Intrathecal delivery of a polymeric nanocomposite hydrogel after spinal cord injury

Baumann, M. Douglas; Kang, Catherine E.; Tator, Charles H.; Shoichet, Molly S.

doi:10.1016/j.biomaterials.2010.07.004

Cited by 155 publications

(116 citation statements)

References 55 publications

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“…The combination of HA with synthetic polymers, such as polylactic/polyglycolic acids was intended to improve the poor biological properties of the latter [55,56]. Mixtures of HA with hydroxyapatite and calcium phosphate ceramics for developing composite biomaterials [57][58][59][60][61] resulted in prolonged scaffold stability and reduced degradation rates, but the composite exhibited impaired biological activity.…”

Section: Immunohistochemical Stainingmentioning

confidence: 99%

Calcite Biohybrids as Microenvironment for Stem Cells

2012

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Abstract:A new type of composite 3D biomaterial that provides extracellular cues that govern the differentiation processes of mesenchymal stem cells (MSCs) has been developed. In the present study, we evaluated the chondrogenecity of a biohybrid composed of a calcium carbonate scaffold in its calcite polymorph and hyaluronic acid (HA). The source of the calcite scaffolding is an exoskeleton of a sea barnacle Tetraclita rifotincta (T. rifotincta), Pilsbry (1916). The combination of a calcium carbonate-based bioactive scaffold with a natural polymeric hydrogel is designed to mimic the organic-mineral composite of developing bone by providing a fine-tuned microenvironment. The results indicate that the calcite-HA interface creates a suitable microenvironment for the chondrogenic differentiation of MSCs, and therefore, the biohybrid may provide a tool for tissue-engineered cartilage.

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Section: Immunohistochemical Stainingmentioning

confidence: 99%

Calcite Biohybrids as Microenvironment for Stem Cells

2012

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“…Thus, neither oral nor intravenous delivery provides the optimal desired benefit of neuroprotective or neuroregenerative drugs. The physical inaccessibility of the spinal cord is usually dealt with using alternative measures, such as local epidural or intrathecal delivery (by bolus injection or catheter/implant insertion) [11,12]. The delivery of drugs to the microenvironment of the spinal cord through intrathecal administration in polymeric hydrogels and in situ has been reported to be promising in SCI, with advantages including improved safety, prolonged delivery (up to 4 weeks), and reduced dosage (frequency) [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Development of an <i>in</i> situ polymeric hydrogel implant of methylprednisolone for spinal injuries

Guan¹,

Zhu²,

Ma³

et al. 2017

Trop. J. Pharm Res

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“…Autotransplantation of stem cells, Schwann cells, and olfactory ensheathing cells in the damaged spinal cord, at both short and long time periods after injury, and implantation of artificial materials have been performed with various results. 6,8,15,24,32,34,35,37,42,51,52 Hyaluronic acid is especially interesting in light of the fact that not only is it a natural part of the extracellular matrix and is nonimmunogenic, but also it has been used commercially in the skin and joints and intraabdominally. 26,31,38,49 It has also shown strong neurite-promoting characteristics in vitro.…”

Section: Discussionmentioning

confidence: 99%

Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury

Kushchayev

Giers

Eng

et al. 2016

SPI

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OBJECTIVE Spinal cord injury occurs in 2 phases. The initial trauma is followed by inflammation that leads to fibrous scar tissue, glial scarring, and cavity formation. Scarring causes further axon death around and above the injury. A reduction in secondary injury could lead to functional improvement. In this study, hyaluronic acid (HA) hydrogels were implanted into the gap formed in the hemisected spinal cord of Sprague-Dawley rats in an attempt to attenuate damage and regenerate tissue. METHODS A T-10 hemisection spinal cord injury was created in adult male Sprague-Dawley rats; the rats were assigned to a sham, control (phosphate-buffered saline), or HA hydrogel–treated group. One cohort of 23 animals was followed for 12 weeks and underwent weekly behavioral assessments. At 12 weeks, retrograde tracing was performed by injecting Fluoro-Gold in the left L-2 gray matter. At 14 weeks, the animals were killed. The volume of the lesion and the number of cells labeled from retrograde tracing were calculated. Animals in a separate cohort were killed at 8 or 16 weeks and perfused for immunohistochemical analysis and transmission electron microscopy. Samples were stained using H & E, neurofilament stain (neurons and axons), silver stain (disrupted axons), glial fibrillary acidic protein stain (astrocytes), and Iba1 stain (mononuclear cells). RESULTS The lesions were significantly smaller in size and there were more retrograde-labeled cells in the red nuclei of the HA hydrogel–treated rats than in those of the controls; however, the behavioral assessments revealed no differences between the groups. The immunohistochemical analyses revealed decreased fibrous scarring and increased retention of organized intact axonal tissue in the HA hydrogel–treated group. There was a decreased presence of inflammatory cells in the HA hydrogel–treated group. No axonal or neuronal regeneration was observed. CONCLUSIONS The results of these experiments show that HA hydrogel had a neuroprotective effect on the spinal cord by decreasing the magnitude of secondary injury after a lacerating spinal cord injury. Although regeneration and behavioral improvement were not observed, the reduction in disorganized scar tissue and the retention of neurons near and above the lesion are important for future regenerative efforts. In addition, this gel would be useful as the base substrate in the development of a more complex scaffold.

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Intrathecal delivery of a polymeric nanocomposite hydrogel after spinal cord injury

Cited by 155 publications

References 55 publications

Calcite Biohybrids as Microenvironment for Stem Cells

Calcite Biohybrids as Microenvironment for Stem Cells

Development of an <i>in</i> situ polymeric hydrogel implant of methylprednisolone for spinal injuries

Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury

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