Mechanical and biological characterization of a composite annulus fibrosus repair strategy in an endplate delamination model

Alexeev, Dmitriy; Cui, Shangbin; Grad, Sibylle; Li, Zhen; Ferguson, Stephen J.

doi:10.1002/jsp2.1107

Cited by 8 publications

(6 citation statements)

References 64 publications

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“…For surgical methods of IVDD induction, there was significant variation in the models reported. Needle‐puncture models as described by Lipson and Muir (1981) in the rabbit, 119 have evolved to include scalpel blades (annulotomy), 46 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 annulectomies, 112 total discectomies, partial and complete nuclectomies, 8 nucleus pulposus aspiration 14 , 20 , 133 , 134 , 135 , 136 and drill bit injuries. 7 , 16 , 137 , 138 Clearly, these surgical insults vary in the burden suffered to the animal and therefore, the degree of IVDD that is induced.…”

Section: Discussionmentioning

confidence: 99%

Preclinical in vivo animal models of intervertebral disc degeneration. Part 1: A systematic review

et al. 2022

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Intervertebral disc degeneration (IVDD), a widely recognized cause of lower back pain, is the leading cause of disability worldwide. A myriad of preclinical in vivo animal models of IVDD have been described in the literature. There is a need for critical evaluation of these models to better inform researchers and clinicians to optimize study design and ultimately, enhance experimental outcomes. The purpose of this study was to conduct an extensive systematic literature review to report the variability of animal species, IVDD induction method, and experimental timepoints and endpoints used in in vivo IVDD preclinical research. A systematic literature review of peer‐reviewed manuscripts featured on PubMed and EMBASE databases was conducted in accordance with PRISMA guidelines. Studies were included if they reported an in vivo animal model of IVDD and included details of the species used, how disc degeneration was induced, and the experimental endpoints used for analysis. Two‐hundred and fifty‐nine (259) studies were reviewed. The most common species, IVDD induction method and experimental endpoint used was rodents(140/259, 54.05%), surgery (168/259, 64.86%) and histology (217/259, 83.78%), respectively. Experimental timepoint varied greatly between studies, ranging from 1 week (dog and rodent models), to >104 weeks in dog, horse, monkey, rabbit, and sheep models. The two most common timepoints used across all species were 4 weeks (49 manuscripts) and 12 weeks (44 manuscripts). A comprehensive discussion of the species, methods of IVDD induction and experimental endpoints is presented. There was great variability across all categories: animal species, method of IVDD induction, timepoints and experimental endpoints. While no animal model can replicate the human scenario, the most appropriate model should be selected in line with the study objectives to optimize experimental design, outcomes and improve comparisons between studies.

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Section: Discussionmentioning

confidence: 99%

Preclinical in vivo animal models of intervertebral disc degeneration. Part 1: A systematic review

et al. 2022

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“…The AF plays important roles in linking adjacent vertebrae and withstanding mechanical forces, allowing bending, flexion, and torsion of the spine. Acute and chronic injuries of the AF can lead to IVD degeneration and herniation 2,3 . While discectomy is a common surgical treatment method, unrepaired AF defects after discectomy can lead to reherniation in 10%–30% of cases, which results in recurrent pain and progressive disc degeneration 4–6 .…”

Section: Introductionmentioning

confidence: 99%

“…IVD degeneration and herniation. 2,3 While discectomy is a common surgical treatment method, unrepaired AF defects after discectomy can lead to reherniation in 10%-30% of cases, which results in recurrent pain and progressive disc degeneration. [4][5][6] AF repair is a challenge due to its complex structure, high mechanical loading environment, and poor self-healing capability as a virtually avascular tissue.…”

mentioning

confidence: 99%

The function of CD146 in human annulus fibrosus cells and mechanism of the regulation by TGF‐β

Guo

Häckel

et al. 2021

Journal Orthopaedic Research

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The mouse outer annulus fibrosus (AF) was previously shown to contain CD146+ AF cells, while in vitro culture and exposure to transforming growth factor‐beta (TGF‐β) further increased the expression of CD146. However, neither the specific function of CD146 nor the underlying mechanism of TGF‐β upregulation of CD146+AF cells have been elucidated yet. In the current study, CD146 expression and its role in cultured human AF cells was investigated studying the cells’ capacity for matrix contraction and gene expression of functional AF markers. In addition, TGF‐β pathways were blocked by several pathway inhibitors and short hairpin RNAs (shRNAs) targeting SMAD and non‐SMAD pathways to investigate their involvement in TGF‐β‐induced CD146 upregulation. Results showed that knockdown of CD146 led to reduction in AF cell‐mediated collagen gel contraction, downregulation of versican and smooth muscle protein 22α (SM22α), and upregulation of scleraxis. TGF‐β‐induced CD146 upregulation was significantly blocked by inhibition of TGF‐β receptor ALK5, and partially inhibited by shRNA against SMAD2 and SMAD4 and by an Protein Kinase B (AKT) inhibitor. Interestingly, the inhibition of extracellular signal‐regulated kinases (ERK) pathway induced CD146 upregulation. In conclusion, CD146 was shown to be crucial to maintain the cell contractility of human AF cells in vitro. Furthermore, TGF‐β upregulated CD146 via ALK5 signaling cascade, partially through SMAD2, SMAD4, and AKT pathway, whereas, ERK was shown to be a potential negative modulator. Our findings suggest that CD146 can potentially be used as a functional marker in AF repair strategies.

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“…[ 108 ] Posttreatment of electrospun polycaprolactone (PCL) scaffold and fibrin–genipin (FibGen) adhesive hydrogel exhibited higher minimum strain than the intact disc in an endplate delamination injury model for AF repair. [ 109 ]…”

Section: Rationale Precision Biomaterial‐based Tissue Engineering Tar...mentioning

confidence: 99%

Intervertebral Disc Degeneration: Biomaterials and Tissue Engineering Strategies toward Precision Medicine

Isa

Mokhtar

Abbah

et al. 2022

Adv Healthcare Materials

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Intervertebral disc degeneration is a common cause of discogenic low back pain resulting in significant disability. Current conservative or surgical intervention treatments do not reverse the underlying disc degeneration or regenerate the disc. Biomaterial-based tissue engineering strategies exhibit the potential to regenerate the disc due to their capacity to modulate local tissue responses, maintain the disc phenotype, attain biochemical homeostasis, promote anatomical tissue repair, and provide functional mechanical support. Despite preliminary positive results in preclinical models, these approaches have limited success in clinical trials as they fail to address discogenic pain. This review gives insights into the understanding of intervertebral disc pathology, the emerging concept of precision medicine, and the rationale of personalized biomaterial-based tissue engineering tailored to the severity of the disease targeting early, mild, or severe degeneration, thereby enhancing the efficacy of the treatment for disc regeneration and ultimately to alleviate discogenic pain. Further research is required to assess the relationship between disc degeneration and lower back pain for developing future clinically relevant therapeutic interventions targeted towards the subgroup of degenerative disc disease patients.

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Mechanical and biological characterization of a composite annulus fibrosus repair strategy in an endplate delamination model

Cited by 8 publications

References 64 publications

Preclinical in vivo animal models of intervertebral disc degeneration. Part 1: A systematic review

Preclinical in vivo animal models of intervertebral disc degeneration. Part 1: A systematic review

The function of CD146 in human annulus fibrosus cells and mechanism of the regulation by TGF‐β

Intervertebral Disc Degeneration: Biomaterials and Tissue Engineering Strategies toward Precision Medicine

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