An Innovative Delivery System of Oxygen-Releasing Nanospheres and Self-Healing Hydrogels Enhances the Therapeutic Effectiveness of Bone Marrow Mesenchymal Stem Cells for Chronic Limb-Threatening Ischemia.

IF 6.6 2区医学 Q1 NANOSCIENCE & NANOTECHNOLOGY International Journal of Nanomedicine Pub Date : 2024-11-19 eCollection Date: 2024-01-01 DOI:10.2147/IJN.S483541

Moyan Zhao, Zixuan Zhou, Amir Sherchan, Weizhong Yuan, Xiaoyun Xie, Maoquan Li

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Abstract

Purpose: Bone marrow mesenchymal stem cells (BMSCs) have emerged as promising candidate for postoperative therapeutics in chronic limb-threatening ischemia (CLTI). Nevertheless, their effectiveness is limited by their low survival rate and impaired functionality in the ischemic microenvironment. To overcome these challenges, we have devised an innovative delivery approach to support the utilization of BMSCs in CLTI therapy.

Methods: We synthesized oxygen-releasing nanospheres and self-healing hydrogels. The in vivo functionality of the hydrogel-nanosphere delivery system was evaluated via a multimodality animal live imaging system. A unilateral lower limb ischemia model was established in mice, and a delivery system loaded with BMSCs was administered. The experimental groups included normal mice, ischemic mice, ischemic mice treated with BMSCs in PBS, and ischemic mice treated with BMSCs in the delivery system. Blood perfusion was quantitatively measured via a laser doppler flowmeter (LDF). Immunofluorescence, Masson's trichrome staining, immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were also used.

Results: For cell viability analysis 80 μg.mL^-1 was considered the optimal concentration for cell survival. In vivo, 18 days after injection, the cell membrane fluorescence signal in the delivery system was significantly greater (5.655¹⁰±8.226⁸) p/s/cm²/sr than that in the other groups (p=0.043). Ischemic mice treated with BMSCs in the delivery system presented an improved limb salvage rate (0.926±0.12)% compared with that of ischemic mice treated with BMSCs in PBS (0.841±0.029)% at the 5th week after ischemia establishment (p=0.0033).

Conclusion: Our findings suggest that the survival time of BMSCs is prolonged in this innovative delivery system. The combination of nanospheres and hydrogels effectively restored vascular blood perfusion while exerting minimal toxicity on BMSCs. This novel approach combining oxygen-releasing nanospheres and self-healing hydrogels as a delivery system represents an advancement in enhancing the functionality of BMSCs to treat CLTI.

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释放氧气的纳米球和自愈合水凝胶的创新输送系统增强了骨髓间充质干细胞对慢性肢体缺血的治疗效果。

目的：骨髓间充质干细胞（BMSCs）已成为慢性肢体缺血（CLTI）术后治疗的理想候选细胞。然而，它们在缺血微环境中的低存活率和受损功能限制了它们的有效性。为了克服这些挑战，我们设计了一种创新的输送方法，以支持在 CLTI 治疗中利用 BMSCs：方法：我们合成了释放氧气的纳米球和自愈合水凝胶。方法：我们合成了氧气释放纳米球和自愈合水凝胶，并通过多模态动物活体成像系统对水凝胶-纳米球输送系统的体内功能进行了评估。在小鼠中建立了单侧下肢缺血模型，并施用了装载有 BMSCs 的输送系统。实验组包括正常小鼠、缺血小鼠、经 PBS 中的 BMSCs 处理的缺血小鼠和经输送系统中的 BMSCs 处理的缺血小鼠。通过激光多普勒血流计（LDF）对血液灌注进行定量测量。此外还使用了免疫荧光、马森三色染色、免疫组织化学和酶联免疫吸附试验（ELISA）：在细胞存活率分析中，80 μg.mL-1 被认为是细胞存活的最佳浓度。在体内，注射 18 天后，给药系统的细胞膜荧光信号（5.65510±8.2268）p/s/cm²/sr 明显高于其他组（p=0.043）。缺血小鼠在缺血建立后第5周的肢体救活率（0.926±0.12）%高于用 BMSCs 在 PBS 中处理的缺血小鼠的肢体救活率（0.841±0.029）%（P=0.0033）：结论：我们的研究结果表明，这种创新的输送系统延长了 BMSCs 的存活时间。纳米球和水凝胶的结合有效恢复了血管血液灌注，同时对 BMSCs 的毒性极小。这种将释放氧气的纳米球和自愈合水凝胶结合在一起作为输送系统的新方法，在增强 BMSCs 治疗 CLTI 的功能方面取得了进步。

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来源期刊

International Journal of Nanomedicine NANOSCIENCE & NANOTECHNOLOGY-PHARMACOLOGY & PHARMACY

CiteScore

14.40

自引率

3.80%

发文量

511

审稿时长

1.4 months

期刊介绍： The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area. With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field. Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.