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通过纤维微支架载体进行骨髓间充质干细胞的微创椎间盘内递送

Minimally Invasive Intradiscal Delivery of BM-MSCs via Fibrous Microscaffold Carriers.

作者信息

Nakielski Paweł, Rybak Daniel, Jezierska-Woźniak Katarzyna, Rinoldi Chiara, Sinderewicz Emilia, Staszkiewicz-Chodor Joanna, Haghighat Bayan Mohammad Ali, Czelejewska Wioleta, Urbanek Olga, Kosik-Kozioł Alicja, Barczewska Monika, Skomorowski Mateusz, Holak Piotr, Lipiński Seweryn, Maksymowicz Wojciech, Pierini Filippo

机构信息

Department of Biosystems and Soft Matter, Institute of Fundamental Technological Research, Polish Academy of Sciences, Pawińskiego 5B, Warsaw 02-106, Poland.

Laboratory for Regenerative Medicine, Department of Neurosurgery, School of Medicine, University of Warmia and Mazury, Warszawska 30, Olsztyn 10-082, Poland.

出版信息

ACS Appl Mater Interfaces. 2023 Dec 20;15(50):58103-58118. doi: 10.1021/acsami.3c11710. Epub 2023 Nov 29.

Abstract

Current treatments of degenerated intervertebral discs often provide only temporary relief or address specific causes, necessitating the exploration of alternative therapies. Cell-based regenerative approaches showed promise in many clinical trials, but limitations such as cell death during injection and a harsh disk environment hinder their effectiveness. Injectable microscaffolds offer a solution by providing a supportive microenvironment for cell delivery and enhancing bioactivity. This study evaluated the safety and feasibility of electrospun nanofibrous microscaffolds modified with chitosan (CH) and chondroitin sulfate (CS) for treating degenerated NP tissue in a large animal model. The microscaffolds facilitated cell attachment and acted as an effective delivery system, preventing cell leakage under a high disc pressure. Combining microscaffolds with bone marrow-derived mesenchymal stromal cells demonstrated no cytotoxic effects and proliferation over the entire microscaffolds. The administration of cells attached to microscaffolds into the NP positively influenced the regeneration process of the intervertebral disc. Injectable poly(l-lactide--glycolide) and poly(l-lactide) microscaffolds enriched with CH or CS, having a fibrous structure, showed the potential to promote intervertebral disc regeneration. These features collectively address critical challenges in the fields of tissue engineering and regenerative medicine, particularly in the context of intervertebral disc degeneration.

摘要

目前针对退变椎间盘的治疗方法往往只能提供暂时缓解或针对特定病因,因此有必要探索其他替代疗法。基于细胞的再生方法在许多临床试验中显示出前景,但诸如注射过程中的细胞死亡以及恶劣的椎间盘环境等限制因素阻碍了其有效性。可注射微支架通过为细胞递送提供支持性微环境并增强生物活性提供了一种解决方案。本研究评估了用壳聚糖(CH)和硫酸软骨素(CS)修饰的电纺纳米纤维微支架在大型动物模型中治疗退变髓核组织的安全性和可行性。微支架促进细胞附着并作为一种有效的递送系统,在高椎间盘压力下防止细胞泄漏。将微支架与骨髓来源的间充质基质细胞相结合未显示出细胞毒性作用,且细胞在整个微支架上增殖。将附着于微支架的细胞注入髓核可积极影响椎间盘的再生过程。富含CH或CS、具有纤维结构的可注射聚(L-丙交酯-乙交酯)和聚(L-丙交酯)微支架显示出促进椎间盘再生的潜力。这些特性共同解决了组织工程和再生医学领域的关键挑战,尤其是在椎间盘退变的背景下。

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