Comparative Physicochemical Analysis among 1,4-Butanediol Diglycidyl Ether Cross-Linked Hyaluronic Acid Dermal Fillers

(1) Background: Injectable hyaluronic acid (HA) dermal fillers are used in several chirurgical practices and in aesthetic medicine. HA filler stability can be enhanced through different cross-linking technologies; one of the most frequently cross-linker used is 1,4-butanediol diglycidyl ether (BDDE), also present in the HA-BDDE dermal filler family of the company Matex Lab S.p.A. (Brindisi, Italy). Our overview is focused on their characterization, drawing a correlation between matrix structure, rheological and physicochemical properties related to their cross-linking technologies. (2) Methods: Four different injectable HA hydrogels were characterized through optical microscopic examination and rheological behavior investigation. (3) Results: The cross-linked HA dermal fillers showed a fibrous “spiderweb-like” matrix structure and an elastic and solid-like profile. (4) Conclusions: The comparative analysis represents a preliminary characterization of these injectable medical devices in order to identify their best field of application.

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Toward Physicochemical and Rheological Characterization of Different Injectable Hyaluronic Acid Dermal Fillers Cross-Linked with Polyethylene Glycol Diglycidyl Ether

Polymers ◽

10.3390/polym13060948 ◽

2021 ◽

Vol 13 (6) ◽

pp. 948

Author(s):

Nicola Zerbinati ◽

Sabrina Sommatis ◽

Cristina Maccario ◽

Maria Chiara Capillo ◽

Giulia Grimaldi ◽

...

Keyword(s):

Hyaluronic Acid ◽

Polyethylene Glycol ◽

Biological Activities ◽

Diglycidyl Ether ◽

Dermal Filler ◽

Cross Linking ◽

Matrix Structure ◽

Dermal Fillers ◽

Rheological Characterization

(1) Background: Injectable hyaluronic acid (HA) dermal fillers are used to restore volume, hydration and skin tone in aesthetic medicine. HA fillers differ from each other due to their cross-linking technologies, with the aim to increase mechanical and biological activities. One of the most recent and promising cross-linkers is polyethylene glycol diglycidyl ether (PEGDE), used by the company Matex Lab S.p.A., (Brindisi, Italy) to create the HA dermal filler PEGDE family. Over the last few years, several studies have been performed to investigate the biocompatibility and biodegradability of these formulations, but little information is available regarding their matrix structure, rheological and physicochemical properties related to their cross-linking technologies, the HA content or the degree of cross-linking. (2) Methods: Seven different injectable HA hydrogels were subjected to optical microscopic examination, cohesivity evaluation and rheological characterization in order to investigate their behavior. (3) Results: The analyzed cross-linked dermal fillers showed a fibrous “spiderweb-like” matrix structure, with each medical device presenting different and peculiar rheological features. Except for HA non cross-linked hydrogel 18 mg/mL, all showed an elastic and cohesive profile. (4) Conclusions: The comparative analysis with other literature works makes a preliminary characterization of these injectable medical devices possible.

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Cetuximab associated dermal filler reaction

BMJ Case Reports ◽

10.1136/bcr-2018-228882 ◽

2019 ◽

Vol 12 (8) ◽

pp. e228882 ◽

Cited By ~ 1

Author(s):

Shivanshan Pathmanathan ◽

Marcin Dzienis

Keyword(s):

Epidermal Growth Factor Receptor ◽

Radiation Therapy ◽

Hyaluronic Acid ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Growth Factor Receptor ◽

Dermal Filler ◽

Dermal Fillers ◽

Epidermal Growth ◽

Receptor Inhibitor

A 52-year-old male patient with hyaluronic acid-based dermal fillers injected in his cheeks was diagnosed with glossotonsillary malignancy, and managed with concurrent cetuximab (epidermal growth factor receptor inhibitor) and radiation therapy. He developed significant inflammation around the dermal filler sites after first cycle of cetuximab which improved with dissolution of the dermal fillers with hyaluronidase. This suggests that cetuximab can lead to inflammation around the dermal filler sites, which can be treated with dissolution of the filler.

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Characterization of porous collagen/hyaluronic acid scaffold modified by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide cross-linking

Biomaterials ◽

10.1016/s0142-9612(01)00235-6 ◽

2002 ◽

Vol 23 (4) ◽

pp. 1205-1212 ◽

Cited By ~ 376

Author(s):

Si-Nae Park ◽

Jong-Chul Park ◽

Hea Ok Kim ◽

Min Jung Song ◽

Hwal Suh

Keyword(s):

Hyaluronic Acid ◽

Cross Linking

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Dermal filler migration complications following lip augmentation procedures

Journal of Aesthetic Nursing ◽

10.12968/joan.2020.9.7.276 ◽

2020 ◽

Vol 9 (7) ◽

pp. 276-281

Author(s):

Danielle Davy

Keyword(s):

Hyaluronic Acid ◽

Rare Complication ◽

Post Treatment ◽

The Body ◽

Dermal Filler ◽

Dermal Fillers ◽

Short Term ◽

Lip Augmentation ◽

Permanent Fillers

Filler migration is a rare complication of dermal filler treatment. Although most research has found that more permanent fillers, such as silicone, are more likely to migrate due to their long-term presence in the body, there have also been reported cases of filler migration from short-term hyaluronic acid-based dermal fillers. As lip augmentation procedures are fast becoming one of the most frequently requested treatments in medical aesthetics, this article looks at the longevity of hyaluronic acid lip dermal fillers, while also aiming to assess the cause of dermal filler post-treatment migration and evaluating how to minimise its risk.

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HA-based dermal filler: downstream process comparison, impurity quantitation by validated HPLC-MS analysis, and in vivo residence time study

Journal of Applied Biomaterials & Functional Materials ◽

10.1177/2280800019867075 ◽

2019 ◽

Vol 17 (3) ◽

pp. 228080001986707 ◽

Cited By ~ 2

Author(s):

Cristian Guarise ◽

Carlo Barbera ◽

Mauro Pavan ◽

Susi Panfilo ◽

Riccardo Beninatto ◽

...

Keyword(s):

Residence Time ◽

Rabbit Model ◽

Diglycidyl Ether ◽

In Vitro Cytotoxicity ◽

Dermal Filler ◽

Dermal Fillers ◽

Process Comparison ◽

Hygroscopic Properties

The success of hyaluronic acid (HA)-based dermal fillers, with more than 2 million minimally invasive procedures conducted in 2016 in the US alone, is due to their hygroscopic properties of biocompatibility and reversibility. The type and density of HA cross-linkage, as well as the manufacturing technology, may influence not only the in vivo persistence but also the safety profile of dermal fillers. 1,4-Butanediol diglycidyl ether (BDDE) is the cross-linker used in most market-leading HA fillers; 1,4-butanediol di-(propan-2,3-diolyl) ether (BDPE) is the major impurity obtained from the HA–BDDE cross-linking (HBC) process. In this work, a new process to obtain high purity HBC fillers was developed. A new HPLC-MS method was validated for the quantification of BDPE content in HBC dermal fillers. In vitro cytotoxicity of BDPE was evaluated in fibroblasts (IC50 = 0.48 mg/mL). The viscoelasticity was monitored during the shelf-life of the HBC-10% hydrogel and was correlated with in vitro hyaluronidase resistance and in vivo residence time in a rabbit model. This analysis showed that elasticity is the best parameter to predict the in vivo residence time. Finally, a series of parameters were investigated in certain marketed dermal fillers and were compared with the results of the HBC-10% hydrogel.

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Dermal Filler types, Effect on soft tissue and Life Style correlation

Journal of Medicine and Health Sciences Research ◽

10.21839/jmhsr.2020.v3.315 ◽

2020 ◽

Vol 3 ◽

pp. 1

Author(s):

Dalia A Mohamed

Keyword(s):

Hyaluronic Acid ◽

Soft Tissue ◽

Life Style ◽

Dermal Filler ◽

Dermal Fillers ◽

Bovine Collagen ◽

The World ◽

History Of ◽

Facial Contours ◽

Common Manifestation

One of the most common manifestation in our time, especially among girls, is those procedures on the skin or maintaining or to modify some of the changes in the skin, such as those that come due to aging or any other cosmetic reasons. Fillers and Botox are two of the most popular procedures. Dermal fillers are effective treatments used to soften and reduce wrinkles and deep lines, fill out the cheeks and smooth facial contours. There are four main types of injectable dermal fillers, including fat, collagen, hyaluronic acid, and microsphere-containing carriers of another material such as polymethyl methacrylate (PMMA). So that to understand any type of injection, it is important to look at its history for valuable lessons and for successful progress. Honestly, it is very interesting to see what and where the world gets in the last 40 years of injectable. Today, we will be examining the brief history of dermal fillers from their bovine collagen roots, to the advanced fillers that are available today. In this review, we aimed to show some types of dermal fillers including a variety of its complication in soft tissue. Also, we try to correlate the factor of lifestyle with its variant effects.

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Processing and Characterization of a Composite of Hyaluronic Acid (HA) and Microspheres Biphasic Calcium Phosphate (BCP) for Dermal Repair

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.529-530.421 ◽

2012 ◽

Vol 529-530 ◽

pp. 421-425

Author(s):

Edirlaine Soares Silva ◽

Deny Gomes de Freitas ◽

Sidney Nicodemos da Silva

Keyword(s):

Hyaluronic Acid ◽

Calcium Phosphate ◽

Soft Tissue ◽

Biphasic Calcium Phosphate ◽

Soft Tissues ◽

Biological Response ◽

Water Soluble ◽

Potential Candidate ◽

Dermal Fillers

Dermal fillers are injectable implants made of biological materials (collagen, autologous fat and hyaluronic acid animal) or synthetic (PMMA microparticles of hydroxyapatite and non-animal hyaluronic acid), biodegradable or not, that include features such as ideal biocompatibility, durability, non-profile migration and ability to promote a smooth, natural-looking correction. Its main indication is intended to treat contour defects caused by aging, photo damage, disease, trauma or scarification. The fact of biodegradable fillers are absorbed within a year after application resulted in the emergence of products permanent and semi-permanent to offer patients long-lasting effects. Currently, one of the most effective strategies has been the development of scaffolds formed by combining two or more biomaterials seeking the restoration of tissue function. The bioceramic associated with water-soluble polymers have been developed as substitutes for the repair of soft tissues with optimal biological response. The objective of this study was to process and characterize a composite hydrogel in the form of hyaluronic acid (HA) microspheres and biphasic calcium phosphate (BCP) in order injectable applications for repair of soft tissue. The powders of HA and BCP were characterized by Infrared Spectroscopy Fourier Transform (FTIR) and X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM). The characterization of the hydrogel injectability pure and the composite with different ratios of HA and BCP was performed. The components were characterized compatible for use as dermal fillers. The composite of hyaluronic acid (HA) and biphasic calcium phosphate (BCP) had adequate characterization and injetabilidade proving to be a potential candidate for restoration of soft tissue.

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Synthesis and Characterization of Covalently Crosslinked pH-Responsive Hyaluronic Acid Nanogels: Effect of Synthesis Parameters

Polymers ◽

10.3390/polym11040742 ◽

2019 ◽

Vol 11 (4) ◽

pp. 742 ◽

Cited By ~ 6

Author(s):

Maiz-Fernández ◽

Pérez-Álvarez ◽

Ruiz-Rubio ◽

Pérez González ◽

Sáez-Martínez ◽

...

Keyword(s):

Hyaluronic Acid ◽

Diglycidyl Ether ◽

Ph Responsive ◽

Poly Ethylene Glycol ◽

Covalent Crosslinking ◽

Synthesis Parameters ◽

Pka Value ◽

Poly Ethylene ◽

Crosslinking Agents

Stable hyaluronic acid nanogels were obtained following the water-in-oil microemulsion method by covalent crosslinking with three biocompatible crosslinking agents: Divinyl sulfone, 1,4-butanediol diglycidyl ether (BDDE), and poly(ethylene glycol) bis(amine). All nanoparticles showed a pH-sensitive swelling behavior, according to the pKa value of hyaluronic acid, as a consequence of the ionization of the carboxylic moieties, as it was corroborated by zeta potential measurements. QELS studies were carried out to study the influence of the chemical structure of the crosslinking agents on the particle size of the obtained nanogels. In addition, the effect of the molecular weight of the biopolymer and the degree of crosslinking on the nanogels dimensions was also evaluated for BDDE crosslinked nanoparticles, which showed the highest pH-responsive response.

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