Silk-Elastin-like Polymers for Acute Intraparenchymal Treatment of the Traumatically Injured Spinal Cord: A First Systematic Experimental Approach

Abstract

Despite the promising potential of hydrogel-based therapeutic approaches for spinal cord injury (SCI), the need for new biomaterials to design effective strategies for SCI treatment and the outstanding properties of silk-elastin-like polymers (SELP), the potential use of SELPs in SCI is currently unknown. In this context, we assessed the effects elicited by the in vivo acute intraparenchymal injection of an SELP named (EIS)2-RGD6 in a clinically relevant model of SCI. After optimization of the injection system, the distribution, structure, biodegradability, and cell infiltration capacity of (EIS)2-RGD6 were assessed. Finally, the effects exerted by the (EIS)2-RGD6 injection—in terms of motor function, myelin preservation, astroglial and microglia/macrophage reactivity, and fibrosis—were evaluated. We found that (EIS)2-RGD6 can be acutely injected in the lesioned spinal cord without inducing further damage, showing a widespread distribution covering all lesioned areas with a single injection and facilitating the formation of a slow-degrading porous scaffold at the lesion site that allows for the infiltration and/or proliferation of endogenous cells with no signs of collapse and without inducing further microglial and astroglial reactivity, as well as even reducing SCI-associated fibrosis. Altogether, these observations suggest that (EIS)2-RGD6—and, by extension, SELPs—could be promising polymers for the design of therapeutic strategies for SCI treatment.

Functionalization of 3D-Printed Titanium Scaffolds with Elastin-like Recombinamers to Improve Cell Colonization and Osteoinduction

“…The ELR genes were synthesized following recombinant DNA technologies, and the protein recombinamers were produced using the Escherichia coli expression system as previously described [ 30 , 31 ]. The ELRs were purified from the bacterial biomass by several cycles of temperature-dependent reversible precipitation [ 32 ].…”

Nanomaterial payload delivery to central nervous system glia for neural protection and repair

“…Conductive hydrogels with nanoparticles ( Yang et al, 2022 ) or nanosheets ( Chen et al, 2022 ) following stimulated spinal cord injury demonstrated decreases in GFAP-labeled astrocytes, as well as decreases in chondroitin sulfate proteoglycans and increased neuronal markers ( Table 2 ). Studies using nanofiber hydrogels (NFH) have shown different outcomes, with NFH alone demonstrating no induction of astrocytes ( Gonzalez et al, 2022 ), while increased amounts of astrocytes at the injury site were seen using an NFH construct combined with BMSCs ( Li et al, 2020 ; Haggerty et al, 2022 ). Nanoparticle hydrogel composites have also shown varying results ( Serafin et al, 2022 ).…”