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Review
. 2025 Jun 6.
doi: 10.1007/s00266-025-04904-x. Online ahead of print.

Combined and Hybrid Treatments of Hyaluronic Acid (HA) and Calcium Hydroxylapatite (CaHA): A Systematic Review of Mechanisms of Action, Aesthetic Effectiveness, Satisfaction, and Safety Profile

Renald Meçani  1   2 , Mojgan Amiri  3 , Jonathan Kadouch  4 , Dusan Sajic  5   6   7 , Frank Lin  8 , Jessie Cheung  9 , Diana Barrera  10   11   12 , Omar Haroon  13 , Susana Sil-Zavaleta  14   15 , Yates Chao  16 , Taulant Muka  3
Affiliations
Review

Combined and Hybrid Treatments of Hyaluronic Acid (HA) and Calcium Hydroxylapatite (CaHA): A Systematic Review of Mechanisms of Action, Aesthetic Effectiveness, Satisfaction, and Safety Profile

Renald Meçani et al. Aesthetic Plast Surg. .

Abstract

Background: The use of dermal fillers has become increasingly popular in aesthetic medicine for facial rejuvenation and skin enhancement. Hyaluronic acid (HA) and calcium hydroxylapatite (CaHA) are particularly well-known for their unique benefits. This systematic review evaluates the combinations (e.g., using two separate treatments together) and hybrid treatments of HA and CaHA (e.g., direct syringe-to-syringe mixing), focusing on their mechanisms of action, aesthetic effectiveness, patient satisfaction, and safety.

Methods: Six bibliographic databases were searched for human and non-human studies that explored the mechanistic effects of combined and hybrid HA and CaHA treatments, and their aesthetic effectiveness, skin quality, satisfaction, and safety were included. Due to high heterogeneity among included studies, a qualitative synthesis of the evidence was performed.

Results: The combination of HA and CaHA stimulates collagen synthesis through different molecular pathways. The combined and hybrid treatments are associated with high aesthetic effectiveness in various facial areas, as reported by both investigators and subjects. Additionally, the combinations and hybrid treatments show high satisfaction rates and have a safe profile, with minor, self-resolving adverse effects. A trend of slight decline in both aesthetic improvement and treatment satisfaction was observed after six months.

Conclusions: The combinations and hybrid treatments of HA and CaHA appear to be a promising, safe, and efficacious treatment for facial rejuvenation, offering both immediate volumizing effects and longer-term benefits through collagen synthesis. Future research should employ rigorous study designs aimed at refining treatment protocols and generating strong, long-term evidence for the safety and effectiveness of this combination or hybrid therapy in aesthetic medicine.

Level of evidence ii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Keywords: Aesthetics; Calcium hydroxylapatite; Cosmetic; Dermatology; Fillers; Hyaluronic acid.

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Conflict of interest statement

Declarations. Conflict of Interest: FL has provided consultancy services for Merz Aesthetics, received honoraria from Merz Aesthetics, and had travel/accommodation expenses covered or reimbursed by Merz Aesthetics. JC has received financial compensation for consultancy from Galderma Aesthetics and honoraria from Merz Aesthetics. DB has provided consultancy services for Merz Aesthetics and participated in advisory boards. They serve as a speaker on behalf of Merz Aesthetics, supporting local and regional events and presentations. DB has had travel/accommodation expenses covered or reimbursed by Merz Aesthetics. SD has provided consultancy for Merz, Galderma, AbbVie, Xcite Technologies, and Derma Research Group. They have received grants from Merz, Galderma, Derma Research Group, and AbbVie, as well as honoraria from AbbVie. They have received financial compensation for the development of educational presentations, including service on speakers' bureaus, from Merz and Galderma. They have also had travel/accommodation expenses covered or reimbursed by Merz, Galderma, and AbbVie. Additionally, they are the cofounder and CEO of Derma Research Group. TM has received grants from Merz Aesthetics and is the founder and CEO of Epistudia. JK has provided consultancy services for Merz Aesthetics and has had travel/accommodation expenses covered or reimbursed by Merz Aesthetics. SSZ is employed as a regional speaker for Merz Aesthetics Pharma and has received financial compensation for the development of educational presentations, including service on speakers' bureaus, for Merz Aesthetics Pharma. Human and Animal Rights, or Ethical Approval: This article does not contain any studies with human participants or animals performed by any of the authors. Informed Consent: For this type of study, informed consent is not required.

References

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