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用于3D打印具有多尺度孔隙率支架的纳米脂质体功能化胶体GelMA墨水

Nanoliposome functionalized colloidal GelMA inks for 3D printing of scaffolds with multiscale porosity.

作者信息

Omidvari Elaheh, Samandari Mohamadmahdi, Ghanbariamin Delaram, Lara Evelyn Mollocana, Quint Jacob, Saeedinejad Farnoosh, Bouizi Younes, Bouguet-Bonnet Sabine, Elkhoury Kamil, Sanchez-Gonzalez Laura, Chen Yupeng, Kahn Cyril, Tamayol Ali, Arab-Tehrany Elmira

机构信息

Université de Lorraine LIBio, F-54000 Nancy, France.

Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT 06030, United States of America.

出版信息

Biofabrication. 2024 Dec 27;17(1). doi: 10.1088/1758-5090/ad9a01.

DOI:10.1088/1758-5090/ad9a01
PMID:39626352
Abstract

Bioprinting has enabled the creation of intricate scaffolds that replicate the physical, chemical, and structural characteristics of natural tissues. Recently, hydrogels have been used to fabricate such scaffolds for several biomedical applications and tissue engineering. However, the small pore size of conventional hydrogels impedes cellular migration into and remodeling of scaffolds, diminishing their regenerative potential. Porous scaffolds have been utilized for their improved diffusion of nutrients, dissolved oxygen, and waste products. However, traditional methods of generating porous structures require multiple processing steps, making them incompatible with bioprinting. Recently, we developed a method to generate multi-scale porous structures by foaming hydrogel precursors prior to printing to form colloidal bioinks. Here, to further improve the biological, mechanical, and physical properties, we functionalize colloidal bioinks with nanoliposomes (NLs), one of the most promising methods for bioactive delivery. We assess the impact of the concentration of NL on the characteristics of bioinks made from gelatin methacryloyl (GelMA) and their resulting scaffolds. Anionic liposomes made from rapeseed lecithin of 110 nm were synthesized and found to be stable over several weeks. Increasing concentrations of NL decreased the zeta potential and increased the viscosity of foamed bioinks, improving their rheological properties for printing. Furthermore, the incorporation of NL allowed for precise adjustment of the macropore size and bulk mechanical properties without any chemical interaction or impact on photocrosslinking. The nanofunctionalized foam bioinks, composed exclusively of natural components, demonstrated significant antioxidant activity and were printed into multilayered scaffolds with high printability. The foam-embedded NL showed remarkable biocompatibility with myoblasts, and cell-laden bioinks were able to be successfully bioprinted. Due to their high biocompatibility, tunable mechanical properties, printability, and antioxidant behavior, the nanofunctionalized porous scaffolds have promise for a variety of biomedical applications, including those that require precise delivery of therapeutic substances and tissue engineering.

摘要

生物打印技术已能够制造出复杂的支架,这些支架可复制天然组织的物理、化学和结构特征。最近,水凝胶已被用于制造此类支架,用于多种生物医学应用和组织工程。然而,传统水凝胶的小孔径阻碍了细胞向支架内迁移以及对支架的重塑,从而降低了它们的再生潜力。多孔支架因其在营养物质、溶解氧和代谢废物扩散方面的改善而被采用。然而,传统的生成多孔结构的方法需要多个加工步骤,这使得它们与生物打印不兼容。最近,我们开发了一种方法,通过在打印前使水凝胶前体发泡来生成多尺度多孔结构,以形成胶体生物墨水。在此,为了进一步改善生物学、力学和物理性能,我们用纳米脂质体(NLs)对胶体生物墨水进行功能化,这是生物活性递送最有前景的方法之一。我们评估了NL浓度对由甲基丙烯酰化明胶(GelMA)制成的生物墨水及其所得支架特性的影响。合成了由110纳米油菜籽卵磷脂制成的阴离子脂质体,并发现其在数周内稳定。NL浓度的增加降低了zeta电位并增加了发泡生物墨水的粘度,改善了它们用于打印的流变性能。此外,NL的加入允许精确调节大孔尺寸和整体力学性能,而无需任何化学相互作用或对光交联产生影响。完全由天然成分组成的纳米功能化泡沫生物墨水表现出显著的抗氧化活性,并被打印成具有高可打印性的多层支架。嵌入泡沫的NL对成肌细胞表现出显著的生物相容性,并且负载细胞的生物墨水能够成功地进行生物打印。由于其高生物相容性、可调的力学性能、可打印性和抗氧化行为,纳米功能化多孔支架在包括那些需要精确递送治疗物质的生物医学应用和组织工程方面具有前景。

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