Abstract

Spinal Cord Injury (SCI) promotes a cascade of inflammatory events that are responsible for neuronal death and glial scar formation at the site of the injury, hindering tissue neuroregeneration. Among the main approaches for the treatment of SCI, the use of biomaterials, especially gelatin methacryloyl (GelMA), has been proposed because it is biocompatible, has excellent mechanical properties, favoring cell adhesion and proliferation. In addition, it can act as a carrier of anti-inflammatory drugs, preventing the formation of glial scars. The present work presents the development and in situ application of a light-curing formulation based on GelMA containing a natural extract rich in anti-inflammatory, antioxidant and neuroprotective substances (hydroalcoholic extract of red propolis—HERP) in an experimental model of SCI in rats. The formulations were prepared and characterized by time of UV exposition, FTIR, swelling and degradation. The hydrogels containing 1 mg/mL of HERP were obtained by the exposure to UV radiation of 2 μL of the formulation for 60 s. The locomotor evaluation of the animals was performed by the scale (BBB) and demonstrated that after 3 and 7 days of the injury, the GelMA-HERP group (BBB = 5 and 7) presented greater recovery compared to the GelMA group (BBB = 4 and 5). Regarding the inflammatory process, using histomorphological techniques, there was an inflammation reduction in the groups treated with GelMA and GelMA-HERP, with decreases of cavitation in the injury site. Therefore, it is possible to conclude that the use of GelMA and GelMA-HERP hydrogel formulations is a promising strategy for the treatment of SCI when applied in situ, as soon as possible after the injury, improving the clinical and inflammatory conditions of the treated animals.

Highlights

  • Spinal cord injury (SCI) can be caused by trauma, disease or birth defect that may cause moderate or severe neurological sequels

  • This work describes the development of a new formulation based on gelatin methacryloyl (GelMA) containing hydroethanolic extract of red propolis (HERP), to be applied in situ in a murine model of Spinal Cord Injury (SCI), in order to inhibit the formation of glial scar at the site of injury, as well as the cascade of secondary events from the anti-inflammatory potential of HERP

  • The yield of the red propolis extraction process was 51.2%, similar to what was found by Almeida et al (2013) [32], who obtained 48.8%

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Summary

Introduction

Spinal cord injury (SCI) can be caused by trauma, disease or birth defect that may cause moderate or severe neurological sequels. One of great interest is red propolis, which contains molecules, such as flavonoids, in its chemical composition, with several activities, among which anti-inflammatory [12,13,14,15] and neuroprotective [3,16] activities stand out These pharmacological effects are extremely relevant to modulate the inflammatory response that occurs at the site of injury. This work describes the development of a new formulation based on GelMA containing hydroethanolic extract of red propolis (HERP), to be applied in situ in a murine model of SCI, in order to inhibit the formation of glial scar at the site of injury, as well as the cascade of secondary events from the anti-inflammatory potential of HERP

Materials
Preparation of Extract
Methacrylated Gelatin Synthesis
Development of the GelMA Hydrogel with and without Extract
Fourier Transform Infrared Spectroscopy
Hydrogel Swelling Analysis
GelMA Biodegradation
Experimental Groups and Spinal Cord Injury Surgery
Assessment of Recovery of Locomotion
Histological Analysis
2.10. Statistical Analysis
Results and Discussion
Functional assessment byand the GelMA-HERP
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