The transpedicular approach for the study of intervertebral disc regeneration strategies: in vivo characterization

Vadalà, Gianluca; Strobel, Francesca De; Bernardini, Marco; Denaro, Luca; D’Avella, Domenico; Denaro, Vincenzo

doi:10.1007/s00586-013-3007-y

Cited by 42 publications

(36 citation statements)

References 25 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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“…As an alternative route to the IVD, the transpedicular approach through the end‐plate (EP) allows access to the NP, whilst maintaining structural integrity of the AF . Previously, we have characterized the transpedicular approach to the NP in vitro and in vivo, showing its reliability and reproducibility for in vivo delivery of IVD regenerative biologics such as new cell therapies and tissue engineering based strategies …”

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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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“…To keep the AF intact, the transpedicular approach via the EP route was developed in a sheep model. This method, which can be safely performed without obvious morbidity, is feasible for and repeatable by other researchers (Russo, Hartman, Bell, et al, 2017;Vadala, De Strobel, Bernardini, et al, 2013;Vadala, Russo, Pattappa, et al, 2015). Nevertheless, the damage to the bony and cartilaginous EPs should be given serious consideration.…”

Section: How To Deliver the Biomaterials Smoothlymentioning

confidence: 89%

Biomaterials for intervertebral disc regeneration: Current status and looming challenges

Huang

et al. 2018

J Tissue Eng Regen Med

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A biomaterial-based strategy is employed to regenerate the degenerated intervertebral disc, which is considered a major generator of neck and back pain. Although encouraging enhancements in the anatomy and kinematics of the degenerative disc have been gained by biomaterials with various formulations in animals, the number of biomaterials tested in humans is rare. At present, most studies that involve the use of newly developed biomaterials focus on regeneration of the degenerative disc, but not pain relief. In this review, we summarise the current state of the art in the field of biomaterial-based regeneration or repair for the nucleus pulposus, annulus fibrosus, and total disc transplantation in animals and humans, and we then provide essential suggestions for the development and clinical translation of biomaterials for disc regeneration. It is important for researchers to consider the commonly neglected issues instead of concentrating solely on biomaterial development and fabrication.

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The transpedicular approach for the study of intervertebral disc regeneration strategies: in vivo characterization

Cited by 42 publications

References 25 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

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

Biomaterials for intervertebral disc regeneration: Current status and looming challenges

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