In Vitro Generated Intervertebral Discs: Toward Engineering Tissue Integration

2017 ◽  
Vol 23 (17-18) ◽  
pp. 1001-1010 ◽  
Author(s):  
Jonathan Iu ◽  
Eric Massicotte ◽  
Shu-Qiu Li ◽  
Mark B. Hurtig ◽  
Ehsan Toyserkani ◽  
...  
Keyword(s):  
Intervertebral Discs ◽  
Tissue Integration

scholarly journals Pro-Inflammatory and Neurotrophic Factor Responses of Cells Derived from Degenerative Human Intervertebral Discs to the Opportunistic Pathogen Cutibacterium acnes

2021 ◽  
Vol 22 (5) ◽  
pp. 2347
Author(s):  
Manu N. Capoor ◽  
Anna Konieczna ◽  
Andrew McDowell ◽  
Filip Ruzicka ◽  
Martin Smrcka ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Acne Vulgaris ◽  
Opportunistic Pathogen ◽  
Intervertebral Discs ◽  
Disc Disease ◽  
Gene Target ◽  
Cutibacterium Acnes ◽  
Pre Treatment

Previously, we proposed the hypothesis that similarities in the inflammatory response observed in acne vulgaris and degenerative disc disease (DDD), especially the central role of interleukin (IL)-1β, may be further evidence of the role of the anaerobic bacterium Cutibacterium (previously Propionibacterium) acnes in the underlying aetiology of disc degeneration. To investigate this, we examined the upregulation of IL-1β, and other known IL-1β-induced inflammatory markers and neurotrophic factors, from nucleus-pulposus-derived disc cells infected in vitro with C. acnes for up to 48 h. Upon infection, significant upregulation of IL-1β, alongside IL-6, IL-8, chemokine (C-C motif) ligand 3 (CCL3), chemokine (C-C motif) ligand 4 (CCL4), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), was observed with cells isolated from the degenerative discs of eight patients versus non-infected controls. Expression levels did, however, depend on gene target, multiplicity and period of infection and, notably, donor response. Pre-treatment of cells with clindamycin prior to infection significantly reduced the production of pro-inflammatory mediators. This study confirms that C. acnes can stimulate the expression of IL-1β and other host molecules previously associated with pathological changes in disc tissue, including neo-innervation. While still controversial, the role of C. acnes in DDD remains biologically credible, and its ability to cause disease likely reflects a combination of factors, particularly individualised response to infection.

scholarly journals The pathophysiologic role of the protein kinase Cδ pathway in the intervertebral discs of rabbits and mice: In vitro, ex vivo, and in vivo studies

2012 ◽  
Vol 64 (6) ◽  
pp. 1950-1959 ◽  
Author(s):  
Michael B. Ellman ◽  
Jae-Sung Kim ◽  
Howard S. An ◽  
Jeffrey S. Kroin ◽  
Xin Li ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Ex Vivo ◽  
Intervertebral Discs ◽  
In Vivo Studies ◽  
Protein Kinase Cδ

Biomechanical in Vitro and Finite Element Study On Different Sagittal Alignment Postures of the Lumbar Spine During Multiaxial Daily Motion

2021 ◽  
Author(s):  
Nadja Wilmanns ◽  
Agnes Beckmann ◽  
Luis Fernando Nicolini ◽  
Christian Herren ◽  
Rolf Sobottke ◽  
...  
Keyword(s):  
Finite Element ◽  
Lumbar Spine ◽  
Planning Process ◽  
Axial Rotation ◽  
Intervertebral Discs ◽  
Fe Model ◽  
Bending Moments ◽  
Sagittal Spinal Alignment ◽  
Biomechanical Response

Abstract Lumbar Lordotic correction (LLC), the gold standard treatment for Sagittal Spinal malalignment (SMA), and its effect on sagittal balance have been critically discussed in recent studies. This paper assesses the biomechanical response of the spinal components to LLC as an additional factor for the evaluation of LLC. Human lumbar spines (L2L5) were loaded with combined bending moments in Flexion (Flex)/Extension (Ex) or Lateral Bending (LatBend) and Axial Rotation (AxRot) in a physiological environment. We examined the dependency of AxRot range of motion (RoM) on the applied bending moment. The results were used to validate a Finite Element (FE) model of the lumbar spine. With this model, the biomechanical response of the intervertebral discs (IVD) and facet joints under daily motion was studied for different sagittal spinal alignment (SA) postures, simulated by a motion in Flex/Ex direction. Applied bending moments decreased AxRot RoM significantly (all P<0.001). A stronger decline of AxRot RoM for Ex than for Flex direction was observed (all P<0.0001). Our simulated results largely agreed with the experimental data (all R2>0.79). During daily motion, the IVD was loaded higher with increasing lumbar lordosis (LL) for all evaluated values at L2L3 and L3L4 and posterior Annulus Stress (AS) at L4L5 (all P<0.0476). The results of this study indicate that LLC with large extensions of LL may not always be advantageous regarding the biomechanical loading of the IVD. This finding may be used to improve the planning process of LLC treatments.

scholarly journals Thermo-Responsive Antimicrobial Hydrogel for the In-Situ Coating of Mesh Materials for Hernia Repair

Polymers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1245
Author(s):  
Bárbara Pérez-Köhler ◽  
Gemma Pascual ◽  
Selma Benito-Martínez ◽  
Juan Manuel Bellón ◽  
David Eglin ◽  
...  
Keyword(s):  
Hernia Repair ◽  
Rabbit Model ◽  
Study Groups ◽  
Tissue Integration ◽  
Great Performance ◽  
In Vitro Antibacterial Activity ◽  
Surgical Field

The prophylactic coating of prosthetic mesh materials for hernia repair with antimicrobial compounds is commonly performed before implantation of the mesh in the abdominal wall. We propose a novel alternative, which is a rifampicin-loaded thermo-responsive hydrogel formulation, to be applied on the mesh after its implantation. This formulation becomes a gel in-situ once reached body temperature, allowing an optimal coating of the mesh along with the surrounding tissues. In vitro, the hydrogel cytotoxicity was assessed using rabbit fibroblasts and antimicrobial efficacy was determined against Staphylococcus aureus. An in vivo rabbit model of hernia repair was performed; implanted polypropylene meshes (5 × 2 cm) were challenged with S. aureus (106 CFU), for two study groups—unloaded (n = 4) and 0.1 mg/cm2 rifampicin-loaded hydrogel (n = 8). In vitro, antibacterial activity of the hydrogel lasted for 5 days, without sign of cytotoxicity. Fourteen days after implantation, meshes coated with drug-free hydrogel developed a strong infection and resulted in poor tissue integration. Coating meshes with the rifampicin-loaded hydrogel fully prevented implant infection and permitted an optimal tissue integration. Due to its great performance, this, degradable, thermo-responsive antimicrobial hydrogel could potentially be a strong prophylactic armamentarium to be combined with prosthesis in the surgical field.

scholarly journals Disc nucleus fortification for lumbar degenerative disc disease: a biomechanical study

2016 ◽  
Vol 24 (5) ◽  
pp. 708-714 ◽  
Author(s):  
Derrick A. Dupré ◽  
Daniel J. Cook ◽  
J. Brad Bellotte ◽  
Michael Y. Oh ◽  
Donald Whiting ◽  
...  
Keyword(s):  
Lumbar Disc ◽  
Hysteresis Loops ◽  
Intervertebral Discs ◽  
Biomechanical Study ◽  
Load Testing ◽  
Disc Disease ◽  
Partial Restoration ◽  
Disc Bulge ◽  
Posterior Elements

OBJECTIVE Spinal stability is attributed in part to osteoligamentous structures, including the vertebral body, facets, intervertebral discs, and posterior elements. The materials in this study provide an opportunity to augment the degenerated nucleus without removing native disc material, a procedure introduced here as “fortification.” The objective of this study was to determine the effect of nucleus fortification on lumbar disc biomechanics. METHODS The authors performed in vitro analysis of human cadaveric functional spinal units (FSUs), along with characterization and quantification of movement of the units using biomechanical data in intact, disc-only, and fortified specimens. The units underwent removal of all posterior elements and annulus and were fortified by injecting a biogel into the nucleus pulposus. Each specimen was subjected to load testing, range of motion (ROM) quantification, and disc bulge measurements. Optoelectric tracking was used to quantify disc bulge. These criteria were assessed in the intact, disc-only, and fortified treatments. RESULTS Disc-only FSUs resulted in increased ROM when compared with intact and fortified conditions. Fortification of the FSU resulted in partial restoration of normal ROM in the treatment groups. Analysis of hysteresis loops showed more linear response in the fortified groups when compared with the intact and disc-only groups. CONCLUSIONS Disc nucleus fortification increases linearity and decreases ROM.

scholarly journals Human amniotic epithelial cells ameliorate kidney damage in ischemia-reperfusion mouse model of acute kidney injury

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yifei Ren ◽  
Ying Chen ◽  
Xizi Zheng ◽  
Hui Wang ◽  
Xin Kang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Kidney Injury ◽  
Renal Function ◽  
Mouse Model ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Mouse Bone Marrow ◽  
Tissue Integration

Abstract Background Acute kidney injury (AKI) is a common clinical disease with complex pathophysiology and limited therapeutic choices. This prompts the need for novel therapy targeting multiple aspects of this disease. Human amnion epithelial cell (hAEC) is an ideal stem cell source. Increasing evidence suggests that exosomes may act as critical cell–cell communicators. Accordingly, we assessed the therapeutic potential of hAECs and their derived exosomes (hAECs-EXO) in ischemia reperfusion mouse model of AKI and explored the underlying mechanisms. Methods The hAECs were primary cultured, and hAECs-EXO were isolated and characterized. An ischemic-reperfusion injury-induced AKI (IRI-AKI) mouse model was established to mimic clinical ischemic kidney injury with different disease severity. Mouse blood creatinine level was used to assess renal function, and kidney specimens were processed to detect cell proliferation, apoptosis, and capillary density. Macrophage infiltration was analyzed by flow cytometry. hAEC-derived exosomes (hAECs-EXO) were used to treat hypoxia-reoxygenation (H/R) injured HK-2 cells and mouse bone marrow-derived macrophages to evaluate their protective effect in vitro. Furthermore, hAECs-EXO were subjected to liquid chromatography-tandem mass spectrometry for proteomic profiling. Results We found that systematically administered hAECs could improve mortality and renal function in IRI-AKI mice, decrease the number of apoptotic cells, prevent peritubular capillary loss, and modulate kidney local immune response. However, hAECs showed very low kidney tissue integration. Exosomes isolated from hAECs recapitulated the renal protective effects of their source cells. In vitro, hAECs-EXO protected HK-2 cells from H/R injury-induced apoptosis and promoted bone marrow-derived macrophage polarization toward M2 phenotype. Proteomic analysis on hAECs-EXO revealed proteins involved in extracellular matrix organization, growth factor signaling pathways, cytokine production, and immunomodulation. These findings demonstrated that paracrine of exosomes might be the key mechanism of hAECs in alleviating renal ischemia reperfusion injury. Conclusions We reported hAECs could improve survival and ameliorate renal injury in mice with IRI-AKI. The anti-apoptotic, pro-angiogenetic, and immunomodulatory capabilities of hAECs are at least partially, through paracrine pathways. hAECs-EXO might be a promising clinical therapeutic tool, overcoming the weaknesses and risks associated with the use of native stem cells, for patients with AKI.

scholarly journals Overlapping of mononuclear cells derived from bone marrow in rats' intervertebral discs: an in vitro study

2010 ◽  
Vol 40 (4) ◽  
pp. 900-906
Author(s):  
Erica Batista Fontes ◽  
Andréa Pacheco Batista Borges ◽  
Ney Luis Pippi ◽  
Maurício Rosa ◽  
Arícia Sprada ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Intervertebral Disc ◽  
Mononuclear Cells ◽  
Morphological Changes ◽  
In Vitro Study ◽  
Intervertebral Discs ◽  
Histopathological Analysis ◽  
Disc Regeneration ◽  
Intervertebral Disc Regeneration

In this study, bone marrow mononuclear cells (BM-MNC) derived from rats were used in order to promote intervertebral disc regeneration. These cells were isolated after centrifugation in a Ficoll-Paque™ PLUS density gradient and then placed in plastic dishes to proliferate during a period of 14 days. The BM-MNCs were previously labeled with the fluorescent membrane marker Chloromethyl-benzamidodialkylcarbocyanine (CM-DIL), and thereafter were implanted in rats' intervertebral discs explants as an in vitro experimental model. Daily analyses of the cells under a fluorescence microscope revealed morphological changes, which assumed a thin and elongated shape similar to cells that originally form the annulus fibroses. Histopathological analysis demonstrated the presence of mononuclear cells interspersed within collagen fibers. The presence of viable cells, in which were found morphological changes and their disposal in the same pattern of the layers that originate the annulus fibrosus, is an indicator that they engrafted and proliferated on the intervertebral disc. Therefore, morphological changes presented by these cells indicate that they presented mesenchymal stem-like cell characteristics.

Effects of exogenous crosslinking on in vitro tensile and compressive moduli of lumbar intervertebral discs

2007 ◽  
Vol 22 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Shih-Youeng Chuang ◽  
Russell M. Odono ◽  
Thomas P. Hedman
Keyword(s):  
Intervertebral Discs

Review of the fluid flow within intervertebral discs - How could in vitro measurements replicate in vivo?

2016 ◽  
Vol 49 (14) ◽  
pp. 3133-3146 ◽  
Author(s):  
Hendrik Schmidt ◽  
Sandra Reitmaier ◽  
Friedmar Graichen ◽  
Aboulfazl Shirazi-Adl
Keyword(s):  
Fluid Flow ◽  
Intervertebral Discs ◽  
In Vitro Measurements
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