Cartilage Tissue Engineering Using Stem Cells and Bioprinting Technology—Barriers to Clinical Translation

Francis, Sam L.; Bella, Claudia Di; Wallace, Gordon G.; Choong, Peter

doi:10.3389/fsurg.2018.00070

Cited by 70 publications

(39 citation statements)

References 88 publications

(96 reference statements)

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“…Chondrocytes, BMSCs, and adipose-derived stem cells (ADSCs), as well as other cells have all been explored for their potential as an ideal cell source for cartilage regeneration [27, 28]. Chondrocytes, the predominant cell type in cartilage, synthesize matrix components and were the first seeding cells used in cartilage tissue engineering because chondrocytes are the only cell found in native cartilage, while the poor proliferation ability and the dedifferentiation of chondrocytes are bottlenecks in the clinical application of chondrocytes [32]. Recently, there has been increasing interest in stem cell-based cartilage tissue engineering options in surgical practice to deal with lost or damaged cartilage tissue, and BMSCs could be promising cell sources for use in cartilage regeneration [21].…”

Section: Discussionmentioning

confidence: 99%

Cartilage progenitor cells combined with PHBV in cartilage tissue engineering

et al. 2019

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Background Bone marrow-derived stem cells (BMSCs) and chondrocytes have been reported to present “dedifferentiation” and “phenotypic loss” during the chondrogenic differentiation process in cartilage tissue engineering, and cartilage progenitor cells (CPCs) are novel seeding cells for cartilage tissue engineering. In our previous study, cartilage progenitor cells from different subtypes of cartilage tissue were isolated and identified in vitro, but the study on in vivo chondrogenic characteristics of cartilage progenitor cells remained rarely. In the current study, we explored the feasibility of combining cartilage progenitor cells with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) to produce tissue-engineered cartilage and compared the proliferation ability and chondrogenic characteristics of cartilage progenitor cells with those of bone marrow-derived stem cells and chondrocytes. Methods These three cells combined with PHBV were cultured in vitro for 1 week without chondrogenic induction and then transplanted subcutaneously into nude mice for 6 weeks. The cell-PHBV constructs were evaluated by gross observation, histological staining, glycosaminoglycan content measurement, biomechanical analysis and RT-PCR. Results The chondrocyte-PHBV constructs and CPC-PHBV constructs became an ivory-whitish cartilage-like tissue, while the BMSC-PHBV constructs became vascularized 6 weeks after the subcutaneous implantation. Histological examination showed that many typical cartilage structures were present in the chondrocyte group, some typical cartilage structures were observed in the CPC group, while no typical cartilage structures were observed in the BMSC group. Conclusions Cartilage progenitor cells may undergo chondrogenesis without chondrogenic induction and are better at chondrogenesis than BMSCs but worse than chondrocytes in the application of cartilage tissue engineering.

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Section: Discussionmentioning

confidence: 99%

Cartilage progenitor cells combined with PHBV in cartilage tissue engineering

et al. 2019

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“…Finally, laser techniques include laser-assisted bioprinting based on the laser-induced forward-transfer (LIFT) where a pulsed laser forms a bubble that transfers the ink to an absorbing layer below [32] and stereolithography (SLA) that patterns photosensitive solutions by light exposure [33]. SLA is sometimes considered a separate technique because of its need for photopolymerization [34]. It is a quick and accurate method, but with a limited choice of biomaterials and requiring an intense-ultraviolet (UV) exposure.…”

Section: 3d Bioprinting Techniquesmentioning

confidence: 99%

“…The successful outcome of MACI clinical trials promises a bright future for the clinical translation of bioprinted scaffolds. There have been promising in vitro and in vivo studies looking at 3D bioprinting of engineered cartilage tissue [34]. Thus far, extrusion-based bioprinting using alginate and scaffold-free bioinks have resulted in the best outcome for cartilage regeneration [61,66].…”

Section: Bioprinting Ipsc Differentiated Ipscmentioning

confidence: 99%

iPSC Bioprinting: Where are We at?

2019

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Here, we present a concise review of current 3D bioprinting technologies applied to induced pluripotent stem cells (iPSC). iPSC have recently received a great deal of attention from the scientific and clinical communities for their unique properties, which include abundant adult cell sources, ability to indefinitely self-renew and differentiate into any tissue of the body. Bioprinting of iPSC and iPSC derived cells combined with natural or synthetic biomaterials to fabricate tissue mimicked constructs, has emerged as a technology that might revolutionize regenerative medicine and patient-specific treatment. This review covers the advantages and disadvantages of bioprinting techniques, influence of bioprinting parameters and printing condition on cell viability, and commonly used iPSC sources, and bioinks. A clear distinction is made for bioprinting techniques used for iPSC at their undifferentiated stage or when used as adult stem cells or terminally differentiated cells. This review presents state of the art data obtained from major searching engines, including Pubmed/MEDLINE, Google Scholar, and Scopus, concerning iPSC generation, undifferentiated iPSC, iPSC bioprinting, bioprinting techniques, cartilage, bone, heart, neural tissue, skin, and hepatic tissue cells derived from iPSC.

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“…Our approach takes advantage of using a low MSC density, which is more representative of native cartilage. Although MSCs are not often used in cartilage bioprinting [28][29][30][31][32], they are very promising for cartilage engineering because of their chondrogenic potential and their excellent availability (e.g., from the bone marrow) for autologous or allogeneic grafts. To this end, we first evaluated the biocompatibility of the bioink and the effect of the 3D bioextrusion process on MSC metabolism and their genic expression profile and ECM production, at two different cell concentrations, that mimicked the cell density of native cartilage.…”

Section: Introductionmentioning

confidence: 99%

Combining Innovative Bioink and Low Cell Density for the Production of 3D-Bioprinted Cartilage Substitutes: A Pilot Study

Henrionnet

Pourchet

Neybecker

et al. 2020

Stem Cells International

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3D bioprinting offers interesting opportunities for 3D tissue printing by providing living cells with appropriate scaffolds with a dedicated structure. Biological advances in bioinks are currently promising for cell encapsulation, particularly that of mesenchymal stem cells (MSCs). We present herein the development of cartilage implants by 3D bioprinting that deliver MSCs encapsulated in an original bioink at low concentration. 3D-bioprinted constructs (10×10×4 mm) were printed using alginate/gelatin/fibrinogen bioink mixed with human bone marrow MSCs. The influence of the bioprinting process and chondrogenic differentiation on MSC metabolism, gene profiles, and extracellular matrix (ECM) production at two different MSC concentrations (1 million or 2 million cells/mL) was assessed on day 28 (D28) by using MTT tests, real-time RT-PCR, and histology and immunohistochemistry, respectively. Then, the effect of the environment (growth factors such as TGF-β1/3 and/or BMP2 and oxygen tension) on chondrogenicity was evaluated at a 1 M cell/mL concentration on D28 and D56 by measuring mitochondrial activity, chondrogenic gene expression, and the quality of cartilaginous matrix synthesis. We confirmed the safety of bioextrusion and gelation at concentrations of 1 million and 2 million MSC/mL in terms of cellular metabolism. The chondrogenic effect of TGF-β1 was verified within the substitute on D28 by measuring chondrogenic gene expression and ECM synthesis (glycosaminoglycans and type II collagen) on D28. The 1 M concentration represented the best compromise. We then evaluated the influence of various environmental factors on the substitutes on D28 (differentiation) and D56 (synthesis). Chondrogenic gene expression was maximal on D28 under the influence of TGF-β1 or TGF-β3 either alone or in combination with BMP-2. Hypoxia suppressed the expression of hypertrophic and osteogenic genes. ECM synthesis was maximal on D56 for both glycosaminoglycans and type II collagen, particularly in the presence of a combination of TGF-β1 and BMP-2. Continuous hypoxia did not influence matrix synthesis but significantly reduced the appearance of microcalcifications within the extracellular matrix. The described strategy is very promising for 3D bioprinting by the bioextrusion of an original bioink containing a low concentration of MSCs followed by the culture of the substitutes in hypoxic conditions under the combined influence of TGF-β1 and BMP-2.

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Cartilage Tissue Engineering Using Stem Cells and Bioprinting Technology—Barriers to Clinical Translation

Cited by 70 publications

References 88 publications

Cartilage progenitor cells combined with PHBV in cartilage tissue engineering

Cartilage progenitor cells combined with PHBV in cartilage tissue engineering

iPSC Bioprinting: Where are We at?

Combining Innovative Bioink and Low Cell Density for the Production of 3D-Bioprinted Cartilage Substitutes: A Pilot Study

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