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J. Funct. Biomater. 2022, 13, 27 23 of 36 optimized zinc ion release to target bacteria. It was found optimized 500 μg mL−1 ZIF- 8@PVA improves wound closure after 11 days due to its cytocompatibility (Figure 13c–e) [129]. MXenes can also be applied as biomaterials for tissue engineering, cellular growth and osteogenesis differentiation of bone marrow derived mesenchymal stem cells (BMSCs). In a study doped Ti3C2 MXene composite nanofibers were obtained via electro- spinning showing hydrophilicity due to the functional groups on the surface [17]. Cellular fluorescent images of MXene composite nanofibers after 5 days of culture revealed uni- form cellular spread compared to a control group. Reverse transcription polymerase chain reaction (RT-PCR) analysis was employed to evaluate osteogenic differentiation perfor- mance by detecting the marker genes, and the results of cells cultured on MXene compo- site nanofibers after 14 days of culture demonstrated much better osteogenic differentia- tion than that on control groups [17]. Pan and co-workers used Ti3C2 MXene to kill bone tumor as well as expedite bone tissue regeneration in the presence of composite 3D-print- ing bioactive glass (BG) scaffolds in vivo [130]. Observation and microcomputed tomog- raphy (micro-CT) analysis of Ti3C2-BG scaffold (TBGS) implants in Sprague–Dawley rats after 24 weeks displayed boosted bone-tissue regeneration, which confirmed better oste- ogenic performance of TBGS compared to the bare one (Figure 13f–h). The long-term tox- icity of implanted bone defects was also tested after 24 weeks by collecting venous blood from major organs of rats and demonstrated no alteration compared to the control group [130]. Black phosphorus nanosheet (BPN)-based hydrogel was prepared by cross-linking gelatin methacrylamide, BPNs and cationic arginine-based unsaturated poly (ester am- ide)s (BP/PEA/GelMA hydrogel) in which BPNs can degrade into phosphorus ions and capture calcium ions to regenerate bone defect in vivo [131]. In vitro investigation of min- eralization capacity was conducted by immersing BP-modified hydrogel in body fluid under natural light for 15 days, which showed white mineralization in SEM images (Fig- ure 13i). It was found that BPN-containing hydrogels improved osteogenic differentiation of human dental pulp stem cells, where the protein levels of Col-1, BMP4, and RUNX2 were significantly greater for BPN-containing hydrogels compared to other hydrogels af- ter 14 days of incubation. Moreover, phosphorus-rich hydrogels also enhanced bone re- generation in vivo [131]. The enhancement of cell proliferation and osteogenesis was also reported by Liu and co-workers through synergic hybrid of 2D black phosphorus and graphene oxide in a 3D printed poly (propylene fumarate) scaffold (3D-PPF-Amine-GO@BP scaffold) [132]. Im- munofluorescence observation by confocal imaging demonstrated increased cell prolifer- ation on 3D-PPF-Amine-GO@BP hybrid scaffold with higher cell density after 6 days of culture. In fact, the wrapped BP in GO nanosheets allow slow oxidation of BP which con- tinuously releases phosphate ions as an osteoblast differentiation facilitator. The gradual release of phosphate ions demonstrated an increase in mineralization with calcium phos- phate NPs compared to bare 3D scaffold (Figure 13k,l). Therefore, in 3D-PPF-Amine- GO@BP scaffold each part plays its role to improve mineralization, phosphate ion gener- ation, biocompatibility, and osteogenic capacity of the whole scaffold. GO nanosheets with large surface area helped improve protein and cell adhesion; BP nanosheets allowed for continuous phosphate release from scaffolds; BP and GO nanosheets synergetic corre- lation also led to highest cell proliferation and osteogenesis properties [132]. All in all, 2D materials seems to help improve loading capacity, biocompatibility and osteogenesis properties compared to conventional nanoparticles in scaffolds.PDF Image | Nanomaterials beyond Graphene for Biomedical Applications
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