TY - JOUR
T1 - Application of Adipose Extracellular Matrix and Reduced Graphene Oxide Nanocomposites for Spinal Cord Injury Repair
AU - Verstappen, Kest
AU - Bieler, Lara
AU - Barroca, Nathalie
AU - Bronkhorst, Ewald M
AU - Couillard-Després, Sébastien
AU - Leeuwenburgh, Sander C G
AU - Marques, Paula A A P
AU - Klymov, Alexey
AU - Walboomers, X Frank
N1 - Bieler, Couillard-Després: Institute of Experimental Neuroregeneration, Paracelsus Medical University, Salzburg, 5020 Austria
PY - 2024/12/12
Y1 - 2024/12/12
N2 - Graphene-based materials (GBMs) hold strong promise to restore the spinal cord microenvironment and promote functional recovery after spinal cord injury (SCI). Nanocomposites consisting of reduced graphene oxide (rGO) and adipose tissue-derived extracellular matrix (adECM) are known to promote neuronal growth in vitro and to evoke a biocompatible response in vivo when implanted on top of the intact spinal cord. In this study, pristine adECM and adECM-rGO nanocomposites are implanted directly after hemisection SCI in rats. Scaffolds composed of collagen type I (COL) are applied as negative control, based on evidence that COL triggers integrin-mediated astrogliosis. However, COL scaffolds induce orthotopic bone formation in the lesion site and are therefore excluded from further analyses. Compared to pristine adECM, adECM-rGO nanocomposites completely restore spinal cord integrity. Macrophage-mediated uptake and clearance of rGO remnants is observed as early as 3 weeks post-implantation. Nanocomposites show an elevated presence of βIII-tubulin-positive axons in the host-material interface after 8 weeks, yet scaffold penetration by axons is only occasionally observed. This is partially due to an increased expression of chondroitin sulfate proteoglycans (CSPGs) within the nanocomposites, even though reactive astrogliosis is unaltered. Despite the complete restoration of tissue architecture, adECM-rGO treatment does not significantly improve functional recovery.
AB - Graphene-based materials (GBMs) hold strong promise to restore the spinal cord microenvironment and promote functional recovery after spinal cord injury (SCI). Nanocomposites consisting of reduced graphene oxide (rGO) and adipose tissue-derived extracellular matrix (adECM) are known to promote neuronal growth in vitro and to evoke a biocompatible response in vivo when implanted on top of the intact spinal cord. In this study, pristine adECM and adECM-rGO nanocomposites are implanted directly after hemisection SCI in rats. Scaffolds composed of collagen type I (COL) are applied as negative control, based on evidence that COL triggers integrin-mediated astrogliosis. However, COL scaffolds induce orthotopic bone formation in the lesion site and are therefore excluded from further analyses. Compared to pristine adECM, adECM-rGO nanocomposites completely restore spinal cord integrity. Macrophage-mediated uptake and clearance of rGO remnants is observed as early as 3 weeks post-implantation. Nanocomposites show an elevated presence of βIII-tubulin-positive axons in the host-material interface after 8 weeks, yet scaffold penetration by axons is only occasionally observed. This is partially due to an increased expression of chondroitin sulfate proteoglycans (CSPGs) within the nanocomposites, even though reactive astrogliosis is unaltered. Despite the complete restoration of tissue architecture, adECM-rGO treatment does not significantly improve functional recovery.
U2 - 10.1002/adhm.202402775
DO - 10.1002/adhm.202402775
M3 - Original Article
C2 - 39668418
SN - 2192-2640
SP - e2402775
JO - ADVANCED HEALTHCARE MATERIALS
JF - ADVANCED HEALTHCARE MATERIALS
ER -