Bacterial infection represents a prevalent challenge during the bone repair process, often resulting in implant failure. However, the extensive use of antibiotics has limited local antibacterial effects at the infection site and is prone to side effects. In order to address the issue of bacterial infection during the transplantation of bone implants, four types of bone scaffold implants with long-term antimicrobial functionality have been constructed, including direct contact antimicrobial scaffold, dissolution–penetration antimicrobial scaffold, photocatalytic antimicrobial scaffold, and multimodal synergistic antimicrobial scaffold. The direct contact antimicrobial scaffold involves the physical penetration or disruption of bacterial cell membranes by the scaffold surface or hindrance of bacterial adhesion through surface charge, microstructure, and other factors. The dissolution–penetration antimicrobial scaffold releases antimicrobial substances from the scaffold's interior through degradation and other means to achieve local antimicrobial effects. The photocatalytic antimicrobial scaffold utilizes the absorption of light to generate reactive oxygen species (ROS) with enhanced chemical reactivity for antimicrobial activity. ROS can cause damage to bacterial cell membranes, deoxyribonucleic acid (DNA), proteins, and other components. The multimodal synergistic antimicrobial scaffold involves the combined use of multiple antimicrobial methods to achieve synergistic effects and effectively overcome the limitations of individual antimicrobial approaches. Additionally, the biocompatibility issues of the antimicrobial bone scaffold are also discussed, including in vitro cell adhesion, proliferation, and osteogenic differentiation, as well as in vivo bone repair and vascularization. Finally, the challenges and prospects of antimicrobial bone implants are summarized. The development of antimicrobial bone implants can provide effective solutions to bacterial infection issues in bone defect repair in the foreseeable future.
Iron metal possesses good biocompatibility and excellent mechanical strength, though it degrades too slowly. In this work, selective laser melting (SLM) was applied to fabricate iron-manganese (Fe-Mn) biodegradable scaffold. Results shown Fe-Mn scaffold exhibited a uniform pore structure with a porosity of 66.72 ± 2.3%, which highly matched with as-designed model. Phase analysis revealed Fe-Mn scaffold mainly contained α-Fe, martensitic and austenitic phases. Due to the potential difference among these different phases, galvanic corrosion occurred in Fe matrix. In addition, a small amount of Mn distributed at grain boundaries also contributed to the formation of galvanic corrosion. Thus, the corrosion rate increased from 0.09 ± 0.02 mm/year to 0.23 ± 0.05 mm/year. The scaffold exhibited suitable mechanical properties with a yield strength of 137 ± 8.4 MPa, an ultimate strength of 221.7 ± 10.9 MPa. Moreover, cell assays demonstrated its good cytocompatibility. Taking these positive results into consideration, SLM processed Fe-Mn scaffold was a promising material for bone repair application.
1 July 2019 in International Journal of Bioprinting
Mg alloys degrade rather rapidly in a physiological environment, although they have good biocompatibility and favorable mechanical properties. In this study, Ti was introduced into AZ61 alloy fabricated by selective laser melting, aiming to improve the corrosion resistance. Results indicated that Ti promoted the formation of Al-enriched eutectic α phase and reduced the formation of β-Mg17Al12 phase. With Ti content reaching to 0.5 wt.%, the Al-enriched eutectic α phase constructed a continuous net-like structure along the grain boundaries, which could act as a barrier to prevent the Mg matrix from corrosion progression. On the other hand, the Al-enriched eutectic α phase was less cathodic than β-Mg17Al12 phase in AZ61, thus alleviating the corrosion progress due to the decreased potential difference. As a consequence, the degradation rate dramatically decreased from 0.74 to 0.24 mg·cm-2·d-1. Meanwhile, the compressive strength and microhardness were increased by 59.4% and 15.6%, respectively. Moreover, the Ti-contained AZ61 alloy exhibited improved cytocompatibility. It was suggested that Ti-contained AZ61 alloy was a promising material for bone implants application.
Background: Tumour repopulation initiated by residual tumour cells in response to cytotoxic therapy has been described clinically and biologically, but the mechanisms are unclear. Here, we aimed to investigate the mechanisms for the tumour‐promoting effect in dying cells and for tumour repopulation in surviving tongue cancer cells.Methods: Tumour repopulation in vitro and in vivo was represented by luciferase activities. The differentially expressed cytokines in the conditioned medium (CM) were identified using a cytokine array. Gain or loss of function was investigated using inhibitors, neutralising antibodies, shRNAs and ectopic overexpression strategies.Results: We found that dying tumour cells undergoing cytotoxic therapy increase the growth of living tongue cancer cells in vitro and in vivo. Dying tumour cells create amphiregulin (AREG)‐ and basic fibroblast growth factor (bFGF)‐based extracellular environments via cytotoxic treatment‐induced endoplasmic reticulum stress. This environment stimulates growth by activating lysine acetyltransferase 6B (KAT6B)‐dependent nuclear factor‐kappa B (NF‐κB) signalling in living tumour cells. As direct targets of NF‐κB, miR‐22 targets KAT6B to repress its expression, but long noncoding RNAs (lncRNAs) (XLOC_003973 and XLOC_010383) counter the effect of miR‐22 to enhance KAT6B expression. Moreover, we detected increased AREG and bFGF protein levels in the blood of tongue cancer patients with X‐box binding protein‐1 (XBP1) activation in tumours under cytotoxic therapy and found that XBP1 activation is associated with poor prognosis of patients. We also detected activation of miR‐22/lncRNA/KAT6B/NF‐κB signalling in recurrent cancers compared to paired primary tongue cancers.Conclusions: We identified the molecular mechanisms of cell death‐induced tumour repopulation in tongue cancer. Such insights provide new avenues to identify predictive biomarkers and effective strategies to address cancer progression.
Cuprous oxide (Cu2O) has great potential in photodynamic therapy for implant-associated infections due to its good biocompatibility and photoelectric properties. Nevertheless, the rapid recombination of electrons and holes weakens its photodynamic antibacterial effect. In this work, a new nanosystem (Cu2O@rGO) with excellent photodynamic performance was designed via the in situ growth of Cu2O on reduced graphene oxide (rGO). Specifically, rGO with lower Fermi levels served as an electron trap to capture photoexcited electrons from Cu2O, thereby promoting electron-hole separation. More importantly, the surface of rGO could quickly transfer electrons from Cu2O owing to its excellent conductivity, thus efficiently suppressing the recombination of electron-hole pairs. Subsequently, the Cu2O@rGO nanoparticle was introduced into poly-L-lactic acid (PLLA) powder to prepare PLLA/Cu2O@rGO porous scaffolds through selective laser sintering. Photochemical analysis showed that the photocurrent of Cu2O@rGO increased by about two times after the incorporation of GO nanosheets, thus enhancing the efficiency of photogenerated charge carriers and promoting electron-hole separation. Moreover, the ROS production of the PLLA/Cu2O@rGO scaffold was significantly increased by about two times as compared with that of the PLLA/Cu2O scaffold. The antibacterial results showed that PLLA/Cu2O@rGO possessed antibacterial rates of 83.7% and 81.3% against Escherichia coli and Staphylococcus aureus, respectively. In summary, this work provides an effective strategy for combating implant-related infections.