Table 2.
Recent in vitro and in vivo studies using 3D bioprinting for cartilage tissue engineering applications.
| Biomaterials and GFs | Cells | Main results | References |
|---|---|---|---|
| Extrusion-based bioprinting | |||
| Agarose, Alginate, GelMA and PEGMA + TGFβ-3 | BMSCs | High levels of MSC viability observed post-printing in all bioinks. Alginate and agarose hydrogels supported the development of hyaline-like cartilage phenotype. GelMA and PEGMA-based hydrogel supported the development of fibrocartilage-like tissue. PCL microfibers increased the compressive moduli of the bioink (544 fold increase for alginate, 45 fold for GelMA). Obtained values were comparable to articular cartilage. |
Daly [21] |
| COL type II hydrogel | Chondrocytes | Stable cell distribution patterns throughout the culture period with formation of new ECM with gradient distribution. | Ren [92] |
| dECM/PCL | hTMSCs | High cell viability and significant chondrogenic differentiation in vitro. | Pati [17] |
| GelMA | ACPCs, BMSCs and Chondrocytes | Neo-cartilage synthesis in layered co-cultures in a zonal-like architecture in vitro. Higher elastic modulus of the hydrogel correlates with higher cartilage matrix synthesis. |
Levato [94] |
| GelMA/HAMA | IFP-MSCs | Rapid generation of Core/Shell GelMa/HAMA bioscaffolds with high compressive modulus and cell viability. | Duchi [96] |
| GelMA/HAMA | IFP-MSCs | Intraoperative bioprinting using the ‘biopen’ to treat chondral defect in sheeps showed better macroscopic and microscopic cartilage characteristics. | Di Bella [93] |
| GelMA/HAMA/CSMA | Chondrocytes | The addition of HAMA and CSMA to GelMA constructs resulted in more rounded cell morphologies, enhanced chondrogenesis, ECM production and increased compressive moduli. | Levett [13] |
| GelMA-Tyr | Chondrocytes | Neo-cartilage formation in vitro. Better integration in vivo with no damage of the surrounding tissue after in situ crosslinking with visible light. |
Lim [97] |
| PCL/Alginate + TGFβ3 | Chondrocytes | Enhanced cartilage tissue and type II collagen fibril formation after four weeks of implantation in nude mice. | Kundu [27] |
| PCL/Pluronic F-127 | Chondrocytes | High cell viability, new cartilage tissue formation and increase of GAG content in vivo of human ear–shaped cartilage constructs. | Kang [25] |
| SA, SA/COL, SA/AG | Chondrocytes | SA/COL showed better compressive strength, cell adhesion, proliferation and cartilage-specific gene expression. SA/COL also suppressed the de-differentiation of chondrocytes and preserved their phenotype. |
Yang [95] |
| Stereolitography | |||
| GelMA, HAMA | Chondrocytes | Both materials supported cartilage ECM formation and recovery of chondrocyte phenotype in vitro. Influence of cell density on the differentiation pattern. |
Lam [90] |
| Inkjet-based bioprinting | |||
| PCL microchambers | BMSCs and Chondrocytes | PCL microchambers promoted growth and fusion of cellular spheroids. Formation of stratified cartilage formation with collagen fibre architecture, composition and biomechanical properties comparable to the native tissue. |
Daly [26] |
Abbreviations: [GelMa] Gelatin methacrylamide, [PEGMA] Poly(ethylene glycol) methacrylate, [TGFβ-3] Transforming growth factor-3, [BMSCs] Bone marrow-derived mesenchymal stem cells, [COL] collagen, [dECM] decellularized extracellular matrix, [PCL] poly(caprolactone), [hTMSCs] human nasal inferior turbinate tissue-derived mesenchymal stromal cells, [ACPCs] Cartilage-resident chondroprogenitor cells, [HAMA] hyaluronic acid methacrylate, [CSMA] chondroitin sulfate methacrylate, [IFP-MSCs] infrapatellar fat pad derived mesenchymal stem cells, [GelMA-Tyr] Gelatin methacrylamide-tyramine, [SA] Sodium Alginate, [AG] agarose.