Spinal Progenitor-Laden Bridges Support Earlier Axon Regeneration Following Spinal Cord Injury

Munsell, Mary K.; Carlson, Mitchell A.; Cummings, Brian J.; Anderson, Aileen J.; Shea, Lonnie D.

doi:10.1089/ten.tea.2018.0053

Cited by 16 publications

(33 citation statements)

References 84 publications

(191 reference statements)

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“…Mice receiving the hydrogel tubes and bridges also recovered greater locomotor function compared to the controls, that corroborate the histological findings. Interestingly, the increased axon density at 8 weeks in the 5-tube composites (1744 axons/mm 2 ) is an improvement over that observed in PLG bridges (740 axons/mm 2 ) implanted into a mouse hemisection model [36,37], which may be due to the more closely matched mechanical properties of the hydrogel to the nervous tissue (1-300 kPa [63][64][65]). Vascular tissue and muscle require high tensile strength, and there are a number of modifications to the material that can be made to properly match these tissues.…”

Section: Discussionmentioning

confidence: 88%

“…For example, the spinal cord is a highly organized structure with predominantly rostral-caudal alignment of axons and myelin, making it an ideal tissue for evaluating aligned biomaterial bridges. Previous work using multi-channel bridges has shown robust directed axon elongation [9,[36][37][38][39][40]. An additional design feature of these bridges is their high degree of porosity [37], allowing for infdtration of progenitors that differentiate into myelinating oligodendrocytes resulting in not only axon regrowth, but also myelination of these axons [36,41].…”

Section: Introductionmentioning

confidence: 99%

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Aligned hydrogel tubes guide regeneration following spinal cord injury

et al. 2019

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Directing the organization of cells into a tissue with defined architectures is one use of biomaterials for regenerative medicine. To this end, hydrogels are widely investigated as they have mechanical properties similar to native soft tissues and can be formed in situ to conform to a defect. Herein, we describe the development of porous hydrogel tubes fabricated through a twostep polymerization process with an intermediate microsphere phase that provides macroscale porosity (66.5%) for cell infiltration. These tubes were investigated in a spinal cord injury model, with the tubes assembled to conform to the injury and to provide an orientation that guides axons through the injury. Implanted tubes had good apposition and were integrated with the host tissue due to cell infiltration, with a transient increase in immune cell infiltration at 1 week that resolved by 2 weeks post injury compared to a gelfoam control. The glial scar was significantly reduced relative to control, which enabled robust axon growth along the inner and outer surface of the tubes. Axon density within the hydrogel tubes (1744 axons/mm 2) was significantly increased more than 3-fold compared to the control (456 axons/mm 2), with approximately 30% of axons within the tube myelinated. Furthermore, implantation of hydrogel tubes enhanced functional recovery

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Aligned hydrogel tubes guide regeneration following spinal cord injury

et al. 2019

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“…13 Delivery of mouse E14 spinal progenitors, loaded onto multichannel PLGA bridges providing a guidance architecture, showed marked improvement of axonal and functional regeneration in a mouse model of thoracic SCI. 196 However, another study found that collagen microfibers combined with neural progenitor cells from an alternative source failed to form a bridge across the injury site, or recovery of the motor function in a mouse SCI model. 39 It has been proposed that the combination of human MSCs and biomimetic hydrogels could modulate the immune cell microenvironment in SCI, leading to increased proregenerative M2 macrophage population.…”

Section: Reproduced Withmentioning

confidence: 99%

Regenerative Therapies for Spinal Cord Injury

Ashammakhi

Kim

Ehsanipour

et al. 2019

Tissue Engineering Part B: Reviews

121

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Spinal cord injury (SCI) is a serious problem that primarily affects younger and middle-aged adults at its onset. To date, no effective regenerative treatment has been developed. Over the last decade, researchers have made significant advances in stem cell technology, biomaterials, nanotechnology, and immune engineering, which may be applied as regenerative therapies for the spinal cord. Although the results of clinical trials using specific cell-based therapies have proven safe, their efficacy has not yet been demonstrated. The pathophysiology of SCI is multifaceted, complex and yet to be fully understood. Thus, combinatorial therapies that simultaneously leverage multiple approaches will likely be required to achieve satisfactory outcomes. Although combinations of biomaterials with pharmacologic agents or cells have been explored, few studies have combined these modalities in a systematic way. For most strategies, clinical translation will be facilitated by the use of minimally invasive therapies, which are the focus of this review. In addition, this review discusses previously explored therapies designed to promote neuroregeneration and neuroprotection after SCI, while highlighting present challenges and future directions.

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“…Smaller myelin debris was removed via density gradient centrifugation (63). In brief, a gradient was prepared such that a 35% (v/v) 1:1 4-morpholinepropanesulfonic acid (MOPS):Opti-prep (Sigma) solution in HBSS was layered on top of a 20% (v/v) 1:1 MOPS:Opti-prep solution in HBSS.…”

Section: Primary Preganglionic Sympathetic Neuron Isolationmentioning

confidence: 99%

Innervated adrenomedullary microphysiological system to model prenatal nicotine and opioid exposure

Soucy

Burchett

Brady

et al. 2020

Preprint

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The transition to extrauterine life results in a critical surge of catecholamines necessary for increased cardiovascular, respiratory, and metabolic activity. The mechanisms mediating adrenomedullary catecholamine release are poorly understood, given the sympathetic adrenomedullary control systems' functional immaturity. Important mechanistic insight is provided by newborns delivered by cesarean section or subjected to prenatal nicotine or opioid exposure, demonstrating the impaired release of adrenomedullary catecholamines. To investigate mechanisms regulating adrenomedullary innervation, we developed compartmentalized 3D microphysiological systems (MPS) by exploiting the meniscus pinning effect via GelPins, capillary pressure barriers between cell-laden hydrogels. The MPS comprises discrete 3D cultures of adrenal chromaffin cells and preganglionic sympathetic neurons within a contiguous bioengineered microtissue. Using this model, we demonstrate that adrenal chromaffin innervation plays a critical role in hypoxia-medicated catecholamine release. Furthermore, opioids and nicotine were shown to affect adrenal chromaffin cell response to a reduced oxygen environment, but neurogenic control mechanisms remained intact. GelPin containing MPS represent an inexpensive and highly adaptable approach to study innervated organ systems and improve drug screening platforms by providing innervated microenvironments.

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Spinal Progenitor-Laden Bridges Support Earlier Axon Regeneration Following Spinal Cord Injury

Cited by 16 publications

References 84 publications

Aligned hydrogel tubes guide regeneration following spinal cord injury

Aligned hydrogel tubes guide regeneration following spinal cord injury

Regenerative Therapies for Spinal Cord Injury

Innervated adrenomedullary microphysiological system to model prenatal nicotine and opioid exposure

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