Table 2.
Nano/microparticles systems to encapsulate GFs, mainly BMP2 growth factor. Most of them are in the microscopic scale and were used to be entrapped into scaffold of different characteristics. PVA has been the more used surfactant-stabilizer. It is possible to find both, encapsulation and surface adsorption of the growth factors with high-moderate efficiency. The use of heparin as stabilizer reduces significantly the initial burst release, favoring a sustained release in the time. The bioactivity of the GF was preserved in most of the systems and coencapsulation with other biomolecules seems to have a similar effect than the use of surfactants as stabilizers.
| Polymers | Stabilizer | Size | Encapsulation % EE |
Release | Biological activity | Reference |
|---|---|---|---|---|---|---|
| PLGA | PVA | 10–20 µm | Adsorbed rhBMP2 | 20 ng/mL of constant sustained release | Better bone formation after 8 weeks | Fu et al. 2013 [44] |
|
| ||||||
| PLGA | PVA | 10–100 μm | rhBMP2-BSA 69% (BMP) |
Burst (20%) Sustained until 77% (28 days) |
BMP2 molecules with bioactivity | Tian et al. 2012 [45] |
|
| ||||||
| PLGA 75 : 25 | PVA | 182 μm | 82% | — | Good bone defect repair outcomes within 8−12 weeks |
Rodríguez-Évora et al. 2014 [46] |
|
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| PLGA | PVA | 228 μm | 60,5% | 30% initial burst. Slower release of 4% per week. After 8 weeks 60% released | No loss of bioactivity | Reyes et al. 2013 [47] |
|
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| PLGA/PEG | No double emulsion synthesis | 100–200 μm | Adsorbed BMP2 | 13% initial burst. Slower release of 0.01–8% per day. After 23 days 70% released | Substantial bone regeneration of the scaffold | Rahman et al. 2014 [48] |
|
| ||||||
| Different PLGA | PVA | 20–100 μm | 30% (uncapped PLGA) 90% (capped PLGA) |
26–49% (1 day) Total after 2 weeks |
No loss of bioactivity | Lupu-Haber et al. 2013 [49] |
|
| ||||||
| PLGA 75 : 25 | PVA | 5–125 μm | — | Initial burst 30% (1 day) Sustained 35 days |
Higher volumes and surface area coverage of new bone | Wink et al. 2014 [50] |
|
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| PLGA | Heparin | 200–800 nm | Adsorbed BMP2 94% |
No initial burst. Sustained over 4 weeks | Significant reduction of the BMP2 dose for good bone formation | La et al. 2010 [51] |
|
| ||||||
| PLGA | Heparin- Poloxamer | 160 nm | Adsorbed BMP2 100% |
Initial burst (4–7%) linear profile | Higher matrix mineralization of regenerated bone | Chung et al. 2007 [52] |
|
| ||||||
| PLGA | Heparin | 100–250 nm | Adsorbed 94% | Initial burst 10% (1 day) 60% after 30 days |
No loss of bioactivity Efficacy of administration, amount 50-fold lower |
Jeon et al. 2008 [53] |
|
| ||||||
| PLGA | PVA | ~300 nm | 80% | 85% initial burst (1 day) | No loss of bioactivity | Yilgor et al. 2009 [54] |
|
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| PLGA (in rings) | PVA | 215 μm | 66% | Moderate burst Sustained release over 6 weeks |
60% of calvaria defect were healed | Rodríguez-Évora et al. 2013 [55] |
|
| ||||||
| PLGA-Poloxamer 188 Blend | Poloxamer | 150 nm | FGF-BSA-Heparin 60–80% |
40% initial burst (1 day), 60% (30 days) | No loss of bioactivity | d'Angelo et al. 2010 [56] |
|
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| Different PLGA polymers | PVA | μm order | rhBMP2 adsorption 40–75% |
20–80% initial burst (1 day) | — | Schrier et al. 2001 [57] |
|
| ||||||
| PLGA/PEG | PVA | 37–67 μm | 72–99% | 33% initial burst (1 day) | Little loss of bioactivity | Lochmann et al. 2010 [58] |
|
| ||||||
| PLGA/PLGA-PEG-PLGA | PVA | 100 μm | HSA-BMP2 60% |
70% initial burst (1 day) | No loss of bioactivity | White et al. 2013 [59] |
|
| ||||||
| PLGA | PVA | 100–1000 nm |
Α-1-antitrypsin 90% |
30% initial burst (1 day) 50% after 24 days |
Biological activity was preserved using BSA and β-cyclodextrine. | Pirooznia et al. 2012 [60] |