研究动态
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一种具有光活化药物传递的3D生物打印纳米工程水凝胶,通过巨噬细胞免疫调节诱导肿瘤凋亡和同时骨再生。

A 3D Bioprinted Nanoengineered Hydrogel with Photo-activated Drug Delivery for Tumor Apoptosis and Simultaneous Bone Regeneration via Macrophage Immunomodulation.

发表日期:2023 Apr 23
作者: Sayan Deb Dutta, Keya Ganguly, Jin Hexiu, Aayushi Randhawa, Md Moniruzzaman, Ki-Taek Lim
来源: Cellular & Molecular Immunology

摘要:

骨组织工程(BTE)中一个重要的挑战是愈合创伤组织缺陷,这需要更长的恢复时间,因为会引起局部感染和迟缓的血管生成。各种策略,如水凝胶敷料、生长因子输送和干细胞疗法已经显示出潜在的创伤组织修复替代方案;然而,由于社会经济负担的限制,它们的实际临床应用受到限制。在这里,我们报道了一种3D打印多功能水凝胶支架,由聚酚碳量子点(CQDs,100 ug mL-1)和明胶甲基丙烯酰胺(GelMA,12 wt.%)组成,用于骨再生和抗肿瘤治疗。CQDs是通过简便的湿化学方法从植物的生物活性分子1,3,5-三羟基苯(多酚)合成的。3D打印的GelMA-CQDs水凝胶表现出典型的剪切变薄行为,具有良好的可打印性。我们的结果表明,纳米复合3D水凝胶通过上调抗炎基因(例如IL-4和IL10)促进巨噬细胞(Raw 264.7)细胞的M2极化,并诱导人类骨间充质干细胞(hBMSCs)的血管生成和骨生成。在GelMA-CQDs水凝胶存在下,生物打印的hBMSCs能够在培养14天后产生血管状结构。此外,3D打印支架还在808 nm NIR光(1.0 W cm-2)照射下表现出显着的近红外(NIR)响应特性,并在pH 6.5下显示出抗肿瘤药物的受控释放(约49%),从而杀死骨肉瘤细胞。因此,我们期望3D打印的GelMA-CQDs支架具有组织再生和治疗潜力的修复能力,通过增强血管生成和加速免疫调节成为创伤组织再生的有希望的替代方案。本文受版权保护。版权所有。
One of the significant challenges in bone tissue engineering (BTE) is the healing of traumatic tissue defects which requires longer time to recover owing to the recruitment of local infection and delayed angiogenesis. Various strategies, such as hydrogel dressings, growth factors delivery, and stem cell therapy has been shown potential alternative to the traumatic tissue repair; however, limited their actual clinical application due to the socio-economic burden. Herein, we reported a 3D printable multi-functional hydrogel scaffold composing polyphenolic carbon quantum dots (CQDs, 100 ug mL-1 ) and gelatin methacryloyl (GelMA, 12 wt.%) for bone regeneration and anti-tumor therapy. The CQDs was synthesized from a plant-inspired bioactive molecule, 1, 3, 5-trihydroxybenzene (a polyphenol) via facile wet chemistry method. The 3D printed GelMA-CQDs hydrogels displayed typical shear-thinning behavior with excellent printability. Our results demonstrated that the nanocomposite 3D hydrogel promoted M2 polarization of macrophage (Raw 264.7) cells via upregulation of anti-inflammatory genes (e.g., IL-4 and IL10), and induced angiogenesis and osteogenesis of human bone mesenchymal stem cells (hBMSCs). The bioprinted hBMSCs were able to produced vessel-like structures in the presence of GelMA-CQDs hydrogel after 14 days of incubation. Furthermore, the 3D printed scaffolds also showed remarkable near infra-red (NIR) responsive properties under 808 nm NIR light (1.0 W cm-2 ) irradiation and showed controlled release of antitumor drugs (∼49%) at pH 6.5, and thereby killing the osteosarcoma cells. Therefore, we anticipate that the tissue regeneration and healing ability with therapeutic potential of the 3D printed GelMA-CQDs scaffolds may provide a promising alternative for traumatic tissue regeneration via augmenting angiogenesis and accelerated immunomodulation. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.