Dual Functionalization of Hyaluronan Dermal Fillers with Vitamin B3: Efficient Combination of Bio-Stimulation Properties with Hydrogel System Resilience Enhancement
Abstract
:1. Introduction
2. Results and Discussion
2.1. HAR Hydrogel Systems: Technical Benchmarking Study and Product Formulation Analyses
2.2. HAR Hydrogel Rheological Characterization
2.3. HAR Hydrogel Multi-Parametric Accelerated Degradation Assays
2.4. HAR Hydrogel System Cohesivity and Injectability Assays
2.5. HAR Hydrogel Bio-Stimulatory Attribute Assessment in a Cutaneous Cell Model
2.6. Study Limitations and Future Perspectives
3. Conclusions
4. Materials and Methods
4.1. Reagents and Consumables Used for the Study
4.2. Hydrogel Rheological Characterization Method
4.3. Hydrogel Accelerated Degradation Assays with Rheological Readouts
4.4. Hydrogel Cohesivity Analysis Method
4.5. Hydrogel Injectability Analysis Method
4.6. Product Biological Effect Evaluations in an In Vitro Dermal Fibroblast Model
4.6.1. In Vitro Assessment of Cellular Viability/Metabolic Activity
4.6.2. In Vitro Assessment of Collagen Synthesis Stimulation Activity
4.6.3. In Vitro Assessment of Total Protein Synthesis Stimulation Activity
4.7. Statistical Analyses and Data Presentation
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
List of Abbreviations
AAPH | 2,2′-azobis(2-amidinopropane) dihydrochloride |
BCA | Bicinchoninic acid |
BDDE | 1,4-butanediol diglycidylether |
BSA | Bovine serum albumin |
CaHA | Calcium hydroxylapatite |
CHUV | Lausanne University Hospital |
CMC | Carboxymethylcellulose |
DMEM | Dulbecco’s modified Eagle medium |
ECM | Extracellular matrix |
FBS | Fetal bovine serum |
FDA | US Food and Drug Administration |
G′ | Storage modulus |
G″ | Loss modulus |
HA | Hyaluronic acid |
HAR | Boosting dermal fillers |
HYAL | Hyaluronidase |
H2O2 | Hydrogen peroxide |
LVE | Linear viscoelastic region |
MD | Medical device |
min | Minute |
NA | Non-applicable |
NMR | Nuclear magnetic resonance |
NO | Nitric oxide |
ns | Non-significant |
Pa | Pascals |
Pa·s | Pascal seconds |
PBS | Phosphate-buffered saline |
PLLA | Poly-l-lactic acid |
ROS | Reactive oxygen species |
s | Second |
SEC-MS | Size-exclusion chromatography with mass spectrometry |
USA | United States of America |
UV | Ultraviolet |
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Product Commercial Name | Intended Product Uses 1 | Needle Gauge 2 (G) | HA Concentration 3 | Cross-Linker | Manufacturing Technology |
---|---|---|---|---|---|
HAR-1 “Instant Refine” | Fine lines; Peri-oral lines; Tear through | 30 G | 15 mg/mL | BDDE | Boost and Fusion |
HAR-3 “Maxi Lift” | Volumizer | 27 G | 20 mg/mL | BDDE | Boost and Fusion |
JUVÉDERM® VOLBELLA® | Fine lines; Tear through | 30 G | 15 mg/mL | BDDE | VYCROSS® |
JUVÉDERM® VOLUMA® | Volumizer | 27 G | 20 mg/mL | BDDE | VYCROSS® |
Product Parameters | Hydrogel Product | |
---|---|---|
HAR-1 | HAR-3 | |
HA Concentration (mg/mL) | 15.0 | 20.0 |
Vitamin B3 Concentration 1 (mg/mL) | 7.50 | 7.50 |
Lidocaine Concentration (mg/mL) | 3.00 | 3.00 |
Degree of HA Modification (%) | ~3.8 | ~4.2 |
Product Name | Plateau Injection Force (N) | Maximum Injection Force (N) |
---|---|---|
HAR-1 “Instant Refine” | 43.78 ± 0.51 | 44.62 ± 0.58 |
HAR-3 “Maxi Lift” | 23.33 ± 0.65 | 23.49 ± 0.65 |
Empty Syringe Control 1 | 2.39 ± 0.13 | 2.48 ± 0.16 |
Product Name | Intended Clinical Uses (Experimental Uses) | Product Conditioning 1 (Sample Preparation Method) | Main Product Composition | Ratio Prepared Product: Culture Medium 2 |
---|---|---|---|---|
HAR-1 “Instant Refine” | Fine lines; Peri-oral lines; Tear through | 1 mL syringe | HA; Vitamin B3 | 1:1 |
HAR-3 “Maxi Lift” | Volumizer | 1 mL syringe | HA; Vitamin B3 | 1:1 |
Radiesse® | Moderate to severe facial wrinkles and folds; Lipoatrophy (Bio-stimulant control) | 1.5 mL syringe (mixed with 6 mL water) | CaHA; CMC; Glycerin | 1:1 |
Sculptra™ | Volumizer; Lipoatrophy (Bio-stimulant control) | 1 vial (lyophilizate resuspended in 5 mL water) | PLLA; CMC; Mannitol | 1:1 |
JUVÉDERM® VOLUMA® | Volumizer (Volumizer control) | 1 mL syringe | HA | 1:1 |
PBS | (Sham control) | 500 mL bottle | Monopotassium phosphate; Disodium phosphate; Sodium chloride | 1:1 |
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Porcello, A.; Chemali, M.; Marques, C.; Scaletta, C.; Lourenço, K.; Abdel-Sayed, P.; Raffoul, W.; Hirt-Burri, N.; Applegate, L.A.; Laurent, A. Dual Functionalization of Hyaluronan Dermal Fillers with Vitamin B3: Efficient Combination of Bio-Stimulation Properties with Hydrogel System Resilience Enhancement. Gels 2024, 10, 361. https://doi.org/10.3390/gels10060361
Porcello A, Chemali M, Marques C, Scaletta C, Lourenço K, Abdel-Sayed P, Raffoul W, Hirt-Burri N, Applegate LA, Laurent A. Dual Functionalization of Hyaluronan Dermal Fillers with Vitamin B3: Efficient Combination of Bio-Stimulation Properties with Hydrogel System Resilience Enhancement. Gels. 2024; 10(6):361. https://doi.org/10.3390/gels10060361
Chicago/Turabian StylePorcello, Alexandre, Michèle Chemali, Cíntia Marques, Corinne Scaletta, Kelly Lourenço, Philippe Abdel-Sayed, Wassim Raffoul, Nathalie Hirt-Burri, Lee Ann Applegate, and Alexis Laurent. 2024. "Dual Functionalization of Hyaluronan Dermal Fillers with Vitamin B3: Efficient Combination of Bio-Stimulation Properties with Hydrogel System Resilience Enhancement" Gels 10, no. 6: 361. https://doi.org/10.3390/gels10060361
APA StylePorcello, A., Chemali, M., Marques, C., Scaletta, C., Lourenço, K., Abdel-Sayed, P., Raffoul, W., Hirt-Burri, N., Applegate, L. A., & Laurent, A. (2024). Dual Functionalization of Hyaluronan Dermal Fillers with Vitamin B3: Efficient Combination of Bio-Stimulation Properties with Hydrogel System Resilience Enhancement. Gels, 10(6), 361. https://doi.org/10.3390/gels10060361