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Nucleotomy is a common surgical procedure and is also performed in ex vivo mechanical testing to model decreased nucleus pulposus (NP) pressurization that occurs with degeneration. Here, we implement novel and noninvasive methods using magnetic resonance imaging (MRI) to study internal 3D annulus fibrosus (AF) deformations after partial nucleotomy and during axial compression by evaluating changes in internal AF deformation at reference loads (50 N) and physiological compressive loads (∼10% strain). One particular advantage of this methodology is that the full 3D disc deformation state, inclusive of both in-plane and out-of-plane deformations, can be quantified through the use of a high-resolution volumetric MR scan sequence and advanced image registration. Intact grade II L3-L4 cadaveric human discs before and after nucleotomy were subjected to identical mechanical testing and imaging protocols. Internal disc deformation fields were calculated by registering MR images captured in each loading state (reference and compressed) and each condition (intact and nucleotomy). Comparisons were drawn between the resulting three deformation states (intact at compressed load, nucleotomy at reference load, nucleotomy at compressed load) with regard to the magnitude of internal strain and direction of internal displacements. Under compressed load, internal AF axial strains averaged −18.5% when intact and −22.5% after nucleotomy. Deformation orientations were significantly altered by nucleotomy and load magnitude. For example, deformations of intact discs oriented in-plane, whereas deformations after nucleotomy oriented axially. For intact discs, in-plane components of displacements under compressive loads oriented radially outward and circumferentially. After nucleotomy, in-plane displacements were oriented radially inward under reference load and were not significantly different from the intact state at compressed loads. Re-establishment of outward displacements after nucleotomy indicates increased axial loading restores the characteristics of internal pressurization. Results may have implications for the recurrence of pain, design of novel therapeutics, or progression of disc degeneration.

Lumbar intervertebral body fusion devices (L-IBFDs) are intended to provide stability to promote fusion in patients with a variety of lumbar pathologies. Different L-IBFD designs have been developed to accommodate various surgical approaches for lumbar interbody fusion procedures including anterior, lateral, posterior, and transforaminal lumbar interbody fusions (ALIF, LLIF, PLIF, and TLIF, respectively). Due to design differences, there is a potential for mechanical performance differences between ALIF, LLIF, PLIF, and TLIF devices. To evaluate this, mechanical performance and device dimension data were collected from 124 Traditional 510(k) submissions to the FDA for L-IBFDs cleared for marketing from 2007 through 2016. From these submissions, mechanical test results were aggregated for seven commonly performed tests: static and dynamic axial compression, compression-shear, and torsion testing per ASTM F2077, and subsidence testing per ASTM F2267. The Kruskal-Wallis test and Wilcoxon signed-rank test were used to determine if device type (ALIF, LLIF, PLIF, TLIF) had a significant effect on mechanical performance parameters (static testing: stiffness and yield strength; dynamic testing: runout load; subsidence testing: stiffness [Kp]). Generally, ALIFs and LLIFs were found to be stiffer, stronger, and had higher subsidence resistance than PLIF and TLIF designs. These results are likely due to the larger footprints of the ALIF and LLIF devices. The relative mechanical performance and subsidence resistance can be considered when determining the appropriate surgical approach and implant for a given patient. Overall, the mechanical performance data presented here can be utilized for future L-IBFD development and design verification.

Tissue strain is an important indicator of mechanical function, but is difficult to noninvasively measure in the intervertebral disc. The objective of this study was to generate a disc strain template, a 3D average of disc strain, of a group of human L4-L5 discs loaded in axial compression. To do so, magnetic resonance images of uncompressed discs were used to create an average disc shape. Next, the strain tensors were calculated pixel-wise by using a previously developed registration algorithm. Individual disc strain tensor components were then transformed to the template space and averaged to create the disc strain template. The strain template reduced individual variability while highlighting group trends. For example, higher axial and circumferential strains were present in the lateral and posterolateral regions of the disc, which may lead to annular tears. This quantification of group-level trends in local 3D strain is a significant step forward in the study of disc biomechanics. These trends were compared to a finite element model that had been previously validated against the disc-level mechanical response. Depending on the strain component, 81-99% of the regions within the finite element model had calculated strains within one standard deviation of the template strain results. The template creation technique provides a new measurement technique useful for a wide range of studies, including more complex loading conditions, the effect of disc pathologies and degeneration, damage mechanisms, and design and evaluation of treatments. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1264-1273, 2016.

Intervertebral disc degeneration is implicated as a major cause of low-back pain. There is a pressing need for new regenerative therapies for disc degeneration that restore native tissue structure and mechanical function. To that end we investigated the therapeutic potential of an injectable, triple-interpenetrating-network hydrogel comprised of dextran, chitosan, and teleostean, for functional regeneration of the nucleus pulposus (NP) of the intervertebral disc in a series of biomechanical, cytotoxicity, and tissue engineering studies. Biomechanical properties were evaluated as a function of gelation time, with the hydrogel reaching ∼90% of steady-state aggregate modulus within 10 h. Hydrogel mechanical properties evaluated in confined and unconfined compression were comparable to native human NP properties. To confirm containment within the disc under physiological loading, toluidine-blue-labeled hydrogel was injected into human cadaveric spine segments after creation of a nucleotomy defect, and the segments were subjected to 10,000 cycles of loading. Gross analysis demonstrated no implant extrusion, and further, that the hydrogel interdigitated well with native NP. Constructs were next surface-seeded with NP cells and cultured for 14 days, confirming lack of hydrogel cytotoxicity, with the hydrogel maintaining NP cell viability and promoting proliferation. Next, to evaluate the potential of the hydrogel to support cell-mediated matrix production, constructs were seeded with mesenchymal stem cells (MSCs) and cultured under prochondrogenic conditions for up to 42 days. Importantly, the hydrogel maintained MSC viability and promoted proliferation, as evidenced by increasing DNA content with culture duration. MSCs differentiated along a chondrogenic lineage, evidenced by upregulation of aggrecan and collagen II mRNA, and increased GAG and collagen content, and mechanical properties with increasing culture duration. Collectively, these results establish the therapeutic potential of this novel hydrogel for functional regeneration of the NP. Future work will confirm the ability of this hydrogel to normalize the mechanical stability of cadaveric human motion segments, and advance the material toward human translation using preclinical large-animal models.

Objectives: To compare the in vitro biomechanical properties of a 4.5mm narrow locking compression plate (PIP-LCP) with 2 abaxially located transarticular screws and a 4.5mm limited contact dynamic compression plate (LC-DCP) with 2 abaxially located transarticular screws using equine pasterns. Study Design: Experimental. Paired in vitro biomechanical testing of 2 methods for stabilizing adult equine forelimb PIP joints. Animal: Adult equine forelimbs (n=8 pairs). Methods: Each pair of PIP joints were randomly instrumented with either a PIP-LCP or LC-DCP plate axially and 2 parasagitally positioned 5.5mm transarticular screws. The proximal aspect of the proximal phalanx (P1) and the distal aspect of the middle phalanx (P2) were embedded to allow for mounting on a mechanical testing machine. Each construct was tested in both cyclic and subsequently single cycle to failure in 4-point bending. The displacement required to maintain a target load of 1kN over 3600 cycles at 1Hz was recorded. Maximum bending moment at failure and construct stiffness was calculated from the single cycle to failure testing. Results: In cyclic testing, significantly more displacement occurred in the LC-DCP (0.46±0.10mm) than for the PIP-LCP (0.17±0.11mm) constructs (P=.016). During single cycle testing there was no significant difference in the bending moment between the LC-DCP (148.7±19.4Nm) and the PIP-LCP (164.6±17.6Nm) constructs (P=.553) and the stiffness of the LC-DCP (183.9±26.9Nmm) was significantly lower than for the PIP-LCP (279.8±15.9N/mm) constructs (P=.011). All constructs failed by fracture of the bone associated with the transarticular screws and subsequently bending of the plates at the middle hole. Conclusions: Use of the PIP-LCP resulted in a stiffer construct of the same strength as the LC-DCP in vitro using this 4-point bending model.

Experimental measurement and normalization of in vitro disc torsion mechanics and collagen content for several animal species used in intervertebral disc research and comparing these with the human disc.To aid in the selection of appropriate animal models for disc research by measuring torsional mechanical properties and collagen content.There is lack of data and variability in testing protocols for comparing animal and human disc torsion mechanics and collagen content.Intervertebral disc torsion mechanics were measured and normalized by disc height and polar moment of inertia for 11 disc types in 8 mammalian species: the calf, pig, baboon, goat, sheep, rabbit, rat, and mouse lumbar discs, and cow, rat, and mouse caudal discs. Collagen content was measured and normalized by dry weight for the same discs except the rat and the mouse. Collagen fiber stretch in torsion was calculated using an analytical model.Measured torsion parameters varied by several orders of magnitude across the different species. After geometric normalization, only the sheep and pig discs were statistically different from human discs. Fiber stretch was found to be highly dependent on the assumed initial fiber angle. The collagen content of the discs was similar, especially in the outer annulus where only the calf and goat discs were statistically different from human. Disc collagen content did not correlate with torsion mechanics.Disc torsion mechanics are comparable with human lumbar discs in 9 of 11 disc types after normalization by geometry. The normalized torsion mechanics and collagen content of the multiple animal discs presented are useful for selecting and interpreting results for animal disc models. Structural organization of the fiber angle may explain the differences that were noted between species after geometric normalization.

The modeling and assembly of devices that interface with the human body pose unique design problems due to the complexity of human surfaces, the absence of traditional mechanical design techniques that apply to biomechanical design, and the lack of parametric strategies for biomechanical products. This paper presents a design strategy that utilizes top-down assembly modeling techniques using human scan data as the base part in an assembly. This method allows for the identification of mating conditions of products, the product-human interfaces, and aids in defining geometric relationships between product geometry and the human body. This method also identifies parametric strategies that utilize these geometric relationships to allow for the exploration of mass customization for products that interface with the human body.

Despite the prevalence of disc degeneration and its contributions to low back problems, many current treatments are palliative only and ultimately fail. To address this, nucleus pulposus replacements are under development. Previous work on an injectable hydrogel nucleus pulposus replacement composed of n-carboxyethyl chitosan, oxidized dextran, and teleostean has shown that it has properties similar to native nucleus pulposus, can restore compressive range of motion in ovine discs, is biocompatible, and promotes cell proliferation. The objective of this study was to determine if the hydrogel implant will be contained and if it will restore mechanics in human discs undergoing physiologic cyclic compressive loading. Fourteen human lumbar spine segments were tested using physiologic cyclic compressive loading while intact, following nucleotomy, and again following treatment of injecting either phosphate buffered saline (PBS) (sham, n = 7) or hydrogel (implant, n = 7). In each compressive test, mechanical parameters were measured immediately before and after 10,000 cycles of compressive loading and following a period of hydrated recovery. The hydrogel implant was not ejected from the disc during 10,000 cycles of physiological compression testing and appeared undamaged when discs were bisected following all mechanical tests. For sham samples, creep during cyclic loading increased (+15%) from creep during nucleotomy testing, while for implant samples creep strain decreased (−3%) toward normal. There was no difference in compressive modulus or compressive strains between implant and sham samples. These findings demonstrate that the implant interdigitates with the nucleus pulposus, preventing its expulsion during 10,000 cycles of compressive loading and preserves disc creep within human L5–S1 discs. This and previous studies provide a solid foundation for continuing to evaluate the efficacy of the hydrogel implant.

Tissue strain is an important indicator of mechanical function, but is difficult to noninvasively measure in the intervertebral disc. The objective of this study was to generate a disc strain template, a 3D average of disc strain, of a group of human L4-L5 discs loaded in axial compression. To do so, magnetic resonance images of uncompressed discs were used to create an average disc shape. Next, the strain tensors were calculated pixel-wise by using a previously developed registration algorithm. Individual disc strain tensor components were then transformed to the template space and averaged to create the disc strain template. The strain template reduced individual variability while highlighting group trends. For example, higher axial and circumferential strains were present in the lateral and posterolateral regions of the disc, which may lead to annular tears. This quantification of group-level trends in local 3D strain is a significant step forward in the study of disc biomechanics. These trends were compared to a finite element model that had been previously validated against the disc-level mechanical response. Depending on the strain component, 81-99% of the regions within the finite element model had calculated strains within one standard deviation of the template strain results. The template creation technique provides a new measurement technique useful for a wide range of studies, including more complex loading conditions, the effect of disc pathologies and degeneration, damage mechanisms, and design and evaluation of treatments. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1264-1273, 2016.

The first objective of this study was to determine the effects of physiological cyclic loading followed by unloaded recovery on the mechanical response of human intervertebral discs. The second objective was to examine how nucleotomy alters the disc׳s mechanical response to cyclic loading. To complete these objectives, 15 human L5-S1 discs were tested while intact and subsequent to nucleotomy. The testing consisted of 10,000 cycles of physiological compressive loads followed by unloaded hydrated recovery. Cyclic loading increased compression modulus (3%) and strain (33%), decreased neutral zone modulus (52%), and increased neutral zone strain (31%). Degeneration was not correlated with the effect of cyclic loading in intact discs, but was correlated with cyclic loading effects after nucleotomy, with more degenerate samples experiencing greater increases in both compressive and neutral zone strain following cyclic loading. Partial removal of the nucleus pulposus decreased the compression and neutral zone modulus while increasing strain. These changes correspond to hypermobility, which will alter overall spinal mechanics and may impact low back pain via altered motion throughout the spinal column. Nucleotomy also reduced the effects of cyclic loading on mechanical properties, likely due to altered fluid flow, which may impact cellular mechanotransduction and transport of disc nutrients and waste. Degeneration was not correlated with the acute changes of nucleotomy. Results of this study provide an ideal protocol and control data for evaluating the effectiveness of a mechanically-based disc degeneration treatment, such as a nucleus replacement.

The intervertebral disc plays a critical role in providing structural support to the spine while permitting extensive flexibility in a number of orientations. Axial rotation is a key parameter in spine function and torsional instability is related to spinal degeneration [1]. Animal models are integral components in many in vivo disc studies, however each animal varies in availability, size, cost, and scientific criteria such as cell phenotype and biomechanics. Selection of an appropriate animal model requires knowledge of the similarities and differences in biomechanical and biochemical factors between the model and human discs. Previous studies have often compared the characteristics of a single animal model with the human disc [2, 3]. However, variations in animal models and testing protocols between groups hinder comparisons and interpretations between different studies. This is especially relevant in torsion mechanics, where the magnitude of an applied compressive load and other testing parameters significantly affect the apparent torsional stiffness of the disc [4]. The objective of this study was to measure and compare the torsion mechanical properties of the human disc and 11 disc types from 8 mammalian species.

To compare the in vitro biomechanical properties of a 4.5 mm narrow locking compression plate (PIP-LCP) with 2 abaxially located transarticular screws and a 4.5 mm limited contact dynamic compression plate (LC-DCP) with 2 abaxially located transarticular screws using equine pasterns.Experimental. Paired in vitro biomechanical testing of 2 methods for stabilizing adult equine forelimb PIP joints.Adult equine forelimbs (n = 8 pairs).Each pair of PIP joints were randomly instrumented with either a PIP-LCP or LC-DCP plate axially and 2 parasagitally positioned 5.5 mm transarticular screws. The proximal aspect of the proximal phalanx (P1) and the distal aspect of the middle phalanx (P2) were embedded to allow for mounting on a mechanical testing machine. Each construct was tested in both cyclic and subsequently single cycle to failure in 4-point bending. The displacement required to maintain a target load of 1 kN over 3600 cycles at 1 Hz was recorded. Maximum bending moment at failure and construct stiffness was calculated from the single cycle to failure testing.In cyclic testing, significantly more displacement occurred in the LC-DCP (0.46 ± 0.10 mm) than for the PIP-LCP (0.17 ± 0.11 mm) constructs (P = .016). During single cycle testing there was no significant difference in the bending moment between the LC-DCP (148.7 ± 19.4 N m) and the PIP-LCP (164.6 ± 17.6 N m) constructs (P = .553) and the stiffness of the LC-DCP (183.9 ± 26.9 N mm) was significantly lower than for the PIP-LCP (279.8 ± 15.9 N/mm) constructs (P = .011). All constructs failed by fracture of the bone associated with the transarticular screws and subsequently bending of the plates at the middle hole.Use of the PIP-LCP resulted in a stiffer construct of the same strength as the LC-DCP in vitro using this 4-point bending model.