A 3D Collagen–Alginate Hydrogel Model for Mechanoregulation of Autophagy in Periodontal Ligament Cells

TL;DR

This paper introduces a 3D hydrogel model to study how mechanical compression affects autophagy in periodontal ligament cells, revealing a key role for AKT-mTOR signaling.

Contribution

A novel 3D hydrogel model was developed to study mechanoregulation of autophagy in periodontal ligament cells under realistic compression.

Findings

Cells under compression showed increased autophagy markers like ATG7, Beclin1, and LC3-II/LC3-I within 4-8 hours.

Pharmacological inhibition of AKT-mTOR enhanced autophagy, identifying it as a negative regulator.

The hydrogel model mimics native matrix properties and enables quantitative studies of periodontal remodeling.

Abstract

Mechanical loading is a central cue in periodontal tissues, where compression of the periodontal ligament guides remodeling and orthodontic tooth movement (OTM). However, most mechanobiology studies have used two-dimensional cultures with poorly defined loading, and the role of autophagy under realistic three-dimensional compression remains unclear. In this study, we constructed a three-dimensional static compression model by encapsulating human periodontal ligament cells in collagen–alginate–CaSO4 hydrogels, whose swelling, degradation, and viscoelasticity approximate those of native matrix. When exposed to a controlled static compressive stress, the cells exhibited an early autophagic response with increased ATG7, Beclin1, and LC3-II/LC3-I; accumulation of LC3-positive puncta; and reduced p62 expression between 4 and 8 h. Pharmacological modulation showed that activation of AKT-mTOR signaling suppressed this response, whereas its inhibition further augmented autophagy, identifying AKT-mTOR as a negative regulator of compression-induced autophagy. Together, these findings demonstrate that moderate static compression drives AKT-mTOR-dependent autophagy in periodontal ligament cells and establish a simple hydrogel platform for quantitative studies of periodontal remodeling.

Figures