Revista de Odontologia da UNESP
https://revodontolunesp.com.br/article/doi/10.1590/1807-2577.20250043
Revista de Odontologia da UNESP
Artigo Original

Fibroblast cellular responses to calcium hydroxyapatite-based biomaterials

Respostas celulares de fibroblastos a biomateriais à base de hidroxiapatita de cálcio

Roger KIRSCHNER; Henrique Ballassini ABDALLA; Juliana Trindade CLEMENTE-NAPIMOGA; Marcelo Henrique NAPIMOGA

Downloads: 0
Views: 26

Abstract

Introduction: Calcium hydroxyapatite (CaHa) is widely used in aesthetic procedures as a collagen biostimulator.

Objective: This study evaluated how different concentrations of CaHA (0.5% to 2.5%) in three commercial formulations (Stiim®, Rennova®, and Radiesse®) influence cell viability, human fibroblast proliferation, and gene expression of extracellular matrix markers, including type I and III collagen, osteocalcin, and osteopontin.

Material and method: CaHa were evaluated on cell viability, proliferation, and gene expression of extracellular matrix markers in human fibroblasts (n=3, each time-point). Cell viability was assessed using MTT and trypan blue exclusion assays, proliferation by cell counting, and gene expression of type I and III collagen, osteocalcin, and osteopontin by RT-PCR.

Result: Stiim® showed a significant increase in viability at lower concentrations (1% and 2%) after 24 h and at 0.5% and 1% after 72 h, while the 2.5% concentration drastically reduced viability. Radiesse® demonstrated greater stability, with early proliferation stimulation and sustained induction of both type I and III collagen. Rennova® exhibited a later and more variable response, with reduced proliferation at intermediate concentrations. Osteocalcin and osteopontin expression varied between formulations, with Radiesse® showing a stronger stimulatory effect. The results indicate that HA effects on fibroblasts are formulation- and concentration-dependent, directly influencing cellular behavior and biostimulatory potential.

Conclusion: These gene expression findings suggest that CaHA may promote pathways associated with dermal neocollagenesis.

Keywords

Calcium hydroxyapatite; aesthetic; dermal cosmetic; dermatology; orofacial harmonization; collagen; fibroblastos; biomaterials; STIIM; Diamond; Radiesse

Resumo

Introdução: A hidroxiapatita de cálcio (CaHa) é amplamente utilizada em procedimentos estéticos como bioestimulador de colágeno.

Objetivo: Este estudo avaliou como diferentes concentrações de CaHA (0,5% a 2,5%) em três formulações comerciais (Stiim®, Rennova® e Radiesse®) influenciam a viabilidade celular, a proliferação de fibroblastos humanos e a expressão gênica de marcadores da matriz extracelular, incluindo colágeno tipo I e III, osteocalcina e osteopontina.

Material e método: As CaHa foram avaliadas quanto à viabilidade celular, proliferação e expressão gênica de marcadores de matriz extracelular em fibroblastos humanos (n=3, por tempo avaliado). A viabilidade celular foi analisada pelos ensaios de MTT e exclusão por azul de tripano, a proliferação por contagem celular e a expressão gênica de colágeno tipo I e III, osteocalcina e osteopontina por RT-PCR.

Resultado: Stiim® apresentou aumento significativo da viabilidade em baixas concentrações (1% e 2%) após 24 h e em 0,5% e 1% após 72 h, enquanto a concentração de 2,5% reduziu drasticamente a viabilidade. Radiesse® demonstrou maior estabilidade, com estímulo precoce de proliferação e indução sustentada de colágeno tipo I e III. Rennova® exibiu resposta mais tardia e variável, com redução da proliferação em concentrações intermediárias. A expressão de osteocalcina e osteopontina variou entre as formulações, com Radiesse® apresentando efeito estimulatório mais intenso. Os resultados indicam que os efeitos da CaHa sobre fibroblastos dependem da formulação e da concentração, influenciando diretamente o comportamento celular e o potencial bioestimulador.

Conclusão: Esses achados, baseados em expressão genica, sugerem que a CaHA pode estimular a neocolagênese.

Palavras-chave

Hidroxiapatita de cálcio; estética; cosmético dérmico; dermatologia; harmonização orofacial; colágeno; fibroblastos; biomateriais; STIIM; Diamond; Radiesse

Referências

1 Figueredo VO, Miot HA, Soares Dias J, Nunes GJB, Barros de Souza M, Bagatin E. Efficacy and safety of 2 injection techniques for hand biostimulatory treatment with diluted calcium hydroxylapatite. Dermatol Surg. 2020 Oct;46(Suppl 1):S54-61. https://doi.org/10.1097/DSS.0000000000002334. PMid:32976172.

2 Mazzuco R, Evangelista C, Gobbato DO, de Almeida LM. Clinical and histological comparative outcomes after injections of poly-L-lactic acid and calcium hydroxyapatite in arms: a split side study. J Cosmet Dermatol. 2022 Dec;21(12):6727-33. https://doi.org/10.1111/jocd.15356. PMid:36098704.

3 Dallara JM, Baspeyras M, Bui P, Cartier H, Charavel MH, Dumas L. Calcium hydroxylapatite for jawline rejuvenation: consensus recommendations. J Cosmet Dermatol. 2014 Mar;13(1):3-14. https://doi.org/10.1111/jocd.12074. PMid:24641600.

4 Berlin AL, Hussain M, Goldberg DJ. Calcium hydroxylapatite filler for facial rejuvenation: a histologic and immunohistochemical analysis. Dermatol Surg. 2008 Jun;34(Suppl 1):S64-7. https://doi.org/10.1097/00042728-200806001-00014. PMid:18547184.

5 Nowag B, Casabona G, Kippenberger S, Zöller N, Hengl T. Calcium hydroxylapatite microspheres activate fibroblasts through direct contact to stimulate neocollagenesis. J Cosmet Dermatol. 2023 Feb;22(2):426-32. https://doi.org/10.1111/jocd.15521. PMid:36575882.

6 Amiri M, Meçani R, Niehot CD, Phillips T, Kolb J, Daughtry H, et al. Skin regeneration-related mechanisms of calcium hydroxylapatite (CaHA): a systematic review. Front Med (Lausanne). 2023 Jun;10:1195934. https://doi.org/10.3389/fmed.2023.1195934. PMid:37332763.

7 Marmur ES, Phelps R, Goldberg DJ. Clinical, histologic and electron microscopic findings after injection of a calcium hydroxylapatite filler. J Cosmet Laser Ther. 2004 Dec;6(4):223-6. https://doi.org/10.1080/147641704100003048. PMid:16020207.

8 Younesi FS, Miller AE, Barker TH, Rossi FMV, Hinz B. Fibroblast and myofibroblast activation in normal tissue repair and fibrosis. Nat Rev Mol Cell Biol. 2024 Aug;25(8):617-38. https://doi.org/10.1038/s41580-024-00716-0. PMid:38589640.

9 Rosenfeldt H, Grinnell F. Fibroblast quiescence and the disruption of ERK signaling in mechanically unloaded collagen matrices. J Biol Chem. 2000 Feb;275(5):3088-92. https://doi.org/10.1074/jbc.275.5.3088. PMid:10652290.

10 Moretti D, Teixeira LN, Perri de Carvalho PS, Vedovatto E, Martinez EF. Biologic behavior of pressed lithium disilicate ceramic and zirconia on human gingival fibroblasts: an in vitro study. Int J Periodont Restor Dent. 2022 Sep-Oct;42(5):e153-9. https://doi.org/10.11607/prd.5978. PMid:36044702.

11 Coleman KM, Voigts R, DeVore DP, Termin P, Coleman WP 3rd. Neocollagenesis after injection of calcium hydroxylapatite composition in a canine model. Dermatol Surg. 2008 Jun;34(Suppl 1):S53-5. https://doi.org/10.1111/j.1524-4725.2008.34243.x. PMid:18547182.

12 Thuy Ba Linh N, Mondal D, Lee BT. In vitro study of CaTiO3-hydroxyapatite composites for bone tissue engineering. ASAIO J. 2014 Nov-Dec;60(6):722-9. https://doi.org/10.1097/MAT.0000000000000126. PMid:25238497.

13 van Loghem J. Calcium hydroxylapatite in regenerative aesthetics: mechanistic insights and mode of action. Aesthet Surg J. 2025 Mar;45(4):393-403. https://doi.org/10.1093/asj/sjae196. PMid:39365034.

14 Hong JY, Park KY. Dual Benefits of calcium hydroxyapatite filler: a prospective study on midface volume restoration and skin quality enhancement. J Cosmet Dermatol. 2025 Jun;24(6):e70265. https://doi.org/10.1111/jocd.70265. PMid:40439277.

15 Courderot-Masuyer C, Robin S, Tauzin H, Humbert P. Evaluation of lifting and antiwrinkle effects of calcium hydroxylapatite filler. In vitro quantification of contractile forces of human wrinkle and normal aged fibroblasts treated with calcium hydroxylapatite. J Cosmet Dermatol. 2016 Sep;15(3):260-8. https://doi.org/10.1111/jocd.12215. PMid:26990784.

16 Bargowo L, Kusumawardhani B, Perdana S, Wijaksana IKE, Saskianti T, Ridwan RD, et al. Expression of osteopontin and osteocalcin in Osteoblast cells exposed to a combination of polymethylmethacrylate (PMMA) and hydroxyapatite (HAp): a prospective observational study. Medicine (Baltimore). 2024 Oct;103(42):e40088. https://doi.org/10.1097/MD.0000000000040088. PMid:39432596.

17 Mera P, Laue K, Ferron M, Confavreux C, Wei J, Galán-Díez M, et al. Osteocalcin signaling in myofibers is necessary and sufficient for optimum adaptation to exercise. Cell Metab. 2016 Jun;23(6):1078-92. https://doi.org/10.1016/j.cmet.2016.05.004. PMid:27304508.

18 Ashkar S, Weber GF, Panoutsakopoulou V, Sanchirico ME, Jansson M, Zawaideh S, et al. Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science. 2000 Feb;287(5454):860-4. https://doi.org/10.1126/science.287.5454.860. PMid:10657301.
 


Submetido em:
11/11/2025

Aceito em:
07/03/2026

69ef5fe5a9539511b20c6743 rou Articles
Links & Downloads

Rev. odontol. UNESP

Share this page
Page Sections