Bone Morphogenetic Proteins, Carriers, and Animal Models in the Development of Novel Bone Regenerative Therapies
Abstract
:1. Introduction
2. Bone Regeneration by Bone Morphogenetic Protein Devices
3. Animal Models
3.1. Initial Evaluation in Rodents
3.1.1. Ectopic Models
3.1.2. Bone Defect Models
3.2. Intermediate Evaluation in Rabbits
3.2.1. Segmental Defect Model
3.2.2. Posterolateral Spinal Fusion (PLF) Model
3.3. Advanced Evaluation of Bone Regeneration Therapies
3.3.1. Dog and Sheep Segmental Defect Model
3.3.2. Sheep PLF Model
3.3.3. Non-human Primate (NHP) PLF Model
3.4. Anatomical Characteristics of the Species
3.4.1. Segmental Bone Defect
3.4.2. PLF
4. Appropriate Bone Morphogenetic Proteins Dosing
5. Duration of the Observation Period
6. Sample Size
7. Study Outcomes
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Mouse Ectopic Model | |||||
---|---|---|---|---|---|
Author (Year) | Carrier | BMP Dose (µg) | Time (Weeks or Days) | Sample Size (n) | |
Kato et al. (2006) | PLA-DX-PEG, PLA-DX-PEG/TCP, TCP | 2 and 5 | 3 and 6 weeks | 6 | |
Roldan et al. (2010) | BCP | 12 weeks | 8 | ||
Liang et al. (2014) | TCP | 50 | 3, 7, 14, 21, and 28 days | 5 | |
Bolander et al. (2016) | CaP granules/Collagen | 1.06 and 1.77 | 5 weeks | 4 | |
Ji et al. (2018) | CaP-based materials | 0.81, 3.24, and 5.67 | 2 and 5 weeks | 3 | |
Hashimoto et al. (2020) | Collagen | 2.5 | 7, 10, 14, and 21 days | ||
Mouse Calvarial Defect Model | |||||
Author (Year) | Calvarial Defect Size (mm) | Carrier | BMP Dose (µg) | Time (Weeks) | Sample Size (n) |
La et al. (2012) | 4 | TCP, Heparin—conjugated fibrin | 0.3 | 8 | 10 |
Yang et al. (2012) | 4 | Collagen, Apatite—coated collagen | 0.5, 0.75, 1, 2, and 3 | 8 | 6 |
Fan et al. (2015) | 3 | PLGA/Apatite layer | 0.3, 0.6, and 1 | 6 | 8, 12 |
Gronowitz et al. (2017) | 3.5 | Collagen/HA | 2 | 3 | 4 |
Herberg et al. (2017) | 5 | Acellular dermis | 0.542 | 4 | 10 |
Huang et al. (2017) | 3.5 | PLA | 50 | 2, 4, 6, and 8 | 16 |
Seo et al. (2017) | 5 | Poly(phosphazene) hydrogels Poly(phosphazene) hydrogels/BCP | 5 and 10 | 8 | 3 |
Terauchi et al. (2017) | 3.5 | Sulphopropyl ether—modified polyrotaxanes/Collagen | 0.1 | 4 | 5, 6 |
Maisani et al. (2018) | 3.5 | Hydrogel | 1 | 8 | 6 |
Reyes et al. (2018) | 4 | PLGA | 0.1, 0.3, and 0.6 | 4 and 8 | 4 |
Mouse Femoral Defect Model | |||||
Author (Year) | Femoral Defect Size (mm) | Carrier | BMP Dose (µg) | Time (Weeks) | Sample Size (n) |
Alaee et al. (2014) | 2 | Collagen | 5 | 4 days, 1, 2, 3, 4, and 8 | 6 |
Bougrouli et al. (2016) | 2 | Collagen | 5 | 1, 2, 4, and 8 | 6 |
Zwingenbergen et al. (2016) | 3 | Heparin/functionalized mineralized collagen matrix | 2.5 and 15 | 6 | 11 |
Rat Ectopic Model | ||||
---|---|---|---|---|
Author (Year) | Carrier | BMP Dose (µg) | Time (Weeks) | Sample Size (n) |
Kuboki et al. (1998) | HA | 1, 2, 3, and 4 | ||
Tsuruga et al. (1998) | HA | 4 | 1, 2, 3, and 4 | 3 |
Alam et al. (2000) | TCP, HA, BCP | 1.5 and 10 | 2 and 4 | 3 |
Vehof et al. (2002) | HA | 8 | 3, 5, 7, and 9 | 3 |
Kim Chang-Sung et al. (2004) | TCP, Collagen | 5 | 2 and 8 | 10 |
Tazaki et al. (2006) | HA | 0.5, 1, and 5 | 3 | |
Tazaki et al. (2008) | HA, TCP | 0.5, 1, and 5 | 3 | 3 |
Luca et al. (2010) | Chitosan/Hyaluronan hydrogel | 150 | 3 | 3, 6 |
Reves et al. (2011) | Chitosan-nano-HA | 36 | 4 | 6 |
Park et al. (2011) | BCP | 2.5 | 2 and 8 | 5–8 |
Bhakta et al. (2012) | Hyaluronan-based hydrogel | 5 | 8 | 6 |
Strobel et al. (2012) | BCP | 1.6 | 2, 4, and 6 | 6 |
Kisiel et al. (2013) | Hyaluronan hydrogel/Fibronectin fragments | 4 | 7 | 6 |
Ma et al. (2014) | BCP | 20 | 8 | 6 |
Mumcuoglu et al. (2018) | Collagen-based microspheres/Alginate | 0.3, 1, and 10 | 10 | 8 |
Lin et al. (2019) | Coralline HA | 20 | 5 | 6 |
Rat Calvarial Defect Model | ||||
Author (Year) | Carrier | BMP Dose (µg) | Time (Weeks) | Sample Size (n) |
Jung et al. (2006) | TCP | 2.5 | 2 and 8 | 20 |
Kim et al. (2011) | BCP | 50 and 250 | 2 and 8 | 20 |
Park et al. (2011) | BCP | 2.5 | 2 and 8 | 5–8 |
Notodihardjo et al. (2011) | HA | 10 | 4 | 5 |
Jang et al. (2012) | BCP | 2.5, 5, 10, and 20 | 2 and 8 | 8 |
Lee JH et al. (2013) | TCP, HA, BCP | 5 | 4 and 8 | 13 |
Bae et al. (2017) | PCL/TCP | 5 | 4 | 7 |
Rat Femoral Defect Model | ||||
Author (Year) | Carrier | BMP Dose (µg) | Time (Weeks) | Sample Size (n) |
Chu et al. (2006) | Poly(propylene fumarate)/TCP/DCP | 10 | 6 and 15 | 4, 7 |
Johnson et al. (2011) | Collagen, Collagen/Heparin, Heparin | 3 | 12 | 7, 9 |
Diab et al. (2011) | PCL/Silk fibroin hydrogel | 5 | 12 | 10 |
Lee et al. (2012) | BCP | 1000 | 4 and 8 | 6 |
Rodriguez-Evora et al. (2013) | Segmented polyurethane/PLGA/ TCP ceramics | 1.6 and 6.5 | 12 | 9 |
Wai-Ching et al. (2014) | Bioactive glass/DCP | 10 | 15 | 8, 9 |
Williams et al. (2015) | Collagen | 25, 50, 75 and 100 | 8 | 8, 11 |
Krishnan et al. (2015) | Nanofiber mesh alginate | 5 µg | 12 | 14 |
Rabbit Segmental Defect Model | |||||
---|---|---|---|---|---|
Author (Year) | Model | Carrier | BMP Dose (µg) | Time (Weeks) | Sample Size (n) |
Yoneda et al. (2004) | Femur (1.5 cm) | PLA-DX-PEG/TCP | 50 | 24 | 5 |
Yamamoto et al. (2006) | Ulna (2 cm) | Gelatin hydrogel | 17 | 6 | 3 |
Liu et al. (2009) | Radius (1.5 cm) | Gelatin/nanoHA/Fibrin | 100 | 4, 8, and 12 | 5 |
Luca et al. (2010) | Radius (1.5 cm) | Chitosan hydrogel/TCP | 150 | 8 | 1 (pilot) |
Zhu et al. (2010) | Radius | nanoHA | 4, 8, and 12 | 10 | |
Bae et al. (2011) | Ulna (1.5 cm) | PCL/fibrin | 75 | 8 | 5 |
Fujita et al. (2011) | Ulna (2 cm) | Gelatin/TCP | 17 | 4 and 8 | 6, 10 |
Sun-Woong et al. (2012) | Ulna (2 cm) | PCL | 15 | 12 | 6 |
Hou et al. (2012) | Radius (1.5 cm) | Collagen, Collagen/Chitosan | 50 | 2, 4, 8, and 12 | 3, 5 |
Choi et al. (2014) | Radius (2 cm) | Collagen, Fibrin glue | 50 | 6 and 12 | 4 |
Wu et al. (2014) | Radius (1.5 cm) | CaP cement, Hydroxypropylmethyl cellulose/CaP cement | 50 | 2, 4, 8, and 12 | 5 |
Yamamoto et al. (2015) | Ulna (2 cm) | Gelatin/TCP | 17 | 6 | 6 |
Peng et al. (2016) | Femur (1 cm) | PEG-PLGA hydrogel | 5, 10, and 20 | 12 | 6 |
Pan et al. (2017) | Femur (2 cm) | Bioglass/TCP | 20 | 4 and 8 | 5 |
Kuroiwa et al. (2018) | Femur (2 cm) | TCP | 50 | 12 and 24 | 10 |
Grgurevic et al. (2019) | Ulna (1.5 cm) | Autologous blood coagulum | 25, 50, and 100 | 23 | 5 |
Huang et al. (2021) | Ulna (2 cm) | TCP | 20 | 8 | 5 |
Rabbit PLF Model | ||||
---|---|---|---|---|
Author (Year) | Carrier | BMP Dose (µg) | Time (Weeks) | Sample Size (n) |
Boden et al. (1995) | DBM, Biocoral/ Collagen | 100 and 300 | 5 | 14–16 |
Itoh et al. (1999) | Collagen | 10, 50, and 200 | 24 | 6 |
Louis-Ugbo et al. (2001) | BCP, Collagen/BCP | 3000/mL | 5 | 18 |
Jenis et al. (2002) | Collagen | - | 3 and 12 | 8 |
Konishi et al. (2002) | Autograft/HA | 200 | 2, 4, and 6 | 2–7 |
Suh et al. (2002) | Collagen/BCP, BCP | 860 | 5 | 14 |
Minamide et al. (2003) | TCP cement, True bone ceramics, Collagen | 100 | 3 and 6 | 5–10 |
Namikawa et al. (2005) | TCP/PLA-DX-PEG | 7.5, 15, and 30 | 6 | 5 |
Valdes et al. (2007) | - | 6 | 18 | |
Dohzono et al. (2009) | TCP | 5, 15, 50, and 150 | 4 and 8 | 5–8 |
Lee JW et al. (2011) | Heparin—conjugated PLGA nanospheres, PLGA nanospheres | 20 | 12 | 12 |
Lee JH et al. (2012) | HA | 10, 50, 200, and 500 | 3 and 6 | 14 |
Vukicevic et al. (2019) | Autologous blood coagulum, Autologous blood coagulum/Allograft | 125, 250, 500, and 1000 | 14 | 4 |
Dog Segmental Defect Model | |||||
---|---|---|---|---|---|
Author (Year) | Model | Carrier | BMP Dose (µg) | Time (Weeks) | Sample Size (n) |
Itoh (1998) | Ulna (2 cm) | PLGA/Gelatin | 40, 160, and 640 | 16 | 4 |
Tuominen (2000) | Ulna (2 cm) | Coral | - | 16 and 36 | 3, 6 |
Hu (2003) | Radius (2 cm) | HA/Collagen/PLA | - | 24 | 6 |
Jones (2008) | Ulna (2.5 cm) | Collagen/Allograft, Collagen/BCP ceramics | 210, 430, and 650 | 12 | 6 |
Harada (2012) | Ulna (2.5 cm) | TCP | 35, 140, 560, and 2240 | 12 | 3 |
Minier (2014) | Ulna (2 cm) | CaP/Hydrogel | 330 | 20 | 5 |
Sheep Segmental Defect Model | |||||
Author (Year) | Model | Carrier | BMP Dose (µg) | Time (Weeks) | Sample Size (n) |
Den Boer et al. (2003) | Tibia (3 cm) | HA | 2500 | 12 | 8 |
Pluhar et al. (2006) | Tibia (5 cm) | Carboxymethylcellulose/Bovine collagen, Collagen | 3500 | 16 | 10 |
Reichert et al. (2012) | Tibia (3 cm) | mPCL-TCP | 3500 | 12 and 52 | 8 |
Cipitria et al. (2013) | Tibia (3 cm) | mPCL-TCP | 1750 and 3500 | 12 | 8 |
Lammens et al. (2020) | Tibia (3 and 4.5 cm) | CaP ceramics | 344, 1500, and 3800 | 16 | 4, 8, 13 |
Sheep PLF Model | ||||
---|---|---|---|---|
Author (Year) | Carrier | BMP Dose (µg) | Time (Weeks) | Sample Size (n) |
Pelletier et al. (2014) | TCP | 1050, 3500, and 10,500 | 12 | 12 |
Toth et al. (2016) | Collagen/BCP, Collagen-ceramic sponge | 750 and 1500/cm3 | 24 | 12–24 |
Grgurevic et al. (2020) | Autologous blood coagulum, Autologous blood coagulum/Allograft | 500 and 1500 | 27 | 6–10 |
NHP PLF Model | ||||
Author (Year) | Carrier | BMP Dose (µg) | Time (Weeks) | Sample Size (n) |
Boden et al. (1999) | BCP | 6000, 9000, and 12,000 | 24 | 4–12 |
Suh et al. (2002) | Ceramic/Collagen | 9000 | 24 | 4 |
Akamaru et al. (2003) | Collagen/BCP Collagen/Allograft | 3000 | 24 | 6 |
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Stokovic, N.; Ivanjko, N.; Maticic, D.; Luyten, F.P.; Vukicevic, S. Bone Morphogenetic Proteins, Carriers, and Animal Models in the Development of Novel Bone Regenerative Therapies. Materials 2021, 14, 3513. https://doi.org/10.3390/ma14133513
Stokovic N, Ivanjko N, Maticic D, Luyten FP, Vukicevic S. Bone Morphogenetic Proteins, Carriers, and Animal Models in the Development of Novel Bone Regenerative Therapies. Materials. 2021; 14(13):3513. https://doi.org/10.3390/ma14133513
Chicago/Turabian StyleStokovic, Nikola, Natalia Ivanjko, Drazen Maticic, Frank P. Luyten, and Slobodan Vukicevic. 2021. "Bone Morphogenetic Proteins, Carriers, and Animal Models in the Development of Novel Bone Regenerative Therapies" Materials 14, no. 13: 3513. https://doi.org/10.3390/ma14133513