非脉冲红光无痕光聚合实现3D可打印载细胞水凝胶。

Traceless Photopolymerization with Non-Pulsed Red Light Enables 3D-Printable Cell-Laden Hydrogels.

作者信息

Eftekhari Ali, de Graaf Kelsey Rianne, Takmakova Ekaterina, Jongprasitkul Hatai, Efimov Alexander, Turunen Sanna, Kerr Andrew, Kellomäki Minna, Luxenhofer Robert, Laaksonen Timo, Durandin Nikita

机构信息

Faculty of Engineering and Natural Sciences, Tampere University, Tampere, 33720, Finland.

Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, 00014, Finland.

出版信息

Adv Mater. 2025 Jul;37(30):e2502386. doi: 10.1002/adma.202502386. Epub 2025 May 16.

Abstract

Photocrosslinking of hydrogels with non-pulsed red light offers improved biocompatibility and deep tissue penetration in contrast to traditional UV-initiated methods. However, hydrogels fabricated upon red-light excitation are always colored by a photoinitiator, limiting their use in applications requiring high optical transparency, such as (bio)sensors, ophthalmological applications, or wound dressings. Additionally, the cytotoxicity of a photoinitiator is always a concern, especially in bioapplications. Herein, a photoinitiating system composed of an FDA-approved methylene blue photosensitizer and cytocompatible triethanolamine is introduced. The system can induce photopolymerization upon 625 nm irradiation and leaves no visible trace of the methylene blue color afterward, thus named "traceless". With this approach, gelatine methacrylate hydrogel is successfully polymerized under ambient conditions. The hydrogel is permanently colorless with well-controlled stiffness due to the light-dependent nature of the polymerization process. The system is further successfully applied in extrusion-based 3D-bioprinting with NIH-3T3 fibroblasts, followed by photocuring to produce cell-laden 3D structures, indicating its potential for tissue engineering. Upon culturing the cell-laden constructs, the fibroblasts are able to proliferate and adhere to the hydrogel material. The red-light excitation enables polymerization through at least 5 mm of biological tissue, projecting, inter alia, its use for transdermal photopolymerization in minimally invasive implantation.

摘要

与传统的紫外线引发方法相比,用非脉冲红光对水凝胶进行光交联可提高生物相容性并实现更深的组织穿透。然而,在红光激发下制备的水凝胶总是会被光引发剂染色,这限制了它们在需要高光学透明度的应用中的使用,例如(生物)传感器、眼科应用或伤口敷料。此外,光引发剂的细胞毒性始终是一个问题,尤其是在生物应用中。在此,引入了一种由美国食品药品监督管理局(FDA)批准的亚甲蓝光敏剂和细胞相容性三乙醇胺组成的光引发体系。该体系在625nm照射下可引发光聚合反应,之后不会留下亚甲蓝颜色的可见痕迹,因此被称为“无痕”。通过这种方法,甲基丙烯酸明胶水凝胶在环境条件下成功聚合。由于聚合过程的光依赖性,该水凝胶永久无色且刚度可控。该体系进一步成功应用于基于挤出的3D生物打印,与NIH-3T3成纤维细胞一起,随后进行光固化以产生载有细胞的3D结构,表明其在组织工程中的潜力。在培养载有细胞的构建体时,成纤维细胞能够增殖并附着在水凝胶材料上。红光激发能够通过至少5毫米的生物组织进行聚合反应,尤其突出了其在微创植入中的经皮光聚合应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d32/12306389/05d528a1b904/ADMA-37-2502386-g004.jpg

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