Biomechanical Properties of the Spinal Cord: Implications for Tissue Engineering and Clinical Translation

Bartlett, Richard D.; Choi, David; Phillips, James B.

doi:10.2217/rme-2016-0065

Cited by 35 publications

(28 citation statements)

References 94 publications

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“…strain of tensile measures 59 or frequency of oscillatory rheology 60 ) can affect the modulus of elasticity determined. Notably, higher strain increases the measured modulus of elasticity 61 , 62 but changes in strain rate have been reported not to have an effect 58 (for a review see Bartlett et al, 63 ). For example, bovine spinal cord white matter measured by tensile measurement was reported to have a modulus of elasticity of 1.05 MPa with a strain of 40% and 115 kPa with a strain of 5% in the same study.…”

Section: Discussionmentioning

confidence: 99%

Stiffness-matched biomaterial implants for cell delivery: clinical, intraoperative ultrasound elastography provides a ‘target’ stiffness for hydrogel synthesis in spinal cord injury

et al. 2020

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Safe hydrogel delivery requires stiffness-matching with host tissues to avoid iatrogenic damage and reduce inflammatory reactions. Hydrogel-encapsulated cell delivery is a promising combinatorial approach to spinal cord injury therapy, but a lack of in vivo clinical spinal cord injury stiffness measurements is a barrier to their use in clinics. We demonstrate that ultrasound elastography – a non-invasive, clinically established tool – can be used to measure spinal cord stiffness intraoperatively in canines with spontaneous spinal cord injury. In line with recent experimental reports, our data show that injured spinal cord has lower stiffness than uninjured cord. We show that the stiffness of hydrogels encapsulating a clinically relevant transplant population (olfactory ensheathing cells) can also be measured by ultrasound elastography, enabling synthesis of hydrogels with comparable stiffness to canine spinal cord injury. We therefore demonstrate proof-of-principle of a novel approach to stiffness-matching hydrogel-olfactory ensheathing cell implants to ‘real-life’ spinal cord injury values; an approach applicable to multiple biomaterial implants for regenerative therapies.

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Section: Discussionmentioning

confidence: 99%

Stiffness-matched biomaterial implants for cell delivery: clinical, intraoperative ultrasound elastography provides a ‘target’ stiffness for hydrogel synthesis in spinal cord injury

et al. 2020

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“…Tissue engineering is rather demanding, it requires looking not only from the crosslinking rate perspective, but also from a mechanical and biological point of view. For lower MC concentrations, the final storage modulus (DMA) s comparable to native human tissues such as liver [13], spinal cord [14], or cartilage [33]. From biological tests, it was found that at low concentrations, MC provided a good cellular response and non-toxic environment.…”

Section: Discussionmentioning

confidence: 99%

“…Considering its effective support in cells regeneration [8] and having been approved by the Food and Drug Administration (USA), MC is an attractive material for tissue engineering or drug delivery systems [9]. Contrary to other natural hydrogels (e.g., alginate), MC constitutes a stable structure in physiological conditions, with mechanical properties similar to native tissues (e.g., meniscus, liver, or spinal cord) [10,11,12,13,14]. From the perspective of tissue engineering, the thermosensitive crosslinking of MC aqueous solution seems very promising, as it prevents the use of toxic crosslinking agents [15].…”

Section: Introductionmentioning

confidence: 99%

Crosslinking Kinetics of Methylcellulose Aqueous Solution and Its Potential as a Scaffold for Tissue Engineering

et al. 2019

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Thermosensitive, physically crosslinked injectable hydrogels are in the area of interests of various scientific fields. One of the representatives of this materials group is an aqueous solution of methylcellulose. At ambient conditions, methylcellulose (MC) is a sol while on heating up to 37 °C, MC undergoes physical crosslinking and transforms into a gel. Injectability at room temperature, and crosslinkability during subsequent heating to physiological temperature raises hopes, especially for tissue engineering applications. This research work aimed at studying crosslinking kinetics, thermal, viscoelastic, and biological properties of MC aqueous solution in a broad range of MC concentrations. It was evidenced by Differential Scanning Calorimetry (DSC) that crosslinking of MC is a reversible two-stage process, manifested by the appearance of two endothermic effects, related to the destruction of water cages around methoxy groups, followed by crosslinking via the formation of hydrophobic interactions between methoxy groups in the polymeric chains. The DSC results also allowed the determination of MC crosslinking kinetics. Complementary measurements of MC crosslinking kinetics performed by dynamic mechanical analysis (DMA) provided information on the final storage modulus, which was important from the perspective of tissue engineering applications. Cytotoxicity tests were performed using mouse fibroblasts and showed that MC at low concentration did not cause cytotoxicity. All these efforts allowed to assess MC hydrogel relevance for tissue engineering applications.

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“…It is essential that any tissue engineered therapy for spinal cord injury is designed with desirable mechanical characteristics in order to avoid implant-induced damage and to, maximize cellular response, regeneration and functional recovery 43 . Whilst biomechanical studies of spinal cord tissue have reported a range of modulus values (0.12–15.2 kPa) 44 , depending upon species and measurement methods, low stiffness and viscoelasticity are key parameters in selection of appropriate biomaterials. All the hydrogels assessed in this study had maximum moduli less than 1 kPa and meet these requirements.…”

Section: Discussionmentioning

confidence: 99%

Stem cells from the dental apical papilla in extracellular matrix hydrogels mitigate inflammation of microglial cells

Tatic

Rose

Rieux

et al. 2019

Sci Rep

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After spinal cord injury (SCI) chronic inflammation hampers regeneration. Influencing the local microenvironment after SCI may provide a strategy to modulate inflammation and the immune response. The objectives of this work were to determine whether bone or spinal cord derived ECM hydrogels can deliver human mesenchymal stem cells from the apical papilla (SCAP) to reduce local inflammation and provide a regenerative microenvironment. Bone hydrogels (8 and 10 mg/ml, B8 and B10) and spinal cord hydrogels (8 mg/ml, S8) supplemented with fibrin possessed a gelation rate and a storage modulus compatible with spinal cord implantation. S8 and B8 impact on the expression of anti and pro-inflammatory cytokines (Arg1, Nos2, Tnf) in LPS treated microglial cells were assessed using solubilised and solid hydrogel forms. S8 significantly reduced the Nos2/Arg1 ratio and solubilised B8 significantly reduced Tnf and increased Arg1 whereas solid S8 and B8 did not impact inflammation in microglial cells. SCAP incorporation within ECM hydrogels did not impact upon SCAP immunoregulatory properties, with significant downregulation of Nos2/Arg1 ratio observed for all SCAP embedded hydrogels. Tnf expression was reduced with SCAP embedded in B8, reflecting the gene expression observed with the innate hydrogel. Thus, ECM hydrogels are suitable vehicles to deliver SCAP due to their physical properties, preservation of SCAP viability and immunomodulatory capacity.

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Biomechanical Properties of the Spinal Cord: Implications for Tissue Engineering and Clinical Translation

Cited by 35 publications

References 94 publications

Stiffness-matched biomaterial implants for cell delivery: clinical, intraoperative ultrasound elastography provides a ‘target’ stiffness for hydrogel synthesis in spinal cord injury

Stiffness-matched biomaterial implants for cell delivery: clinical, intraoperative ultrasound elastography provides a ‘target’ stiffness for hydrogel synthesis in spinal cord injury

Crosslinking Kinetics of Methylcellulose Aqueous Solution and Its Potential as a Scaffold for Tissue Engineering

Stem cells from the dental apical papilla in extracellular matrix hydrogels mitigate inflammation of microglial cells

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