Development of a New Formulation Based on In Situ Photopolymerized Polymer for the Treatment of Spinal Cord Injury

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.

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

“…The application of GelMA as an immunotherapeutic platform for SCI is limited, with therapeutic cell delivery and tissue regeneration instead taking the focus. [67,37,43,68,70,71] However, cell graft survival and axonal regeneration cannot occur successfully in the harsh SCI immune microenvironment. [12,109,110] Therefore, immunomodulation is a critical therapeutic approach that should be incorporated into future biomaterial-based design strategies.…”

“…[40][41][42] Hydrogels in particular offer an injectable platform to fill irregularly shaped SCI lesions, with post-filling in situ polymerization to immobilize or enhance structural fidelity, and tuneable biodegradability for custom therapeutic release profiles. [43][44][45] When designing a therapeutic hydrogel, it is important to consider the existence of context-specific "biocompatible" properties. For example, in SCI applications, hydrogels should; have similar mechanical properties to those of spinal cord tissue with local regions as low as 70-130 Pa; [46][47][48] exhibit minimal swelling to avoid increased intraspinal pressure; [49,50] and be biodegradable with non-toxic by-products.…”

Formononetin: A Pathway to Protect Neurons

“…In addition, Novais et al (2021) further developed a GelMA-hydroalcoholic extract of red propolis (HERP) formulation (the main bioactive maker of the formulation is FMN), and verified the function of the formulation in the experimental model of rat SCI. The results showed that the formulations containing FMN had greater post-injury recovery rates compared to formulations without FMN.…”