A Nucleotomy Model with Intact Annulus Fibrosus to Test Intervertebral Disc Regeneration Strategies

Vadalà, Gianluca; Russo, Fabrizio; Pattappa, Girish; Peroglio, Marianna; Stadelmann, Vincent A.; Roughley, Peter J.; Grad, Sibylle; Alini, Mauro; Denaro, Vincenzo

doi:10.1089/ten.tec.2015.0086

Cited by 24 publications

(28 citation statements)

References 33 publications

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“…This might move forward cell therapy to the translation from bench to bedside. Ongoing ex vivo tests in a bioreactor system and an in vivo study in an animal model will provide more evidences for IVD regeneration mediated by the transplanted MSCs in combination with the novel hydrogel.…”

Section: Discussionmentioning

confidence: 99%

Clinically relevant hydrogel‐based on hyaluronic acid and platelet rich plasma as a carrier for mesenchymal stem cells: Rheological and biological characterization

Vadalà

Russo

Musumeci

et al. 2017

Journal Orthopaedic Research

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Intervertebral disc regeneration is quickly moving towards clinical applications. However, it is still missing an ideal injectable hydrogel to support mesenchymal stem cells (MSC) delivery. Herein, a new injectable hydrogel composed of platelet rich plasma (PRP) and hyaluronic acid (HA) blended with batroxobin (BTX) as gelling agent, was designed to generate a clinically relevant cell carrier for disc regeneration. PRP/HA/BTX blend was tested for rheological properties. Amplitude sweep, frequency sweep, and rotational measurements were performed and viscoelastic properties were evaluated. Human MSC encapsulated in PRP/HA/BTX hydrogel were cultured in both growing medium and medium with or without TGF-β1 up to day 21. The amount of glycosaminoglycan was evaluated. Quantitative gene expression evaluation for collagen type II, aggrecan, and Sox 9 was also performed. Rheological tests showed that the hydrogel jellifies in 15 min 20°C and in 3 min at 37°C. Biological test showed that MSCs cultured in the hydrogel maintain high cell viability and proliferation. Human MSC within the hydrogel cultured with or without TGF-β1 showed significantly higher GAG production compared to control medium. Moreover, MSCs in the hydrogel underwent differentiation to chondrocyte-like cells with TGF-β1, as shown by histology and gene expression analysis. This novel hydrogel improves viability and proliferation of MSCs supporting the differentiation process toward chondrocyte-like cells. Rheology tests showed optimal gelation kinetics at room temperature for manipulation and faster gelation after transplantation (37°C). The clinical availability of all components of the hydrogel will allow a rapid translation of this regenerative approach into the clinical scenario. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2109-2116, 2017.

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Section: Discussionmentioning

confidence: 99%

Clinically relevant hydrogel‐based on hyaluronic acid and platelet rich plasma as a carrier for mesenchymal stem cells: Rheological and biological characterization

Vadalà

Russo

Musumeci

et al. 2017

Journal Orthopaedic Research

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“…Recently, some investigation have been performed to get a subject-specific modeling of the IVD [42], but the inclusion of the anatomical, mechanical and degenerative properties of the disc into a unique model is a big issue [43]. Long and colleagues [43] have defined some design requirements for the repair hydrogels for human disc, but no information are available for the ovine one, despite it is often used in research [44,45,46,47,48,49,50]. …”

Section: Discussionmentioning

confidence: 99%

“…First, the FE model used for this investigation did not take into account the viscoelastic and poroelastic properties of the IVD, although many FE models of the human IVD have been developed [48,49,50,51,52,53,54]. However, the poroelastic parameters of the ovine disc are not available and only the failure properties of the tissue were investigated, therefore a hyperelastic model was preferred.…”

Section: Discussionmentioning

confidence: 99%

Numerical Prediction of the Mechanical Failure of the Intervertebral Disc under Complex Loading Conditions

et al. 2017

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Finite element modeling has been widely used to simulate the mechanical behavior of the intervertebral disc. Previous models have been generally limited to the prediction of the disc behavior under simple loading conditions, thus neglecting its response to complex loads, which may induce its failure. The aim of this study was to generate a finite element model of the ovine lumbar intervertebral disc, in which the annulus was characterized by an anisotropic hyperelastic formulation, and to use it to define which mechanical condition was unsafe for the disc. Based on published in vitro results, numerical analyses under combined flexion, lateral bending, and axial rotation with a magnitude double that of the physiological ones were performed. The simulations showed that flexion was the most unsafe load and an axial tensile stress greater than 10 MPa can cause disc failure. The numerical model here presented can be used to predict the failure of the disc under all loading conditions, which may support indications about the degree of safety of specific motions and daily activities, such as weight lifting.

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“…Using a 2 mm diameter shaver blade under aspiration, it is possible to perform a partial nucleotomy that allows the injection of reproducible volumes of hydrogel into the disc space. The EP tunnel can be sealed using a bone inductive scaffold that can be press‐fitted at the EP edge . Nevertheless, further in vivo studies are needed to better characterize the effects of the EP tunnel on the NP, the partial nucleotomy, and the EP repair strategy over time.…”

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confidence: 99%

Novel stepwise model of intervertebral disc degeneration with intact annulus fibrosus to test regeneration strategies

Vadalà

Russo

Strobel

et al. 2018

Journal Orthopaedic Research

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Novel preclinical models that do not damage the annulus fibrosus (AF) of the intervertebral disc are required to study the efficacy of new regenerative strategies for the nucleus pulposus (NP). The aim of the study was to characterize a preclinical ovine model of intervertebral disc degeneration (IDD) induced by endplate (EP) damage and repair via the transpedicular approach, with or without partial nucleotomy, while keeping the AF intact. Twelve adult sheep were used. By the transpedicular approach, a 2 mm tunnel was drilled to the NP through the EP. A partial-nucleotomy was performed. The tunnel was sealed using a polyurethane scaffold. Lumbar discs were assigned to different groups: L1-2: nucleotomy; L2-3: EP tunnel; L3-4: nucleotomy + EP repair; L4-5: EP tunnel + repair; L5-6: control. X-Ray and MRI were performed at 0, 1, 3, and 6 months after surgery. Disc height and MRI indexes were calculated. Macro- and micro-morphology were analyzed. Pfirrmann and Thompson grades were assigned. The treated discs exhibited a progressive decrease in NP signal intensity and MRI index, displaying specific grades of degeneration based on the surgical treatment. According to Pfirrmann and Thompson grades different procedures were staged as: EP tunnel + repair: grade-II; EP tunnel: grade-III, nucleotomy + EP repair: grade-IV; nucleotomy: grade-V. A new stepwise model of IDD to study and test safety and efficacy of novel strategies for NP regeneration has been characterized. The different degrees of IDD have been observed similar to Pfirrmann and Thompson grading system. The intact AF allows for loading studies and eliminating the need for AF closure. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2460-2468, 2018.

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A Nucleotomy Model with Intact Annulus Fibrosus to Test Intervertebral Disc Regeneration Strategies

Cited by 24 publications

References 33 publications

Clinically relevant hydrogel‐based on hyaluronic acid and platelet rich plasma as a carrier for mesenchymal stem cells: Rheological and biological characterization

Clinically relevant hydrogel‐based on hyaluronic acid and platelet rich plasma as a carrier for mesenchymal stem cells: Rheological and biological characterization

Numerical Prediction of the Mechanical Failure of the Intervertebral Disc under Complex Loading Conditions

Novel stepwise model of intervertebral disc degeneration with intact annulus fibrosus to test regeneration strategies

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