Investigation of Crosslinking Parameters and Characterization of Hyaluronic Acid Dermal Fillers: From Design to Product Performances
Abstract
:1. Introduction
2. Results and Discussion
2.1. Crosslinking Parameters Modulate Hydrogel Rheology
2.2. Characterization of Hyal System Dermal Products
2.2.1. Rheological and Physicochemical Characterization
2.2.2. Extrudability
2.3. Linear HA and ACP Improve Extrudability
2.4. Dynamic Viscosity and Needle Size Influence Hydrogel Extrusion
2.5. Cell Migration with Linear and Crosslinked HA
3. Conclusions
4. Materials and Methods
4.1. Materials
4.2. Preparation of Crosslinked HA Hydrogels
4.3. Rheological Measurements
4.4. Determination of Degree of Modification
4.5. Cohesivity
4.6. Particle Size
4.7. Soluble fraction
4.8. Swelling Factor
4.9. Extrusion Force Measurements
4.10. Cell Culture
4.11. Migration Assay
4.12. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Technology | Manufacturer | Product-by-Process Claims | Patent Reference | Literature Reference |
---|---|---|---|---|
Non-Animal Stabilized HA (NASHA®) | Galderma |
| EP3013866B1 | [5] |
Optimal Balance Technology (OBT®) |
| WO2018104426A1 | [11] | |
Hylacross® | Allergan |
| US 8357795 B2 | [13] |
Vycross® |
| US 7741476 B2 | [14] | |
Cohesive Polydensified Matrix (CPM®) | Merz |
| EP1968711B1 | [9] |
Resilient HA (RHA®) | Teoxane |
| EP2429486B1 | [10] |
Parameter | Unit | Hyal System | ||||
---|---|---|---|---|---|---|
1.8% | ACP | DUO | LIP | VOL | ||
Concentration | mg/mL | 18 | 20 | 25 | 25 | 25 |
% linear HA | 100 | 0 | 0 | 7 ± 3 | 4 ± 3 | |
Composition | % ester crosslinked HA | 0 | 100 | 25 ± 5 | 0 | 0 |
% ether crosslinked HA | 0 | 0 | 75 ± 5 | 93 ± 3 | 96 ± 3 | |
G′ (1 Hz) | Pa | 12.3 ± 4.1 | 23.9 ± 7.9 | 27.5 ± 9.1 | 76.5 ± 25.2 | 89.2 ± 29.4 |
G″ (1 Hz) | Pa | 27.9 ± 9.2 | 10.6 ± 3.5 | 14.6 ± 4.8 | 29.1 ± 5.3 | 25.7 ± 8.5 |
% elasticity (1 Hz) | - | 30.6 ± 4.9 | 69.3 ± 11.1 | 65.3 ± 10.5 | 72.4 ± 11.6 | 77.6 ± 12.4 |
HA conc. x % elasticity | mg/mL | 551 ± 88 | 1386 ± 222 | 1633 ± 263 | 1811 ± 290 | 1941 ± 310 |
Tan delta | - | 2.3 ± 0.7 | 0.4 ± 0.1 | 0.5 ± 0.2 | 0.4 ± 0.1 | 0.3 ± 0.1 |
Dynamic viscosity (1 Hz) | Pa. | 12.6 ± 4.2 | 22.5 ± 7.4 | 84.6 ± 27.9 | 110.8 ± 36.6 | 103.5 ± 34.1 |
Cohesivity | mg/drop | 21.2 ± 3.6 | 23.5 ± 4.0 | 40.2 ± 6.9 | 52.3 ± 8.9 | 52.5 ± 8.9 |
Particle size (d 0.5) | µm | - | 481 ± 72 | 425 ± 64 | 45 ±7 | 99 ± 15 |
Soluble fraction | % | 103.5 ± 3.1 | 39.9 ± 15.2 | 50.2 ± 19.1 | 27.3 ± 10.4 | 16.2 ± 6.2 |
Swelling factor | % | n.a. | 120.6 ± 36.4 | 400.1 ± 61.0 | 450.1 ± 96.2 | 423.3 ± 38.4 |
Degree of modification | % mol/mol | 0 | 0 | 4.1 ± 0.1 | 5.2 ± 1.2 | 8.5 ± 0.7 |
Parameter | Unit | Hyal System | ||||||
---|---|---|---|---|---|---|---|---|
1.8% | ACP | DUO | LIP | VOL | ||||
Needle size | - | 30 G × 1/2″ (0.3 × 13 mm) | 30 G × 3/16″ (0.3 × 4 mm) | 30 G × 1/2″ (0.3 × 13 mm) | 27 G × 1/2″ (0.4 × 13 mm) | 27 G × 1/2″ (0.4 × 13 mm) | 27 G × 3/4″ (0.4 × 19 mm) | 27 G × 1/2″ (0.4 × 13 mm) |
Average extrusion force | N | 7.1 ± 0.2 | 7.9 ± 0.7 | 10.6 ± 0.5 | 11.7 ± 0.3 | 12.9 ± 0.7 | 17.1 ± 0.1 | 15.4 ± 0.4 |
Extrusion force slope | N/s | 0.4 ± 0.1 | 1.1 ± 1.0 | 1.4 ± 0.6 | 0.7 ± 0.1 | 4.6 ± 1.5 | 5.2 ± 1.1 | 5.0 ± 4.3 |
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Pluda, S.; Salvagnini, C.; Fontana, A.; Marchetti, A.; Di Lucia, A.; Galesso, D.; Guarise, C. Investigation of Crosslinking Parameters and Characterization of Hyaluronic Acid Dermal Fillers: From Design to Product Performances. Gels 2023, 9, 733. https://doi.org/10.3390/gels9090733
Pluda S, Salvagnini C, Fontana A, Marchetti A, Di Lucia A, Galesso D, Guarise C. Investigation of Crosslinking Parameters and Characterization of Hyaluronic Acid Dermal Fillers: From Design to Product Performances. Gels. 2023; 9(9):733. https://doi.org/10.3390/gels9090733
Chicago/Turabian StylePluda, Stefano, Cecilia Salvagnini, Anna Fontana, Anna Marchetti, Alba Di Lucia, Devis Galesso, and Cristian Guarise. 2023. "Investigation of Crosslinking Parameters and Characterization of Hyaluronic Acid Dermal Fillers: From Design to Product Performances" Gels 9, no. 9: 733. https://doi.org/10.3390/gels9090733