NK cells encapsulated in micro/macropore-forming hydrogels via 3D bioprinting for tumor immunotherapy.

IF 11.3 1区 医学 Q1 Medicine
Dahong Kim, Seona Jo, Dongjin Lee, Seok-Min Kim, Ji Min Seok, Seon Ju Yeo, Jun Hee Lee, Jae Jong Lee, Kangwon Lee, Tae-Don Kim, Su A Park
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引用次数: 1

Abstract

Background: Patients face a serious threat if a solid tumor leaves behind partial residuals or cannot be completely removed after surgical resection. Immunotherapy has attracted attention as a method to prevent this condition. However, the conventional immunotherapy method targeting solid tumors, that is, intravenous injection, has limitations in homing in on the tumor and in vivo expansion and has not shown effective clinical results.

Method: To overcome these limitations, NK cells (Natural killer cells) were encapsulated in micro/macropore-forming hydrogels using 3D bioprinting to target solid tumors. Sodium alginate and gelatin were used to prepare micro-macroporous hydrogels. The gelatin contained in the alginate hydrogel was removed because of the thermal sensitivity of the gelatin, which can generate interconnected micropores where the gelatin was released. Therefore, macropores can be formed through bioprinting and micropores can be formed using thermally sensitive gelatin to make macroporous hydrogels.

Results: It was confirmed that intentionally formed micropores could help NK cells to aggregate easily, which enhances cell viability, lysis activity, and cytokine release. Macropores can be formed using 3D bioprinting, which enables NK cells to receive the essential elements. We also characterized the functionality of NK 92 and zEGFR-CAR-NK cells in the pore-forming hydrogel. The antitumor effects on leukemia and solid tumors were investigated using an in vitro model.

Conclusion: We demonstrated that the hydrogel encapsulating NK cells created an appropriate micro-macro environment for clinical applications of NK cell therapy for both leukemia and solid tumors via 3D bioprinting. 3D bioprinting makes macro-scale clinical applications possible, and the automatic process shows potential for development as an off-the-shelf immunotherapy product. This immunotherapy system could provide a clinical option for preventing tumor relapse and metastasis after tumor resection. Micro/macropore-forming hydrogel with NK cells fabricated by 3D bioprinting and implanted into the tumor site.

Abstract Image

Abstract Image

Abstract Image

通过3D生物打印将NK细胞包封在微/大孔形成的水凝胶中用于肿瘤免疫治疗。
背景:如果实体瘤在手术切除后留下部分残余或不能完全切除,患者将面临严重的威胁。免疫疗法作为一种预防这种疾病的方法引起了人们的注意。然而,传统的针对实体瘤的免疫治疗方法,即静脉注射,在肿瘤的归巢和体内扩张方面存在局限性,尚未显示出有效的临床效果。方法:为了克服这些局限性,将NK细胞(自然杀伤细胞)包裹在微/大孔形成的水凝胶中,使用3D生物打印技术靶向实体肿瘤。采用海藻酸钠和明胶制备微大孔水凝胶。海藻酸盐水凝胶中含有的明胶被去除,因为明胶的热敏性,它可以产生相互连接的微孔,在那里明胶被释放。因此,可以通过生物打印形成大孔,利用热敏明胶形成微孔,制成大孔水凝胶。结果:证实有意形成的微孔有利于NK细胞聚集,提高细胞活力、裂解活性和细胞因子释放。使用3D生物打印技术可以形成大孔,使NK细胞能够接受必需的元素。我们还表征了NK 92和zEGFR-CAR-NK细胞在成孔水凝胶中的功能。采用体外模型研究其对白血病和实体瘤的抗肿瘤作用。结论:通过生物3D打印技术,我们证明了包裹NK细胞的水凝胶为NK细胞治疗白血病和实体瘤的临床应用创造了合适的微观宏观环境。3D生物打印使宏观临床应用成为可能,自动过程显示出作为现成的免疫治疗产品的发展潜力。该免疫治疗系统可为预防肿瘤切除术后复发和转移提供临床选择。利用生物3D打印技术制备含有NK细胞的微/大孔形成水凝胶并植入肿瘤部位。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biomaterials Research
Biomaterials Research Medicine-Medicine (miscellaneous)
CiteScore
10.20
自引率
3.50%
发文量
63
审稿时长
30 days
期刊介绍: Biomaterials Research, the official journal of the Korean Society for Biomaterials, is an open-access interdisciplinary publication that focuses on all aspects of biomaterials research. The journal covers a wide range of topics including novel biomaterials, advanced techniques for biomaterial synthesis and fabrication, and their application in biomedical fields. Specific areas of interest include functional biomaterials, drug and gene delivery systems, tissue engineering, nanomedicine, nano/micro-biotechnology, bio-imaging, regenerative medicine, medical devices, 3D printing, and stem cell research. By exploring these research areas, Biomaterials Research aims to provide valuable insights and promote advancements in the biomaterials field.
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