# Calcium Hydroxyapatite and Polymicronutrient Solution on Hand Rejuvenation: A Split‐Hand, Randomized, Double‐Blind Clinical and In Vitro Study

## TL;DR

A study compared using calcium hydroxyapatite mixed with a nutrient solution versus saline for hand rejuvenation, finding similar results in people but better cell activity in lab tests with the nutrient mix.

## Contribution

Demonstrated in vitro biostimulatory enhancement of CaHA when combined with PMN, despite no clinical difference in hand rejuvenation outcomes.

## Key findings

- CaHA + PMN increased fibroblast proliferation and upregulated ECM-related genes (COL1A1, ELN) in vitro.
- Both CaHA + PMN and CaHA + SS improved hand rejuvenation metrics clinically, with no significant differences between groups.
- In vitro biological activity of CaHA was enhanced by PMN, suggesting potential for future complementary use.

## Abstract

Calcium hydroxyapatite (CaHA) is a well‐established biostimulatory filler approved for hand rejuvenation. Recent approaches have explored dilution with polymicronutrient (PMN) solutions to enhance cellular metabolism and extracellular matrix (ECM) regeneration.

To evaluate the biological and clinical effects of CaHA diluted in a PMN solution (CaHA + PMN) compared with the conventional CaHA diluted in saline solution (CaHA + SS) for hand rejuvenation.

An in vitro study was conducted to assess fibroblast proliferation and gene expression of ECM components (COL1A1, COL3A1, and ELN) after exposure to CaHA diluted with PMN or SS. A prospective, split‐hand, double‐blind clinical trial (n = 22) compared both formulations regarding Hand Grading Scale (HGS), Global Aesthetic Improvement Scale (GAIS), skin hydration (corneometry), and dermal thickness (ultrasound imaging) at baseline, 15 and 90 days after treatment.

In vitro, CaHA + PMN induced greater fibroblast proliferation and upregulated COL1A1 and ELN gene expression compared to CaHA + SS. Clinically, both treatments led to significant improvement from baseline in HGS (p < 0.001), skin hydration and dermal/hypodermal thickness, with no statistically significant differences between‐group. Investigator‐assessed GAIS and patient‐reported satisfaction on a 5‐point Likert scale also showed improvement in both groups.

Both treatments demonstrated comparable clinical outcomes, suggesting that the strong biostimulating effect of CaHA may have overshadowed potential additive effects of PMN. Nonetheless, in vitro findings confirmed enhanced biological activity with CaHA + PMN, supporting its investigation as a complementary strategy in future studies.