Dataset Information

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

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.

SUBMITTER: Kim D

PROVIDER: S-EPMC10286468 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Kim Dahong D Jo Seona S Lee Dongjin D Kim Seok-Min SM Seok Ji Min JM Yeo Seon Ju SJ Lee Jun Hee JH Lee Jae Jong JJ Lee Kangwon K Kim Tae-Don TD Park Su A SA

Biomaterials research 20230622 1

<h4>Background</h4>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.<h4>Method</h4>To overcome these limitations, NK cells ...[more]

PMID: 37349810

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Project description:In recent years, there has been increased interest in the use of cellular spheroids, microtissues, and organoids as biological building blocks to engineer functional tissues and organs. Such microtissues are typically formed by the self-assembly of cellular aggregates and the subsequent deposition of a tissue-specific extracellular matrix (ECM). Biofabrication and 3D bioprinting strategies using microtissues may require the development of supporting hydrogels and bioinks to spatially localize such biological building blocks in 3D space and hence enable the engineering of geometrically defined tissues. Therefore, the aim of this work was to engineer scaled-up, geometrically defined cartilage grafts by combining multiple cartilage microtissues within a rapidly degrading oxidized alginate (OA) supporting hydrogel and maintaining these constructs in dynamic culture conditions. To this end, cartilage microtissues were first independently matured for either 2 or 4 days and then combined in the presence or absence of a supporting OA hydrogel. Over 6 weeks in static culture, constructs engineered using microtissues that were matured independently for 2 days generated higher amounts of glycosaminoglycans (GAGs) compared to those matured for 4 days. Histological analysis revealed intense staining for GAGs and negative staining for calcium deposits in constructs generated by using the supporting OA hydrogel. Less physical contraction was also observed in constructs generated in the presence of the supporting gel; however, the remnants of individual microtissues were more observable, suggesting that even the presence of a rapidly degrading hydrogel may delay the fusion and/or the remodeling of the individual microtissues. Dynamic culture conditions were found to modulate ECM synthesis following the OA hydrogel encapsulation. We also assessed the feasibility of 3D bioprinting of cartilage microtissues within OA based bioinks. It was observed that the microtissues remained viable after extrusion-based bioprinting and were able to fuse after 48 h, particularly when high microtissue densities were used, ultimately generating a cartilage tissue that was rich in GAGs and negative for calcium deposits. Therefore, this work supports the use of OA as a supporting hydrogel/bioink when using microtissues as biological building blocks in diverse biofabrication and 3D bioprinting platforms.

Dataset Information

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

Background

Method

Results

Conclusion

Publications

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

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