In Vitro Studies for Investigating Creep of Intervertebral Discs under Axial Compression: A Review of Testing Environment and Results

Abstract

Creep responses of intervertebral discs (IVDs) are essential for spinal biomechanics clarification. Yet, there still lacks a well-recognized investigation protocol for this phenomenon. Current work aims at providing researchers with an overview of the in vitro creep tests reported by previous studies, specifically specimen species, testing environment, loading regimes and major results, based on which a preliminary consensus that may guide future creep studies is proposed. Specimens used in creep studies can be simplified as a “bone–disc–bone” structure where three mathematical models can be adopted for describing IVDs’ responses. The preload of 10–50 N for 30 min or three cycles followed by 4 h-creep under constant compression is recommended for ex vivo simulation of physiological condition of long-time sitting or lying. It is worth noticing that species of specimens, environment temperature and humidity all have influences on biomechanical behaviors, and thus are summarized and compared through the literature review. All factors should be carefully set according to a guideline before tests are conducted to urge comparable results across studies. To this end, this review also provides a guideline, as mentioned before, and specific steps that might facilitate the community of biomechanics to obtain more repeatable and comparable results from both natural specimens and novel biomaterials.

The Radial Bulging and Axial Strains of Intervertebral Discs during Creep Obtained with the 3D-DIC System

“…Subsequently, the formal creep tests were carried out under three different magnitudes of loads (300 N, 400 N, and 500 N) with a loading rate of 5 N/s for 4 h ( Figure 1 b), which was reported to be sufficient by Paul et al [ 29 ]. The loading regime in this study was according to the earlier ex vivo study, conducted by O’Connell et al [ 30 ] and Yang et al [ 31 , 32 ], who adopted 4 h as the loading duration to quantify the time–response during creep. Five specimens were tested under the same conditions at room temperature; after which, the results were averaged.…”

Mitophagy—A New Target of Bone Disease

“…The main pathological features of IVDD are ECM degradation, senescence and apoptosis of nucleus pulposus cells (NPCs), and impaired self-repair function [ 69 ]. As primary cells residing in the nucleus pulposus (NP), NPCs are responsible for the synthesis of ECM and maintain the biological and mechanical properties of the intervertebral disc [ 70 ]. The dysfunction of NP tissue plays a crucial role in the pathological development of IVDD [ 71 ].…”

Repetitive strikes loading organ culture model to investigate the biological and biomechanical responses of the intervertebral disc

“…13,14 Furthermore, bovine caudal discs exhibit notable similarities to mature human discs in essential aspects such as glycosaminoglycan content, cell density, and the absence of notochordal cells. 15,16 Consequently, they are frequently employed as a model for preclinical research.…”

“…Considering these factors, intervertebral disc organ culture has emerged as an appealing approach to compensate the disadvantages associated with in vivo and in vitro conditions 13,14 . Furthermore, bovine caudal discs exhibit notable similarities to mature human discs in essential aspects such as glycosaminoglycan content, cell density, and the absence of notochordal cells 15,16 . Consequently, they are frequently employed as a model for preclinical research.…”