3D bioprinting dual-factor releasing and gradient-structured constructs ready to implant for anisotropic cartilage regeneration

Abstract

Cartilage injury is extremely common and leads to joint dysfunction. Existing joint prostheses do not remodel with host joint tissue. However, developing large-scale biomimetic anisotropic constructs mimicking native cartilage with structural integrity is challenging. In the present study, we describe anisotropic cartilage regeneration by three-dimensional (3D) bioprinting dual-factor releasing and gradient-structured constructs. Dual-factor releasing mesenchymal stem cell (MSC)–laden hydrogels were used for anisotropic chondrogenic differentiation. Together with physically gradient synthetic biodegradable polymers that impart mechanical strength, the 3D bioprinted anisotropic cartilage constructs demonstrated whole-layer integrity, lubrication of superficial layers, and nutrient supply in deep layers. Evaluation of the cartilage tissue in vitro and in vivo showed tissue maturation and organization that may be sufficient for translation to patients. In conclusion, one-step 3D bioprinted dual-factor releasing and gradient-structured constructs were generated for anisotropic cartilage regeneration, integrating the feasibility of MSC- and 3D bioprinting–based therapy for injured or degenerative joints.

Review on Computer-Aided Design and Manufacturing of Drug Delivery Scaffolds for Cell Guidance and Tissue Regeneration

“…In fact, the composite scaffold demonstrated accelerated bone defect healing with higher levels of vessel invasion and less heterotopic bone formation if compared with implants homogeneously loaded with the same total amount of growth factors. Similar hydrogel-PCL composite scaffold strategies were proposed by the group of Sun et al (2020a , b , 2021) to generate living anisotropic cartilaginous tissues ( Figure 2 ). In the case of meniscus, PCL was molten to fabricate the physically supporting structure for the scaffold, choosing needle diameter, layer thickness, and fiber spacing of 200, 200, and 350 μm, respectively.…”

“…In particular, to chemically simulate the anisotropic phenotypes in native meniscus, microcarriers carrying CTGF were positioned in the outer one-third region, while those carrying TGF-β3 were used for the inner two-thirds regions of the meniscus construct. In vivo implantation into sheep showed that the ECM composition of the 3D-bioprinted constructs shared many characteristics of native meniscus, including the heterogeneous zonal expression of types I, II collagen and therewith the conferred anisotropic zonal function properties ( Sun et al, 2020a ). Dual-factor releasing and gradient-structured bioprinted constructs were also used for anisotropic cartilage regeneration ( Sun et al, 2020b ).…”

3D Bioprinted cancer models: Revolutionizing personalized cancer therapy

“…Biochemical gradients in tumor tissues greatly impact cellular processes such as cell adhesion, cell migration, cell proliferation, differentiation and angiogenesis. To provide a chemical gradient to simulate the proper maturation of bioprinted construct, multiple active agents can be loaded as multiple layers with varying layer spacing [114] .…”

The promising rise of bioprinting in revolutionalizing medical science: Advances and possibilities

“…More recently, Sun et al. [ 71 ] developed a dual-factor (BMP4 and TGFβ3) releasing gradient structured human and rabbit cartilage construct using mesenchymal stem cells (MSC) and poly (lactic-co-glycolic acid) (PLGA) resulting in good interconnectivity. Overall, bioprinting of bone and cartilage tissue can provide a potential alternative to xenogeneic or allogeneic bone grafts.…”