Background Tear trough deformity is a prominent periorbital aging manifestation, and minimally invasive filler injection has become a preferred alternative to surgical correction. However, the optimal mixing ratio of collagen (Col) and hyaluronic acid (HA) fillers, as well as refined injection techniques for the delicate infraorbital region, remains a further in-depth investigation. Objective To screen the optimal volume ratio of collagen-HA mixed fillers, verify its anti-photoaging mechanism, and evaluate its clinical efficacy and safety for infraorbital rejuvenation. Methods A multi-modal study was conducted, the in vitro experiments including cell viability, ROS detection, and ELISA assay for effect of the mix fillers on UV-induced photoaged human dermal fibroblasts (HDFs), as well as the injection forces of the mix fillers. The in vivo study was conducted on UV-induced photoaging mice model with histological, immunofluorescence, and ELISA detections. Additionally, a prospective randomized controlled clinical trial combined with an innovative injection technique was performed to further verify the efficacy and safety of the mix fillers. Results In vitro, the Col/HA (2:1) mix filler treated group showed the highest cell viability, most significant ROS reduction, and strongest collagen synthesis promotion. In vivo, this mix filler effectively alleviated UV-induced skin photoaging, restored collagen and elastic fiber structure and content, suppressed cellular senescence and inflammation. In clinical practice, this mix filler treated group maintained the highest AIHS improvement rate and optimal GAIS scores at 6 months, with the lowest incidence of postoperative complications, such as Tyndall phenomenon, and lumpiness. The other two mix filler (Col/HA(1:1) and Col/HA(1:2)) treated groups exhibited inferior efficacy and safety. Conclusion The Col/HA (2:1) mix filler, combined with the innovative short fine needle vertical layered injection technique, exhibits excellent anti-photoaging effects and safety, providing a standardized and refined clinical strategy for minimally invasive infraorbital rejuvenation. 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 <a href="https://link.springer.com/journal/00266">www.springer.com/00266</a>.

Experimental and Clinical Evaluation of Optimized Composite Collagen-Crosslinked Hyaluronic Acid Filler for Infraorbital Rejuvenation

期刊论文
发表日期：

2026年7月14日

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Haigang Feng,
Shasha Xie,
Wanjun Deng,
Lihua Zhou,
Jun Zuo

摘要

Background

Tear trough deformity is a prominent periorbital aging manifestation, and minimally invasive filler injection has become a preferred alternative to surgical correction. However, the optimal mixing ratio of collagen (Col) and hyaluronic acid (HA) fillers, as well as refined injection techniques for the delicate infraorbital region, remains a further in-depth investigation.

Objective

To screen the optimal volume ratio of collagen-HA mixed fillers, verify its anti-photoaging mechanism, and evaluate its clinical efficacy and safety for infraorbital rejuvenation.

Methods

A multi-modal study was conducted, the in vitro experiments including cell viability, ROS detection, and ELISA assay for effect of the mix fillers on UV-induced photoaged human dermal fibroblasts (HDFs), as well as the injection forces of the mix fillers. The in vivo study was conducted on UV-induced photoaging mice model with histological, immunofluorescence, and ELISA detections. Additionally, a prospective randomized controlled clinical trial combined with an innovative injection technique was performed to further verify the efficacy and safety of the mix fillers.

Results

In vitro, the Col/HA (2:1) mix filler treated group showed the highest cell viability, most significant ROS reduction, and strongest collagen synthesis promotion. In vivo, this mix filler effectively alleviated UV-induced skin photoaging, restored collagen and elastic fiber structure and content, suppressed cellular senescence and inflammation. In clinical practice, this mix filler treated group maintained the highest AIHS improvement rate and optimal GAIS scores at 6 months, with the lowest incidence of postoperative complications, such as Tyndall phenomenon, and lumpiness. The other two mix filler (Col/HA(1:1) and Col/HA(1:2)) treated groups exhibited inferior efficacy and safety.

Conclusion

The Col/HA (2:1) mix filler, combined with the innovative short fine needle vertical layered injection technique, exhibits excellent anti-photoaging effects and safety, providing a standardized and refined clinical strategy for minimally invasive infraorbital rejuvenation.

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.