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  4. An In Vitro and Ex Vivo Analysis of the Potential of GelMA Hydrogels as a Therapeutic Platform for Preclinical Spinal Cord Injury

An In Vitro and Ex Vivo Analysis of the Potential of GelMA Hydrogels as a Therapeutic Platform for Preclinical Spinal Cord Injury

Advanced Healthcare Materials, 2023 · DOI: 10.1002/adhm.202300951 · Published: May 12, 2023

Spinal Cord InjuryImmunologyBiomedical

Simple Explanation

Spinal cord injury (SCI) is a severe condition lacking effective treatments. This study explores GelMA hydrogels as a potential therapeutic platform for SCI, focusing on their immunogenicity in the SCI microenvironment. The research identifies 3% GelMA-A as the optimal hydrogel formulation due to its mechanical properties and cytocompatibility. It examines its impact on microglia and macrophages, key immune cells in SCI. The study further investigates the hydrogel's ability to support the culture of spinal cord slices without causing glial reactivity, providing evidence for its potential as an immunotherapeutic platform.

Study Duration
14 days
Participants
P5-6 C57BL/6 mouse pups (n = 6)
Evidence Level
In vitro and Ex vivo study

Key Findings

  • 1
    3% GelMA-A was identified as the optimal hydrogel formulation due to its mechanical properties and cytocompatibility.
  • 2
    3% GelMA-A does not alter the expression profile of key polarization markers in BV2 microglia or RAW264.7 macrophages after 48 h.
  • 3
    3% GelMA-A can support the ex vivo culture of primary murine organotypic spinal cord slices for 14 days with no direct effect on glial fibrillary acidic protein (GFAP+) astrocyte or ionized calcium-binding adaptor molecule 1 (Iba-1+) microglia reactivity.

Research Summary

This study investigates the immunogenicity of GelMA hydrogels for spinal cord injury (SCI) treatment, focusing on their impact on the SCI immune microenvironment. The research identifies 3% GelMA-A as a promising formulation due to its mechanical properties, cytocompatibility, and lack of inflammatory response in vitro and ex vivo. The findings suggest that 3% GelMA-A hydrogels can serve as an immunologically inert platform for delivering immunotherapeutic agents to promote tissue regeneration after SCI.

Practical Implications

Therapeutic Delivery

GelMA hydrogels can be used as a vehicle for delivering therapeutic cells or molecules directly to the site of spinal cord injury, providing sustained and localized treatment.

Immunomodulation

The hydrogel platform can be engineered to incorporate immunomodulatory cues that shift the immune response towards a pro-regenerative state, promoting tissue repair.

Clinical Translation

The use of visible light-based photoinitiation and the demonstration of biocompatibility in ex vivo models support the potential translation of GelMA hydrogels into clinical applications for SCI treatment.

Study Limitations

  • 1
    The endotoxin levels reported here exceed the current FDA limit
  • 2
    The complexity of immune cell polarization and the dynamic, multidimensional immune states that exist in vivo
  • 3
    Monolayer 2D culture conditions do not mimic spinal cord tissue biomechanics, leading to loss of polarization and cell diversity

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