Non‐invasive in vivo monitoring of transplanted stem cells in 3D‐bioprinted constructs using near‐infrared fluorescent imaging

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Abstract

Cell‐based tissue engineering strategies have been widely established. However, the contributions of the transplanted cells within the tissue‐engineered scaffolds to the process of tissue regeneration remain poorly understood. Near‐infrared (NIR) fluorescence imaging systems have great potential to non‐invasively monitor the transplanted cell‐based tissue constructs. In this study, labeling mesenchymal stem cells (MSCs) using a lipophilic pentamethine indocyanine (CTNF127, emission at 700 nm) as a NIR fluorophore was optimized, and the CTNF127‐labeled MSCs (NIR‐MSCs) were printed embedding in gelatin methacryloyl bioink. The NIR‐MSCs‐loaded bioink showed excellent printability. In addition, NIR‐MSCs in the 3D constructs showed high cell viability and signal stability for an extended period in vitro. Finally, we were able to non‐invasively monitor the NIR‐MSCs in constructs after implantation in a rat calvarial bone defect model, and the transplanted cells contributed to tissue formation without specific staining. This NIR‐based imaging system for non‐invasive cell monitoring in vivo could play an active role in validating the cell fate in cell‐based tissue engineering applications.

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Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels.

Kan Yue, Grissel Trujillo-de Santiago, Mario Moisés Alvarez … (2015)

Gelatin methacryloyl (GelMA) hydrogels have been widely used for various biomedical applications due to their suitable biological properties and tunable physical characteristics. GelMA hydrogels closely resemble some essential properties of native extracellular matrix (ECM) due to the presence of cell-attaching and matrix metalloproteinase responsive peptide motifs, which allow cells to proliferate and spread in GelMA-based scaffolds. GelMA is also versatile from a processing perspective. It crosslinks when exposed to light irradiation to form hydrogels with tunable mechanical properties. It can also be microfabricated using different methodologies including micromolding, photomasking, bioprinting, self-assembly, and microfluidic techniques to generate constructs with controlled architectures. Hybrid hydrogel systems can also be formed by mixing GelMA with nanoparticles such as carbon nanotubes and graphene oxide, and other polymers to form networks with desired combined properties and characteristics for specific biological applications. Recent research has demonstrated the proficiency of GelMA-based hydrogels in a wide range of tissue engineering applications including engineering of bone, cartilage, cardiac, and vascular tissues, among others. Other applications of GelMA hydrogels, besides tissue engineering, include fundamental cell research, cell signaling, drug and gene delivery, and bio-sensing.

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Gelatin-Methacryloyl Hydrogels: Towards Biofabrication-Based Tissue Repair.

Barbara J Klotz, Debby Gawlitta, Antoine J.W.P. Rosenberg … (2016)

Research over the past decade on the cell-biomaterial interface has shifted to the third dimension. Besides mimicking the native extracellular environment by 3D cell culture, hydrogels offer the possibility to generate well-defined 3D biofabricated tissue analogs. In this context, gelatin-methacryloyl (gelMA) hydrogels have recently gained increased attention. This interest is sparked by the combination of the inherent bioactivity of gelatin and the physicochemical tailorability of photo-crosslinkable hydrogels. GelMA is a versatile matrix that can be used to engineer tissue analogs ranging from vasculature to cartilage and bone. Convergence of biological and biofabrication approaches is necessary to progress from merely proving cell functionality or construct shape fidelity towards regenerating tissues. GelMA has a critical pioneering role in this process and could be used to accelerate the development of clinically relevant applications.

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Precisely printable and biocompatible silk fibroin bioink for digital light processing 3D printing

Soon Kim, Yeung Yeon, Jung Lee … (2018)

Although three-dimensional (3D) bioprinting technology has gained much attention in the field of tissue engineering, there are still several significant engineering challenges to overcome, including lack of bioink with biocompatibility and printability. Here, we show a bioink created from silk fibroin (SF) for digital light processing (DLP) 3D bioprinting in tissue engineering applications. The SF-based bioink (Sil-MA) was produced by a methacrylation process using glycidyl methacrylate (GMA) during the fabrication of SF solution. The mechanical and rheological properties of Sil-MA hydrogel proved to be outstanding in experimental testing and can be modulated by varying the Sil-MA contents. This Sil-MA bioink allowed us to build highly complex organ structures, including the heart, vessel, brain, trachea and ear with excellent structural stability and reliable biocompatibility. Sil-MA bioink is well-suited for use in DLP printing process and could be applied to tissue and organ engineering depending on the specific biological requirements.

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Author and article information

Contributors

Chan Hum Park:

ORCID: https://orcid.org/0000-0002-9732-361X

hlpch@hallym.ac.kr

Sang Jin Lee:

ORCID: https://orcid.org/0000-0002-3899-1909

sjlee@wakehealth.edu

Journal

Journal ID (nlm-ta): Bioeng Transl Med

Journal ID (iso-abbrev): Bioeng Transl Med

Journal ID (doi): 10.1002/(ISSN)2380-6761

Journal ID (publisher-id): BTM2

Title: Bioengineering & Translational Medicine

Publisher: John Wiley & Sons, Inc. (Hoboken, USA )

ISSN (Electronic): 2380-6761

Publication date (Electronic): 26 March 2021

Publication date Collection: May 2021

Volume: 6

Issue: 2 ( doiID: 10.1002/btm2.v6.2 )

Electronic Location Identifier: e10216

Affiliations

[ ¹ ] Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard Winston‐Salem North Carolina USA

[ ² ] Nano‐Bio Regenerative Medical Institute, College of Medicine, Hallym University Chuncheon Republic of Korea

[ ³ ] Department of Molecular Science and Technology Ajou University Suwon Republic of Korea

[ ⁴ ] Department of Otolaryngology‐Head and Neck Surgery Korea University College of Medicine Seoul Republic of Korea

[ ⁵ ] Gordon Center for Medical Imaging, Department of Radiology Massachusetts General Hospital and Harvard Medical School Boston Massachusetts USA

[ ⁶ ] Department of Otorhinolaryngology‐Head and Neck Surgery Chuncheon Sacred Heart Hospital, School of Medicine, Hallym University Chuncheon Republic of Korea

Author notes

[*] [* ] Correspondence

Chan Hum Park, Department of Otorhinolaryngology‐Head and Neck Surgery, Chuncheon Sacred Heart Hospital, School of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.

Email: hlpch@ 123456hallym.ac.kr

Sang Jin Lee, Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston‐Salem, NC 27157, USA.

Email: sjlee@ 123456wakehealth.edu

Author information

Soon Hee Kim https://orcid.org/0000-0002-7587-9414

Hak Soo Choi https://orcid.org/0000-0002-7982-6483

Chan Hum Park https://orcid.org/0000-0002-9732-361X

Sang Jin Lee https://orcid.org/0000-0002-3899-1909

Article

Publisher ID: BTM210216

DOI: 10.1002/btm2.10216

PMC ID: 8126817

PubMed ID: 34027098

SO-VID: 62eac9ff-03bb-46e9-8f30-cf81e2010461

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

History

Date revision received : 28 February 2021

Date received : 10 September 2020

Date accepted : 01 March 2021

Page count

Figures: 6, Tables: 2, Pages: 13, Words: 8880

Funding

Funded by: Hallym University , open-funder-registry 10.13039/501100002632;

Award ID: Hallym University Research Fund

Funded by: Ministry of Science, ICT and Future Planning , open-funder-registry 10.13039/501100003621;

Award ID: NRF‐2020R1A2C3010040

Funded by: National Institutes of Health , open-funder-registry 10.13039/100000002;

Award ID: P41EB023833

Award ID: R01EB022230

Award ID: R01HL143020

Custom metadata

source-schema-version-number 2.0

cover-date May 2021

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:17.05.2021

Keywords: near‐infrared fluorescence,non‐invasive monitoring,scaffold monitoring,stem cell tracking

Data availability:

Keywords: near‐infrared fluorescence, non‐invasive monitoring, scaffold monitoring, stem cell tracking

Non‐invasive in vivo monitoring of transplanted stem cells in 3D‐bioprinted constructs using near‐infrared fluorescent imaging

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Most cited references 70

Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels.

Gelatin-Methacryloyl Hydrogels: Towards Biofabrication-Based Tissue Repair.

Precisely printable and biocompatible silk fibroin bioink for digital light processing 3D printing

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