneration were significantly enhanced in the experimental group compared with the control group (
= 5;
= 0.013,
= 0.028, and
= 0.018, respectively). However, the amount of newly formed bone did not differ (
= 0.146). Overall, as a translational proof-of-principle study, the hybrid periodontal regenerative method of CPC/BMP+PGA/FGF promoted periodontal regeneration in NHPs. This study warrants the application of CPC/BMP/PGA/FGF in clinical trials. Impact Statement This study validated an earlier successful periodontal regeneration strategy from a rat model into a few spare nonhuman primates (NHPs). The hybrid periodontal regenerative method of calcium phosphate cement (CPC)/bone morphogenetic protein (BMP)-2/propylene glycol alginate (PGA)/fibroblast growth factor (FGF)-2 promoted periodontal regeneration in NHPs, which corroborated the previous rat results. This translational approach was a very practical option and thus reduced the number and species of experimental animals in translational research. These results found in NHPs indicate a consistent conclusion with the earlier findings in the rat model. It further warrants the application of CPC/BMP-2+PGA/FGF-2 in human clinical trials. |
Author | Walboomers, X Frank Ong, Marianne Meng Ann Jansen, John A Yu, Na Chanchareonsook, Nattharee Wang, Bing Mastrogiacomo, Simone Yang, Fang Shao, Jinlong |
Author_xml | – sequence: 1 givenname: Bing surname: Wang fullname: Wang, Bing organization: School of Stomatology, Shandong University, Jinan, Shandong, China – sequence: 2 givenname: Simone surname: Mastrogiacomo fullname: Mastrogiacomo, Simone organization: Laboratory of Functional and Molecular Imaging, NINDS, National Institutes of Health, Bethesda, Maryland – sequence: 3 givenname: Fang surname: Yang fullname: Yang, Fang organization: Department of Dentistry-Biomaterials, Radboud University Medical Center, Nijmegen, The Netherlands – sequence: 4 givenname: Jinlong surname: Shao fullname: Shao, Jinlong organization: School of Stomatology, Shandong University, Jinan, Shandong, China – sequence: 5 givenname: Marianne Meng Ann surname: Ong fullname: Ong, Marianne Meng Ann organization: Duke-NUS Medical School, Singapore, Singapore – sequence: 6 givenname: Nattharee surname: Chanchareonsook fullname: Chanchareonsook, Nattharee organization: Duke-NUS Medical School, Singapore, Singapore – sequence: 7 givenname: John A surname: Jansen fullname: Jansen, John A organization: Department of Dentistry-Biomaterials, Radboud University Medical Center, Nijmegen, The Netherlands – sequence: 8 givenname: X Frank surname: Walboomers fullname: Walboomers, X Frank organization: Department of Dentistry-Biomaterials, Radboud University Medical Center, Nijmegen, The Netherlands – sequence: 9 givenname: Na surname: Yu fullname: Yu, Na organization: Duke-NUS Medical School, Singapore, Singapore |
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Keywords | animal models periodontal regeneration primates methods calcium phosphate cement fibroblast growth factor-2 bone morphogenetic protein-2 |
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Title | Application of BMP-Bone Cement and FGF-Gel on Periodontal Tissue Regeneration in Nonhuman Primates |
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