Augmentation and repair tissue formation of the nucleus pulposus after partial nucleotomy in a rabbit model

Disc degeneration alters disc height and mechanics of the spinal column and is associated with lower back pain. In preclinical studies gel-like materials or resorbable polymer-based implants are frequently used to rebuild the nucleus pulposus, aiming at tissue regeneration and restoration of tissue function. To compare the outcome of tissue repair, freeze-dried resorbable polyglycolic acid–hyaluronan (PGA/HA) implants without any bioactive components or bioactivated fibrin (fibrin-serum) was used in a degenerated disc disease model in New Zealand white rabbits. Animals with partial nucleotomy only served as controls. The T2-weighted/fat suppression sequence signal intensity in the nuclear region of operated discs as assessed by magnet resonance imaging was reduced in operated compared to healthy discs, indicating loss of water and did not change from week 1 to month 6 after surgery. Quantification of histological and immunohistochemical staining indicated that the implantation of PGA/HA leads to significantly more repair tissue compared to nucleotomy only. Type II collagen content of the repair tissue formed after PGA/HA or fibrin-serum treatment is significantly increased compared to controls with nucleotomy only. The data indicate that intervertebral disc augmentation after nucleotomy has a positive effect on repair tissue formation and type II collagen deposition as shown in the rabbit model.     

How do we stand? Variations during repeated standing phases of asymptomatic subjects and low back pain patients

An irreproducible standing posture can lead to mis-interpretation of radiological measurements, wrong diagnoses and possibly unnecessary treatment. This study aimed to evaluate the differences in lumbar lordosis and sacrum orientation in six repetitive upright standing postures of 353 asymptomatic subjects (including 332 non-athletes and 21 athletes – soccer players) and 83 low back pain (LBP) patients using a non-invasive back-shape measurement device.In the standing position, all investigated cohorts displayed a large inter-subject variability in sacrum orientation (∼40°) and lumbar lordosis (∼53°). In the asymptomatic cohort (non-athletes), 51% of the subjects showed variations in lumbar lordosis of 10–20% in six repeated standing phases and 29% showed variations of even more than 20%. In the sacrum orientation, 53% of all asymptomatic subjects revealed variations of >20% and 31% of even more than 30%.It can be concluded that standing is highly individual and poorly reproducible. The reproducibility was independent of age, gender, body height and weight. LBP patients and athletes showed a similar variability as the asymptomatic cohort. The number of standing phases performed showed no positive effect on the reproducibility. Therefore, the variability in standing is not predictable but random, and thus does not reflect an individual specific behavioral pattern which can be reduced, for example, by repeated standing phases.     

Estimation of in vivo inter-vertebral loading during motion using fluoroscopic and magnetic resonance image informed finite element models

Finite element (FE) models driven by medical image data can be used to estimate subject-specific spinal biomechanics. This study aimed to combine magnetic resonance (MR) imaging and quantitative fluoroscopy (QF) in subject-specific FE models of upright standing, flexion and extension. Supine MR images of the lumbar spine were acquired from healthy participants using a 0.5 T MR scanner. Nine 3D quasi-static linear FE models of L3 to L5 were created with an elastic nucleus and orthotropic annulus. QF data was acquired from the same participants who performed trunk flexion to 60° and trunk extension to 20°. The displacements and rotations of the vertebrae were calculated and applied to the FE model. Stresses were averaged across the nucleus region and transformed to the disc co-ordinate system (S1 = mediolateral, S2 = anteroposterior, S3 = axial). In upright standing S3 was predicted to be −0.7 ± 0.6 MPa (L3L4) and −0.6 ± 0.5 MPa (L4L5). S3 increased to −2.0 ± 1.3 MPa (L3L4) and −1.2 ± 0.6 MPa (L4L5) in full flexion and to −1.1 ± 0.8 MPa (L3L4) and −0.7 ± 0.5 MPa (L4L5) in full extension. S1 and S2 followed similar patterns; shear was small apart from S23. Disc stresses correlated to disc orientation and wedging. The results demonstrate that MR and QF data can be combined in a participant-specific FE model to investigate spinal biomechanics in vivo and that predicted stresses are within ranges reported in the literature.     

Animal models of regenerative medicine for biological treatment approaches of degenerative disc diseases

Degenerative disc disease (DDD) is a painful, chronic and progressive disease, which is characterized by inflammation, structural and biological deterioration of the intervertebral disc (IVD) tissues. DDD is specified as cell-, age-, and genetic-dependent degenerative process that can be accelerated by environmental factors. It is one of the major causes of chronic back pain and disability affecting millions of people globally. Current treatment options, such as physical rehabilitation, pain management, and surgical intervention, can provide only temporary pain relief. Different animal models have been used to study the process of IVD degeneration and develop therapeutic options that may restore the structure and function of degenerative discs. Several research works have depicted considerable progress in understanding the biological basis of disc degeneration and the therapeutic potentials of cell transplantation, gene therapy, applications of supporting biomaterials and bioactive factors, or a combination thereof. Since animal models play increasingly significant roles in treatment approaches of DDD, we conducted an electronic database search on Medline through June 2020 to identify, compare, and discuss publications regarding biological therapeutic approaches of DDD that based on intradiscal treatment strategies. We provide an up-to-date overview of biological treatment strategies in animal models including mouse, rat, rabbit, porcine, bovine, ovine, caprine, canine, and primate models. Although no animal model could profoundly reproduce the clinical conditions in humans; animal models have played important roles in specifying our knowledge about the pathophysiology of DDD. They are crucial for developing new therapy approaches for clinical applications.     

Effects of Fusicoccin on the Early Stages of Sorghum Growth at High NaCl Concentrations

The effects of fusicoccin (FC) on the early growth processes in sorghum (Sorghum vulgare M.) seeds germinated in water and in 0.1 M or 0.2 M NaCl solutions were investigated. We studied the rate of seed imbibition, the onset of radicle protrusion, the occurrence of the first mitoses, the mitotic index, the distribution of cells according to the phases of the cell cycle, as well as the length and weight of roots. Seed imbibition was considerably accelerated by treating them with 5 × 10^–6 M FC for 1 h. In these FC-treated seeds placed on NaCl solutions, FC stimulated water influx into seeds, radicle protrusion, and occurrence of the first mitoses. FC pretreatment did not affect substantially the distribution of meristematic cells according to the periods of the cell cycle after 72 h of seed germination on water or 0.1 M NaCl. Root growth was inhibited by 0.1 M NaCl, but it was partially recovered in the presence of FC. 0.2 M NaCl caused a decrease in the mitotic index and in the number of cells in the S phase, an accumulation of cells in the G₂ period and in the prophase, as well as a considerable inhibition of root growth. FC pretreatment of seeds subsequently germinated on 0.2 M NaCl resulted in an increase in the number of cells in the G₁ period, in the mitotic index, and in the root-growth rate. FC virtually did not affect the growth of sorghum in the absence of salt. Pretreatment of seeds with FC followed by salinization resulted in an increase in the water content in seeds. It is suggested that a FC-induced increase in the water content of seeds accelerated metabolic processes in seeds germinating on NaCl solutions, thus regulating ionic homeostasis and thereby stimulating the initial growth processes.__________Translated from Fiziologiya Rastenii, Vol. 52, No. 3, 2005, pp. 378–383.Original Russian Text Copyright © 2005 by Lutsenko, Marushko, Kononenko, Leonova.     

Osmosis and viscoelasticity both contribute to time-dependent behaviour of the intervertebral disc under compressive load: A caprine in vitro study

The mechanical behaviour of the intervertebral disc highly depends on the content and transport of interstitial fluid. It is unknown, however, to what extent the time-dependent behaviour can be attributed to osmosis. Here we investigate the effect of both mechanical and osmotic loading on water content, nucleus pressure and disc height. Eight goat intervertebral discs, immersed in physiological saline, were subjected to a compressive force with a pressure needle inserted in the nucleus. The loading protocol was: 10 N (6 h); 150 N (42 h); 10 N (24 h). Half-way the 150 N-phase (24 h), we eliminated the osmotic gradient by adding 26% poly-ethylene glycol to the surrounding fluid. For 62 additional discs, we determined the water content of both nucleus and annulus after 6, 24, 48, or 72 h. The compressive load was initially counterbalanced by the hydrostatic pressure in the nucleus. The load forced 4.3% of the water out of the nucleus, which reduced nucleus pressure by 44(±6)%. Reduction of the osmotic gradient disturbed the equilibrium disc height, and a significant loss of annulus water content was found. Remarkably, pressure and water content of the nucleus pulposus remained unchanged. This shows that annulus water content is important in the response to axial loading. After unloading, in the absence of an osmotic gradient, there was substantial viscoelastic recovery of 53(±11)% of the disc height, without a change in water content. However, for restoration of the nucleus pressure and for full restoration of disc height, restoration of the osmotic gradient was needed.