Type 2 diabetes impairs annulus fibrosus fiber deformation and rotation under disc compression in the UCD-T2DM rat model

Abstract Understanding the biomechanical behavior of the intervertebral disc is crucial for studying disease mechanisms and developing tissue engineering strategies for managing low back pain. We used synchrotron small-angle x-ray scattering (SAXS) to investigate how changes in collagen behavior contribute to alterations in the disc’s ability to resist compression. Coccygeal motion segments from 6-month-old lean Sprague-Dawley rats (n = 7) and diabetic obese UCDT2DM rats (n = 6, diabetic for 68 ± 7 days) were compressed during simultaneous scanning to measure collagen strain at the nanoscale (beamline 7.3.3 of the Advanced Light Source). After compression, the annulus fibrosus was assayed for non-enzymatic cross-links. In discs from lean rats, resistance to compression involved two main energy-dissipation mechanisms at the nanoscale: 1) rotation of the two groups of collagen fibrils forming the annulus fibrosus; and 2) straightening (uncrimping) and stretching of the collagen fibrils. In discs from diabetic rats, both mechanisms were significantly impaired. Specifically, diabetes reduced fibril rotation by 31% and reduced collagen fibril strain by 41% (compared to lean discs). The stiffening of collagen fibrils in the discs from diabetic rats was consistent with a 21% higher concentration of non-enzymatic cross-links and with evidence of earlier onset plastic deformations such as fibril sliding and fibril-matrix delamination. These findings suggest that fibril reorientation, stretching, and straightening are key deformation mechanisms that facilitate whole-disc compression, and that type 2 diabetes impairs these efficient and low-energy elastic deformation mechanisms, thereby altering whole-disc behavior and inducing the earlier onset of plastic deformation.