In Vitro Evaluation of the Biosafety of Hyaluronic Acid PEG Cross-Linked with Micromolecules of Calcium Hydroxyapatite in Low Concentration


  • Nicola Zerbinati Universita degli Studi dell'Insubria Dipartimento di Scienze Chirurgiche e Morfologiche, Varese
  • Torello Lotti University of Rome "G. Marconi" - Centro Studi per la Ricerca Multidisciplinare e Rigenerativa (CSRMR), Rome
  • Damiano Monticelli Universita degli Studi dell'Insubria Dipartimento di Scienza e Alta Tecnologia, Como
  • Raffaele Rauso University of Foggia - Department of Plastic Reconstructive Surgery, Foggia
  • Pablo González-Isaza Hospital Universitario San Jorge - Head Chief of Urogynecology, Carrera 32410, Pereira, Risaralda 660002
  • Edoardo D'Este Centro Medico Polispecialistico, Pavia
  • Alberto Calligaro University of Pavia - Department of Public Health, Experimental and Forensic Medicine, Pavia
  • Sabrina Sommatis UB-CARE S.r.l. - Spin-off University of Pavia, Pavia
  • Cristina Maccario UB-CARE S.r.l. - Spin-off University of Pavia, Pavia
  • Roberto Mocchi UB-CARE S.r.l. - Spin-off University of Pavia, Pavia
  • Jacopo Lotti University of Rome "G. Marconi" - Department of Nuclear, Subnuclear and Radiation Physics, Rome
  • Uwe Wollina Städtisches Klinikum Dresden, Department of Dermatology and Allergology, 01067 Dresden
  • Georgi Tchernev Department of Dermatology, Venereology and Dermatologic Surgery, Medical Institute of Ministry of Interior (MVR-Sofia), General Skobelev 79, 1606 Sofia; Onkoderma - Policlinic for Dermatology, Venereology and Dermatologic Surgery, General Skobelev 26, 1606, Sofia
  • Katlein França University of Miami School of Medicine, 1400 NW 10th Avenue, Miami, Florida 33136-1015



hyaluronic acid, biosafety, calcium hydroxyapatite, human keratinocytes, Neauvia Stimulate


OBJECTIVE: Neauvia Stimulate is biocompatible, injectable hyaluronic acid (HA) filler (26 mg/ml) PEG cross-linked with 1% of calcium hydroxyapatite (CaHA) for facial soft-tissue augmentation that provides volume to tissues, followed by process of neocollagenesis for improving skin quality.

AIM: The aim of the present study is to evaluate the biosafety of the product (Lot. 160517-26-1/2 PEG) on human keratinocytes cultured in vitro.

MATERIAL AND METHODS: The experimental model proposed, despite being an in vitro system, allows the derivation of useful information to predict the possible activity of the product in further in vivo application. Human keratinocytes (HaCaT cells) were treated with the product for 24h at increasing concentrations of product respect to control (untreated cells).

RESULTS: The biosafety of the product to be tested has been evaluated performing different methods: MTT test, NRU test, Kenacid Blue assay. Moreover, any possible effect on the structure, morphology, and viability of cells has been evaluated.

CONCLUSION: In conclusion, the results obtained by the different methods show that the product Neauvia Stimulate® does not cause any cytotoxic effect and does not affect the correct structure and morphology of cells cultures.


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How to Cite

Zerbinati N, Lotti T, Monticelli D, Rauso R, González-Isaza P, D’Este E, Calligaro A, Sommatis S, Maccario C, Mocchi R, Lotti J, Wollina U, Tchernev G, França K. In Vitro Evaluation of the Biosafety of Hyaluronic Acid PEG Cross-Linked with Micromolecules of Calcium Hydroxyapatite in Low Concentration. Open Access Maced J Med Sci [Internet]. 2018 Jan. 7 [cited 2023 Oct. 3];6(1):15-9. Available from:

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