Hyaluronidases for treating complications by hyaluronic acid dermal fillers: evaluation of the effects on cell cultures and human skin

Cavallini, Maurizio; Antonioli, Barbara; Gazzola, R.; Tosca, Marta Cecilia; Galuzzi, Marta; Rapisarda, Vincenzo; Ciancio, Francesco; Marazzi, Mario

doi:10.1007/s00238-013-0855-y

Cited by 10 publications

(7 citation statements)

References 25 publications

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“…Therefore, the presence of a specific antidote, e.g., hyaluronidase, becomes important for the management of complications during and after filler injection. Hyaluronidases are endoglycosidases, physiologically present in the human body, that cleave HA, reducing its viscosity [15]. Hyaluronidases could be classified into three groups according to their mechanism of action and end products: mammalian hyaluronidase (testis tube), leech/hook worm hyaluronidase, and microbial hyaluronidase [16, 17].…”

Section: Introductionmentioning

confidence: 99%

In VitroEvaluation of the Biological Availability of Hyaluronic Acid Polyethylene Glycols-Cross-Linked Hydrogels to Bovine Testes Hyaluronidase

Zerbinati

Mocchi

Galadari

et al. 2019

BioMed Research International

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During last years, hyaluronic acid- (HA-) based dermal fillers have grown rapidly and continuously, as reported by the American Society of Aesthetic Plastic Surgery (ASAPS). In fact, HA fillers are considered the gold standard technique for soft tissue augmentation, deep skin hydration, and facial recontouring, playing a key role as an alternative to plastic surgery. HA fillers are less invasive, more biocompatible, and safer and with a more natural and immediate result if compared to plastic surgery. Hence, the safety of HA-based dermal fillers plays a crucial role, mostly in terms of biocompatibility and adjustability in case of unpleasant results and side effects such as, tyndall effect, edema, or granulomas. Hyaluronidase is a naturally occurring enzyme, present in the human body, and can degrade HA fillers avoiding more severe complications. In this article, we analyzed the bioavailability of hyaluronidase degradation of five fillers of Neauvia® hydrogels line (MatexLab SA, Lugano, CH), composed of pure hyaluronic acid and based on PEGDE cross-linking (polyethylene glycol) technology that guarantees a higher biocompatibility and an optimal biointegration and rheological characteristics. The performed in vitro testing is based on the colorimetric determination of the N-acetyl-D-glucosamine (NAG) present in solution after incubation with hyaluronidase, determined at different time points in order to assess the kinetic of each product degradation (1h, 3h, 6h, 24h, 48h, 72h, 120h, and 168h). The aim of this study was to assess, in vitro, how the difference in HA content and PEGDE concentration of the analyzed fillers can influence the product biocompatibility, intended as product enzymatic clearance and duration in time. The results demonstrated that the method was reproducible and easy to perform and that all the analyzed fillers are naturally immediately available for hyaluronidase-mediated degradation.

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Section: Introductionmentioning

confidence: 99%

In VitroEvaluation of the Biological Availability of Hyaluronic Acid Polyethylene Glycols-Cross-Linked Hydrogels to Bovine Testes Hyaluronidase

Zerbinati

Mocchi

Galadari

et al. 2019

BioMed Research International

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“…In this kind of complication, an early treatment is the best choice. The gold standard is prompt injection of hyaluronidase 16 .…”

Section: Discussionmentioning

confidence: 99%

Early hyaluronidase use in preventing skin necrosis after treatment with dermal fillers: Report of two cases

et al. 2019

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Injection of dermal fillers, like hyaluronic acid (HA), is a safe procedure, with few and transient side effects such as erythema, bruising and swelling etc. The aim of this report is to provide our protocol for the early treatment of necrotic complications after facial treatment with dermal fillers. We present two cases of skin suffering of the face after dermal infiltration of HA, treated successfully with our early protocol. Our protocol includes the early infiltration of hyaluronidase in the treated areas. We start with infiltration of hyaluronidase distributed over the area to be treated through micro-injections with dosage 40 IU per cm2. Our protocol includes the use of systemic corticosteroids for 4 days, anti-aggregation therapy, oral antibiotic, topical cream with nitric oxide and compresses with gauze and warm water. In the skin complications after dermal filler treatment, marked pain and characteristic reticulated erythema in the skin distribution of the affected vessels is often developed. Due to the implementation of our protocol in these patients, we managed to avoid an irreversible necrotic complication of the face in both cases. In this report, our protocol was compared with results published in the literature and allowed us to avoid complications such as skin necrosis with permanent damage.

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“…Protecting and increasing local persistence of HA is anticipated to be desirable, as HA is known to be beneficial for tissue repair by maintaining moisture, increasing angiogenesis, stimulating anti-inflammatory pathways, and promoting granulation tissue formation. [28][29][30][31] Hyaluronidases are physiologic endoglycosidases that cleave internal beta-N-acetyl-D-glucosaminidic linkages of HA, yielding N-acetylglucosamine and glucuronic acid. [28] Enzymatic degradation of candidate PPS NP/HA hydrogels compared to control PCL NP/HA and HA/HA hydrogels was evaluated by incubating these three hydrogels in the presence of 7 U mL −1 hyaluronidase, which is within a physiologically relevant range for this enzyme.…”

Section: Pps-based Np/ha Hydrogels Display Susceptibility To Oxidativ...mentioning

confidence: 99%

Hybrid Shear‐Thinning Hydrogel Integrating Hyaluronic Acid with ROS‐Responsive Nanoparticles

Bezold

Hanna

Dollinger

et al. 2023

Adv Funct Materials

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Nanoparticle (NP) supra-assembly offers unique opportunities to tune macroscopic hydrogels' mechanical strength, material degradation, and drug delivery properties. Here, synthetic, reactive oxygen species (ROS)-responsive NPs are physically cross-linked with hyaluronic acid (HA) through guest-host chemistry to create shear-thinning NP/HA hydrogels. A library of triblock copolymers composed of poly(propylene sulfide)-b-poly(N,N-dimethylacrylamide)-bpoly(N,N-dimethylacrylamide-co-N-(1-adamantyl)acrylamide) are synthesized with varied triblock architectures and adamantane grafting densities and then self-assembled into NPs displaying adamantane on their surface. Selfassembled NPs are mixed with β-cyclodextrin grafted HA to yield eighteen NP/HA hydrogel formulations. The NP/HA hydrogel platform demonstrates superior mechanical strength to HA-only hydrogels, susceptibility to oxidative/ enzymatic degradation, and inherent cell-protective, antioxidant function. The performance of NP/HA hydrogels is shown to be affected by triblock architecture, guest/host grafting densities, and HA composition. In particular, the length of the hydrophilic second block and adamantane grafting density of self-assembled NPs significantly impacts hydrogel mechanical properties and shear-thinning behavior, while ROS-reactivity of poly(propylene sulfide) protects cells from cytotoxic ROS and reduces oxidative degradation of HA compared to HA-only hydrogels. This study provides insight into polymer structure-function considerations for designing hybrid NP/HA hydrogels and identifies antioxidant, shear-thinning hydrogels as promising injectable delivery platforms for small molecule drugs and therapeutic cells.

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Hyaluronidases for treating complications by hyaluronic acid dermal fillers: evaluation of the effects on cell cultures and human skin

Cited by 10 publications

References 25 publications

In VitroEvaluation of the Biological Availability of Hyaluronic Acid Polyethylene Glycols-Cross-Linked Hydrogels to Bovine Testes Hyaluronidase

In VitroEvaluation of the Biological Availability of Hyaluronic Acid Polyethylene Glycols-Cross-Linked Hydrogels to Bovine Testes Hyaluronidase

Early hyaluronidase use in preventing skin necrosis after treatment with dermal fillers: Report of two cases

Hybrid Shear‐Thinning Hydrogel Integrating Hyaluronic Acid with ROS‐Responsive Nanoparticles

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