Dense fibroadhesive scarring and poor blood vessel-maturation hamper the integration of implanted collagen scaffolds in an experimental model of spinal cord injury

IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL
H. Altinova, Sebastian Hammes, Moniek Palm, Pascal Achenbach, Jose L. Gerardo-Nava, R. Deumens, T. Führmann, S. V. van Neerven, E. Hermans, J. Weis, G. Brook
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引用次数: 9

Abstract

Severe spinal cord injury (SCI) results in permanent functional deficits, which despite pre-clinical advances, remain untreatable. Combinational approaches, including the implantation of bioengineered scaffolds are likely to promote significant tissue repair. However, this critically depends on the extent to which host tissue can integrate with the implant. In the present paper, blood vessel formation and maturation were studied within and around implanted micro-structured type-I collagen scaffolds at 10 weeks post implantation in adult rat mid-cervical spinal cord lateral funiculotomy injuries. Morphometric analysis revealed that blood vessel density within the scaffold was similar to that of the lateral white matter tracts that the implant replaced. However, immunohistochemistry for zonula occludens−1 (ZO-1) and endothelial barrier antigen revealed that scaffold microvessels remained largely immature, suggesting poor blood-spinal cord barrier (BSB) reformation. Furthermore, a band of intense ZO-1-immunoreactive fibroblast-like cells isolated the implant. Spinal cord vessels outside the ZO-1-band demonstrated BSB-formation, while vessels within the scaffold generally did not. The formation of a double-layered fibrotic and astroglial scar around the collagen scaffold might explain the relatively poor implant-host integration and suggests a mechanism for failed microvessel maturation. Targeted strategies that improve implant-host integration for such biomaterials will be vital for future tissue engineering and regenerative medicine approaches for traumatic SCI.
在脊髓损伤的实验模型中,密集的纤维粘连性瘢痕和较差的血管成熟阻碍了植入的胶原支架的整合
严重脊髓损伤(SCI)会导致永久性功能缺陷,尽管在临床前取得了进展,但仍然无法治疗。组合方法,包括植入生物工程支架,可能会促进显著的组织修复。然而,这在很大程度上取决于宿主组织与植入物结合的程度。本文研究了成年大鼠颈中脊髓侧索切开术后10周植入的微结构I型胶原支架内及其周围血管的形成和成熟。形态计量学分析显示,支架内的血管密度与植入物替代的侧白质束的血管密度相似。然而,闭塞小带−1(ZO-1)和内皮屏障抗原的免疫组织化学显示,支架微血管大部分仍不成熟,表明血脊髓屏障(BSB)重建较差。此外,一条强烈的ZO-1免疫反应性成纤维细胞样细胞带分离出植入物。ZO-1带外的脊髓血管显示出BSB形成,而支架内的血管通常没有。胶原支架周围双层纤维和星形胶质瘢痕的形成可能解释了相对较差的植入物-宿主整合,并提示了微血管成熟失败的机制。改善这种生物材料的植入-宿主整合的有针对性的策略对未来创伤SCI的组织工程和再生医学方法至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biomedical materials
Biomedical materials 工程技术-材料科学:生物材料
CiteScore
6.70
自引率
7.50%
发文量
294
审稿时长
3 months
期刊介绍: The goal of the journal is to publish original research findings and critical reviews that contribute to our knowledge about the composition, properties, and performance of materials for all applications relevant to human healthcare. Typical areas of interest include (but are not limited to): -Synthesis/characterization of biomedical materials- Nature-inspired synthesis/biomineralization of biomedical materials- In vitro/in vivo performance of biomedical materials- Biofabrication technologies/applications: 3D bioprinting, bioink development, bioassembly & biopatterning- Microfluidic systems (including disease models): fabrication, testing & translational applications- Tissue engineering/regenerative medicine- Interaction of molecules/cells with materials- Effects of biomaterials on stem cell behaviour- Growth factors/genes/cells incorporated into biomedical materials- Biophysical cues/biocompatibility pathways in biomedical materials performance- Clinical applications of biomedical materials for cell therapies in disease (cancer etc)- Nanomedicine, nanotoxicology and nanopathology- Pharmacokinetic considerations in drug delivery systems- Risks of contrast media in imaging systems- Biosafety aspects of gene delivery agents- Preclinical and clinical performance of implantable biomedical materials- Translational and regulatory matters
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