Inkjet bioprinted-hMSCs in simultaneously photocrosslinked PEG-GelMA hydrogel scaffolds demonstrated an improvement of mechanical properties and osteogenic and chondrogenic differentiation, suggesting its promising potential for usage in bone and cartilage tissue engineering.

The dendritic cell immunoreceptor (official gene symbol Clec4a2, called Dcir here) is a C-type lectin receptor expressed mainly in dendritic cells (DCs) that has a carbohydrate recognition domain in its extracellular portion and an immunoreceptor tyrosine-based inhibitory motif, which transduces negative signals into cells, in its cytoplasmic portion. We found high Dcir expression in the joints of two mouse rheumatoid arthritis models. Because the structural characteristics of Dcir suggest that it may have an immune regulatory role, and because autoimmune-related genes are mapped to the DCIR locus in humans, we generated Dcir-/- mice to learn more about the pathological roles of this molecule. We found that aged Dcir-/- mice spontaneously develop sialadenitis and enthesitis associated with elevated serum autoantibodies. Dcir-/- mice showed a markedly exacerbated response to collagen-induced arthritis. The DC population was expanded excessively in aged and type II collagen-immunized Dcir-/- mice. Upon treatment with granulocyte-macrophage colony-stimulating factor, Dcir-/- mouse-derived bone marrow cells (BMCs) differentiated into DCs more efficiently than did wild-type BMCs, owing to enhanced signal transducer and activator of transcription-5 phosphorylation. These observations indicate that Dcir is a negative regulator of DC expansion and has a crucial role in maintaining the homeostasis of the immune system.

Bioprinting based on thermal inkjet printing is a promising but unexplored approach in bone tissue engineering. Appropriate cell types and suitable biomaterial scaffolds are two critical factors to generate successful bioprinted tissue. This study was undertaken in order to evaluate bioactive ceramic nanoparticles in stimulating osteogenesis of printed bone marrow-derived human mesenchymal stem cells (hMSCs) in poly(ethylene glycol)dimethacrylate (PEGDMA) scaffold. hMSCs suspended in PEGDMA were co-printed with nanoparticles of bioactive glass (BG) and hydroxyapatite (HA) under simultaneous polymerization so the printed substrates were delivered with highly accurate placement in three-dimensional (3D) locations. hMSCs interacted with HA showed the highest cell viability (86.62 ± 6.02%) and increased compressive modulus (358.91 ± 48.05 kPa) after 21 days in culture among all groups. Biochemical analysis showed the most collagen production and highest alkaline phosphatase activity in PEG-HA group, which is consistent with gene expression determined by quantitative PCR. Masson's trichrome staining also showed the most collagen deposition in PEG-HA scaffold. Therefore, HA is more effective comparing to BG for hMSCs osteogenesis in bioprinted bone constructs. Combining with our previous experience in vasculature, cartilage, and muscle bioprinting, this technology demonstrates the capacity for both soft and hard tissue engineering with biomimetic structures.

Inkjet bioprinting is one of the most promising additive manufacturing approaches for tissue fabrication with the advantages of high speed, high resolution, and low cost. The limitation of this technology is the potential damage to the printed cells and frequent clogging of the printhead. Here we developed acrylated peptides and co-printed with acrylated poly(ethylene glycol) (PEG) hydrogel with simultaneous photopolymerization. At the same time, the bone marrow-derived human mesenchymal stem cells (hMSCs) were precisely printed during the scaffold fabrication process so the cells were delivered simultaneously with minimal UV exposure. The multiple steps of scaffold synthesis and cell encapsulation were successfully combined into one single step using bioprinting. The resulted peptide-conjugated PEG scaffold demonstrated excellent biocompatibility, with a cell viability of 87.9 ± 5.3%. Nozzle clogging was minimized due to the low viscosity of the PEG polymer. With osteogenic and chondrogenic differentiation, the bioprinted bone and cartilage tissue demonstrated excellent mineral and cartilage matrix deposition, as well as significantly increased mechanical properties. Strikingly, the bioprinted PEG-peptide scaffold dramatically inhibited hMSC hypertrophy during chondrogenic differentiation. Collectively, bioprinted PEG-peptide scaffold and hMSCs significantly enhanced osteogenic and chondrogenic differentiation for robust bone and cartilage formation with minimal printhead clogging.