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超小型神经植入构建体显示出最小的免疫反应。

Ultraminiaturized neural implanted constructs display minimal immunologic response.

作者信息

Spyrou Argyris, Sandell Mikael, Grankvist Rikard, Iordanidis Theocharis Nikiforos, Stemme Göran, Holmin Staffan, Roxhed Niclas

机构信息

Department of Micro and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden.

MedTechLabs, Karolinska University Hospital, Bioclinicum, Stockholm, Sweden.

出版信息

Mater Today Bio. 2025 Apr 29;32:101819. doi: 10.1016/j.mtbio.2025.101819. eCollection 2025 Jun.


DOI:10.1016/j.mtbio.2025.101819
PMID:40391020
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12088817/
Abstract

Biocompatibility of medical implants poses a significant challenge in medical technology. Neural implants, integral to curative therapies, initially exhibit efficacy but can lead to unforeseen long-term side effects. The material composition and dimensions of implants are critical factors influencing their biocompatibility within brain tissue. Typically, neural implants are identified as foreign entities by the patient's immune system, triggering persistent inflammation and severe adverse effects. In this study, we investigate the host response in mouse brain tissue of implanted microscale constructs measuring 0.1 × 0.1 × 1 mm fabricated from common microfabrication materials. Magnetic Resonance Imaging (MRI) analysis reveals rapid recovery of brain parenchyma at 6 week interval post-implantation, accompanied by negligible or mild adverse immune responses during the experimental period. Histological assessments and cell marker stainings targeting astroglia, macrophages, and microglia demonstrate minimal impacts of the microconstructs on mouse brain tissue throughout the 24-week implantation period. Our findings indicate that untethered microimplants of this scale may have potential applications in medical technology and medical treatment for various brain diseases. In summary, this study supports the development of potentially biocompatible brain microimplants that could be useful for the long-term management of chronic brain disorders.

摘要

医用植入物的生物相容性是医学技术领域面临的一项重大挑战。神经植入物是治疗性疗法不可或缺的一部分,最初能展现出疗效,但可能会导致不可预见的长期副作用。植入物的材料成分和尺寸是影响其在脑组织中生物相容性的关键因素。通常情况下,神经植入物会被患者的免疫系统识别为外来物质,从而引发持续的炎症和严重的不良反应。在本研究中,我们对由常见微加工材料制成的尺寸为0.1×0.1×1毫米的微型植入物在小鼠脑组织中的宿主反应进行了研究。磁共振成像(MRI)分析显示,植入后每隔6周脑实质就能快速恢复,且在实验期间伴随的不良免疫反应可忽略不计或较为轻微。针对星形胶质细胞、巨噬细胞和小胶质细胞的组织学评估和细胞标志物染色显示,在整个24周的植入期内,微型植入物对小鼠脑组织的影响极小。我们的研究结果表明,这种尺寸的无束缚微型植入物可能在医学技术以及各种脑部疾病的治疗中具有潜在应用价值。总之,本研究支持开发具有潜在生物相容性的脑微型植入物,这可能对慢性脑部疾病的长期管理有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3808/12088817/b9f8dfa45750/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3808/12088817/f786ae72d14c/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3808/12088817/687511fcaba6/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3808/12088817/5aa09ad5d4bf/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3808/12088817/cb86557bf5ea/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3808/12088817/9a7ea85ecb20/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3808/12088817/4274ff510092/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3808/12088817/f73793a5f786/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3808/12088817/b9f8dfa45750/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3808/12088817/f786ae72d14c/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3808/12088817/687511fcaba6/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3808/12088817/5aa09ad5d4bf/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3808/12088817/cb86557bf5ea/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3808/12088817/9a7ea85ecb20/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3808/12088817/4274ff510092/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3808/12088817/f73793a5f786/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3808/12088817/b9f8dfa45750/gr7.jpg

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本文引用的文献

[1]
Rise of implantable drugs: A chronicle of breakthroughs in drug delivery systems.

Saudi Pharm J. 2024-12

[2]
Enhancing biocompatibility of the brain-machine interface: A review.

Bioact Mater. 2024-9-11

[3]
Engineering of Bioresorbable Polymers for Tissue Engineering and Drug Delivery Applications.

Adv Healthc Mater. 2024-12

[4]
Ultrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas.

Nat Commun. 2024-6-6

[5]
Implantable magnetically-actuated capsule for on-demand delivery.

J Control Release. 2023-12

[6]
Solid implantable devices for sustained drug delivery.

Adv Drug Deliv Rev. 2023-8

[7]
Commonly Overlooked Factors in Biocompatibility Studies of Neural Implants.

Adv Sci (Weinh). 2023-2

[8]
Obstacles to Glioblastoma Treatment Two Decades after Temozolomide.

Cancers (Basel). 2022-6-30

[9]
Medical Applications of Porous Biomaterials: Features of Porosity and Tissue-Specific Implications for Biocompatibility.

Adv Healthc Mater. 2022-5

[10]
Real-time monitoring of drug pharmacokinetics within tumor tissue in live animals.

Sci Adv. 2022-1-7

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