Safety Considerations in 3D Bioprinting Using Mesenchymal Stromal Cells

Belk, Lucy H.; Tellisi, Nazzar; Macdonald, Hamish; Erdem, Ahmet; Ashammakhi, Nureddin; Pountos, Ippokratis

doi:10.3389/fbioe.2020.00924

Cited by 20 publications

(9 citation statements)

References 137 publications

(156 reference statements)

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“…As depicted in Figure , there was no observed difference in live/dead cells in co-cultures or MSC controls after day 35. This result indicated that the printing process does not significantly reduce the viability of the encapsulated cells compared to previously reported processes such as inkjet and laser printers . This is corroborated by Bian et al , where live/dead staining of human cells revealed that all MSCs and co-cultures (4:1) remained viable after 35 days in hyaluronic acid (HA) hydrogels.…”

Section: Discussionsupporting

confidence: 68%

Bioprinting of Chondrocyte Stem Cell Co-Cultures for Auricular Cartilage Regeneration

et al. 2022

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Advances in 3D bioprinting allows not only controlled deposition of cells or cell-laden hydrogels but also flexibility in creating constructs that match the anatomical features of the patient. This is especially the case for reconstructing the pinna (ear), which is a large feature of the face and made from elastic cartilage that primarily relies on diffusion for nutrient transfer. The selection of cell lines for reconstructing this cartilage becomes a crucial step in clinical translation. Chondrocytes and mesenchymal stem cells are both studied extensively in the area of cartilage regeneration as they are capable of producing cartilage in vitro. However, such monoculture systems involve unfavorable processes and produce cartilage with suboptimal characteristics. Co-cultures of these cell types are known to alleviate these limitations to produce synergically active chondrocytes and cartilage. The current study utilized a 3D bioprinted scaffold made from combined gelatine methacryloyl and methacrylated hyaluronic acid (GelMA/HAMA) to interrogate monocultures and co-cultures of human septal chondrocytes (primary chondrocytes, PCs) and human bone marrow-derived mesenchymal stem cells (BM-hMSCs). This study is also the first to examine co-cultures of healthy human chondrocytes with human BM-hMSCs encapsulated in GelMA/HAMA bioprinted scaffolds. Findings revealed that the combination of MSCs and PCs not only yielded cell proliferation that mimicked MSCs but also produced chondrogenic expressions that mimicked PCs. These findings suggested that co-cultures of BM-hMSCs and healthy septal PCs can be employed to replace monocultures in chondrogenic studies for cartilage regeneration in this model. The opportunity for MSCs used to replace PCs alleviates the requirement of large cartilage biopsies that would otherwise be needed for sufficient cell numbers and therefore can be employed for clinical applications.

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Section: Discussionsupporting

confidence: 68%

Bioprinting of Chondrocyte Stem Cell Co-Cultures for Auricular Cartilage Regeneration

et al. 2022

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“…Afterward, we evaluated the cell performance through indirect and direct contact cytotoxicity assays of bioink-based hydrogels. For this second set of assays, human bone-marrow-derived mesenchymal stromal cells (BM-MSCs) were chosen because of the increasing interest in this type of cells as biological building blocks for 3D bioprinting applications. , In the case of indirect assay, cytotoxicity and cell proliferation evaluation was performed in the presence of bioink-based hydrogel extracts (Figure c,d), showing no sign of cytotoxicity or detriment in proliferation. BM-MSCs were cultured using extracts isolated from the preincubation of bioink-based hydrogels in culture media.…”

Section: Resultsmentioning

confidence: 99%

A Psychrophilic GelMA: Breaking Technical and Immunological Barriers for Multimaterial High-Resolution 3D Bioprinting

et al. 2022

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The increasing demand for tissue replacement has encouraged scientists worldwide to focus on developing new biofabrication technologies. Multimaterials/cells printed with stringent resolutions are necessary to address the high complexity of tissues. Advanced inkjet 3D printing can use multimaterials and attain high resolution and complexity of printed structures. However, a decisive yet limiting aspect of translational 3D bioprinting is selecting the befitting material to be used as bioink; there is a complete lack of cytoactive bioinks with adequate rheological, mechanical, and reactive properties. This work strives to achieve the right balance between resolution and cell support through methacrylamide functionalization of a psychrophilic gelatin and new fluorosurfactants used to engineer a photo-cross-linkable and immunoevasive bioink. The syntonized parameters following optimal formulation conditions allow proficient printability in a PolyJet 3D printer comparable in resolution to a commercial synthetic ink (∼150 μm). The bioink formulation achieved the desired viability (∼80%) and proliferation of co-printed cells while demonstrating in vivo immune tolerance of printed structures. The practical usage of existing high-resolution 3D printing systems using a novel bioink is shown here, allowing 3D bioprinted structures with potentially unprecedented complexity.

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“…The complexity and unpredictability of the 3D organ printing process, including issues such as biomaterial degradation, tissue integration, biocompatibility, and continuous tissue synthesis during material degradation, pose significant challenges. The potential for irreversible risks, such as cancer and dislodgement and migrations of the implant, is a further complication that defies easy resolution [ 12 , 13 , 16 , 18 , 21 , 22 ]. The impossibility of testing the safety of the organ before implantation, due to the organ being custom-made for the person in whom it will be implanted and therefore unable to be tested on others, is a further obstacle.…”

Section: Discussionmentioning

confidence: 99%

Three-Dimensional Bioprinting of Human Organs and Tissues: Bioethical and Medico-Legal Implications Examined through a Scoping Review

Ricci,

Gibelli,

Sirignano

2023

Bioengineering

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Three-dimensional bioprinting is a rapidly evolving technology that holds the promise of addressing the increasing demand for organs, tissues, and personalized medicine. By employing computer-aided design and manufacturing processes, 3D bioprinting allows for the precise deposition of living cells, biomaterials, and biochemicals to create functional human tissues and organs. The potential applications of this technology are vast, including drug testing and development, disease modeling, regenerative medicine, and ultimately, organ transplantation. However, as with any groundbreaking technology, 3D bioprinting presents several ethical, legal, and regulatory concerns that warrant careful consideration. As the technology progresses towards clinical applications, it is essential to address these challenges and establish appropriate frameworks to guide the responsible development of 3D bioprinting. This article, utilizing the Arksey and O’Malley scoping review model, is designed to scrutinize the bioethical implications, legal and regulatory challenges, and medico-legal issues that are intertwined with this rapidly evolving technology.

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Safety Considerations in 3D Bioprinting Using Mesenchymal Stromal Cells

Cited by 20 publications

References 137 publications

Bioprinting of Chondrocyte Stem Cell Co-Cultures for Auricular Cartilage Regeneration

Bioprinting of Chondrocyte Stem Cell Co-Cultures for Auricular Cartilage Regeneration

A Psychrophilic GelMA: Breaking Technical and Immunological Barriers for Multimaterial High-Resolution 3D Bioprinting

Three-Dimensional Bioprinting of Human Organs and Tissues: Bioethical and Medico-Legal Implications Examined through a Scoping Review

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