Mild photothermal therapy assist in promoting bone repair: Related mechanism and materials.

Achieving precision treatment in bone tissue engineering (BTE) remains a challenge. Photothermal therapy (PTT), as a form of precision therapy, has been extensively investigated for its safety and efficacy. It has demonstrated significant potential in the treatment of orthopedic diseases such as bone tumors, postoperative infections and osteoarthritis. However, the high temperatures associated with PTT can lead to certain limitations and drawbacks. In recent years, researchers have explored the use of biomaterials for mild photothermal therapy (MPT), which offers a promising approach for addressing these limitations. This review provides a comprehensive overview of the mechanisms underlying MPT and presents a compilation of photothermal agents and their utilization strategies for bone tissue repair. Additionally, the paper discusses the future prospects of MPT-assisted bone tissue regeneration, aiming to provide insights and recommendations for optimizing material design in this field.

Injectable thermosensitive black phosphorus nanosheet- and doxorubicin-loaded hydrogel for synergistic bone tumor photothermal-chemotherapy and osteogenesis enhancement.

Removing residual tumor cells around bone tissue and promoting bone defect repair pose significant challenges after osteosarcoma resection. Herein, we designed an injectable multifunctional hydrogel therapeutic platform for synergistic photothermal chemotherapy of tumors and promoting osteogenesis. In this study, the black phosphorus nanosheets (BPNS) and doxorubicin (DOX) were encapsulated in an injectable chitosan-based hydrogel (BP/DOX/CS). The BP/DOX/CS hydrogel exhibited excellent photothermal effects under NIR irradiation due to incorporating BPNS. The prepared hydrogel has good drug-loading capacity and can continuously release DOX. In addition, K7M2-WT tumor cells are effectively eliminated under the combined effect of chemotherapy and photothermal stimulation. Furthermore, the BP/DOX/CS hydrogel has good biocompatibility and promotes osteogenic differentiation of MC3T3-E1 cells by releasing phosphate. In vivo results also confirmed that the BP/DOX/CS hydrogel can be injected at the tumor site to eliminate the tumor efficiently without systemic toxicity. This easily prepared multifunctional hydrogel with a synergistic photothermal-chemotherapy effect has excellent potential for clinically treating bone-related tumors.

Performance optimization of biomimetic ant-nest silver nanoparticle coatings for antibacterial and osseointegration of implant surfaces.

Infection prevention and bone-implant integration remain major clinical challenges. Silver nanoparticle (AgNPs) bone-implant coatings have received extensive attention. Balancing the toxicity and antibacterial properties of AgNP coatings has become a significant problem. In this study, inspired by the structure of the ant-nest, a polyetherimide (PEI) coating with ant-nest structure was prepared, aiming to realize the structural modification of the AgNPs coating. AgNPs were loaded in the inner porous area of the PEI ant-nest coating, avoiding direct contact between AgNPs and cells. The nanopores on the surface of the coating ensured the orderly release of silver ions. SEM, FTIR, XPS, and XRD experiments confirmed that the PEI ant-nest coating was successfully prepared. Interestingly, in the PEI ant-nest coating, Ag+ showed a steady increase in the release trend within 28 days, and there was no early burst release phenomenon. In -vivo experiments showed a good control effect for local infection. In order to improve the osteogenic properties of the materials, 45S5 bioactive glasses (BG) were loaded to achieve further osseointegration. In general, this natural ant-nest-inspired surface modification coating for orthopedic prostheses provides a new strategy for balancing the antibacterial and toxic effects of AgNP coatings.

Improved Osteogenesis of Selective-Laser-Melted Titanium Alloy by Coating Strontium-Doped Phosphate With High-Efficiency Air-Plasma Treatment.

Surface treatment and bioactive metal ion incorporation are effective methods for the modification of titanium alloys to be used as biomaterials. However, few studies have demonstrated the use of air-plasma treatment in orthopedic biomaterial development. Additionally, no study has performed a direct comparison between unmodified titanium alloys and air-plasma-treated alloys with respect to their biocompatibility and osteogenesis. In this study, the biological activities of unmodified titanium alloys, air-plasma-treated titanium alloys, and air-plasma-treated strontium-doped/undoped calcium phosphate (CaP) coatings were compared. The strontium-doped CaP (Sr-CaP) coating on titanium alloys were produced by selective laser melting (SLM) technology as well as micro-arc oxidation (MAO) and air-plasma treatment. The results revealed that rapid air-plasma treatment improved the biocompatibility of titanium alloys and that Sr-CaP coating together with air-plasma treatment significantly enhanced both the biocompatibility and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Overall, this study demonstrated that low temperature air-plasma treatment is a fast and effective surface modification which improves the biocompatibility of titanium alloys. Additionally, air-plasma-treated Sr-CaP coatings have numerous practical applications and may provide researchers with new tools to assist in the development of orthopedic implants.

The anti-osteosarcoma property of ailanthone through regulation of miR-126/VEGF-A axis.

Background: Despite the characters of the resistance of tumour of ailanthone (AIL) were found in various tumour cells, its effect on osteosarcoma is still unclear. Herein, we attempted to see the effects of AIL on an osteosarcoma cell line MG63. Methods: MG63 cells were treated by AIL, following which CCK-8 assay, BrdU assay, Transwell assay and Western blot were utilized to detect cell proliferation, migration, invasion and apoptosis. miR-126 expression in osteosarcoma tissues and cell lines was measured by qRT-PCR. Further, the target of miR-126 and the downstream signalling for AIL were studied. Results: Treating MG63 cells with 1.5 µM AIL for 24 h significantly suppressed proliferation, migration, invasion and induced apoptosis. Meanwhile, AIL inhibited PI3K/AKT pathway and up-regulated miR-126 expression. miR-126 of osteosarcoma tissues and cell lines was low expressed, as relative to paracancerous tissues and normal osteoblast. The anti-tumour effects of AIL were attenuated by miR-126 silencing. Further, VEGF-A was a target of miR-126. Conclusions: This study demonstrated that AIL was effective in inhibiting MG63 cells growth, migration and invasion. The anti-tumour properties may be via up-regulating miR-126 and thereby degradation of VEGF-A.

PCAF regulates H3 phosphorylation and promotes autophagy in osteosarcoma cells.

BACKGROUND: Osteosarcoma is one of malignant cancer. Histone phosphorylation is common in tumors. We explored the effects of p300-CBP-associated factor (PCAF) and phosphorylation of H3S28 in osteosarcoma cancer cell autophagy. METHODS: Osteosarcoma cancer cell lines were collected and/or transfected with full length PCAF or interference miRNAs to mimic or silence of PCAF expression. Immunoprecipitation assay and GST pull down was used to target targeting PCAF or H3S28ph. H3-/- SNU-C1 cells were transfected with H3WT- or H3S28F-expressing or enhanced green fluorescent protein (EGFP)-tagged LC3 plasmids, in which H3 was tagged with HA. An in vitro kinase activity assay was performed to test whether recombinant full-length PCAF could phosphorylate H3 in the site of S28. The functions on autophagy was detected by number of autophagosomes, number of EGFP-LC3, LC3-II/I, percentage of degradation and expression of autophagy associated gene (ATG). RESULTS: PCAF positively regulated H3S28ph in osteosarcoma cancer cells; Immunoprecipitation assay and GST pull down demonstrated that PCAF could interact directly with H3 in osteosarcoma cancer cells. In addition, silence of PCAF inhibited the number of autophagosomes, number of EGFP-LC3, LC3-II/I, percentage of degradation and expression of ATG. Moreover, H3S28A (H3S28 mutation) impaired the promoting autophagy effects of PCAF. The PCAF-H3S28ph axis promoted osteosarcoma cancer autophagy viatranscriptional regulation of ATG genes. CONCLUSION: PCAF regulated H3S28 phosphorylation and their axis promotes autophagy in osteosarcoma cancer cells viatargeting ATG5 and ATG7.

Sirt1 modulates H3 phosphorylation and facilitates osteosarcoma cell autophagy.

Abnormal histone modifications have been recognized as an important contributing factor to the initiation and progression of osteosarcoma. Sirtuin 1 (Sirt1) up-regulation has been discovered in osteosarcoma cells. This study tested the influence of Sirt1 on histone H3 phosphorylation at threonine 3 (H3T3ph) in osteosarcoma cells, along with Sirt1-H3T3ph axis on osteosarcoma cell autophagy. Plasmids or si-RNAs transfection was carried out to alter Sirt1 or H3T3ph expressions. Co-immunoprecipitation analysis and GST pull-down assay were done to probe the relationship between Sirt1 and H3T3ph. Phosphoryltransferase activity of Sirt1 was tested by in vitro kinase activity assay. Cell autophagy was measured by a number of autophagosome, conversion of LC3-I to LC3-II, degradation of long-lived protein and ATG protein expressions. We found that Sirt1 directly interacted with H3 and phosphorylate H3T3 at threonine 3 in osteosarcoma cells. Moreover, Sirt1 facilitated osteosarcoma cell autophagy under starvation condition. H3T3ph took part in the Sirt1-facilitated osteosarcoma cell autophagy under starvation condition. Besides, Sirt1-H3T3ph axis facilitated osteosarcoma cell autophagy might be achieved through transcriptional activation of ATG genes. Sirt1 promoted osteosarcoma initiation and progression might be via phosphorylate H3T3 and then facilitate osteosarcoma cell autophagy through activating ATG genes transcription under starvation condition.

Procaine Inhibits Proliferation and Migration and Promotes Cell Apoptosis in Osteosarcoma Cells by Upregulation of MicroRNA-133b.

Procaine (PCA) is a conventional chemotherapeutic agent for osteosarcoma. Recent studies have proposed that the growth-inhibitory effect of PCA is through regulation of microRNAs (miRNAs). miR-133b has been proven to be a tumor suppressor in osteosarcoma, but whether it is involved in the antitumor effects of PCA on osteosarcoma has not been investigated. In this study, we aimed to explore the effects of PCA on osteosarcoma MG63 cells by regulation of miR-133b, as well as its underlying mechanisms. MG63 cells were treated with different concentrations of PCA, and cell viability, apoptosis, and miR-133b expression were then detected by MTT, flow cytometry, and qRT-PCR, respectively. Cells were then transfected with the miR-133b inhibitor and treated with 2 µM PCA. Thereafter, cell viability, migration, and apoptosis were detected. Analysis of signaling pathways was detected by Western blot. Our results showed that PCA significantly inhibited cell viability and promoted apoptosis and the expression level of miR-133b in a dose-dependent manner (p < 0.05 or p < 0.01). Moreover, we observed that PCA + miR-133b inhibitor dramatically reversed the effects of PCA on cell viability, apoptosis, and migration (p < 0.05 or p < 0.01). In addition, PCA significantly decreased the levels of p/t-AKT (p308 or p473), p/t-ERK, and p/t-S6, whereas PCA + miR-133b inhibitor rescued these effects. Our results suggest that PCA inhibits proliferation and migration but promotes apoptosis in osteosarcoma cells by upregulation of miR-133b. These effects may be achieved by inactivation of the AKT/ERK pathways.