Intrinsic Surface Effects of Tantalum and Titanium on Integrin α5ß1/ ERK1/2 Pathway-Mediated Osteogenic Differentiation in Rat Bone Mesenchymal Stromal Cells.

BACKGROUND/AIMS: Accumulating evidence demonstrates the superior osteoinductivity of tantalum (Ta) to that of titanium (Ti); however, the mechanisms underlying these differences are unclear. Thus, the objective of the present study was to examine the effects of Ta and Ti surfaces on osteogenesis using rat bone mesenchymal stromal cells (rBMSCs) as a model. METHODS: Ta and Ti substrates were polished to a mirror finish to minimize the influences of structural factors, and the intrinsic surface effects of the two materials on the integrin α5ß1/mitogen-activated protein kinases 3 and 1 (ERK1/2) cascade-mediated osteogenesis of rBMSCs were evaluated. Alkaline phosphatase (ALP) activity, Alizarin Red staining, real-time polymerase chain reaction, and western blot assays of critical osteogenic markers were conducted to evaluate the effects of the two substrates on cell osteogenesis. Moreover, the role of the integrin α5ß1/ERK1/2 pathway on the osteoinductive performance of Ta and Ti was assessed by up- and down-regulation of integrin α5 and ß1 with RNA interference, as well as through ERK1/2 inhibition with U0126. RESULTS: Osteogenesis of rBMSCs seeded on the Ta surface was superior to that of cells seeded on the Ti surface in terms of ALP activity, extracellular matrix calcification, and the expression of integrin α5, integrin ß1, ERK1/2, Runt-related transcription factor 2, osteocalcin, collagen type I, and ALP at both the mRNA and protein levels. Moreover, down-regulation of integrin α5 or integrin ß1, or ERK1/2 inhibition severely impaired the osteoblastic differentiation on the Ta surface. By contrast, over-expression of integrin α5 or integrin ß1 improved osteogenesis on the Ti substrates, while subsequent ERK1/2 inhibition abrogated this effect. CONCLUSION: The integrin α5ß1/ERK1/2 pathway plays a crucial role in regulating rBMSCs osteogenic differentiation; thus, the greater ability of a Ta surface to trigger integrin α5ß1/ERK1/2 signaling may explain its better osteoinductivity. The different effects of Ta and Ti surfaces on rBMSC osteogenesis are considered to be related to the conductive behaviors between integrin α5ß1 and the oxides spontaneously formed on the two metals. These results should facilitate the development of engineering strategies with Ta and Ti surfaces for improved osteogenesis in endosteal implants.

Multifunctional Theranostic Nanoplatform Based on Fe-mTa2O5@CuS-ZnPc/PCM for Bimodal Imaging and Synergistically Enhanced Phototherapy.

Multifunctional nanotheranostic agent with high performance for tumor site-specific generation of singlet oxygen (1O2) as well as imaging-guidance is crucial to laser-mediated photodynamic therapy. Here, we introduced a versatile strategy to design a smart nanoplatform using phase change material (PCM) to encapsulate photosensitizer (zinc phthalocyanine, ZnPc) in copper sulfide loaded Fe-doped tantalum oxide (Fe-mTa2O5@CuS) nanoparticles. When irradiated by 808 nm laser, the PCM is melted due to the hyperthermia effect from CuS nanoparticles, inducing the release of ZnPc to produce toxic 1O2 triggered by 650 nm light with very low power density (5 mW/cm2). Then, the produced heat and toxic 1O2 can kill tumor cells in vitro and in vivo effectively. Furthermore, the special properties of Fe-mTa2O5 endow the nanoplatform with excellent computed tomography (CT) and T1-weighted magnetic resonance imaging ( T1-MRI) performance for guiding and real-time monitoring of therapeutic effect. This work presents a feasible way to design smart nanoplatform for controllable generation of heat and 1O2, achieving CT/ T1-MRI dual-modal imaging-guided phototherapy.

Application of combined porous tantalum scaffolds loaded with bone morphogenetic protein 7 to repair of osteochondral defect in rabbits.

PURPOSE: Porous tantalum (PT) has been widely used in orthopaedic applications for low modulus of elasticity, excellent biocompatibility, and the microstructures similar to cancellous bone. In order to improve the biological activity of PT, biologically active factors can be combined with the material. The purpose of this study was to investigate if bone morphogenetic protein 7 (BMP-7) modifications could enhance the repairing of cartilage of PT in osteochondral defect in medial femoral condyle of rabbits. METHODS: A cylindrical osteochondral defect model was created on the animal medial femoral condyle of and filled as follows: PT modified with BMP-7 for MPT group, non-modified PT for the PT group, while no implants were used for the blank group. The regenerated osteochondral tissue was assessed and analyzed by histological observations at four, eight and 16 weeks post-operation and evaluated in an independent and blinded manner by five different observers using a histological score. Osteochondral and subchondral bone defect repair was assessed by micro-CT scan at 16 weeks post-operation, while the biomechanical test was performed at 16 weeks post-operation. RESULTS: Briefly, higher overall histological score was observed in the MPT group compared to PT group. Furthermore, more new osteochondral tissue and bone formed at the interface and inside the inner pores of scaffolds of the MPT group compared to PT group. Additionally, the micro-CT data suggested that the new bone volume fractions and the quantity and quality of trabecular bone, as well as the maximum release force of the bone, were higher in the MPT group compared to PT group. CONCLUSIONS: We demonstrated that the applied modified PT with BMP-7 promotes excellent subchondral bone regeneration and may serve as a novel approach for osteochondral defects repair.

Biocompatibility and mineralized nodule formation of Neo MTA Plus and an experimental tricalcium silicate cement containing tantalum oxide.

AIM: To evaluate the biocompatibility and mineralized nodule formation of an experimental tricalcium silicate cement with tantalum oxide (TSC/Ta2 O5 ) as radiopacifier, Neo MTA Plus (Avalon Biomed Inc., Bradenton, FL, USA) and MTA (Angelus, Londrina, PR, Brazil) on human osteoblast-like cells (Saos-2). METHODOLOGY: Biocompatibility was evaluated by 3-(4,5-dimethyl-thiazoyl)-2,5-diphenyl-tetrazolium bromide (MTT) and neutral red (NR) assays, after exposure of Saos-2 to cement extracts at 1 : 1, 1 : 2, 1 : 4 and 1 : 8 dilutions for 24 h. Bioactivity was evaluated by alkaline phosphatase (ALP) activity, and calcium deposits were detected with alizarin red staining (ARS). Statistical analysis was performed with analysis of variance and Bonferroni or Tukey post-test (α = 0.05). RESULTS: The MTT assay revealed lower cytotoxicity for NEO and MTA (P < 0.05), and higher for TSC/Ta2 O5 at 1 : 1 and 1 : 2 dilutions when compared to serum-free medium - control (P > 0.05). At 1 : 4 dilution, the TSC/Ta2 O5 cytotoxicity was similar to the control (P > 0.05). At 1 : 8 dilution, cell viability was significantly greater than the control (P < 0.05). Saos-2 cell viability performed using the NR assay at all dilutions revealed no cytotoxic effect of MTA, NEO and TSC/Ta2 O5 . ALP activity at 1 and 3 days was similar to the control (P > 0.05). TSC/Ta2 O5 had significantly greater ALP activity at 7 days when compared with the control (P < 0.05). All materials induced the production of mineralized nodules, and NEO produced significantly more mineralized nodules than MTA and TSC/Ta2 O5 (P < 0.05). CONCLUSIONS: Neo MTA Plus and TSC/Ta2 O5 were biocompatible and induced ALP activity in Saos-2 cells. Both materials induced mineralized nodule formation by Saos-2 with Neo MTA Plus producing significantly more.

Evaluation of the 3D finite element method using a tantalum rod for osteonecrosis of the femoral head.

BACKGROUND: The aim of this study was to contrast the collapse values of the postoperative weight-bearing areas of different tantalum rod implant positions, fibula implantation, and core decompression model and to investigate the advantages and disadvantages of tantalum rod implantation in different ranges of osteonecrosis in comparison with other methods. MATERIAL AND METHODS: The 3D finite element method was used to establish the 3D finite element model of normal upper femur, 3D finite element model after tantalum rod implantation into different positions of the upper femur in different osteonecrosis ranges, and other 3D finite element models for simulating fibula implant and core decompression. RESULTS: The collapse values in the weight-bearing area of the femoral head of the tantalum rod implant model inside the osteonecrosis area, implant model in the middle of the osteonecrosis area, fibula implant model, and shortening implant model exhibited no statistically significant differences (p>0.05) when the osteonecrosis range was small (60°). The stress values on the artificial bone surface for the tantalum rod implant model inside the osteonecrosis area and the shortening implant model exhibited statistical significance (p<0.01). CONCLUSIONS: Tantalum rod implantation into the osteonecrosis area can reduce the collapse values in the weight-bearing area when osteonecrosis of the femoral head (ONFH) was in a certain range, thereby obtaining better clinical effects. When ONFH was in a large range (120°), the tantalum rod implantation inside the osteonecrosis area, shortening implant or fibula implant can reduce the collapse values of the femoral head, as assessed by other methods.

Experimental titanium alloys for dental applications.

STATEMENT OF PROBLEM: Although the use of titanium has increased, casting difficulties limit routine use. PURPOSE: The purpose of the present study was to compare the mechanical properties and biocompatibility of the experimental titanium alloys titanium-5-zirconium, titanium-5-tantalum, and titanium-5-tantalum-5-zirconium (in wt%) with those of commercially pure titanium. MATERIAL AND METHODS: Specimens of titanium alloys and commercially pure titanium were cast by using plasma. Their modulus of elasticity and ultimate tensile strength were determined in a universal testing machine. Biocompatibility was evaluated with SCC9 cells. In periods of 1, 4, 7, 10, and 14 days, cell proliferation was evaluated by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay, and cell viability was evaluated in the 7-day period. Cell morphology was evaluated at 2, 12, and 24 hours. Modulus of elasticity, ultimate tensile strength, and cell viability were analyzed by 1-way ANOVA and the Bonferroni test; cell proliferation data were compared by 2-way ANOVA (alloy versus time) and by the Bonferroni test; and the cell morphology data were analyzed by split-plot design. All statistical tests were performed at the 95% confidence level (P<.05). RESULTS: Titanium-5-tantalum presented the lowest modulus of elasticity and ultimate tensile strength, whereas titanium-5-zirconium and titanium-5-tantalum-5-zirconium were statistically similar to commercially pure titanium. Cell proliferation and viability were not affected by any alloy being similar to those observed for commercially pure titanium. No noticeably differences were found in the morphology of cells cultured on any alloy and commercially pure titanium. CONCLUSION: Experimental alloys, especially titanium-5-zirconium and titanium-5-tantalum-5-zirconium, presented promising mechanical results for future studies and clinical applications. In addition, these alloys, evaluated by cell proliferation, viability, and morphology, were found to be biocompatible in vitro.

Tantalum Particles Promote M2 Macrophage Polarization and Regulate Local Bone Metabolism via Macrophage-Derived Exosomes Influencing the Fates of BMSCs.

In this study, the regulatory role and mechanisms of tantalum (Ta) particles in the bone tissue microenvironment are explored. Ta particle deposition occurs in both clinical samples and animal tissues following porous Ta implantation. Unlike titanium (Ti) particles promoting M1 macrophage (Mϕ) polarization, Ta particles regulating calcium signaling pathways and promoting M2 Mϕ polarization. Ta-induced M2 Mϕ enhances bone marrow-derived mesenchymal stem cells (BMSCs) proliferation, migration, and osteogenic differentiation through exosomes (Exo) by upregulating miR-378a-3p/miR-221-5p and downregulating miR-155-5p/miR-212-5p. Ta particles suppress the pro-inflammatory and bone resorption effects of Ti particles in vivo and in vitro. In a rat femoral condyle bone defect model, artificial bone loaded with Ta particles promotes endogenous Mϕ polarization toward M2 differentiation at the defect site, accelerating bone repair. In conclusion, Ta particles modulate Mϕ polarization toward M2 and influence BMSCs osteogenic capacity through Exo secreted by M2 Mϕ, providing insights for potential bone repair applications.

Bioactivity evaluation of three calcium silicate-based endodontic materials.

AIM: To compare white ProRoot MTA (WMTA), EndoSequence BC sealer (BC sealer) and Biodentine with regard to their ability to produce apatites and cause Ca and Si incorporation in adjacent human root canal dentine after immersion in phosphate-buffered saline (PBS). METHODOLOGY: Root sections of human single-rooted teeth were filled with one of the materials and immersed in PBS for 1, 7, 30 or 90 days (n = 5 each). Morphology and elemental composition of surface precipitates and interfacial dentine were analysed using a wavelength-dispersive X-ray spectroscopy electron probe microanalyser with image observation function. Ca- and Si-incorporation depths in the interfacial dentine were measured. In addition, the amount of Ca ions released from the test materials was measured by EDTA titration. RESULTS: All materials produced surface precipitates of acicular or lath-like morphology with Ca/P ratio of 1.6 : 2.0. Within dentinal tubules, the three materials formed tag-like structures that were frequently composed of Ca- and P-rich and Si-poor materials, suggesting intratubular precipitation. Ca- and Si-incorporation depths were in the order of Biodentine > WMTA > BC sealer, with a significant difference between BC sealer and the others at several time-points (P < 0.05, anova and Tukey's honestly significant difference test). The concentration of released Ca ions was in the order of Biodentine > WMTA > BC sealer with significant differences between the materials (P < 0.05). CONCLUSIONS: Compared with Biodentine and WMTA, BC sealer showed less Ca ion release and did not show Ca and Si incorporation as deeply in human root canal dentine when immersed in PBS for up to 90 days.

The use of nanocomposite coatings with various physicochemical properties in tissue engineering.

We studied the effect of nanocomposite coatings with various physicochemical properties on the structural and functional properties (adhesion potential, phenotype, gene expression) of mesenchymal stem cells. Of all tested nanocoatings (Al2O3, ZrO2, Ta2O5), oxide coating Al2O3 enriched in vitro monolayer bone marrow cell culture with cells carrying mesenchymal stem cells phenotype markers and stimulated expression of ido gene, which can confer new therapeutic potencies to these cells and extend their application in clinical practice.

Luteolin-loaded biocomposites containing tantalum and polyimide with antibacterial effects for facilitating osteogenic differentiation and bone bonding.

Polymer-based composites are considered promising candidates for bone repair as they possess some outstanding advantages over ceramic/metallic/polymeric biomaterials. Tantalum (Ta)/polyimide (PI) biocomposites (PT) containing 20 v% (PT20) and 40 v% (PT40) Ta nanoparticles were fabricated, and luteolin (LU) was loaded on PT40 (LUPT40). Compared with PT20 and PI, PT40 with a high Ta content displayed high surface behaviors (e.g., roughness, surface energy, and hydrophilicity). PT40 remarkably improved cell adhesion and multiplication, and LUPT40 with LU displayed further enhancement in vitro. Moreover, LUPT40 evidently boosted osteoblastic differentiation while suppressing osteoclastic differentiation. Furthermore, LUPT40 exhibited good antibacterial effects because of the slow release of LU. The in vivo results confirmed that PT40 markedly promoted bone formation and LUPT40 further enhanced bone formation/bone bonding. In brief, the incorporation of Ta particles improved the surface behaviors of PT40, which stimulated cell response/bone formation. Moreover, the slow release of LU from LUPT40 not only promoted cell response/bone formation but also enhanced bone bonding. The synergistic effects of Ta and LU release from LUPT40 enhanced bone formation/bone bonding. Therefore, LUPT40 would have great potential for the repair of bear-loading bone.

Optimize the pore size-pore distribution-pore geometry-porosity of 3D-printed porous tantalum to obtain optimal critical bone defect repair capability.

The treatment and reconstruction of large or critical size bone defects is a challenging clinical problem. Additive manufacturing breaks the technical difficulties of preparing complex conformation and anatomically matched personalized porous tantalum implants, but the ideal pore structure for 3D-printed porous tantalum in critical bone defect repair applications remains unclear. Guiding appropriate bone tissue regeneration by regulating proper pore size-pore distribution-pore geometry-porosity is a challenge for its fabrication and application. We fabricated porous tantalum (PTa) scaffolds with six different combinations of pore structures using powder bed laser melting (L-PBF) technology. In vitro biological experiments were conducted to systematically investigate the effects of pore structure characteristics on osteoblast behaviors, showing that the bionic trabecular structure with both large and small poress facilitated cell permeation, proliferation and differentiation compared to the cubic structure with uniform pore sizes. The osteogenesis of PTa with different porosity of trabecular structures was further investigated by a rabbit condyle critical bone defect model. Synthetically, T70% up-regulated the expression of osteogenesis-related genes (ALP, COLI, OCN, RUNX-2) and showed the highest bone ingrowth area and bone contact rate in vivo after 16 weeks, with the best potential for critical bone defect repair. Our results suggested that the bionic trabecular structure with a pore size distribution of 200-1200 µm, an average pore size of 700 µm, and a porosity of 70 % is the best choice for repairing critical bone defects, which is expected to guide the clinical application of clinical 3D-printed PTa scaffolds.

A review: strategies to reduce infection in tantalum and its derivative applied to implants.

Implant-associated infection is the main reasons for implant failure. Titanium and titanium alloy are currently the most widely used implant materials. However, they have limited antibacterial performance. Therefore, enhancing the antibacterial ability of implants by surface modification technology has become a trend of research. Tantalum is a potential implant coating material with good biological properties. With the development of surface modification technology, tantalum coating becomes more functional through improvement. In addition to improving osseointegration, its antibacterial performance has also become the focus of attention. In this review, we provide an overview of the latest strategies to improve tantalum antibacterial properties. We demonstrate the potential of the clinical application of tantalum in reducing implant infections by stressing its advantageous properties.

Physical, morphological and bioactive properties of Co-Cr-W-Ta alloys: Influence of insertion of tantalum and surface thermochemical treatment on bioactivity.

The development of bioactivity in bioinert metallic alloys is a field of interest aiming to improve some aspects of these materials for implant applications. New Co63 Cr28 W9-x Tax alloys with different Ta concentrations (x = 0, 2, 4, 6, and 9% w/w) were synthesized in the work reported here. The alloys were characterized by x-ray diffraction, volumetric density, Vickers microhardness, atomic force microscopy, scanning electron microscopy (SEM), and energy-dispersion x-ray spectroscopy (EDS). Bioactivity properties were evaluated by in vitro tests with simulated body fluid (SBF). In vivo assays were performed to assess biocompatibility. The influence of surface thermochemical treatment and Ta insertion on the bioactive properties of the alloys was investigated. The results showed that the alloy structure comprises εCo and αCo phases, with cobalt as a matrix with Cr, W, and Ta as a solid solution. TaCo2 phase is observed in the alloys with 4, 6, and 9% w/w of Ta, and its amount increase as Ta concentration increases. Volumetric density is reduced (from 8.78 ± 0.06 to 8.56 ± 0.09 g/cm3 ) as Ta concentration increases (from 0% to 9% w/w) mainly due to the lower density of the tantalum compared to the tungsten metal. On the other hand, the TaCo2 phase contributes to the increase of Vickers's hardness by ~17.6% for the alloy with 9% Ta (394.7 ± 8.1 HV) compared with Co63 Cr28 W9 (336 ± 5 HV). The topographic analysis showed increased roughness and adhesion due to the nucleation of Ta1.1 O1.05 and Ca2 Ta2 O7 crystals after surface thermochemical treatment. The roughness and adhesion increase from 16.9 ± 0.6 nm and 8.3 ± 1.8 nN (untreated surface) to 255.7 ± 17.7 nm and 24.1 ± 12.6 nN (treated surface), respectively, for the Co63 Cr28 Ta9 alloy. These results suggest that thermochemical treatment provides surface conditions favorable to hydroxyapatite (HA) nucleation. The SEM and EDS data showed the nucleation of spongy structures, consistent with HA, composed mainly of Ca and P, indicating that oxides tantalum promoted a bioactive response on the sample's surface. The biological assay corroborated the alloy's safety and applicability, highlighting its potential in biomedical application since no harmful effects were observed.

Nano artificial periosteum PCL/Ta/ZnO accelerates repair of periosteum via antibacterial, promoting vascularization and osteogenesis.

The periosteum plays a critical role in bone development, shaping, remodeling, and fracture healing due to its abundance of osteoprogenitor cells, osteoblasts, and capillary network. However, the role of periosteum in bone injury healing has been underestimated, thus there is an urgent need to develop a multifunctional artificial periosteum that mimics the natural one. To tackle this issue, electrospinning technology was employed to fabricate an artificial periosteum composed of Poly-ε-caprolactone (PCL) doped with tantalum (Ta) and zinc oxide (ZnO) nanoparticles to enhance its antibacterial, osteogenic, and angiogenic properties. The in vitro cell experiments have demonstrated that the PCL/Ta/ZnO artificial periosteum exhibits excellent biocompatibility and can effectively facilitate osteogenic differentiation of BMSCs as well as angiogenic differentiation of EPCs. Antibacterial experiments have demonstrated the excellent bactericidal effects of PCL/Ta/ZnO artificial periosteum against both S. aureus and E. coli. The subcutaneous infection and critical-sized skull bone defect models have validated its in vivo properties of antibacterial activity, promotion of osteogenesis, and angiogenic potential. The PCL/Ta/ZnO artificial periosteum demonstrates remarkable efficacy in infection control and favorable immunomodulation, thereby achieving rapid vascularized bone repair. In conclusion, the utilization of PCL/Ta/ZnO tissue-engineered periosteum has been demonstrated to exhibit antibacterial properties, pro-vascularization effects, and promotion of osteogenesis at the site of bone defects. This promising approach could potentially offer effective treatment for bone defects.

The bio-functionalized membrane loaded with Ta/WH nanoparticles promote bone regeneration through neurovascular coupling.

Electrospinning technology, as a novel approach, has been extensively applied in the field of tissue engineering. Nanofiber membranes prepared by electrospinning can effectively mimic the structure and function of natural bone matrix, providing an ideal scaffold for attachment, proliferation, and differentiation of bone cells while inducing osteogenic differentiation and new bone formation. However, it lacks bioactivities such as osteoinduction, angiogenesis and the ability to promote nerve regeneration. In the presence of complex critical bone defects, a single component electrospun membrane often fails to suffice for bone repair needs. Based on this, we prepared a biofunctionalized membrane loaded with Tantalum(Ta)/Whitlockite(WH) nanoparticles (poly-ε-caprolactone (PCL)/Ta/WH) in order to promote high-quality bone defect repair through neurovascular coupling effect. According to the results of in vitro and in vivo experiments, the early Mg2+ release of WH can effectively increase the local nerve and vascular density, and synergize with Tantalum nanoparticles (TaNPs) to create a rich nerve-vascular microenvironment. This allows the PCL/Ta/WH membrane to repair bone defects in multiple dimensions and achieve high-quality repair of bone tissue, providing new solutions for the treatment of critical bone defects in clinical.

Micro-nano porous structured tantalum-coated dental implants promote osteogenic activity in vitro and enhance osseointegration in vivo.

Due to its excellent biocompatibility and corrosion resistance, tantalum demonstrates versatility as an implant material. However, limited studies investigated the role of tantalum coated titanium-based dental implants. This study aimed to investigate the potential application of micro-nano porous structured tantalum coating on the surface of titanium dental implant. In the present study, micro-nano porous structured tantalum coating was prepared by vacuum plasma spraying (VPS) under selected optimum parameters, various characteristics of tantalum coating (Ta/Ti), including the morphology, potential, constituent, and hydrophilia, were investigated in comparison with its respective control groups, sandblasted titanium (Ti) and titanium coating (Ti/Ti). The adhesion, proliferation, and osteogenic differentiation ability of rat bone marrow mesenchymal cells (BMSCs) on different materials were assessed in vitro. Then the osseointegration capacity of Ti, Ti/Ti, Ta/Ti, and Straumann implants in canine mandible was evaluated with micro-CT, histological sections, and energy dispersive X-ray spectroscopy. These results demonstrated that micro-nanostructured, uneven, and granular tantalum coating was successfully prepared on titanium substrate by VPS with pore size ranging from 50 nm to 5 µm and thickness ranging from 80 to 100 µm. Tantalum coating revealed the highest surface potential, best hydrophilia, and most protein adsorption among Ta/Ti, Ti/Ti, and Ti. Furthermore, Ta/Ti surfaces significantly promoted the adhesion, proliferation, and osteogenic differentiation of BMSCs. In vivo, Ta/Ti implants displayed positive osseointegration capability associated with increased bone mineral density and formation of new bone around implants without tantalum particles released. Together, these findings indicate that tantalum-coated titanium dental implants may serve as a new type of dental implant.

Mussel-Inspired Tantalum Nanocomposite Hydrogels for In Situ Oral Cancer Treatment.

Oral squamous cell carcinoma (OSCC) is one of the most common oral malignancies. Radiotherapy is the primary noninvasive treatment of OSCC for avoiding surgery-induced facial deformities and impaired oral function. However, the specificity of in situ OSCC limits radiotherapeutic effects because of the hypoxia-induced low radiosensitivity of tumors and the low radiation tolerance of surrounding normal tissues. Here, we design a highly efficient and low-toxic radiosensitization strategy. On the one hand, biocompatible poly(vinyl pyrrolidone)-modified tantalum nanoparticles (Ta@PVP NPs) not only have strong X-ray deposition capability to upregulate oxidative stress but also have photothermal conversion efficiency to improve hypoxia for tumor radiosensitivity. On the other hand, to optimize the spatial distribution of Ta@PVP NPs within tumors, mussel-inspired catechol with bioadhesive properties is grafted on tumor microenvironment-responsive sodium alginate (DAA) to form in situ hydrogels for precision radiotherapy. On this basis, we find that Ta@PVP-DAA hydrogels effectively inhibit OSCC development in mice under photothermal-assisted radiotherapy without facial deformities and damage to surrounding normal tissues. Overall, our work not only promotes the exploration of Ta@PVP NPs as new radiosensitizers for OSCC but also develops a nanocomposite hydrogel system strategy as a promising paradigm for the precision treatment of orthotopic tumors.

3D-Printed Porous Tantalum Scaffold Improves Muscle Attachment via Integrin-ß1-Activated AKT/MAPK Signaling Pathway.

3D-printed porous titanium (Ti) alloy scaffolds have been reported for facilitating muscle attachment in our previous study. However, the anti-avulsion ability needs to be improved. In this study, we used 3D-printed porous tantalum (Ta) scaffolds to improve muscle attachment. The differences in chemical and physical characteristics and muscle adhesion between the two scaffolds were tested and compared in the gene and protein level both in vitro and in vivo. The possible molecular mechanism was analyzed and further proved. The results showed that compared with the porous Ti alloy, porous Ta had better cell proliferation, differentiation, migration, and adhesion via the integrin-ß1 (Itgb1)-activated AKT/MAPK signaling pathway in L6 rat myoblasts. When artificially down-regulated the expression of Itgb1, cell adhesion and myogenesis differentiation were affected and the phosphorylation of the AKT/MAPK signaling pathway was suppressed. In rat intramuscular implantation, porous Ta had a significantly higher muscle ingrowth rate (85.63% ± 4.97 vs 65.98% ± 4.52, p < 0.01) and larger avulsion force (0.972 vs 0.823 N/mm2, p < 0.05) than the porous Ti alloy. These findings demonstrate that the 3D-printed porous Ta scaffold is beneficial for further clinical application of muscle attachment.

Combination therapy with BMSCs­exosomes and porous tantalum for the repair of femur supracondylar defects.

In the field of orthopedics, defects in large bones have proven challenging to resolve. The aim of the present study was to address this problem through the combination of tantalum metal (pTa) with exosomes derived from bone marrow mesenchymal stem cells (BMSCs), which have the potential to enhance regeneration of full thickness femoral bone defects in rats. Cell culture results demonstrated that exosomes improved the proliferation and differentiation of BMSCs. Following establishment of a supracondylar femoral bone defect, exosomes and pTa were implanted into the defect area. Results demonstrated that pTa acts as a core scaffold for cell adhesion and exhibits good biocompatibility. Moreover, micro­CT scan results as well as histological examination demonstrated that pTa had a significant effect on osteogenesis, with the addition of exosomes further promoting bone tissue regeneration and repair. In conclusion, this novel composite scaffold can effectively promote bone regeneration in large bone defect areas, providing a new approach for the treatment of large bone defects.

Nano tantalum-coated 3D printed porous polylactic acid/beta-tricalcium phosphate scaffolds with enhanced biological properties for guided bone regeneration.

Bone defects caused by tumors section, traffic accidents, and surgery remain a challenge in clinical. The drawbacks of traditional autografts and allografts limit their clinical application. 3D printed porous scaffolds have monumental potential to repair bone defects but still cannot effectively promote bone formation. Nano tantalum (Ta) has been reported with effective osteogenesis capability. Herein, we fabricated 3D printed PLA/ß-TCP scaffold by using the fused deposition modeling (FDM) technique. Ta was doped on the surface of scaffolds utilizing the surface adhesion ability of polydopamine to improve its properties. The constructed PLA/ß-TCP/PDA/Ta had good physical properties. In vitro studies demonstrated that the PLA/ß-TCP/PDA/Ta scaffolds considerably promote cell proliferation and migration, and it additionally has osteogenic properties. Therefore, Ta doped 3D printed PLA/ß-TCP/PDA/Ta scaffold could incontestably improve surface bioactivity and lead to better osteogenesis, which may provide a unique strategy to develop bioactive bespoke implants in orthopedic applications.