# Comparison of effectiveness of hyaluronic acid and melatonin with guided tissue regeneration (GTR) membrane versus guided tissue regeneration (GTR) membrane alone in the treatment of intra-bony defects in human subjects: A split-mouth randomised controlled clinical trial

**Authors:** Subasree Soundarajan, Sankari Malaiappan

PMC · DOI: 10.1016/j.jobcr.2026.01.001 · 2026-01-16

## TL;DR

This study found that combining hyaluronic acid and melatonin with a GTR membrane improved healing of bone defects in periodontitis patients compared to using the membrane alone.

## Contribution

The study introduces a novel combination of hyaluronic acid and melatonin with GTR for periodontal regeneration.

## Key findings

- Group 1 showed statistically significant improvement in clinical and radiographic parameters compared to Group 2.
- The combination therapy led to better bone regeneration and reduced MMP-1 levels.
- Both groups showed significant improvement from baseline, but Group 1 outperformed Group 2.

## Abstract

Melatonin is one substance that is primarily generated by the pineal gland and numerous other tissues and has vital involvement in many physiological processes, including bone remodeling. Over the last several years, another emerging molecule serving as a potential candidate for periodontal regeneration is the hyaluronic acid (HA), a key extracellular matrix component involved in cell migration. The aim of this study is the additive effect of hyaluronic acid and melatonin with GTR membrane in intrabony defects among patients with chronic periodontitis.

15 bilateral intra-bony defects were treated either with Hyaluronic acid and melatonin along with GTR membrane (Group I), or GTR membrane alone (Group II). Clinical and radiographic parameters assessed were pocket depth, clinical attachment level, and volume of bone defect at baseline and 6 months after the intervention. The biochemical parameter assessed was Matrix metalloproteinase - 1 (MMP-1) and Tissue inhibitor of metalloproteinase (TIMP-1) at baseline and one month after the intervention.

Both the study groups showed statistically significant differences in all the parameters from baseline to follow-up. However, group 1 (Hyaluronic acid + Melatonin + GTR membrane) showed statistically significant improvement in all the study parameters when compared to group 2 (GTR alone).

It can be concluded that the combination of hyaluronic acid and melatonin was effective in the regeneration of intrabony defects among patients with chronic periodontitis. However, further studies with a longer time period and with additional microbiological assessment would be desirable so as to substantiate the current results.

Combination of hyaluronic acid and melatonin was effective in regeneration of intrabony defects among patients with chronic periodontitis in terms of probing depth, clinical attachment level, bone fill, MMP-1 and TIMP-1 levels.

## Linked entities

- **Proteins:** MMP1 (matrix metallopeptidase 1), TIMP1 (TIMP metallopeptidase inhibitor 1)
- **Chemicals:** melatonin (PubChem CID 896)
- **Diseases:** chronic periodontitis (MONDO:0005593)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** TIMP1 (TIMP metallopeptidase inhibitor 1) [NCBI Gene 7076] {aka CLGI, EPA, EPO, HCI, TIMP, TIMP-1}, MMP1 (matrix metallopeptidase 1) [NCBI Gene 4312] {aka CLG}
- **Diseases:** intra-bony defects (MESH:D018213), defects (MESH:D000013), bone defect (MESH:D001847), chronic periodontitis (MESH:D055113)
- **Chemicals:** HA (MESH:D006820), Melatonin (MESH:D008550), GTR membrane (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12834905/full.md

---
Source: https://tomesphere.com/paper/PMC12834905