Tryfonidou leads the Horizon 2020 consortium (iPSpine; 2019–2023) bringing a transdisciplinary team of 21 partners together to address the challenges and bottlenecks of iPS-based advanced therapies towards their transition to the clinic. Here, chronic back pain due to intervertebral disc degeneration is employed as a show case. The project develops the iPS-technology and designed smart biomaterials to carry, protect and instruct the iPS cells within the degenerate disc environment. This work will be presented including ongoing activities focus on translating the developed methodology and tools towards clinically relevant animal models. The consortium optimized the protocol for the differentiated iPS-notochordal-like cells (iPS-NLCs) and shortlisted two biomaterials shortlisted based on their physicochemical, cytotoxicity, biomechanical and biocompatibility testing. Both were shown to be safe and have been tested with the progenitors of iPS-NLCs. An advanced platform (e.g., the dynamic loading bioreactor for disc tissue) was used to evaluate their performance: the biomaterials supported the iPS-NLC progenitors after injection into the degenerate disc and seem to also support their maturation towards NLCs. Furthermore, we confirmed the capacity of these cells to survive inside degenerated discs at 30 days upon injection in sheep, whereafter we continued with their evaluation at 3 months post-injection. We achieved full evaluation of the sheep spines, including biomechanical analysis using the portable spine biomechanics tester prior analysis at the macro- and microscopic, and biochemical level

Introduction. Patients (2.7M in EU) with positive cancer prognosis frequently develop metastases (≈1M) in their remaining lifetime. In 30-70% cases, metastases affect the spine, reducing the strength of the affected vertebrae. Fractures occur in ≈30% patients. Clinicians must choose between leaving the patient exposed to a high fracture risk (with dramatic consequences) and operating to stabilise the spine (exposing patients to unnecessary surgeries). Currently, surgeons rely on their sole experience. This often results in to under- or over-treatment. The standard-of-care are scoring systems (e.g. Spine Instability Neoplastic Score) based on medical images, with little consideration of the spine biomechanics, and of the structure of the vertebrae involved. Such scoring systems fail to provide clear indications in ≈60% patients. Method. The HEU-funded METASTRA project is implemented by biomechanicians, modellers, clinicians, experts in verification, validation, uncertainty quantification and certification from 15 partners across Europe. METASTRA aims to improve the stratification of patients with vertebral metastases evaluating their risk of fracture by developing dedicated reliable computational models based on Explainable Artificial Intelligence (AI) and on personalised Physiology-based biomechanical (VPH) models. Result. The METASTRA-AI model is expected to be able to stratify most patients with limited effort end cost, based on parameters extracted semi-automatically from the medical files and images. The cases which are not reliably stratified through the AI model, are examined through a more detailed and personalised biomechanical VPH model. These METASTRA numerical tools are trained through an unprecedentedly large multicentric retrospective study (2000 cases) and validated against biomechanical ex vivo experiments (120 specimens). Conclusion. The METASTRA decision support system is tested in a multicentric prospective observational study (200 patients). The METASTRA approach is expected to cut down the indeterminate diagnoses from the current 60% down to 20% of cases. METASTRA project funded by the European Union, HEU topic HLTH-2022-12-01, grant 101080135

Osteoarthritis (OA) is a painful and disabling chronic condition that constitutes a major challenge to health care worldwide. There is currently no cure for OA and the analgesic pharmaceuticals available do not offer adequate and sustained pain relief, often being associated with significant undesirable side effects. Another disease associated with degenerating joints is Intervertebral disc degeneration (IVDD) which is a leading cause of chronic back pain and loss of function. It is characterized by the loss of extracellular matrix, specifically proteoglycan and collagen, tissue dehydration, fissure development and loss of disc height, inflammation, endplate sclerosis, cell death and hyperinnervation of nociceptive nerve fibers. The adult human IVD seems incapable of intrinsic repair and there are currently no proven treatments to prevent, stop or even retard disc degeneration. Fusion is currently the most common surgical treatment of symptomatic disc disease. However, radiographic follow-up studies have revealed that many patients develop adjacent segment disc degeneration due to altered spine biomechanics. The development of safe and efficacious disease modifying OA drugs (DMOADs) that treat pain and inflammation in joints will improve our ability to control the disease. I addition, a biologic treatment of IVDD is desirable. This presentation will provide an overview of recent advances and future prospects of a multimodal biologic treatment of OA, and IVDD. We will focus on Link N, a naturally occurring peptide representing the N terminal region of link protein and the first 1–8 residues of Link N (short Link N, sLN) responsible for the biologic therapy in question

Introduction. Functional Spine Units (FSUs) play a vital role in understanding biomechanical characteristics of the spine, particularly bone fracture risk assessment. While established models focus on simulating axial compression of individual bones to assess fracture load, recent models underscore the importance of understanding fracture load within FSUs, offering a better representation of physiological conditions. Despite the limited number of FSU fracture studies, they predominantly rely on a linear material model with an annulus fibrosus Young's modulus set at 500 MPa, significantly higher than stiffness values (ca. 4 MPa) utilized in other FSU and spine section biomechanical models. Thus, this study aims to study the effect of varying annulus fibrosus stiffness on FSU fracture load, aiming to identify physiologically relevant biomechanical parameters. Method. Subject-specific geometry and material properties of bones were derived from computed tomography (CT) image data of five human cadaveric FSU specimens. The annulus fibrosus and nucleus pulposus were manually recreated and assigned linear elastic material properties. By subjecting the model to axial compression, the fracture load of the FSU was deduced from the peak of the force-displacement graph. To explore the effect of stiffness of the annulus fibrosus on simulated fracture load, we conducted a parameter study, varying stiffness values from the high 500 MPa to a more physiologically relevant 25 MPa, aiming to approximate values applied in FSU kinematic models while achieving bone fracture. Result. Significant reductions in fracture load were observed, ranging from 23% to 46%, as annulus stiffness decreased from 500MPa to 25MPa. Additionally, a discernible, gradual decline in fracture load was observed with a decrease in stiffness values. Conclusion. The stiffness of the annulus fibrosus significantly influences the simulated fracture load of an FSU. Future investigations should prioritize biomechanically accurate modeling of the intervertebral disc, ensuring alignment with experimental findings regarding FSU fracture load while maintaining biomechanical fidelity

Aims

The presence of facet tropism has been correlated with an elevated susceptibility to lumbar disc pathology. Our objective was to evaluate the impact of facet tropism on chronic lumbosacral discogenic pain through the analysis of clinical data and finite element modelling (FEM).

The use of lumbar fusion procedures in the USA and Europe has rapidly increased over the last decade and a large number of these procedures involve the use of bone grafts. Despite of technical progress of spinal surgery and operative materials the risk of vertebral fusion failure occurs in 5 – 35 % of cases. Autografting has been considered the gold standard for bone graft procedures. However, the harvesting from the iliac crest can be associated with short and long-term morbidity in up to 22 % of cases. Main goal of this experimental study was to compare newly developed hybrid biodegradable nanocomposit porous implant (HBNPI) against bone craft from iliac crest as a new and better alternative for lumbar interbody fusion. 24 male pigs 4 months old weighting around 40 Kg were included in our study. These pigs were divided into two study groups depending on fusion method. Group A – 12 pigs underwent lateral lumbal interbody fusion (L2/3) with implantation of iliac crest bonegraft. Group B - 12 pigs underwent lateral lumbal interbody fusion (L2/3) with newly developed HBNPI. Each group were divided into two subgroups from these 6 spines were harvested 8 weeks (subgroup A1, B1) and 6 spines 16 weeks (group A2, B2) after surgery. After sacrifice, the lumbar spines were taking out and micro-CT, biomechanical testing and histomorphological analysis in all groups were performed to evaluate a quality of intervertebral fusion. As controls (group N), 6 cadaveric intact lumbar spines underwent biomechanical, micro-CT and histological testing. All 24 animals recovered from general anesthesia without unusual events. The operations lasted between 50–90 minutes (mean 70) in Group A and between 35–72 minutes (mean 43) in Group B. All of the pigs from group A could stand up and were mobile within 20 hours (range 7–20). When bone graft harvesting was not necessary (group B) this time was shortened, ranging from 1 – 1,5 hour. All pigs from Group A were limping on the first postoperative day. No limping animal was observed in group B. Total body weight of the pigs increased from 37 kg (range 36–40) at the start to 85 (range 80–89) at sacrifice. Biomechanics evaluation shows that extension flexural stiffness values are statistically significantly different between A2 (16 weeks post-implant) and A1 (8 weeks post-implant). Group A2 achieves higher values than Group A1, which is attributed to the adhesion of the implant to the surrounding vertebrae. Similarly, this also applies to groups B2 and B1. The flexural stiffness at group B2 extension is statistically significantly higher than the A2 group and also than the native N group. Biomechanical evaluation supports findings on micro-CT and histological specimens, where both adjacent vertebrae are completely fused in groups B2, unlike in group A2, where there is no or incomplete fusion. Newly developed HBNPI represents new possibility how to do intervertebral fusion, and simultaneous become chance how to improve and accelerate bone healing process against standard procedures

The causes of spine disease are often biomechanical ones (e.g. disc degeneration, vertebral fracture). Currently, a deep investigation of the spine biomechanics is missing, due to the high complexity of the spine system (Fung 1980, Brandolini, Cristofolini et al. 2014): vertebrae and intervertebral discs. Recently, the Digital Image Correlation allowed measuring in vitrothe displacement and strain on the surface of soft and hard tissues, upon a specific non-invasive preparation of their surface with a speckle pattern (Palanca, Tozzi et al. 2016). The aim of this explorative work was to evaluate the deformation on spine segments, being able to distinguish between hard and soft tissue in the elastic regime and up to fracture. Segment of four vertebrae were extracted from porcine spines. All ligaments and muscles were removed, without damaging the spine segment (vertebrae and intervertebral discs). A suitable non-conventional white-on-black speckle pattern was prepared on the surface with airbrush airgun to track the movements of the specimen with DIC (Lionello, Sirieix et al. 2014). The endplates of the extreme vertebrae were potted in poly-methyl-methacrylate. The spine segments were tested in pure axial loading with cycles of increasing magnitude, up to fialure. A commercial 3D-DIC (Dantec Dynamics, Denmark) was used. In the present configuration, it allowed a resolution of 30 micrometers. It was used to measure the displacements and strains in a full-field and contactless way on the frontal surface of the spine segments. DIC allowed measuring with success the displacement and strain during the entire test, in the elastic regime and up to failure. The displacements and strains could be measured on the entire specimen, both in the vertebrae (hard tissue) and in the intervertebral discs (soft tissue). The axial strain evaluated prior to failure was close to 10’000 microstrain on the vertebral body surface and exceed 70’000 microstrain on the intervertebral discs, where failure was localized. The pattern, prepared in a dedicated way showed its suitability for both the bone and the disc. The evaluated failure strains were in agreement with the literature (Bayraktar, Morgan et al. 2004) (Spera, Genovese et al. 2011). To the authors' best knowledge, this kind of measurement including strain on soft and hard tissue simultaneously has never been performed before. This work showed the capability of DIC in providing full-field measures on the surface with complex geometry, such as the spine. The assertion of these potentialities could open the way to further application of DIC to study the behaviour of human spines, including improvement of spinal fixation devices

Introduction. Total disc replacement (TDR) provides an alternative to fusion that is designed to preserve motion at the treated level and restore disc height. The effects of TDR on spine biomechanics at the treated and adjacent levels are not fully understood. Thus, the present study investigated facet changes in contact pressure, peak contact pressure, force, peak force, and contact area at the facet joints after TDR. Methods. Seven fresh-frozen human cadaveric lumbar spines were potted at T12 and L5 and installed in a 6-DOF displacement-controlled testing system. Displacements of 15° flexion/extension, 10° right/left bending, and 10° right/left axial rotation were applied. Contact pressure, peak contact pressure, force, peak force and contact area for each facet joint were recorded at L2-L3 and L3-L4 before and after TDR at L3-L4 (ProDisc-L, Synthes Spine). The data were analysed with ANOVAs/t-tests. Results. Axial rotation had the most impact on contact pressure, peak contact pressure, force, peak force, and contact area in intact spines. During lateral bending and axial rotation, TDR resulted in a significant increase in facet forces at the level of treatment and a decrease in contact pressure, peak contact pressure, and peak force at the level superior to the TDR. With flexion/extension, there was a decrease in peak contact pressure and peak contact force at the superior level. Conclusion. Our study demonstrates that rotation is the most demanding motion for the spine. We also found an increase in facet forces at the treated level after TDR. To our knowledge, we are the first to show a decrease in several biomechanical parameters after TDR at the adjacent superior level in a cadaveric model. In general, our findings suggest there is an increase in loading of the facet joints at the level of disc implantation and an overall unloading effect at the level above

Introduction A very specific group within the 80 percent of the population that suffers from low back pain at some stage in life are young cricket fast bowlers. Amongst them a high occurrence of unilateral L4 pars interarticularis fractures exists, which shows a strong statistical correlation to the presence of a contralateral volumetric increase in the Quadratus Lumborum (QL) muscle. However, there is no clear physical link between these two phenomena. To investigate this relationship, we have combined a mathematical model of the lumbar spine muscles with a finite element model of the fourth lumbar vertebra and analysed the stresses occurring in the L4 vertebra throughout the bowling motion. Methods A mathematical model of the lumbar spine muscles has been developed previously at QUT. It contains 170 fascicles representing all major muscles in the lumbar region and allows for analysis of the forces and moments on the intervertebral joints caused by these muscles in any given posture. A Finite Element Model (FEM) of an L4 vertebra and intervertebral disc (IVD) was developed based on one created by Theo Smit and obtainable from the Internet through the BEL Repository of the Istituti Ortopedici Rizzoli, Bologna, Italy. Material properties were obtained from literature, while muscle forces, directions and attachment locations in the different postures came from the mathematical model. Six postures occurring in right-handed fast bowling were modelled to determine the differences in stresses between having symmetric and asymmetric QL muscles. The asymmetric condition consisted of a 30% increase in Physiological Cross-Sectional Area (PCSA) on the right side. In all cases it was assumed the left facet joints were ‘locked up’, to create a presumed worst-case scenario for the stress build-up in the pars. Results It was found that when using muscle activation levels from literature an enlarged right-side QL did not increase the stresses in the left pars noticeably, in fact in some cases it even slightly reduced those stresses. When only the right-side QL muscle was activated, while all other muscles only provided passive muscle force, a 30% PCSA increase of this muscle produced an increase in maximum Von Mises and principal stresses in the left-side pars from typically 30 MPa to 40 MPa but only in the postures close to upright stance. In more extreme postures where the maximum stresses in the pars are higher, the increased PCSA of the right QL only led to small stress increases from typically 125 to 129 MPa. Discussion Even in the worst-case scenario where only the right-side QL is active and the left-side facet joint is locked up, a PCSA increase of that muscle does not cause a large increase in stresses in postures where the stresses are high. Hence, this study has not demonstrated a clear physical link between asymmetric hypertrophy of QL and pars fractures. It may even suggest the hypertrophy is a response to postural overload attempting to reduce stresses in the pars. To clarify this, an improved FEM of the L3 and L4 vertebrae and IVDs, including all ligaments, is currently being developed. We believe that in the future this combination of models can be used for many more purposes where the influence of posture and musculature on the lumbar spine biomechanics needs investigation

Mesenchymal stem-cell based therapies have been proposed as novel treatments for intervertebral disc degeneration, a prevalent and disabling condition associated with back pain. The development of these treatment strategies, however, has been hindered by the incomplete understanding of the human nucleus pulposus phenotype and by an inaccurate interpretation and translation of animal to human research. This review summarises recent work characterising the nucleus pulposus phenotype in different animal models and in humans and integrates their findings with the anatomical and physiological differences between these species. Understanding this phenotype is paramount to guarantee that implanted cells restore the native functions of the intervertebral disc.

Cite this article: Bone Joint Res 2013;2:169–78.

The August 2014 Spine Roundup³⁶⁰ looks at: rhBMP complicates cervical spine surgery; posterior longitudinal ligament revisited; thoracolumbar posterior instrumentation without fusion in burst fractures; risk modelling for VTE events in spinal surgery; the consequences of dural tears in microdiscectomy; trends in revision spinal surgery; radiofrequency denervation likely effective in facet joint pain and hooks optimally biomechanically transition posterior instrumentation.