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Characterization of diabetes-related biomechanical and structural alterations in human deep fasciae using atomic
Chiedozie Kenneth Ugwoke1, Borut Furlani2, Daniel Hadraba3
1Institute of Anatomy, Faculty of Medicine, University of Ljubljana, Ljubljana 1000, Slovenia.
Background:
Type 2 diabetes mellitus (T2DM) is associated with connective-tissue complications, but effects on human deep fascia remain poorly understood. This study employed atomic force microscopy (AFM) nanoindentation and multiphoton imaging to quantify region-specific biomechanical and structural changes of deep fasciae in T2DM.
Methods:
Fascia lata, thoracolumbar fascia, and plantar fascia from 17 T2DM and 17 control male deceased (<24 h post-mortem) donors were analyzed. AFM was used to quantify nanoscale stiffness (Young's modulus) under hydrated conditions. Label-free multiphoton microscopy comprising Second Harmonic Generation (SHG), Two-Photon Excited Fluorescence (TPEF), and Fluorescence Lifetime Imaging Microscopy (FLIM) was used to assess collagen organization, autofluorescence, and fluorescence decay kinetics.
Results:
AFM revealed significantly increased stiffness in diabetic plantar fascia (87 ± 3.1 vs 40 ± 1.2 kPa, p = 0.004) and fascia lata (28 ± 1.2 vs 16 ± 0.5 kPa, p < 0.001) compared to controls, while thoracolumbar fascia stiffness did not differ significantly between groups. Stiffness changes showed no significant association with age or body mass index. SHG forward-to-backward ratios did not differ significantly between groups, suggesting preserved collagen supramolecular organization. However, TPEF ratios were significantly elevated in diabetic plantar fascia and fascia lata, suggesting increased accumulation of autofluorescent species. FLIM revealed a significant decrease in mean fluorescence lifetime (τₘ) in diabetic plantar fascia, indicative of altered collagen microenvironment, possibly due to glycation or oxidative modifications.
Conclusion:
T2DM induces site-specific biomechanical stiffening and biochemical remodeling of human deep fascia, particularly in load-bearing regions. These changes suggest mechanisms involving glycation and oxidative stress, providing mechanistic insights into musculoskeletal complications associated with diabetic fasciopathy.
