Carbon dots with tissue engineering and regenerative medicine applications

Abstract

Carbon dots (CDs) with unique physicochemical features such as exceptional biocompatibility, low cost, eco-friendliness, abundant functional groups (e.g., amino, hydroxyl, and carboxyl), high stability, and electron mobility have been broadly investigated in nano- and biomedicine. In addition, the controlled architecture, tunable fluorescence emission/excitation, light-emitting potential, high photostability, high water solubility, low cytotoxicity, and biodegradability make these carbon-based nanomaterials suitable for tissue engineering and regenerative medicine (TE-RM) purposes. However, there are still limited pre- and clinical assessments, because of some important challenges such as the scaffold inconsistency and non-biodegradability in addition to the lack of non-invasive methods to monitor tissue regeneration after implantation. In addition, the eco-friendly synthesis of CDs exhibited some important advantages such as environmentally friendly properties, low cost, and simplicity compared to the conventional synthesis techniques. Several CD-based nanosystems have been designed with stable photoluminescence, high-resolution imaging of live cells, excellent biocompatibility, fluorescence properties, and low cytotoxicity, which make them promising candidates for TE-RM purposes. Combining attractive fluorescence properties, CDs have shown great potential for cell culture and other biomedical applications. Herein, recent advancements and new discoveries of CDs in TE-RM are considered, focusing on challenges and future perspectives.

Fig. 1. (A) Synthetic approaches for the preparation of CDs along with their advantages and disadvantages, (B) overview of sustainable resources used for the synthesis of CDs. Reproduced with permission from ref. Copyright 2021 American Chemical Society.

Fig. 2. (A) N-doped CDs functionalized with hydroxyapatite NPs (NCDs-HA) with enhanced bone regeneration activity. (B) Possible molecular mechanisms for accelerated osteogenesis by functionalized CDs through the activation of bone morphogenetic protein (BMP) signaling pathway along with the internalization of CDs into the osteoblast cells. RUNX2: runt-related transcription factor 2; ALP: alkaline phosphatase; OCN: osteocalcin. Reproduced with permission from ref. Copyright 2018 American Chemical Society.

Fig. 3. The preparative process of hydrogel scaffolds constructed from GQDs⁻ and GelMA using a UV light-activated photopolymerization; GQDs⁻ incorporated in the porous hydrogel composites could gradually release at the bone defect sites to stimulate in situ bone regeneration. Reproduced with permission from ref. Copyright 2020 Elsevier.

Fig. 4. (A) The preparative process of antibacterial CQDs (CQD_AG)-hydrogel system using carboxymethyl chitosan (CMCS), CQD_AG, and dextran (Dex). (B) Hematoxylin and eosin (H&E) staining of tissues at wound sites to evaluate the healing of wounds for each group after 14 days treatment (blood vessels: red arrows, hair follicles: blue arrows). (C) Masson's trichrome staining of tissues at wound sites to evaluate collagen generation for each group after 14 days treatment (blood vessels: red arrows). Reproduced with permission from ref. Copyright 2020 Elsevier.

Fig. 5. (A) The preparative process of TCDs/CaO₂@ZE film dressing. (B) The mechanism of TCDs/CaO₂@ZE for stimulating chronic wound healing on the full-thickness wound in the streptozotocin-induced diabetic rat model. Reproduced with permission from ref. Copyright 2023 Elsevier.