Correlation of distribution characteristics and dynamic changes of gut microbiota with the efficacy of immunotherapy in EGFR-mutated non-small cell lung cancer.

BACKGROUND: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown. METHODS: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy. RESULTS: The clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites. CONCLUSIONS: The use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC.

Redoxhigh phenotype mediated by KEAP1/STK11/SMARCA4/NRF2 mutations diminishes tissue-resident memory CD8+ T cells and attenuates the efficacy of immunotherapy in lung adenocarcinoma.

Metabolism reprogramming within the tumor microenvironment (TME) can have a profound impact on immune cells. Identifying the association between metabolic phenotypes and immune cells in lung adenocarcinoma (LUAD) may reveal mechanisms of resistance to immune checkpoint inhibitors (ICIs). Metabolic phenotypes were classified by expression of metabolic genes. Somatic mutations and transcriptomic features were compared across the different metabolic phenotypes. The metabolic phenotype of LUAD is predominantly determined by reductase-oxidative activity and is divided into two categories: redoxhigh LUAD and redoxlow LUAD. Genetically, redoxhigh LUAD is mainly driven by mutations in KEAP1, STK11, NRF2, or SMARCA4. These mutations are more prevalent in redoxhigh LUAD (72.5%) compared to redoxlow LUAD (17.4%), whereas EGFR mutations are more common in redoxlow LUAD (19.0% vs. 0.7%). Single-cell RNA profiling of pre-treatment and post-treatment samples from patients receiving neoadjuvant chemoimmunotherapy revealed that tissue-resident memory CD8+ T cells are responders to ICIs. However, these cells are significantly reduced in redoxhigh LUAD. The redoxhigh phenotype is primarily attributed to tumor cells and is positively associated with mTORC1 signaling. LUAD with the redoxhigh phenotype demonstrates a lower response rate (39.1% vs. 70.8%, p = 0.001), shorter progression-free survival (3.3 vs. 14.6 months, p = 0.004), and overall survival (12.1 vs. 31.2 months, p = 0.022) when treated with ICIs. The redoxhigh phenotype in LUAD is predominantly driven by mutations in KEAP1, STK11, NRF2, and SMARCA4. This phenotype diminishes the number of tissue-resident memory CD8+ T cells and attenuates the efficacy of ICIs.

Identification of a risk score model based on tertiary lymphoid structure-related genes for predicting immunotherapy efficacy in non-small cell lung cancer.

BACKGROUND: Tertiary lymphoid structures (TLSs) affect the prognosis and efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC), but the underlying mechanisms are not well understood. METHODS: TLSs were identified and categorized online from the Cancer Digital Slide Archive (CDSA). Overall survival (OS) and disease-free survival (DFS) were analyzed. GSE111414 and GSE136961 datasets were downloaded from the GEO database. GSVA, GO and KEGG were used to explore the signaling pathways. Immune cell infiltration was analyzed by xCell, ssGSEA and MCP-counter. The analysis of WGCNA, Lasso and multivariate cox regression were conducted to develop a gene risk score model based on the SU2C-MARK cohort. RESULTS: TLS-positive was a protective factor for OS according to multivariate cox regression analysis (p = 0.029). Both the TLS-positive and TLS-mature groups exhibited genes enrichment in immune activation pathways. The TLS-mature group showed more activated dendritic cell infiltration than the TLS-immature group. We screened TLS-related genes using WGCNA. Lasso and multivariate cox regression analysis were used to construct a five-genes (RGS8, RUF4, HLA-DQB2, THEMIS, and TRBV12-5) risk score model, the progression free survival (PFS) and OS of patients in the low-risk group were markedly superior to those in the high-risk group (p < 0.0001; p = 0.0015, respectively). Calibration and ROC curves indicated that the combined model with gene risk score and clinical features could predict the PFS of patients who have received immunotherapy more accurately than a single clinical factor. CONCLUSIONS: Our data suggested a pivotal role of TLSs formation in survival outcome and immunotherapy response of NSCLC patients. Tumors with mature TLS formation showed more activated immune microenvironment. In addition, the model constructed by TLS-related genes could predict the response to immunotherapy and is meaningful for clinical decision-making.

Association of COVID-19 and Lung Cancer: Short-Term and Long-Term Interactions.

Background: COVID-19 has been ravaging the globe for more than three years. Due to systemic immunosuppression of anti-tumor therapy, application of chemotherapy and adverse effects of surgery, the short- and long-term prognosis of cancer patients to COVID-19 are of significant concern. Method: This research included three parts of data. The first part of the data came from the public database that covered Veneto residents. The second part of the data included participants in Guangzhou. The third part of the data was used for MR analysis. We assessed the associations by logistic, linear or Cox regression when appropriate. Result: Lung cancer patients with COVID-19 had shorter progression-free survival (PFS) after COVID-19 (Model II: HR: 3.28, 95% CI: 1.6~6.72; Model III: HR: 3.39, 95% CI: 1.45~7.95), compared with lung cancer patients without COVID-19. Targeted therapy patients recovered from SARS-CoV-2 infection more quickly (Model I: ß: -0.58, 95% CI: -0.75~-0.41; Model II: ß: -0.59, 95% CI: -0.76~-0.41; Model III: ß: -0.57; 95% CI: -0.75~-0.40). Conclusions: PFS in lung cancer patients is shortened by COVID-19. The outcome of COVID-19 in lung cancer patients was not significantly different from that of the healthy population. In lung cancer patients, targeted therapy patients had a better outcome of COVID-19, while chemotherapy patients had the worst.

Allelic Context of EGFR C797X-Mutant Lung Cancer Defines Four Subtypes With Heterogeneous Genomic Landscape and Distinct Clinical Outcomes.

INTRODUCTION: EGFR C797X (C797S or C797G) mutation is the most frequent on-target mechanism of resistance to osimertinib. The hypothesis that the allelic context of C797X/T790M has implications for treatment is on the basis of sporadic reports and needs validation with larger cohorts. METHODS: We identified patients with EGFR C797X-mutant NSCLC from nine centers who progressed on osimertinib, all analyzed in a single laboratory through next-generation sequencing. We analyzed genomic profiles and assessed associations between clinical outcomes and C797X status. RESULTS: A total of 365 EGFR C797X-mutant cases were categorized into four subtypes on the basis of allelic context: in cis (75.3%), in trans (6.4%), cis&trans (10.4%), and C797X-only (7.9%). Genomically, the cis&trans subtype displayed the highest frequency of concurrent alterations at osimertinib resistance sites (21.1%), while the in cis subtype had the lowest (8.4%). Clinically, cis&trans patients exhibited the worst progression-free survival (PFS) on both previous (median 7.7 mo) and subsequent treatment (median 1.0 mo) and overall survival (median 3.9 mo). In subsequent treatments, in cis patients exhibited superior PFS with combined brigatinib and cetuximab (median 11.0 mo) compared with other regimens (p = 0.005), while in trans patients exhibited variable outcomes with combined first or second- and third-generation EGFR inhibitor (PFS range: 0.7-8.1 mo, median 2.6 mo). Notably, subtype switching was observed after subsequent treatments, predominantly toward the in cis subtype. CONCLUSIONS: Allelic context could define four EGFR C797X-mutant NSCLC subtypes with heterogeneous genetic landscapes and distinct clinical outcomes. Subsequent treatments further complicate the scenario through subtype switching.

Molybdenum disulfide nanosheet/polyimide composites with improved tribological performances, surface properties, antibacterial effects and osteogenesis for facilitating osseointegration.

Polymeric biocomposites display some advantages over metal or ceramic biomaterials, and are regarded as a promising candidate for artificial joint application. Herein, molybdenum disulfide (MD) nanosheets were prepared and incorporated into polyimide (PI) to form MD/PI composites with a MD content of 20 wt% (PM20) and 40 wt% (PM40). The results revealed that incorporation of MD nanosheets obviously improved the tribological performances, surface properties (e.g., roughness, wettability and surface energy) and protein absorption of the composites, which enhanced with the increase of MD content. In addition, the composites containing MD nanosheets exhibited antibacterial effects, and the antibacterial effects of PM40 were higher than those of PM20 and PI. PM40 significantly stimulated the cellular responses of rat bone mesenchymal stem cells in vitro, which was better than PM20 and PI. Furthermore, PM40 remarkably accelerated osteogenesis and osseointegration in vivo, which was better than PM20 and PI. In summary, the MD content in composites played pivotal roles in improving not only tribological performances, surface properties, antibacterial effects and cellular response in vitro but also osteogenesis and osseointegration in vivo. As a result, PM40 with high MD content exhibited excellent osteogenic bioactivity and antibacterial effects, which would have great potential for artificial joint applications.

Microporous surface containing flower-like molybdenum disulfide submicro-spheres of sulfonated polyimide with antibacterial effect and promoting bone regeneration and osteointegration.

Implanted materials with both osteogenic and antibacterial functions are promising for facilitating osteointegration and preventing infection for orthopedic applications. In this work, we synthesized flower-like molybdenum disulfide (fMD) submicro-spheres containing nanosheets, which were incorporated onto the microporous surface of polyimide (PI) via concentrated sulfuric acid, suspending fMD contents of 5 wt% (SPM1) and 10 wt% (SPM2). Compared with sulfonated polyimide (SPM0), both SPM1 and SPM2 with microporous surfaces containing fMD exhibited nano-submicro-microporous surfaces, which improved the surface roughness, wettability, and surface energy. Due to there being more fMD submicro-spheres on the microporous surface, SPM2 revealed a better antibacterial effect than SPM1. In addition, compared with SPM1 and SPM0, SPM2 with more fMD significantly promoted rat bone marrow-derived stromal cell response in vitro. Moreover, SPM2 remarkably enhanced new bone formation and osteointegration in vivo. In summary, the combination of fMD with the microporous surface of SPM2 resulted in a nano-submicro-microporous surface with optimized surface performance, which possessed not only osteogenic bioactivity but also an antibacterial effect. As a bone implant, SPM2 with osteogenic and antibacterial functions may have enormous potential as a bone tissue substitute.

Tantalum oxide submicro-particles into microporous coating on polyimide possessing antibacterial property and inducing cellular response for orthopedic application.

Surface characteristics of the biomaterials have significant effects on response of osteoblast and formation of new bone tissue. In this study, to improve the bio-performance of polyimide (PI) as an implantable material for bone substitute, concentrated sulfuric acid suspension with tantalum (V) oxide (vTO) submicro-particles of 10w% (PIST10) and 15w% (PIST15) was utilized to modify PI surface. After sulfonation, microporous coatings including vTO particles were created on PI (PIST10 and PIST15) while microporous coating without vTO particles was also created on PI (PIS). Results showed that surface roughness, hydrophilicity and protein adsorption of PIST15 was remarkably higher than PIST10 and PIS. Furthermore, after soaking into simulated body fluid (SBF), no apatite mineralization on PIS was found, while PIST15 with high vTO content exhibited better apatite mineralization compared with PIST10. Moreover, PIS showed low antibacterial property, while PIST15 with high vTO content revealed better antibacterial property compared with PIST10. In addition, cellular response (such as adhesion, proliferation and alkaline phosphatase activity) of bone marrow stromal cells (BMSC) of rat to PIST15 was higher than PIST10 and PIS. In conclusion, the microporous coating of PIST15 including vTO submicro-particles possessed good antibacterial property and bioactivity, which significantly promoted the responses of BMSC. Therefore, PIST15 has potential application prospects for bone substitute.

TIP30 overcomes gefitinib resistance by regulating cytoplasmic and nuclear EGFR signaling in non-small-cell lung cancer.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) (eg, gefitinib) exert potent therapeutic efficacy in non-small-cell lung cancer (NSCLC) harboring EGFR-activating mutations. However, the resistance to EGFR TKIs limits their clinical therapeutic efficacy. TIP30, a newly identified tumor suppressor, appears to be involved in the regulation of cytoplasmic and nuclear EGFR signaling in NSCLC. Our previous study demonstrated that TIP30 regulated EGF-dependent cyclin D1 transcription in human lung adenocarcinoma and suppressed tumorigenesis. In the present study, the involvement of TIP30 in combating gefitinib resistance in NSCLC was determined for the first time in vitro and in vivo. Gain and loss of function studies showed that overexpression of TIP30 effectively sensitized cells to gefitinib in vitro, whereas TIP30 inhibition promoted gefitinib cell resistance. Moreover, TIP30 negatively regulated the activation of the p-AKT and p-MEK signaling pathways in PC9/GR. Importantly, PC9/GR harbored high levels of nuclear EGFR, and overexpression of TIP30 restored irregular EGFR trafficking and degradation from early endosomes to the late endosomes, decreasing the nuclear accumulation of EGFR, which may partly or totally inhibit EGFR-mediated induction of c-Myc transcription. Xenographic tumors induced by overexpression of TIP30 by PC9/GR cells in nude mice were suppressed compared with their original counterparts. Overall, it was revealed that TIP30 overexpression restored gefitinib sensitivity in NSCLC cells and attenuated the cytoplasmic and nuclear EGFR signaling pathways and may be a promising biomarker in gefitinib resistance in NSCLC.

Fabrication of Submicro-Nano Structures on Polyetheretherketone Surface by Femtosecond Laser for Exciting Cellular Responses of MC3T3-E1 Cells/Gingival Epithelial Cells.

PURPOSE: Polyetheretherketone (PEEK) exhibits high mechanical strengths and outstanding biocompatibility but biological inertness that does not excite the cell responses and stimulate bone formation. The objective of this study was to construct submicro-nano structures on PEEK by femtosecond laser (FSL) for exciting the responses of MC3T3-E1 cells and gingival epithelial (GE) cells, which induce regeneration of bone/gingival tissues for long-term stability of dental implants. MATERIALS AND METHODS: In this study, submicro-nano structures were created on PEEK surface by FSL with power of 80 mW (80FPK) and 160 mW (160FPK). RESULTS: Compared with PEEK, both 80FPK and 160FPK with submicro-nano structures exhibited elevated surface performances (hydrophilicity, surface energy, roughness and protein absorption). Furthermore, in comparison with 80FPK, 160FPK further enhanced the surface performances. In addition, compared with PEEK, both 80FPK and 160FPK significantly excited not only the responses (adhesion, proliferation, alkaline phosphatase [ALP] activity and osteogenic gene expression) of MC3T3-E1 cells but also responses (adhesion as well as proliferation) of GE cells of human in vitro. Moreover, in comparison with 80FPK, 160FPK further enhanced the responses of MC3T3-E1 cells/GE cells. CONCLUSION: FSL created submicro-nano structures on PEEK with elevated surface performances, which played crucial roles in exciting the responses of MC3T3-E1 cells/GE cells. Consequently, 160FPK with elevated surface performances and outstanding cytocompatibility would have enormous potential as an implant for dental replacement.

A microporous surface containing Si3N4/Ta microparticles of PEKK exhibits both antibacterial and osteogenic activity for inducing cellular response and improving osseointegration.

As an implantable biomaterial, polyetherketoneketone (PEKK) exhibits good mechanical strength but it is biologically inert while tantalum (Ta) possesses outstanding osteogenic bioactivity but has a high density and elastic modulus. Also, silicon nitride (SN) has osteogenic and antibacterial activity. In this study, a microporous surface containing both SN and Ta microparticles on PEKK (STP) exhibiting excellent osteogenic and antibacterial activity was created by sulfonation. Compared with sulfonated PEKK (SPK) without microparticles, the surface properties (roughness, surface energy, hydrophilicity and protein adsorption) of STP significantly increased due to the SN and Ta particles presence on the microporous surface. In addition, STP also exhibited outstanding antibacterial activity, which inhibited bacterial growth in vitro and prevented bacterial infection in vivo because of the presence of SN particles. Moreover, the microporous surface of STP containing both SN and Ta particles remarkably induced response (e.g., proliferation and differentiation) of rat bone mesenchymal stem (rBMS) cells in vitro. Furthermore, STP significantly improved new bone regeneration and osseointegration in vivo. Regarding the induction of cellular response in vitro and improvement of osseointegration in vivo, the microporous surface containing Ta was better than the surface with SN particles. In conclusion, STP with optimized surface properties activated cellular responses in vitro, enhanced osseointegration and prevented infection in vivo. Therefore, STP possessed the dual biofunctions of excellent osteogenic and antibacterial activity, showing great potential as a bone substitute.

Nanostructured Coating of Non-Crystalline Tantalum Pentoxide on Polyetheretherketone Enhances RBMS Cells/HGE Cells Adhesion.

PURPOSE: As a dental material, polyetheretherketone (PEEK) is bioinert that does not induce cellular response and bone/gingival tissues regeneration. This study was to develop bioactive coating on PEEK and investigate the effects of coating on cellular response. MATERIALS AND METHODS: Tantalum pentoxide (TP) coating was fabricated on PEEK surface by vacuum evaporation and responses of rat bone marrow mesenchymal stem (RBMS) cells/human gingival epithelial (HGE) were studied. RESULTS: A dense coating (around 400 nm in thickness) of TP was closely combined with PEEK (PKTP). Moreover, the coating was non-crystalline TP, which contained many small humps (around 10 nm in size), exhibiting a nanostructured surface. In addition, the roughness, hydrophilicity, surface energy, and protein adsorption of PKTP were remarkably higher than that of PEEK. Furthermore, the responses (adhesion, proliferation, and osteogenic gene expression) of RBMS cells, and responses (adhesion and proliferation) of HGE cells to PKTP were remarkably improved in comparison with PEEK. It could be suggested that the nanostructured coating of TP on PEEK played crucial roles in inducing the responses of RBMS/HGE cells. CONCLUSION: PKTP with elevated surface performances and outstanding cytocompatibility might have enormous potential for dental implant application.

Implantable PEKK/tantalum microparticles composite with improved surface performances for regulating cell behaviors, promoting bone formation and osseointegration.

Polyetherketoneketone (PEKK) exhibits admirable biocompatibility and mechanical performances but bioinert while tantalum (Ta) possesses excellent osteogenesis and osseointegration but high elastic modulus and density, and processing is too difficult and expensive. In the present study, combining of the advantages of both PEKK and Ta, implantable composites of PEKK/Ta were fabricated by blending PEKK with Ta microparticles of 20 v% (PT20) and 40 v% (PT40) content. In comparison with PT20 and PEKK, the surface hydrophilicity, surface energy, roughness and proteins adsorption as well as mechanical performances of PT40 significantly increased because of the higher Ta particles content in PEKK. Furthermore, PT40 exhibited the mechanical performances (e.g., compressive strength and modulus of elasticity) close to the cortical bone of human. Compared with PT20 and PEKK, PT40 with higher Ta content remarkably enhanced the responses (including adhesion, proliferation and osteogenic differentiation) of MC3T3-E1 cells in vitro. Moreover, PT40 markedly improved bone formation as well as osseointegration in vivo. In short, incorporation of Ta microparticles into PEKK created implantable composites with improved surface performances, which played key roles in stimulating cell responses/bone formation as well as promoting osseointegration. PT40 might have great potential for bear-loading bone substitute.

Construction of a hierarchical micro & nanoporous surface for loading genistein on the composite of polyetheretherketone/tantalum pentoxide possessing antibacterial activity and accelerated osteointegration.

Nanoporous tantalum pentoxide (NTP) particles with a pore size of about 10 nm were synthesized and blended with polyetheretherketone (PEEK) to fabricate a PEEK/NTP composite (PN). Subsequently, PN was treated by concentrated sulfuric acid to create a microporous surface (pore size of around 2 µm) on sulfonated PN (SPN), which formed a hierarchical micro & nanoporous surface. Compared with PN, the porous surface of SPN exhibited higher roughness, hydrophilicity, and surface energy. In addition, genistein (GT) was loaded into the porous surface of SPN (SPNG), which showed high GT loading capacity and sustained release of GT into phosphate buffered saline (PBS). Moreover, SPNG revealed excellent antibacterial activity, which inhibited bacterial (E. coli and S. aureus) growth in vitro due to the synergistic effects of both sulfonic acid (SO3H) groups and the sustained release of GT. Compared with PN, SPN significantly improved the adhesion, proliferation, and osteogenic differentiation of bone mesenchymal stem cells in vitro. Moreover, compared with SPN, SPNG further enhances the cell responses. Compared with PN, SPN remarkably improved bone formation and osteointegration in vivo. Furthermore, compared with SPN, SPNG further enhanced the osteointegration. In short, SPNG with a micro & nanoporous surface, SO3H groups, and the sustained release of GT exhibited antibacterial activity and accelerated osteointegration, which would have tremendous potential as drug-loaded implants for bone substitute.

Improvement of rBMSCs Responses to Poly(propylene carbonate) Based Biomaterial through Incorporation of Nanolaponite and Surface Treatment Using Sodium Hydroxide.

Poly(propylene carbonate) (PPC) has aroused extensive attention in the biomaterial field because of its excellent biocompatibility and appropriate degradability, but surface hydrophobicity and bioinertness limit its applications for bone repair and tissue engineering. In this study, a bioactive PPC/laponite (LAP) nanocomposite (PL) was prepared by a melt-blending method, and a microporous surface on PPC and PL (PT and PLT) was created by sodium hydroxide (NaOH) treatment. The results demonstrated that the surface roughness, hydrophilicity, surface energy, and degradability as well as protein adsorption of PLT were obviously improved compared with PPC. Moreover, the degradability of PLT was remarkably enhanced with a slight increase of pH values in Tris-HCl solution. Furthermore, adhesion and proliferation as well as osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) to PLT were significantly promoted compared with PPC. The results suggested that incorporating LAP into PPC obviously improved the surface performance of PL (with nanotopography), and surface treatment with NaOH further enhanced surface properties of PLT (with micronanotopography and hydrophilic groups), which significantly promoted responses of rBMSCs. In short, PLT displayed excellent cytocompatibility, which would have great potential for bone regeneration.

Effects of a Coating of Nano Silicon Nitride on Porous Polyetheretherketone on Behaviors of MC3T3-E1 Cells in Vitro and Vascularization and Osteogenesis in Vivo.

To improve the bioperformances of porous polyetheretherketone (PPK) for bone repair, silicon nitride-coated PPK (CSNPPK) was prepared by a method of suspension coating and melt binding. The results revealed that, as compared with PPK, the surface roughness, compressive strength, and water absorption of CSNPPK increased, while the pore size and porosity of CSNPPK exhibited no obvious changes. In addition, the cellular responses (including attachment, proliferation, and differentiation as well as osteogenically related gene expressions) of the MC3T3-E1 cells to CSNPPK were remarkably promoted compared with PPK and dense polyetheretherketone in vitro. Moreover, in the model of rabbit femoral condyle defects, the results of micro computed tomography and histological and mechanical evaluation revealed that the ingrowth of new vessels and bone tissues into CSNPPK was significantly greater than that into PPK in vivo. Furthermore, the load-displacement and push-out loads for CSNPPK with bone tissues were higher than for PPK, indicating good osseointegration. In short, CSNPPK not only promoted vascularization but also enhanced osteogenesis as well as osseointegration in vivo. Therefore, it can be suggested that CSNPPK with good biocompatibility, osteogenic activity, and vascularization might be a promising candidate as an implant for bone substitute and repair.

Influences of tantalum pentoxide and surface coarsening on surface roughness, hydrophilicity, surface energy, protein adsorption and cell responses to PEEK based biocomposite.

Polyetheretherketone (PEEK) biomaterial has become increasingly popular in orthopedic applications due to its favorable biocompatibility, biostability, mechanical strength and elastic modulus similar to natural bones. In this research, in order to improve the biological performances of PEEK, tantalum pentoxide (Ta2O5) was incorporated into PEEK to fabricate PEEK/Ta2O5 composites (PTC) using a method of cold press-sintering, and surface coarsening of PTC was prepared by sand blasting. The results showed that the Ta2O5 particles were uniformly disperse into PEEK, and thermal and mechanical properties of PTC were enhanced with the increase of Ta2O5 content. In addition, incorporating Ta2O5 into PEEK and surface coarsening could improve surface roughness, hydrophilicity, surface energy and protein absorption of PTC. Furthermore, the adhesion and proliferation as well as osteogenic differentiation of BMSCs on PTC were significantly promoted and regulated by Ta2O5 content and surface coarsening. The results indicated that surface coarsening of PTC (PTCS) with high surface roughness, hydrophilicity and surface energy could induce positive cellular responses, showing good cytocompatibility. PTCS might have a great potential as implants for bone repair.