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Hydrogels as delivery systems for spinal cord injury regeneration.

ABSTRACT: Spinal cord injury is extremely debilitating, both at physiological and psychological levels, changing completely the patient's lifestyle. The introduction of biomaterials has opened a new window to develop a therapeutic approach to induce regeneration after injury due to similarities with extracellular matrix. Particularly, hydrogels have the ability to support axonal growth and endogenous regeneration. Moreover, they can also act as potential matrixes in which to load and deliver therapeutic agents at injury site. In this review, we highlight some important characteristics to be considered when designing hydrogels as delivery systems (DS), such as rheology, mesh size, swelling, degradation, gelation temperature and surface charge. Additionally, affinity-based release systems, incorporation of nanoparticles, or ion-mediated interactions are also pondered. Overall, hydrogel DS aim to promote a sustained, controlled and prolonged release at injury site, allowing a targeted oriented action of the therapeutic agent that will be used.

SUBMITTER: Silva D

PROVIDER: S-EPMC7905359 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Hydrogels as delivery systems for spinal cord injury regeneration.

Silva D D Sousa R A RA Salgado A J AJ

Materials today. Bio 20210122

Spinal cord injury is extremely debilitating, both at physiological and psychological levels, changing completely the patient's lifestyle. The introduction of biomaterials has opened a new window to develop a therapeutic approach to induce regeneration after injury due to similarities with extracellular matrix. Particularly, hydrogels have the ability to support axonal growth and endogenous regeneration. Moreover, they can also act as potential matrixes in which to load and deliver therapeutic a ...[more]

PMID: 33665602

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Project description:ObjectiveNerve growth factor (NGF) has potential in spinal cord injury (SCI) therapy, but limited by the poor physicochemical stability and low ability to cross the blood spinal cord barrier. Novel heparin-poloxamer (HP) thermo-sensitive hydrogel was constructed to enhance the NGF regeneration on SCI.MethodNGF-HP thermo-sensitive hydrogel was prepared and related characteristics including gelation temperature, rheological behavior and micromorphology were measured. Local NGF delivery to the injured spinal cord was achieved by in situ injection in the injured space. The cellular uptake of NGF-HP hydrogel was evaluated with PC12 cells in vitro. Pathologic characteristics and neuron regeneration effects on the SCI rats were studied to evaluate the enhanced therapy of NGF-HP hydrogel. Endoplasmic reticulum (ER) stress-induced apoptosis was analyzed to explore the related mechanism in SCI regeneration.ResultsNGF-HP hydrogel showed good morphology and stable bioactivity of NGF in vitro. NGF-HP hydrogel combined treatment significantly enhanced the efficiency of NGF cellular uptake (P<0.05) without obvious cytotoxicity. Significant improvements in both neuron functions and tissue morphology on the SCI rats were observed in NGF-HP hydrogel group. Compared with free HP hydrogel and NGF treatment groups, NGF-HP hydrogel group showed significant inhibition on the formation of glial scars in the extreme crushed rat SCI model. The neuroprotective effects of NGF-HP were related to the inhibition of chronic ER stress-induced apoptosis.ConclusionsHP hydrogel combined with orthotopic injection technique might be an effective method to deliver NGF into the injured site, which will provide an effective strategy for SCI regeneration.Statement of significanceSpinal cord injury (SCI) is a devastating condition that can lead to sudden loss of sensory and autonomic function. Current treatment includes decompression surgery, injury stabilization, secondary complications prevention and rehabilitation. However, neurological recovery is limited. Nerve growth factor (NGF) has potential in SCI therapy, but limited by the poor physicochemical stability and low ability to cross the blood spinal cord barrier. Hydrogels have good affinity and compatibility to biological tissue. In this study, we developed a novel heparin-poloxamer (HP) thermo-sensitive hydrogel to enhance the spinal cord regeneration of NGF. From SCI rat experiment, HP hydrogel combined with orthotopic injection technique showed best neuroprotective effects among experimental groups. This novel combined technique will provide an effective strategy for SCI regeneration.

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.

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Hydrogels as delivery systems for spinal cord injury regeneration.

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Hydrogels as delivery systems for spinal cord injury regeneration.

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