A 3D Bioprinted Nanoengineered Hydrogel with Photo-activated Drug Delivery for Tumor Apoptosis and Simultaneous Bone Regeneration via Macrophage Immunomodulation.

One of the significant challenges in bone tissue engineering (BTE) is the healing of traumatic tissue defects which requires longer time to recover owing to the recruitment of local infection and delayed angiogenesis. Various strategies, such as hydrogel dressings, growth factors delivery, and stem cell therapy has been shown potential alternative to the traumatic tissue repair; however, limited their actual clinical application due to the socio-economic burden. Herein, we reported a 3D printable multi-functional hydrogel scaffold composing polyphenolic carbon quantum dots (CQDs, 100 ug mL-1 ) and gelatin methacryloyl (GelMA, 12 wt.%) for bone regeneration and anti-tumor therapy. The CQDs was synthesized from a plant-inspired bioactive molecule, 1, 3, 5-trihydroxybenzene (a polyphenol) via facile wet chemistry method. The 3D printed GelMA-CQDs hydrogels displayed typical shear-thinning behavior with excellent printability. Our results demonstrated that the nanocomposite 3D hydrogel promoted M2 polarization of macrophage (Raw 264.7) cells via upregulation of anti-inflammatory genes (e.g., IL-4 and IL10), and induced angiogenesis and osteogenesis of human bone mesenchymal stem cells (hBMSCs). The bioprinted hBMSCs were able to produced vessel-like structures in the presence of GelMA-CQDs hydrogel after 14 days of incubation. Furthermore, the 3D printed scaffolds also showed remarkable near infra-red (NIR) responsive properties under 808 nm NIR light (1.0 W cm-2 ) irradiation and showed controlled release of antitumor drugs (∼49%) at pH 6.5, and thereby killing the osteosarcoma cells. Therefore, we anticipate that the tissue regeneration and healing ability with therapeutic potential of the 3D printed GelMA-CQDs scaffolds may provide a promising alternative for traumatic tissue regeneration via augmenting angiogenesis and accelerated immunomodulation. This article is protected by copyright. All rights reserved.