An additive manufacturing-based PCL-alginate-chondrocyte bioprinted scaffold for cartilage tissue engineering

Abstract

Regenerative medicine is targeted to improve, restore or replace damaged tissues or organs using a combination of cells, materials and growth factors. Both tissue engineering and developmental biology currently deal with the process of tissue self-assembly and extracellular matrix (ECM) deposition. In this investigation, additive manufacturing (AM) with a multihead deposition system (MHDS) was used to fabricate three-dimensional (3D) cell-printed scaffolds using layer-by-layer (LBL) deposition of polycaprolactone (PCL) and chondrocyte cell-encapsulated alginate hydrogel. Appropriate cell dispensing conditions and optimum alginate concentrations for maintaining cell viability were determined. In vitro cell-based biochemical assays were performed to determine glycosaminoglycans (GAGs), DNA and total collagen contents from different PCL-alginate gel constructs. PCL-alginate gels containing transforming growth factor-β (TGFβ) showed higher ECM formation. The 3D cell-printed scaffolds of PCL-alginate gel were implanted in the dorsal subcutaneous spaces of female nude mice. Histochemical [Alcian blue and haematoxylin and eosin (H&E) staining] and immunohistochemical (type II collagen) analyses of the retrieved implants after 4 weeks revealed enhanced cartilage tissue and type II collagen fibril formation in the PCL-alginate gel (+TGFβ) hybrid scaffold. In conclusion, we present an innovative cell-printed scaffold for cartilage regeneration fabricated by an advanced bioprinting technology.

3D bioprinting for cell culture and tissue fabrication

“…In another study displayed in Fig. 3b, the porous 3D scaffold was bioprinted using PCL and alginate laden with chondrocytes [63]. The results indicated the formation of type II collagen and cartilaginous tissue in the printed scaffold.…”

3D printing of hydrogel composite systems: Recent advances in technology for tissue engineering

“…The degradation rate of silica coated collagen/alginate scaffolds was significantly reduced while the elastic modulus of silica coated collagen/ Figure 10. Schematics of (A) the 3D printing process of chondrocyte-incorporated alginate-PCL hybrid scaffold for cartilage application (reproduced with permission from [111]. Copyright 2013, John Wiley & Sons, Ltd) and (B) the direct bioprinting process of collagenfibrinogen with stem cells onto skin wound of rat (reproduced with permission from [116].…”

“…Incorporation of hydroxyapatite increased the elastic modulus of printed hydrogel composites and HAMA in GelMA hydrogels improved chondrogenesis. The polycaprolactone (PCL) and alginate were printed layerby-layer with a multihead deposition system as shown in ( Figure 10A) [111] . These hydrogel composites combined chondrocyte cells and transforming growth factor beta (TGFbeta) to mimic the properties of cartilage.…”

3D bioprinting for tissue engineering: Stem cells in hydrogels

“…A study on methacrylated hyaluronic acid combined with methacrylated gelatin showed that not only could cell viability be maintained but by varying the concentrations of the two materials, the stiffness and viscosity of the hybrid could be controlled [83] . Other researchers have used a similar approach to bioprint scaffolds for a range of uses, including cartilage engineering [84] and to tune material properties for a range of scaffolds [85] .…”