Table 3.
Overview of Publications on the (Bio)fabrication of Osteochondral Regenerative Constructs.
| Bio-Ink |
(Bio)printed Constructs |
|||||
|---|---|---|---|---|---|---|
| Reference | Printing Technique | Material(s) | Cells and/or Biological Cues | Mechanical Properties | Tissue Formation | Remarks |
| *Lee et al. (2010)44 | Extrusion printing | PCL with hydroxyapatite | • Cell free • PCL network infused with a TGF-β3 laden collagen type I hydrogel (cartilage) • Different pore size for bone and cartilage |
• Not reported for the construct prior to implantation • Compressive modulus (unconfined) ~5500 kPa at explanation |
In vivo • Rabbits, orthotopic; cells migrated into the scaffolds and produced cartilage-like tissue after 4 months in the presence of TGF-β3 |
• Demonstrated the feasibility of cartilage regeneration via cell-free scaffolds that attract host cells |
| *Cohen et al. (2010)69 | Extrusion printing | Alginate (cartilage)Gelatin (bone) | • Cell free • Demineralized bone matrix (bone) |
• Not reported |
Ex vivo • Printing directly into an (osteo)chondral defect in a bovine femur |
• First demonstration of printing directly into a defect with automatic geometric feedback during printing |
| *Shim et al. (2012)92 | Extrusion bioprinting | Alginate reinforced with PCL | • Nasal human chondrocytes (cartilage)• Human osteoblast cell line (MG63, bone) | • Not reported |
In vitro • Viability, ~90-95% • Cells proliferated during 7 days of culture |
• Proof of concept for printing with multiple cell types that remain in their separate compartments during culture |
| Fedorovich et al. (2012)48 | Extrusion bioprinting | Alginate | • Full thickness human articular chondrocytes (cartilage)• Human mesenchymal stromal cells (bone)• Biphasic calcium phosphate particles (bone) | • Compressive modulus (unconfined) ~4-15 kPa (dependent on construct porosity) |
In vitro • Viability, ~89% • Bone-like and cartilage-like tissue formation in the separate regions of the constructs after 3 weeks of differentiation In vivo• Immunodeficient mice, subcutaneous; bone-like and cartilage-like tissue formation in the separate regions after 6 weeks |
• Demonstrated the feasibility of printing heterogeneous tissue constructs with distinctive tissue formation in osteo and chondral regions |
| Levato et al. (2014)49 | Extrusion bioprinting | GelMA with gellan gum | • Murine mesenchymal stromal cells (cartilage/bone)• Polylactic acid microcarriers (bone) | • Compressive modulus (unconfined) ~25-50 kPa (dependent on concentration of microcarriers) | In vitro• Viability, ~60-90% | • Demonstrated the feasibility to extrude larger aggregates (cells on microcarriers)• Focus paper on bone compartment, osteochondral constructs as proof of concept |
*
Proof of concept study.
PCL = polycaprolactone; PEGDMA = poly(ethylene) glycol dimethacrylate; TGF = transforming growth factor; FGF = fibroblast growth factor; GelMA = gelatin-methacryloyl; pHMGCL/PCL = poly(hydroxylmethylglycolide-co-ϵ-caprolactone)/poly(ϵ-caprolactone); HAMA = methacrylated hyaluronic acid; HA-pNIPAAM = poly(N-isopropylacrylamide) grafted hyaluronan; polyHPMA-lac-PEG = polyethylene glycol midblock flanked by two poly[N-(2-hydroxypropyl) methacrylamide mono/dilactate]; CSMA = methacrylated chondroitin sulfate; PEGT-PBT = poly(ethylene glycol)-terephthalate-poly(butylene terephthalate).