Verstappen Kest, Bieler Lara, Barroca Nathalie, Bronkhorst Ewald M, Couillard-Després Sébastien, Leeuwenburgh Sander C G, Marques Paula A A P, Klymov Alexey, Walboomers X Frank
Department of Dentistry-Regenerative Biomaterials, Radboud University Medical Center, Nijmegen, 6525 EX, The Netherlands.
Institute of Experimental Neuroregeneration, Paracelsus Medical University, Salzburg, 5020, Austria.
Adv Healthc Mater. 2025 Jan;14(3):e2402775. doi: 10.1002/adhm.202402775. Epub 2024 Dec 12.
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.
基于石墨烯的材料（GBMs）有望恢复脊髓微环境并促进脊髓损伤（SCI）后的功能恢复。已知由还原氧化石墨烯（rGO）和脂肪组织衍生的细胞外基质（adECM）组成的纳米复合材料在体外可促进神经元生长，并且当植入完整脊髓顶部时在体内可引发生物相容性反应。在本研究中，将原始adECM和adECM-rGO纳米复合材料在大鼠半切脊髓损伤后直接植入。基于I型胶原（COL）触发整合素介导的星形胶质细胞增生的证据，将由COL组成的支架用作阴性对照。然而，COL支架在损伤部位诱导原位骨形成，因此被排除在进一步分析之外。与原始adECM相比，adECM-rGO纳米复合材料可完全恢复脊髓完整性。早在植入后3周就观察到巨噬细胞介导的rGO残余物的摄取和清除。8周后，纳米复合材料在宿主-材料界面显示βIII-微管蛋白阳性轴突的存在增加，但仅偶尔观察到轴突对支架的穿透。这部分是由于纳米复合材料中硫酸软骨素蛋白聚糖（CSPGs）的表达增加，尽管反应性星形胶质细胞增生未改变。尽管组织结构完全恢复，但adECM-rGO治疗并未显著改善功能恢复。
