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The effect of a nanofiber-hydrogel composite on neural tissue repair and regeneration in the contused spinal cord.

ABSTRACT: An injury to the spinal cord causes long-lasting loss of nervous tissue because endogenous nervous tissue repair and regeneration at the site of injury is limited. We engineered an injectable nanofiber-hydrogel composite (NHC) with interfacial bonding to provide mechanical strength and porosity and examined its effect on repair and neural tissue regeneration in an adult rat model of spinal cord contusion. At 28 days after treatment with NHC, the width of the contused spinal cord segment was 2-fold larger than in controls. With NHC treatment, tissue in the injury had a 2-fold higher M2/M1 macrophage ratio, 5-fold higher blood vessel density, 2.6-fold higher immature neuron presence, 2.4-fold higher axon density, and a similar glial scar presence compared with controls. Spared nervous tissue volume in the contused segment and hind limb function was similar between groups. Our findings indicated that NHC provided mechanical support to the contused spinal cord and supported pro-regenerative macrophage polarization, angiogenesis, axon growth, and neurogenesis in the injured tissue without any exogenous factors or cells. These results motivate further optimization of the NHC and delivery protocol to fully translate the potential of the unique properties of the NHC for treating spinal cord injury.

SUBMITTER: Li X

PROVIDER: S-EPMC8787820 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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The effect of a nanofiber-hydrogel composite on neural tissue repair and regeneration in the contused spinal cord.

Li Xiaowei X Zhang Chi C Haggerty Agnes E AE Yan Jerry J Lan Michael M Seu Michelle M Yang Mingyu M Marlow Megan M MM Maldonado-Lasunción Inés I Cho Brian B Zhou Zhengbing Z Chen Long L Martin Russell R Nitobe Yohshiro Y Yamane Kentaro K You Hua H Reddy Sashank S Quan Da-Ping DP Oudega Martin M Mao Hai-Quan HQ

Biomaterials 20200316

An injury to the spinal cord causes long-lasting loss of nervous tissue because endogenous nervous tissue repair and regeneration at the site of injury is limited. We engineered an injectable nanofiber-hydrogel composite (NHC) with interfacial bonding to provide mechanical strength and porosity and examined its effect on repair and neural tissue regeneration in an adult rat model of spinal cord contusion. At 28 days after treatment with NHC, the width of the contused spinal cord segment was 2-fo ...[more]

PMID: 32217415

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Project description: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 two-step 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/mm2) was significantly increased more than 3-fold compared to the control (456 axons/mm2), with approximately 30% of axons within the tube myelinated. Furthermore, implantation of hydrogel tubes enhanced functional recovery relative to control. This modular assembly of porous tubes to fill a defect and directionally orient tissue growth could be extended beyond spinal cord injury to other tissues, such as vascular or musculoskeletal tissue. STATEMENT OF SIGNIFICANCE: Tissue engineering approaches that mimic the native architecture of healthy tissue are needed following injury. Traditionally, pre-molded scaffolds have been implemented but require a priori knowledge of wound geometries. Conversely, hydrogels can conform to any injury, but do not guide bi-directional regeneration. In this work, we investigate the feasibility of a system of modular hydrogel tubes to promote bi-directional regeneration after spinal cord injury. This system allows for tubes to be cut to size during surgery and implanted one-by-one to fill any injury, while providing bi-directional guidance. Moreover, this system of tubes can be broadly applied to tissue engineering approaches that require a modular guidance system, such as repair to vascular or musculoskeletal tissues.

Project description:BackgroundTo determine the effects of gelatin methacryloyl (GelMA) hydrogel on nerve repair and regeneration in mice with spinal cord injury (SCI).MethodsA total of 30 ICR mice (6-8 weeks old) were randomly assigned into the control group, the model group, and the experimental group via the random digits table method. There were 10 mice in each group. All mice underwent a T8 laminectomy. For mice in the experimental group and the model group, after the T8 laminectomy, SCI models were constructed by clamping the mice spinal cord tissue for 1 minute using an aneurysm clip (25 g). Additionally, the SCI area of each mouse in the experimental group was locally injected with 0.05-0.7 mL GelMA hydrogel [10% (w/v)] and photocrosslinking was initiated under a blue light source with a wavelength of 405 nm. The exercise performance of each mouse was tested via the bedside mobility scale (BMS) on post-operative days 1, 3, 7, and 14. After 14 days, mice were sacrificed and the dorsal root ganglion (DRG) sensory neurons were isolated and cultured for 3 days in vitro. The axon lengths of the neurons were then evaluated. Immunohistochemical staining was performed to assess the development of syringomyelia in the area. Western blots (WB) and immunofluorescence staining were performed to quantify the expression of glial fibrillary acidic protein (GFAP), growth associated protein (GAP)43, and nestin in the DRG neurons from each group of mice.ResultsCompared with mice in the control group, mice in the SCI model group showed a notable decrease in exercise ability, while the exercise ability of mice in the experimental group recovered markedly after treatment with GelMA hydrogel. Administration of GelMA hydrogel lengthened the axon of DRG neurons in mice and reduced the area of syringomyelia. Furthermore, GelMA hydrogel inhibited scar formation and promoted the recovery of neurological function by upregulating GAP43 and nestin expression and downregulating GFAP expression.ConclusionsIn mice with SCI, local injection of GelMA hydrogel strongly inhibited scar formation, reduced the area of syringomyelia, and promoted nerve regeneration and recovery of limb movement function.

Dataset Information

The effect of a nanofiber-hydrogel composite on neural tissue repair and regeneration in the contused spinal cord.

Publications

The effect of a nanofiber-hydrogel composite on neural tissue repair and regeneration in the contused spinal cord.

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