# Hybrid Cooperative Complexes of Low- and High-Molecular-Weight Hyaluronic Acid in Aesthetic Medicine

## TL;DR

This review explores how combining low- and high-molecular-weight hyaluronic acid improves aesthetic treatments by enhancing durability and skin health.

## Contribution

The paper introduces Hybrid Cooperative Complexes (HCCs) as a novel formulation combining low- and high-molecular-weight hyaluronic acid for aesthetic medicine.

## Key findings

- HCCs improve fibroblast, keratinocyte, and adipocyte vitality and stimulate collagen and elastin production.
- HCCs accelerate wound closure in co-cultures and delay senescence in mesenchymal stromal cells.
- Clinical trials show reduced wrinkle severity, improved skin hydration, and increased satisfaction with treatment.

## Abstract

In this review we present a comprehensive overview of the published literature related to the use of Hybrid Cooperative Complexes (HCCs) of low- and high-molecular-weight hyaluronic acid in aesthetic medicine. HCCs have been developed to overcome the shortcomings of traditional hyaluronic based dermal fillers. Specifically, HCCs deliver both high- and low-molecular-weight hyaluronic acid (HA), maximizing their complementary effects. They are biocompatible and formulated without the addition of foreign agents. Cooperative hydrogen bonds extend their durability and make them more resistant to hyaluronidase compared to high-molecular-weight HA. The rheological properties of HCC formulations allow for easy exertion through the needle and diffusion in the tissue compared to high-molecular-weight HA alone. In vitro studies have shown that HCCs improve vitality of fibroblasts, keratinocytes and adipocytes, and stimulate production of collagen and elastin. Studies on scratched co-cultures of immortalized human keratinocytes and human dermal fibroblasts demonstrated that HCCs accelerate wound closure. Furthermore, HCCs delayed senescence of mesenchymal stromal cells to a greater extent than high-molecular-weight HA or low-molecular-weight HA alone. Clinical studies show a reduction in wrinkle severity, improvement in skin roughness profile and reduction of skin laxity with pronounced improvement in superficial skin hydration lasting up to 6 months. The formulation intended for restoration of fat compartments demonstrated reduction in cheek volume loss and improvement in skin thickness. Subjects report moderate-to-high satisfaction and are likely to recommend the treatment. Limitations of the published studies are also addressed, as well as reported adverse events and published safety data.