Delivery of Alginate Scaffold Releasing Two Trophic Factors for Spinal Cord Injury Repair

Abstract

Spinal cord injury (SCI) has been implicated in neural cell loss and consequently functional motor and sensory impairment. In this study, we propose an alginate -based neurobridge enriched with/without trophic growth factors (GFs) that can be utilized as a therapeutic approach for spinal cord repair. The bioavailability of key GFs, such as Epidermal Growth factor (EGF) and basic Fibroblast Growth Factor (bFGF) released from injected alginate biomaterial to the central lesion site significantly enhanced the sparing of spinal cord tissue and increased the number of surviving neurons (choline acetyltransferase positive motoneurons) and sensory fibres. In addition, we document enhanced outgrowth of corticospinal tract axons and presence of blood vessels at the central lesion. Tissue proteomics was performed at 3, 7 and 10 days after SCI in rats indicated the presence of anti-inflammatory factors in segments above the central lesion site, whereas in segments below, neurite outgrowth factors, inflammatory cytokines and chondroitin sulfate proteoglycan of the lectican protein family were overexpressed. Collectively, based on our data, we confirm that functional recovery was significantly improved in SCI groups receiving alginate scaffold with affinity-bound growth factors (ALG +GFs), compared to SCI animals without biomaterial treatment.

Proteomic Analysis of the Spatio-temporal Based Molecular Kinetics of Acute Spinal Cord Injury Identifies a Time- and Segment-specific Window for Effective Tissue Repair

“…The distance between injections was 1 mm, avoiding vessels. Intraspinal injections were followed by procedure published in our study (16). After injecting the dose of saline or CD-20 antibody, the needle was maintained in the tissue for an additional 30 s. No antibiotic treatment was performed during animal's survival.…”

Neurotrophic Factors Used to Treat Spinal Cord Injury

“…Intrathecal administration typically involves osmotic pumps to continuously deliver FGF to (or near) the lesion over days or weeks Kojima & Tator, 2002;Lee et al, 1999;Rabchevsky et al, 1999). FGF has also been delivered in association with Schwann cells or peripheral nerve (PN) grafts, released by carriers such as gelfoam, gelatin, fibrin glue, HEMA-MOETACL hydrogels alginate scaffolds or from nanoparticles (Chen et al, 2015;Furuya et al, 2013;Grulova et al, 2015;Guzen et al, 2012;Kang et al, 2013;Lee et al, 2008Lee et al, , 2010Meijs et al, 2004;Meng et al, 2008;Shin et al, 2014;Tsai et al, 2006;Wu et al, 2008). A recent study successfully delivered FGF2 (a known mitogen for stem cell self-renewal) via subcutaneous injection to give improved outcomes (Goldshmit et al, 2014).…”

Injectable Hydrogels for Spinal Cord Repair: A Focus on Swelling and Intraspinal Pressure

“…It is interesting to note that the resulting networks are fundamentally more inhomogeneous than step-growth polymerized hydrogels, containing hydrophobic 'pockets' throughout. Other noncovalent crosslinking includes the calcium-mediated crosslinking of alginate hydrogels [Prang et al, 2006;Ansorena et al, 2013;des Rieux et al, 2014;Grulova et al, 2015;Gunther et al, 2015;Pawar et al, 2015b] and self-assembly of amphiphilic polymers [Silva et al, 2004;Tysseling-Mattiace et al, 2008;Song et al, 2012;Yang et al, 2013], with both types of hydrogels reporting swelling of about 40%. Self-assembled hydrogels are often fabricated from designer polypeptides, which provides a high degree of control over network assembly as each amino acid is user specified.…”