Calcium Hydroxyapatite Versus Hyaluronic Acid: A Systematic Literature Review on Efficacy in Facial Rejuvenation and Collagen Biostimulation in Aesthetic Biomedicine
DOI:
https://doi.org/10.69849/d2vqg119Keywords:
Skin Aging, Aesthetic Biomedicine, Calcium Hydroxyapatite, Hyaluronic Acid, Facial RejuvenationAbstract
Skin aging is a multifactorial process characterized by structural changes in the extracellular matrix, reduced fibroblast activity, and decreased collagen and elastin synthesis, resulting in sagging, volume loss, and wrinkle formation. In aesthetic biomedicine, dermal fillers and collagen biostimulators have been widely used as effective strategies for facial rejuvenation, with hyaluronic acid and calcium hydroxyapatite standing out due to their distinct mechanisms of action and tissue responses. The aim of this study was to systematically review the recent scientific literature on the efficacy, safety, and mechanisms of action of calcium hydroxyapatite compared to hyaluronic acid in facial rejuvenation, with emphasis on collagen biostimulation, extracellular matrix remodeling, and tissue quality. This is a systematic literature review, conducted according to the PICO strategy. Searches were performed in the PubMed, Lilacs, and Cochrane databases using the descriptors "calcium hydroxyapatite," "hyaluronic acid," "aesthetics," and "rejuvenation." Experimental studies published in the last five years, available in full text, written in English or Portuguese, and addressing the efficacy and safety of calcium hydroxyapatite compared to hyaluronic acid were included. After applying the inclusion and exclusion criteria, seven articles were selected for qualitative analysis, following the PRISMA protocol guidelines. The results showed that calcium hydroxyapatite has a dual effect, promoting immediate volumization and progressive collagen biostimulation, with increased dermal thickness, extracellular matrix remodeling, and sustained clinical results over time. Hyaluronic acid demonstrated high efficacy in volume replacement and skin hydration, with results dependent on its rheological properties and application technique. Both materials presented a favorable safety profile and high patient satisfaction rates. It is concluded that calcium hydroxyapatite exhibits greater durability of biostimulating effects, reinforcing its clinical relevance in contemporary facial rejuvenation protocols.
References
ALBARGAWI, Salma; NAGSHABANDI, Khalid Nabil; SHADID, Asem. Dermal filler-induced alopecia: a case report and literature review. Journal of Cosmetic Dermatology, v. 24, n. 2, p. e16684, 2025. https://doi.org/10.1111/jocd.16684
ALSHARIF, Sahar Hasan et al. Treatment of striae distensae with filler injection: a systematic review. Clinical, Cosmetic and Investigational Dermatology, v. 16, p. 837–845, 2023. https://doi.org/10.2147/CCID.S405715
ANSARY, Tuba M. et al. Inflammatory molecules associated with ultraviolet radiation-mediated skin aging. International Journal of Molecular Sciences, v. 22, n. 8, p. 3974, 2021. https://doi.org/10.3390/ijms22083974
BAUMANN, Leslie. Skin ageing and its treatment. The Journal of Pathology, v. 211, n. 2, p. 241–251, 2007. https://doi.org/10.1002/path.2098
BARONE, Mauro; SALZILLO, Rosa; PERSICHETTI, Paolo. Minimally invasive facial rejuvenation with the hybrid filler HArmonyCa™. Aesthetic Plastic Surgery, v. 48, n. 23, p. 5251–5253, 2024. https://doi.org/10.1007/s00266-023-03649-9
BOȚA, Mihaela et al. The impact of injectable biostimulatory substances on current trends in aesthetic medicine: focus on poly-L-lactic acid, polycaprolactone, and calcium hydroxyapatite. Medicine in Evolution, v. 31, n. 2, p. 177–186, 2025.
BRAVO, Bruna Souza Felix et al. Dermal thickness increase and aesthetic improvement with hybrid product combining hyaluronic acid and calcium hydroxyapatite: a clinical and sonographic analysis. Plastic and Reconstructive Surgery – Global Open, v. 11, n. 6, p. e5055, 2023. https://doi.org/10.1097/GOX.0000000000005055
CHAUDHRY, Mohammed. First reported use of AIVA® re-Verse, a novel combination injection protocol for facial rejuvenation: a report of three cases. Cureus, v. 17, n. 8, p. e89664, 2025. https://doi.org/10.7759/cureus.89664
CHENG, Dangdang et al. Facial skin aging: effect of aging in different layers of the skin on wrinkles and sagging. Journal of Biophotonics, v. 18, n. 9, p. e70028, 2025. https://doi.org/10.1002/jbio.70028
DURKIN, Alan et al. Single-center, prospective comparison of calcium hydroxylapatite and Vycross-20L in midface rejuvenation. Journal of Cosmetic Dermatology, v. 20, n. 2, p. 442–450, 2021. https://doi.org/10.1111/jocd.13682
FAKIH-GOMEZ, Nabil et al. Jawline sharp contouring with hybrid filler. Aesthetic Plastic Surgery, v. 49, n. 1, p. 334–340, 2025a. https://doi.org/10.1007/s00266-024-04226-4
FAKIH-GOMEZ, Nabil et al. The hybrid filler technique: a 5-year retrospective analysis. Aesthetic Plastic Surgery, v. 49, n. 3, p. 618–626, 2025b. https://doi.org/10.1007/s00266-024-04387-2
FARIA, Gladstone Eustaquio de Lima et al. Hand rejuvenation with customizable hybrid fillers. Aesthetic Plastic Surgery, v. 48, n. 15, p. 2887–2894, 2024. https://doi.org/10.1007/s00266-024-04145-4
FARIA, Gladstone Eustaquio de Lima et al. Treatment of the temples: Brazilian consensus. Aesthetic Plastic Surgery, v. 49, n. 11, p. 2871–2879, 2025. https://doi.org/10.1007/s00266-024-04614-w
GOLDIE, Kate et al. Consensus agreements on regenerative aesthetics. Dermatologic Surgery, v. 50, n. 11S, p. S172–S176, 2024. https://doi.org/10.1097/DSS.0000000000004076
GRITTI, Alessandro et al. A prospective, open-label, post marketing study of a hyaluronic acid and calcium hydroxyapatite hybrid injectable. Journal of Cosmetic Dermatology, v. 24, n. 9, p. e70430, 2025. https://doi.org/10.1111/jocd.70430
GUO, Yanping et al. Effect of a new hyaluronic acid hydrogel dermal filler. Aesthetic Surgery Journal, v. 44, n. 1, p. NP87–NP97, 2023. https://doi.org/10.1093/asj/sjad171
LAGES, Renata Bandeira et al. Associação de preenchedores e bioestimuladores no rejuvenescimento facial. Simmetria - Orofacial Harmonization in Science, v. 2, n. 6, p. 22–27, 2021.
LI, Kelun et al. Application of nonsurgical modalities in improving facial aging. International Journal of Dentistry, v. 2022, p. 8332631, 2022. https://doi.org/10.1155/2022/8332631.
LI, Xinxin et al. Cooperation of TGF-β and FGF signalling pathways in skin development. Cell Proliferation, v. 56, n. 11, p. e13489, 2023. https://doi.org/10.1111/cpr.13489.
LU, Jasmine Thai; LEE, Kachiu C. Global facial rejuvenation with one treatment. International Journal of Women’s Dermatology, v. 9, n. 4, p. e124, 2023. https://doi.org/10.1097/JW9.0000000000000124.
MILLS, Alexandra; HAQ, Syed. HarmonyCa: a first-in-class hybrid dermal filler. Journal of Aesthetic Nursing, v. 12, Suppl. 8, p. S6–S12, 2023. https://doi.org/10.12968/joan.2023.12.Sup8.S6.
OLIVEIRA, Luísa Mara Xavier de; DINIZ, Helen Cristina Maurício Milagre. Filling in mandibular contour with hyaluronic acid. Health and Society, v. 2, n. 4, p. 100–122, 2022.
PAGE, Matthew J. et al. The PRISMA 2020 statement: an updated guideline for reporting
systematic reviews. BMJ, v. 372, n. 71, 2021. https://doi.org/10.1136/bmj.n71.
PAVANI, Alessandra Alves et al. Harmonização orofacial com associação de ácido hialurônico. Revista Cathedral, v. 3, n. 2, p. 45–59, 2021.
PROIETTI, Ilaria et al. HarmonyCa™ hybrid filler to restore connective tissue: a clinical and histological analysis. Journal of Cosmetic Dermatology, v. 23, n. 12, p. 3883–3892, 2024. https://doi.org/10.1111/jocd.16088.
RIBEIRO, Camila Gonçalves et al. Aplicações clínicas do ácido hialurônico. Revista Eletrônica Acervo Saúde, v. 15, n. 2, p. e9774, 2022. https://doi.org/10.25248/reas.e9774.2022.
SOUZA, Lorena Leticia Jesus de; FREITAS, Gabriel Lima de. Rejuvenescimento facial na biomedicina estética. Revista FT, v. 28, n. 138, p. 3–4, 2024. https://doi.org/10.5281/zenodo.10467383.
SOUZA, Wanessa de Oliveira. Aspectos gerais do uso do ácido hialurônico. RCMOS - Revista Científica Multidisciplinar O Saber, v. 1, n. 4, p. 154–177, 2024. https://doi.org/10.51473/rcmos.v1i4.2021.60.
SUNDARAM, Hema et al. Global aesthetics consensus: hyaluronic acid fillers and botulinum toxin type A - recommendations for combined treatment and optimizing outcomes in diverse patient populations. Plastic and Reconstructive Surgery, v. 147, n. 5S, p. 12S–25S, 2021. https://doi.org/10.1097/PRS.0000000000007785.
TAMURA, Bruno Massayuki. Bioestimuladores de colágeno na harmonização orofacial. Surgical & Cosmetic Dermatology, v. 11, n. 3, p. 204–212, 2019.
TEZEL, Ahmet; FREDRICKSON, Glenn H. The science of hyaluronic acid dermal fillers. Journal of Cosmetic and Laser Therapy, v. 10, n. 1, p. 35–42, 2008. https://doi.org/10.1080/14764170701774901.
TRINDADE, Adriana Pereira et al. Perfil do biomédico esteta e a segurança do paciente. Revista Eletrônica Acervo Saúde, v. 12, n. 10, p. e4783, 2020. https://doi.org/10.25248/reas.e4783.2020.
WELLS, G. A. et al. The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute, 2014. Disponível em: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Acesso em: 19 mar. 2026.
WU, Larry; SALTI, Giovanni. Combined forehead and temporal lifting. Journal of Cosmetic Dermatology, v. 24, n. 1, p. e16583, 2025. https://doi.org/10.1111/jocd.16583.
ZARRA, Ivana. Aging and skin rejuvenation: cellular and molecular mechanisms. Clinics in Dermatology, v. 40, n. 4, p. 401–407, 2022.
https://doi.org/10.1016/j.clindermatol.2022.03.003.
ZERBINATI, Nicola et al. Efficacy of pegylated hyaluronic acid filler enriched with calcium hydroxyapatite. Journal of Functional Biomaterials, v. 14, n. 7, p. 345, 2023. https://doi.org/10.3390/jfb14070345.
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Copyright (c) 2026 Jackson Pereira Lopes, Rizia Laysa Soares Braga, Lauann Rickelmy Cardial da Silva, Ana Carolina Machado Leódido, Manoel Dias de Souza Filho (Autor)
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