Biocompatibility Evaluation of Novel Ti-15Zr-TCP composite fabricated by powder metallurgy to enhance the antibacterial performance for dental implant application

Biocompatibility Evaluation of Novel Ti-15Zr-TCP composite fabricated by powder metallurgy to enhance the antibacterial performance for dental implant application | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Biocompatibility Evaluation of Novel Ti-15Zr-TCP composite fabricated by powder metallurgy to enhance the antibacterial performance for dental implant application Emayavaramban M, Prakash T, Manuneethicholan S, Deborah Gnana Selvam A This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7729902/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract The growing clinical demand for durable and biologically safe dental implants has accelerated the development of novel material systems that address both mechanical and biological challenges. One major limitation of conventional titanium-based implants is their insufficient antibacterial activity, which increases the risk of postoperative infections and implant failure. In this study, titanium–zirconium–β-tricalcium phosphate (Ti–15Zr–xTCP, x = 5, 10, 15, 20, 25, 30, 35 wt.%) composites were fabricated via powder metallurgy for testing to overcome this drawback. The objective was to enhance antibacterial properties while preserving biocompatibility. In vitro analyses confirmed that all compositions were non-hemolytic (< 5%). Antibacterial efficiency, assessed by the zone of inhibition, improved with increasing TCP content, with the 35 wt.% group exhibiting the largest inhibition zone of 14mm. This composition also demonstrated the highest MG-63 cell viability (96.27%) and supported favorable osteoblastic morphology. These findings suggest that Ti–15Zr–xTCP composites with 35 wt.% TCP offer an effective balance of antibacterial activity, cytocompatibility, and mechanical integrity, making them strong candidates for next-generation dental implants. Antibacterial activity Biocompatibility Dental implants Hemolysis Powder metallurgy Zone of inhibition Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 1 Introduction Dental implants are artificial tooth roots that are used to replace missing teeth. Dental implants are inert devices made of biocompatible materials that are placed in the mandible or maxilla to treat tooth loss. It helps repair lost orofacial structures brought on by neoplasia, trauma, and birth abnormalities ( 1 ). It becomes a popular and trusted solution in modern dentistry because it helps restore the function and appearance of natural teeth. Dental implants improve chewing ability, speech, and overall comfort. They also boost a patient’s confidence by enhancing aesthetics and providing a permanent alternative to removable dentures. The most popular kind of dental implant is endosseous, which consists of a single, isolated item usually a screw with cylinder shape inserted into a drilled hole in the dentoalveolar or basal bone ( 2 ). It represented in Fig. 1 . As the need for more reliable and long-lasting implants increases, researchers and manufacturers are focusing on finding the best materials that not only provide strength but are also safe and compatible with the human body. Tooth loss remains a significant global health concern, affecting approximately 178 million adults in the U.S. alone, with nearly 40 million completely edentulous individuals ( 4 , 5 ). About 703 million people aged 65 and over suffered from dental issues in 2019, and by 2050, that number is predicted to rise to 1.5 billion senior citizens globally ( 6 ). The number of people with oral disorders is rising in tandem with the aging of the population. Worldwide, about 7% of people aged over 60 experience complete tooth loss. As a direct response, over 3 million dental implants are placed annually in the U.S., contributing to a global market estimated at USD 4.9 billion in 2024, projected to grow to nearly USD 9.6 billion by 2034 ( 7 ). Millions of patients receive implant treatment each year, and it is anticipated that this number will quadruple globally over the next 10 years. The primary cause of this is the aging of the global population, which raises the demand for oral therapies. Although the placement of dental implants has a high clinical achievement rate, 3.1% of patients still require revision surgery after the procedure ( 8 ). Crown fractures, ceramic implant abutment fractures, and aesthetic issues are the most frequent technical issues with fixed implant-retained single crowns. The most common technical issue with multiple-unit, implant-retained fixed dental prostheses is veneering ceramic chipping or fracture ( 9 ). Compared to the surrounding bone, metal implants are significantly stiffer. It is generally accepted that they hinder osseointegration into the implant by encouraging the development of fibrous connective tissues. Consequently, this lowers the long-term durability of the implant ( 10 ). To prevent stress shielding, dental implants should have an elastic modulus that is comparable to that of dental bone (~ 10–30 GPa) ( 11 ). In order to support bone formation, the implant material should be strong enough to support body stresses and have an appropriate amount of porosity (less than 30%); nevertheless, too much porosity damages the implant ( 12 ). To prevent the main cause of bone resorption and aseptic loosening, this issue must be resolved by designing an implant with a stiffness that is closer to that of the bone ( 13 ). Orthopedic implants are commonly made of stainless steel, titanium, and cobalt-chromium alloys due to their durability and strength. Additionally, ceramics and polymers like polyethylene and polymethyl methacrylate are utilized for certain functions. Among all materials used for dental implants, titanium (Ti) and its alloys are the most commonly used due to their outstanding mechanical strength, corrosion resistance, and excellent biocompatibility ( 14 – 16 ). Furthermore, titanium's mechanical qualities provide a superb mix of strength, rigidity, and fatigue resistance, enabling it to support loads on bones and joints without deforming ( 17 , 18 ). However, One major concern is the high elastic modulus of Ti, which significantly exceeds that of cortical bone (~ 110 GPa vs. ~20 GPa), potentially causing stress shielding and subsequent bone resorption around the implant site ( 19 ). Additionally, although Ti exhibits passive corrosion resistance, it has limited biological activity and may not induce sufficient osseointegration in all cases ( 20 ). To address these limitations, alloying titanium with elements such as zirconium (Zr), niobium (Nb), tantalum (Ta), and molybdenum (Mo) has been explored ( 21 – 23 ). Zr, in particular, has been shown to improve corrosion resistance and lower the elastic modulus, making it an attractive candidate for biomedical applications ( 24 ). Zr also promotes apatite formation and enhances bioactivity when incorporated into titanium alloys ( 25 ). Moreover, the Ti-Zr system has demonstrated higher tensile strength and fracture toughness than commercially pure titanium, along with better soft tissue compatibility ( 26 , 27 ). It was discovered that the Ti–15Zr alloy had a strength that was 10–15% greater than that of pure titanium without sacrificing fracture toughness or reducing tensile elongation. Additionally, there was a roughly 30% increase in the fatigue endurance limit. Additional implant fatigue testing revealed that Ti–15Zr performed better than Ti in terms of fatigue ( 28 , 29 ). TCP, particularly in its β-phase (TCP), has shown promise as an osteoconductive and antibacterial agent in multiple composite systems( 30 ). The release of calcium and phosphate ions during degradation creates a local environment that can elevate pH and disturb bacterial membranes, thereby reducing biofilm formation ( 31 , 32 ). Several studies have investigated TCP-incorporated coatings and composites for orthopaedic and dental use, reporting enhanced osseointegration and reduced microbial activity ( 30 , 33 – 35 ). Furthermore, studies have shown that TCP-containing surfaces modulate immune responses and may reduce inflammation during healing ( 36 ) Despite these improvements, implant-associated infections remain a major challenge, with microbial colonization leading to peri-implantitis and implant failure in approximately 10–15% of cases ( 37 , 38 ). Therefore, a new generation of implant materials must not only be mechanically strong and biologically compatible but also possess antibacterial properties. One approach is the incorporation of bioactive ceramics such as tricalcium phosphate (TCP), which is chemically similar to bone mineral and supports osteoblast adhesion, bone regeneration, and controlled biodegradability ( 39 ). In addition to solid implants, the orthopedic industry has been interested in porous implants. These implants improve long-term implant fixation and encourage the formation of new bone tissue ( 40 , 41 ). A porous structure improves the biological and mechanical properties of implant material, according to the findings of numerous studies ( 42 , 43 ). Metal additive manufacturing (AM) is a technique that can be utilized to create porous implant structures, but it has drawbacks, including high cost and key process parameters ( 44 ). However, powder metallurgy has few restrictions, including problems with die design, compacting, and ball milling, and can be used to create porous structures (45,46). Without taking these concerns into account, porous structures can be created, leading to implants with reduced stiffness profiles ( 47 ). However, decreased strength is a significant disadvantage of porous hip stems. Therefore, while creating porous implants, a balance between stiffness, strength, and porosity must be struck. Isoelastic stems were developed as a result of the previous consideration of using a variety of materials to decrease implant stiffness ( 48 , 49 ). Recent research has shifted toward developing hybrid materials such as combination of metal and ceramics, aiming to enhance the toughness and corrosion resistance of Ti alloys with the superior osteoinductive and antibacterial nature ( 50 ). These composites also provide an opportunity to tune the mechanical behaviour and degradation profile by varying the ceramic content, enabling custom implant performance ( 39 ). While previous works have explored Ti-based and TCP-based systems independently or in coatings, there remains a lack of detailed studies investigating fully integrated hybrid Ti-15Zr-x TCP composites fabricated via powder metallurgy. This present work focuses on developing and evaluating such composites with TCP content varying from 5% to 35%. The aim is to investigate the effect of TCP concentration on influences of antibacterial performance, cytocompatibility, blood compatibility of the material, with the goal of identifying an optimal formulation for dental implant applications. 2 Materials and methods 2.1 Material Selection Materials such as titanium, zirconium, and β-tricalcium phosphate (TCP) were chosen for this investigation. Medical-grade titanium powder with a 99.5% purity and a 150-micron particle size was used for this study. Both Zr powder (particle size: 70 microns, purity: 99.9%) and TCP (particle size: 70 microns, purity: 99.9%) were used. The characteristics of the biomaterial utilized in the composite are displayed in Table 1 . Table 1 Material properties. Materials Young's Modulus, GPa Poisson ratio Density, g/cm3 Compressive strength, MPa Ti 120 0.34 4.54 170 Zr 88 0.34 6.52 165 TCP 38 0.2 3.14 1.74 2.2 Fabrication of sample The Ti–15Zr–xTCP (x = 5, 10, 15, 20, 25, 30, 35 wt.%) composites were fabricated using powder metallurgy (PM), a technique widely acknowledged for its capacity to process high melting point materials and fabricate homogeneously distributed metal-ceramic systems with controlled microstructures ( 51 ). Titanium, zirconium, and β-tricalcium phosphate powders were weighed in stoichiometric proportions using a digital analytical balance to ensure compositional accuracy. Figure 2 represents the powder metallurgy process used to fabricate Ti-Zr-TCP composites The powders were dry mixed and homogenized using a planetary ball mill for 6 h at 300 rpm, with tungsten carbide balls in an ethanol medium to prevent particle agglomeration and promote uniform distribution. The slurry was oven-dried at 60°C for 24 h to remove any residual ethanol. The resulting powders were compacted using a uniaxial hydraulic press into cylindrical pellets (10 mm diameter × 5 mm height) at a pressure of 600 MPa. This pressing process ensured green bodies with high density and mechanical integrity. The green compacts were sintered in a vacuum furnace at 900°C for 1 h with a heating rate of 5°C/min, followed by controlled furnace cooling. The selected sintering temperature was based on literature recommendations to preserve the β-TCP phase while achieving sufficient densification and bonding via solid-state diffusion. Sintering below the melting points of the constituent elements prevents phase degradation and improves mechanical performance by refining the interfacial adhesion between TCP particles and the Ti-Zr matrix. Powder metallurgy is preferred over conventional melting or casting because of its low energy consumption, dimensional accuracy, reduced material waste, and proven success in fabricating titanium-based biomedical devices. This method allows precise control over porosity, microstructure, and elemental distribution, which are crucial for load-bearing bio-implants where optimal stress distribution and osseointegration are essential.( 52 – 54 ). 2.3 Biological Testing 2.3.1 Antibacterial testing The antibacterial activity of the sintered Ti-15Zr-xTCP composite was evaluated using the agar diffusion method, commonly known as the Zone of Inhibition (ZOI) test. This procedure is widely used to assess the antimicrobial efficacy of implant materials under simulated biological conditions. Mueller-Hinton Agar (MHA) served as the nutrient medium, and Escherichia coli (E. coli), a Gram-negative bacterium relevant to peri-implantitis and oral biofilm formation, was selected as the test organism due to its clinical relevance in implant-associated infections. A 100 µL aliquot of E. coli suspension (10⁶ CFU/mL) was evenly spread onto the surface of sterile MHA plates to establish a consistent bacterial lawn. Fabricated Ti–15Zr–xTCP samples were gently positioned on the inoculated agar and incubated at 37°C for 24 hours to allow for material-bacteria interaction. Post incubation, the diameter of the clear zone formed around each sample indicative of inhibited bacterial growth was measured using a digital Vernier calliper to quantify antibacterial performance ( 55 , 56 ). This method evaluates the passive ion release and contact inhibition properties of the material. The TCP component is known to promote calcium and phosphate ion exchange, which in turn can alter local pH and impair bacterial membrane integrity a mechanism frequently utilized in bioactive ceramic assessments 2.3.2 Hemolysis Hemolysis testing was conducted to evaluate the blood compatibility of the Ti–15Zr–xTCP composites, with specific attention to the interaction between the sintered samples and human red blood cells (RBCs). Given that dental implants can come into transient contact with blood during surgical insertion, it is essential that implant materials exhibit non-haemolytic behaviour to avoid triggering haemolytic reactions, thrombosis, or inflammatory responses. The procedure was performed in accordance with ISO 10993-4:2017 and ASTM F756-17 standards, which are widely recognised for assessing the hemocompatibility of biomaterials. Figure 3 represents the testing procedure of Hemolysis. Fresh human blood was collected and anticoagulated using EDTA to prevent coagulation. The blood was diluted with phosphate-buffered saline (PBS) in a 1:10 ratio to mimic physiological ionic strength. Three test groups were prepared: (i) negative control (1 mL blood + 1 mL PBS), (ii) positive control (1 mL blood + 1 mL distilled water), and (iii) experimental group (1 mL blood + 1 mL PBS containing sintered Ti-Zr-TCP composite powder). All samples were incubated at 37°C for 1 hour to replicate body temperature conditions. Following incubation, the tubes were centrifuged at 3000 rpm for 10 minutes. The supernatant was collected, and haemoglobin release was quantified using a UV–Visible spectrophotometer at a wavelength of 540 nm, corresponding to the maximum absorption of free haemoglobin ( 57 , 58 ) The absorbance readings were used to calculate the percentage of Hemolysis using Eq. (1) Where, \(\:{A}_{Sample}\) is the absorbance of the test sample, \(\:{A}_{PBS}\) is that of the negative control, and \(\:{A}_{DW}\) represents the positive control (distilled water). As per ASTM F756-17 standards, materials exhibiting Hemolysisrates below 5% are categorized as non-hemolytic and are therefore considered safe for blood-contacting biomedical applications ( 59 , 60 ). 2.3.3 Cytocompatibility MTT (3–4, 5-dimethylthiazol-2yl-2, 5-diphenyl tetrazolium bromide) assay is based on the ability of a mitochondrial dehydrogenase enzyme of viable cells to cleave the tetrazolium rings of the pale yellow MTT and form a dark blue formazan crystal, which is largely impermeable to cell membranes, resulting in its accumulation within healthy cells. Solubilization of cells by the addition of detergents (DMSO) results in the liberation of crystals, which are then solubilized. The number of surviving cells is directly proportional to the level of formazan products. Color can be quantified using a multi-well plate reader ( 59 , 61 ). The test sample (Ti-Zr- xTCP) was tested for in vitro cytotoxicity using MG-63 cells via the MTT assay. Briefly, the cultured MG-63 cells were harvested by trypsinization and pooled in a 15 mL tube. The cells were then plated at a density of 1×10⁵ cells/mL cells/well (200 µL) into a 96-well tissue culture plate in DMEM containing 10% FBS and 1% antibiotic solution for 24–48 h at 37°C. The wells were washed with sterile PBS and treated with various concentrations of the test sample in serum-free DMEM. Each sample was tested in triplicate, and the cells were incubated at 37°C in a humidified 5% CO₂ incubator for 24 h. After incubation, MTT (10 µL of 5 mg/mL) was added to each well, and the cells were incubated for another 2–4 h until purple precipitates were visible under an inverted microscope. Finally, the medium and MTT (220 µL) were aspirated off the wells and washed with 1X PBS (200 µL). Furthermore, to dissolve the formazan crystals, DMSO (100 µL) was added, and the plate was shaken for 5 min ( 62 , 63 ). The absorbance of each well was measured at 570 nm using a microplate reader (Thermo Fisher Scientific, USA), and the percentage cell viability and IC₅₀ value were calculated using GraphPad Prism 6.0 software (USA). 3. Results and Discussion 3.1 Antibacterial Activity The antibacterial efficacy of the Ti-15Zr- xTCP composites was investigated using the zone of inhibition (ZOI) test. This study demonstrated a direct correlation between increasing TCP content and antibacterial effectiveness as shown in Fig. 6 . The Ti-15Zr-25TCP composition produced the widest inhibition zone (~ 15 mm), indicating its superior antibacterial activity. This inhibition zone is notably larger than values reported for TCP-coated Ti and Ti-Zr composites in previous studies, which typically ranged between 9–12 mm under similar agar diffusion conditions( 32 , 33 , 56 ) This improvement is attributed to the sustained ionic release of calcium and phosphate from the β-TCP phase, which can elevate the local pH and disrupt bacterial membrane integrity. The ZOI findings validate the role of TCP in imparting intrinsic antimicrobial behavior to the Ti-Zr matrix, supporting its potential as a multifunctional dental implant material. Safi et al.( 30 ) and Stipniece et al.( 56 ) highlighted that the antimicrobial effect of TCP largely stems from ion release and membrane disruption, which is further enhanced in hybrid metal–ceramic composites due to prolonged ion exchange. The Ti- 15Zr- 25TCP combination leverages both these effects, offering a synergistic enhancement over ceramic coatings alone. Notably, while a higher TCP content enhanced the antimicrobial action, compositions beyond 25 wt. % slightly compromised mechanical stability. Therefore, Ti-15Zr-25TCP presents the most optimal balance between antibacterial effect and structural performance. These results confirm that the developed composite provides superior antibacterial performance compared to conventional implant materials studied in literature, while retaining mechanical integrity and cytocompatibility. 3.2 Cell Viability According to the quantitative analyses of the MTT assay results for the Ti–15Zr–xTCP composites, there was a clear trend of cell viability with respect to the TCP amount. The highest viability among all compositions was for Ti–15Zr–25TCP (96.27%), a value close to that of the control (100%) as shown in Fig. 5 . This is significantly greater than the value obtained for the traditional Ti-Zr alloys that usually attain an 85% viability in MG-63 cell test (Bosco et al. ( 27 ). It is also higher than that reported for cement-coated zirconia and other conventional Ti implants (67). As presented in Table 2 , the lowest viability was observed for Ti–15Zr–5TCP (48.89%), demonstrating scarce cytocompatibility at the lower percentage of TCP. The cell viability gradually increased with the increase of TCP content, for example, the cell viabilities of Ti–15Zr–20TCP and Ti–15Zr–30TCP were 81.93% and 94.96%, respectively. Apart form 5 and 10 wt.% of TCP, All other formulations exhibited cell viability exceeding 70% -a standard specified by ISO 10993-5 for cytocompatibility, to indicate that the materials are nontoxic. These results also matched what was seen when looking at the shape of MG-63 cells under a microscope (Fig. 4 ). The groups without TCP and with 35TCP (Pictures A and F) looked normal, with healthy, long cells that stuck well and were alive. Compared to the group with no TCP (Picture A), the cells with 5TCP and 10TCP (Pictures B and C) were a bit smaller, and the cells with 15TCP and 20TCP (Pictures D and E) looked somewhat different, which lined up with them not living as well. What we saw with our eyes backs up the different levels of cell death and further proves the numbers we got. Previous works on surfaces with more TCP has discovered that cells usually live between 70–90% of the time, and this greatly depends on how much TCP is present and how quickly ions are released (31,67). The information in this research shows that cells live very well when there isn't much TCP and do great with 35TCP, which suggests that the TCP helping bone grow and the strong Ti–Zr mix on the surface might work well together. This matched what Bajantri et al. found in their research (67), where they said that MG-63 cells lived up to about 90% of the time on implant surfaces covered in ceramic. The mix we have now is even better than that, showing that it could be very useful for putting inside the body for medical reasons. Table 2 Cytocompatibility evaluation of Ti–15Zr–xTCP composites using MG-63 cells. MG-63 Control (0) wt.% of TCP 5TCP 10TCP 15TCP 20TCP 25TCP 30TCP 35TCP Sample Blank 0.033 0.504 0.682 0.745 0.848 0.968 0.982 0.996 0.033 0.506 0.685 0.748 0.851 0.971 0.985 0.998 0.038 0.508 0.684 0.749 0.846 0.969 0.981 0.992 Ave 1.035 0.506 0.684 0.747 0.848 0.969 0.983 0.996 % Diff 0 51 34 28 18 6 5 4 Viability (%) 100 48.89 66.09 72.17 81.93 93.62 94.96 96.27 3.3 Hemocompatibility Hemolysis testing, performed in compliance with ISO 10993-4 and ASTM F756-17 standards, demonstrated that all Ti-15Zr-xTCP samples-maintained Hemolysis levels below the 5% threshold, classifying them as non-haemolytic. The Ti-15Zr-5TCP and Ti- 15Zr- 25TCP samples exhibited the lowest Hemolysis rate of 3.2% and 3.15% respectivily as shown in Fig. 6 , indicating excellent blood compatibility with minimal red blood cell membrane disruption. These values are lower than those reported by Brunello et al.( 58 ) ,who observed ~ 4.5% Hemolysis in zirconium nitride-coated titanium abutments, and are comparable to cobalt-deposited titanium discs which showed Hemolysis rates between 3–4% ( 59 ). These results confirm the safety of these composites for temporary or incidental blood contact during implant placement and reinforce their suitability for biomedical applications which are blood compatibility is a crucial criterion. Similar conclusions were drawn by Xie et al.( 60 ), where Fe/Zn-modified TCP materials showed comparable hemocompatibility but lacked the added mechanical robustness offered by the Ti-Zr matrix in the present work. 3.4 Comparison of experimental results to selected literatures A comparative analysis of Ti–15Zr–35TCP with previously reported biomaterials is presented in Fig. 7 , focusing on three critical biological parameters such as zone of inhibition, Hemolysis percentage, and cell viability. The proposed composite shows excellent biocompatibility with the highest cell viability (96%) and the lowest Hemolysis rate (3.91%), outperforming many earlier materials. Additionally, it exhibits the largest zone of inhibition (14 mm), indicating superior antibacterial properties. These results suggest that the Ti–15Zr–35TCP composite not only supports osteoblast proliferation but also provides an effective defense against microbial colonization, making it a promising candidate for long-term dental and orthopedic applications. Conclusion This study demonstrated that incorporating β-tricalcium phosphate (TCP) into Ti-15Zr via powder metallurgy significantly enhances antibacterial activity and cytocompatibility while retaining adequate mechanical stability. A clear trend of increasing antibacterial efficacy with higher TCP content was observed, with the Ti–15Zr–35TCP composite exhibiting the most favorable performance, including the widest inhibition zone (~ 14 mm), highest cell viability (~ 96%), and low hemolysis (~ 3.91%). These findings highlight Ti–15Zr–35TCP as a promising candidate for biomedical implant applications. Future work will focus on advanced mechanical characterizations, including fatigue and wear resistance, as well as in vivo studies to validate long-term biological performance and clinical applicability. Declarations Acknowledgment The authors gratefully acknowledge the management of Thiagarajar College of Engineering, Madurai, for providing constant support and access to the Metallurgy Laboratory, Department of Mechanical Engineering facilities to conduct this research. The authors also extend their sincere thanks to the management of The American College, Madurai, for their support and for providing access to the Microbiology Laboratory facilities used in this study. Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding The author(s) received no financial support for the research, authorship, and/or publication of this article. 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1","display":"","copyAsset":false,"role":"figure","size":299474,"visible":true,"origin":"","legend":"\u003cp\u003eDental implants (Source: (3)) (a) primary component arrangement; (b) post-installation view in the bone.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7729902/v1/93f8fb5c1c751c942a224b3f.png"},{"id":93231168,"identity":"5e253658-f684-4b94-80c2-41891da137cc","added_by":"auto","created_at":"2025-10-10 13:10:44","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":136251,"visible":true,"origin":"","legend":"\u003cp\u003eSchematic overview of the powder metallurgy process used to fabricate Ti-Zr-TCP composites\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7729902/v1/75492609b5b4c26828a3bbd1.jpeg"},{"id":93231482,"identity":"3ec4ffb6-9dda-4117-877d-7060b4208312","added_by":"auto","created_at":"2025-10-10 13:18:44","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1144601,"visible":true,"origin":"","legend":"\u003cp\u003eHemolysis testing procedure: (a) preparation of blood sample mixtures, (b) incubation at 37 °C, (c) centrifugation to isolate plasma, (d) extraction of supernatant, and (e) absorbance measurement via UV-Vis Spectroscopy.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7729902/v1/f582c6ef04bd36ae21290da5.png"},{"id":93231170,"identity":"2d310683-7b91-4604-86f3-185231375d4d","added_by":"auto","created_at":"2025-10-10 13:10:44","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":744257,"visible":true,"origin":"","legend":"\u003cp\u003eMicroscopic image of MG-63 cells at different concentrations of Ti-15Zr-TCP extract. A) control, B) 5wt.% TCP, C) 10wt.% TCP, D) 15wt.% TCP, E) 20wt.% TCP, F) 35wt.% TCP\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7729902/v1/3a80a2eeaee3311d9a0c04c9.png"},{"id":93231480,"identity":"ac3309a1-49e7-4a22-aafb-a752f608b139","added_by":"auto","created_at":"2025-10-10 13:18:44","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":22427,"visible":true,"origin":"","legend":"\u003cp\u003eCell viability against TCP wt.%.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7729902/v1/c1cc178d32e5bf640eec2317.png"},{"id":93231484,"identity":"04ce9531-2de1-4acd-8220-9743c1f36e9b","added_by":"auto","created_at":"2025-10-10 13:18:44","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":21596,"visible":true,"origin":"","legend":"\u003cp\u003eVariation of antibacterial activity (ZOI diameter) and hemolysis percentage with different TCP w%.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-7729902/v1/e01690ccdaf47272dbbfd897.png"},{"id":93231174,"identity":"5e64b18d-0ac0-48c5-adb9-0c2a038f3be3","added_by":"auto","created_at":"2025-10-10 13:10:44","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":12906,"visible":true,"origin":"","legend":"\u003cp\u003eComparative analysis of biological properties: zone of inhibition, Hemolysis, and cell viability for Ti- 15Zr- 25TCP and reported implant materials\u003c/p\u003e","description":"","filename":"floatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-7729902/v1/2526b3dfbb46d4c92697b105.png"},{"id":93234301,"identity":"aee0d9c8-9956-42f9-abbb-5381afe5a2c9","added_by":"auto","created_at":"2025-10-10 13:42:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3485741,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7729902/v1/eaf270cd-5d40-4087-98eb-ce0420b8169a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Biocompatibility Evaluation of Novel Ti-15Zr-TCP composite fabricated by powder metallurgy to enhance the antibacterial performance for dental implant application","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eDental implants are artificial tooth roots that are used to replace missing teeth. Dental implants are inert devices made of biocompatible materials that are placed in the mandible or maxilla to treat tooth loss. It helps repair lost orofacial structures brought on by neoplasia, trauma, and birth abnormalities (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). It becomes a popular and trusted solution in modern dentistry because it helps restore the function and appearance of natural teeth. Dental implants improve chewing ability, speech, and overall comfort. They also boost a patient\u0026rsquo;s confidence by enhancing aesthetics and providing a permanent alternative to removable dentures.\u003c/p\u003e\u003cp\u003eThe most popular kind of dental implant is endosseous, which consists of a single, isolated item usually a screw with cylinder shape inserted into a drilled hole in the dentoalveolar or basal bone (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). It represented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAs the need for more reliable and long-lasting implants increases, researchers and manufacturers are focusing on finding the best materials that not only provide strength but are also safe and compatible with the human body. Tooth loss remains a significant global health concern, affecting approximately 178\u0026nbsp;million adults in the U.S. alone, with nearly 40\u0026nbsp;million completely edentulous individuals (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). About 703\u0026nbsp;million people aged 65 and over suffered from dental issues in 2019, and by 2050, that number is predicted to rise to 1.5\u0026nbsp;billion senior citizens globally (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe number of people with oral disorders is rising in tandem with the aging of the population. Worldwide, about 7% of people aged over 60 experience complete tooth loss. As a direct response, over 3\u0026nbsp;million dental implants are placed annually in the U.S., contributing to a global market estimated at USD 4.9\u0026nbsp;billion in 2024, projected to grow to nearly USD 9.6\u0026nbsp;billion by 2034 (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Millions of patients receive implant treatment each year, and it is anticipated that this number will quadruple globally over the next 10 years. The primary cause of this is the aging of the global population, which raises the demand for oral therapies. Although the placement of dental implants has a high clinical achievement rate, 3.1% of patients still require revision surgery after the procedure (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Crown fractures, ceramic implant abutment fractures, and aesthetic issues are the most frequent technical issues with fixed implant-retained single crowns. The most common technical issue with multiple-unit, implant-retained fixed dental prostheses is veneering ceramic chipping or fracture (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Compared to the surrounding bone, metal implants are significantly stiffer. It is generally accepted that they hinder osseointegration into the implant by encouraging the development of fibrous connective tissues. Consequently, this lowers the long-term durability of the implant (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eTo prevent stress shielding, dental implants should have an elastic modulus that is comparable to that of dental bone (~\u0026thinsp;10\u0026ndash;30 GPa) (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). In order to support bone formation, the implant material should be strong enough to support body stresses and have an appropriate amount of porosity (less than 30%); nevertheless, too much porosity damages the implant (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). To prevent the main cause of bone resorption and aseptic loosening, this issue must be resolved by designing an implant with a stiffness that is closer to that of the bone (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Orthopedic implants are commonly made of stainless steel, titanium, and cobalt-chromium alloys due to their durability and strength. Additionally, ceramics and polymers like polyethylene and polymethyl methacrylate are utilized for certain functions.\u003c/p\u003e\u003cp\u003eAmong all materials used for dental implants, titanium (Ti) and its alloys are the most commonly used due to their outstanding mechanical strength, corrosion resistance, and excellent biocompatibility (\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Furthermore, titanium's mechanical qualities provide a superb mix of strength, rigidity, and fatigue resistance, enabling it to support loads on bones and joints without deforming (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). However, One major concern is the high elastic modulus of Ti, which significantly exceeds that of cortical bone (~\u0026thinsp;110 GPa vs. ~20 GPa), potentially causing stress shielding and subsequent bone resorption around the implant site (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Additionally, although Ti exhibits passive corrosion resistance, it has limited biological activity and may not induce sufficient osseointegration in all cases (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eTo address these limitations, alloying titanium with elements such as zirconium (Zr), niobium (Nb), tantalum (Ta), and molybdenum (Mo) has been explored (\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Zr, in particular, has been shown to improve corrosion resistance and lower the elastic modulus, making it an attractive candidate for biomedical applications (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Zr also promotes apatite formation and enhances bioactivity when incorporated into titanium alloys (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Moreover, the Ti-Zr system has demonstrated higher tensile strength and fracture toughness than commercially pure titanium, along with better soft tissue compatibility (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIt was discovered that the Ti\u0026ndash;15Zr alloy had a strength that was 10\u0026ndash;15% greater than that of pure titanium without sacrificing fracture toughness or reducing tensile elongation. Additionally, there was a roughly 30% increase in the fatigue endurance limit. Additional implant fatigue testing revealed that Ti\u0026ndash;15Zr performed better than Ti in terms of fatigue (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). TCP, particularly in its β-phase (TCP), has shown promise as an osteoconductive and antibacterial agent in multiple composite systems(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). The release of calcium and phosphate ions during degradation creates a local environment that can elevate pH and disturb bacterial membranes, thereby reducing biofilm formation (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Several studies have investigated TCP-incorporated coatings and composites for orthopaedic and dental use, reporting enhanced osseointegration and reduced microbial activity (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). Furthermore, studies have shown that TCP-containing surfaces modulate immune responses and may reduce inflammation during healing (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eDespite these improvements, implant-associated infections remain a major challenge, with microbial colonization leading to peri-implantitis and implant failure in approximately 10\u0026ndash;15% of cases (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). Therefore, a new generation of implant materials must not only be mechanically strong and biologically compatible but also possess antibacterial properties. One approach is the incorporation of bioactive ceramics such as tricalcium phosphate (TCP), which is chemically similar to bone mineral and supports osteoblast adhesion, bone regeneration, and controlled biodegradability (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn addition to solid implants, the orthopedic industry has been interested in porous implants. These implants improve long-term implant fixation and encourage the formation of new bone tissue (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e). A porous structure improves the biological and mechanical properties of implant material, according to the findings of numerous studies (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e). Metal additive manufacturing (AM) is a technique that can be utilized to create porous implant structures, but it has drawbacks, including high cost and key process parameters (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eHowever, powder metallurgy has few restrictions, including problems with die design, compacting, and ball milling, and can be used to create porous structures (45,46). Without taking these concerns into account, porous structures can be created, leading to implants with reduced stiffness profiles (\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e). However, decreased strength is a significant disadvantage of porous hip stems. Therefore, while creating porous implants, a balance between stiffness, strength, and porosity must be struck. Isoelastic stems were developed as a result of the previous consideration of using a variety of materials to decrease implant stiffness (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eRecent research has shifted toward developing hybrid materials such as combination of metal and ceramics, aiming to enhance the toughness and corrosion resistance of Ti alloys with the superior osteoinductive and antibacterial nature (\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e). These composites also provide an opportunity to tune the mechanical behaviour and degradation profile by varying the ceramic content, enabling custom implant performance (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eWhile previous works have explored Ti-based and TCP-based systems independently or in coatings, there remains a lack of detailed studies investigating fully integrated hybrid Ti-15Zr-x TCP composites fabricated via powder metallurgy. This present work focuses on developing and evaluating such composites with TCP content varying from 5% to 35%. The aim is to investigate the effect of TCP concentration on influences of antibacterial performance, cytocompatibility, blood compatibility of the material, with the goal of identifying an optimal formulation for dental implant applications.\u003c/p\u003e"},{"header":"2 Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003e2.1 Material Selection\u003c/h2\u003e\n \u003cp\u003eMaterials such as titanium, zirconium, and \u0026beta;-tricalcium phosphate (TCP) were chosen for this investigation. Medical-grade titanium powder with a 99.5% purity and a 150-micron particle size was used for this study. Both Zr powder (particle size: 70 microns, purity: 99.9%) and TCP (particle size: 70 microns, purity: 99.9%) were used. The characteristics of the biomaterial utilized in the composite are displayed in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMaterial properties.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMaterials\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eYoung\u0026apos;s Modulus, GPa\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePoisson ratio\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDensity, g/cm3\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCompressive strength, MPa\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTi\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e170\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eZr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e165\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003e2.2 Fabrication of sample\u003c/h2\u003e\n \u003cp\u003eThe Ti\u0026ndash;15Zr\u0026ndash;xTCP (x\u0026thinsp;=\u0026thinsp;5, 10, 15, 20, 25, 30, 35 wt.%) composites were fabricated using powder metallurgy (PM), a technique widely acknowledged for its capacity to process high melting point materials and fabricate homogeneously distributed metal-ceramic systems with controlled microstructures (\u003cspan class=\"CitationRef\"\u003e51\u003c/span\u003e). Titanium, zirconium, and \u0026beta;-tricalcium phosphate powders were weighed in stoichiometric proportions using a digital analytical balance to ensure compositional accuracy. Figure \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e represents the powder metallurgy process used to fabricate Ti-Zr-TCP composites\u003c/p\u003e\n \u003cp\u003eThe powders were dry mixed and homogenized using a planetary ball mill for 6 h at 300 rpm, with tungsten carbide balls in an ethanol medium to prevent particle agglomeration and promote uniform distribution. The slurry was oven-dried at 60\u0026deg;C for 24 h to remove any residual ethanol. The resulting powders were compacted using a uniaxial hydraulic press into cylindrical pellets (10 mm diameter \u0026times; 5 mm height) at a pressure of 600 MPa. This pressing process ensured green bodies with high density and mechanical integrity.\u003c/p\u003e\n \u003cp\u003eThe green compacts were sintered in a vacuum furnace at 900\u0026deg;C for 1 h with a heating rate of 5\u0026deg;C/min, followed by controlled furnace cooling. The selected sintering temperature was based on literature recommendations to preserve the \u0026beta;-TCP phase while achieving sufficient densification and bonding via solid-state diffusion. Sintering below the melting points of the constituent elements prevents phase degradation and improves mechanical performance by refining the interfacial adhesion between TCP particles and the Ti-Zr matrix.\u003c/p\u003e\n \u003cp\u003ePowder metallurgy is preferred over conventional melting or casting because of its low energy consumption, dimensional accuracy, reduced material waste, and proven success in fabricating titanium-based biomedical devices. This method allows precise control over porosity, microstructure, and elemental distribution, which are crucial for load-bearing bio-implants where optimal stress distribution and osseointegration are essential.(\u003cspan class=\"CitationRef\"\u003e52\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e54\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003e2.3 Biological Testing\u003c/h2\u003e\n \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e\n \u003ch2\u003e2.3.1 Antibacterial testing\u003c/h2\u003e\n \u003cp\u003eThe antibacterial activity of the sintered Ti-15Zr-xTCP composite was evaluated using the agar diffusion method, commonly known as the Zone of Inhibition (ZOI) test. This procedure is widely used to assess the antimicrobial efficacy of implant materials under simulated biological conditions. Mueller-Hinton Agar (MHA) served as the nutrient medium, and Escherichia coli (E. coli), a Gram-negative bacterium relevant to peri-implantitis and oral biofilm formation, was selected as the test organism due to its clinical relevance in implant-associated infections.\u003c/p\u003e\n \u003cp\u003eA 100 \u0026micro;L aliquot of E. coli suspension (10⁶ CFU/mL) was evenly spread onto the surface of sterile MHA plates to establish a consistent bacterial lawn. Fabricated Ti\u0026ndash;15Zr\u0026ndash;xTCP samples were gently positioned on the inoculated agar and incubated at 37\u0026deg;C for 24 hours to allow for material-bacteria interaction. Post incubation, the diameter of the clear zone formed around each sample indicative of inhibited bacterial growth was measured using a digital Vernier calliper to quantify antibacterial performance (\u003cspan class=\"CitationRef\"\u003e55\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e56\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eThis method evaluates the passive ion release and contact inhibition properties of the material. The TCP component is known to promote calcium and phosphate ion exchange, which in turn can alter local pH and impair bacterial membrane integrity a mechanism frequently utilized in bioactive ceramic assessments\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e\n \u003ch2\u003e2.3.2 Hemolysis\u003c/h2\u003e\n \u003cp\u003eHemolysis testing was conducted to evaluate the blood compatibility of the Ti\u0026ndash;15Zr\u0026ndash;xTCP composites, with specific attention to the interaction between the sintered samples and human red blood cells (RBCs). Given that dental implants can come into transient contact with blood during surgical insertion, it is essential that implant materials exhibit non-haemolytic behaviour to avoid triggering haemolytic reactions, thrombosis, or inflammatory responses. The procedure was performed in accordance with ISO 10993-4:2017 and ASTM F756-17 standards, which are widely recognised for assessing the hemocompatibility of biomaterials. Figure \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e represents the testing procedure of Hemolysis. Fresh human blood was collected and anticoagulated using EDTA to prevent coagulation.\u003c/p\u003e\n \u003cp\u003eThe blood was diluted with phosphate-buffered saline (PBS) in a 1:10 ratio to mimic physiological ionic strength. Three test groups were prepared: (i) negative control (1 mL blood\u0026thinsp;+\u0026thinsp;1 mL PBS), (ii) positive control (1 mL blood\u0026thinsp;+\u0026thinsp;1 mL distilled water), and (iii) experimental group (1 mL blood\u0026thinsp;+\u0026thinsp;1 mL PBS containing sintered Ti-Zr-TCP composite powder). All samples were incubated at 37\u0026deg;C for 1 hour to replicate body temperature conditions. Following incubation, the tubes were centrifuged at 3000 rpm for 10 minutes. The supernatant was collected, and haemoglobin release was quantified using a UV\u0026ndash;Visible spectrophotometer at a wavelength of 540 nm, corresponding to the maximum absorption of free haemoglobin (\u003cspan class=\"CitationRef\"\u003e57\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e58\u003c/span\u003e) The absorbance readings were used to calculate the percentage of Hemolysis using Eq.\u0026nbsp;(1)\u003c/p\u003e\n \u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/58895_8739fc6c57c1c19a/58895_custom_files/img1760101508.png\" width=\"962\" height=\"97\"\u003e\u003c/p\u003e\n \u003cp\u003eWhere, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{A}_{Sample}\\)\u003c/span\u003e\u003c/span\u003e is the absorbance of the test sample, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{A}_{PBS}\\)\u003c/span\u003e\u003c/span\u003e is that of the negative control, and \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{A}_{DW}\\)\u003c/span\u003e\u003c/span\u003e represents the positive control (distilled water). As per ASTM F756-17 standards, materials exhibiting Hemolysisrates below 5% are categorized as non-hemolytic and are therefore considered safe for blood-contacting biomedical applications (\u003cspan class=\"CitationRef\"\u003e59\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e60\u003c/span\u003e).\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e\n \u003ch2\u003e2.3.3 Cytocompatibility\u003c/h2\u003e\n \u003cp\u003eMTT (3\u0026ndash;4, 5-dimethylthiazol-2yl-2, 5-diphenyl tetrazolium bromide) assay is based on the ability of a mitochondrial dehydrogenase enzyme of viable cells to cleave the tetrazolium rings of the pale yellow MTT and form a dark blue formazan crystal, which is largely impermeable to cell membranes, resulting in its accumulation within healthy cells. Solubilization of cells by the addition of detergents (DMSO) results in the liberation of crystals, which are then solubilized. The number of surviving cells is directly proportional to the level of formazan products. Color can be quantified using a multi-well plate reader (\u003cspan class=\"CitationRef\"\u003e59\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e61\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eThe test sample (Ti-Zr- xTCP) was tested for in vitro cytotoxicity using MG-63 cells via the MTT assay. Briefly, the cultured MG-63 cells were harvested by trypsinization and pooled in a 15 mL tube. The cells were then plated at a density of 1\u0026times;10⁵ cells/mL cells/well (200 \u0026micro;L) into a 96-well tissue culture plate in DMEM containing 10% FBS and 1% antibiotic solution for 24\u0026ndash;48 h at 37\u0026deg;C. The wells were washed with sterile PBS and treated with various concentrations of the test sample in serum-free DMEM. Each sample was tested in triplicate, and the cells were incubated at 37\u0026deg;C in a humidified 5% CO₂ incubator for 24 h. After incubation, MTT (10 \u0026micro;L of 5 mg/mL) was added to each well, and the cells were incubated for another 2\u0026ndash;4 h until purple precipitates were visible under an inverted microscope. Finally, the medium and MTT (220 \u0026micro;L) were aspirated off the wells and washed with 1X PBS (200 \u0026micro;L). Furthermore, to dissolve the formazan crystals, DMSO (100 \u0026micro;L) was added, and the plate was shaken for 5 min (\u003cspan class=\"CitationRef\"\u003e62\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e63\u003c/span\u003e). The absorbance of each well was measured at 570 nm using a microplate reader (Thermo Fisher Scientific, USA), and the percentage cell viability and IC₅₀ value were calculated using GraphPad Prism 6.0 software (USA).\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"3. Results and Discussion","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.1 Antibacterial Activity\u003c/h2\u003e\u003cp\u003eThe antibacterial efficacy of the Ti-15Zr- xTCP composites was investigated using the zone of inhibition (ZOI) test. This study demonstrated a direct correlation between increasing TCP content and antibacterial effectiveness as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e. The Ti-15Zr-25TCP composition produced the widest inhibition zone (~\u0026thinsp;15 mm), indicating its superior antibacterial activity. This inhibition zone is notably larger than values reported for TCP-coated Ti and Ti-Zr composites in previous studies, which typically ranged between 9\u0026ndash;12 mm under similar agar diffusion conditions(\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e) This improvement is attributed to the sustained ionic release of calcium and phosphate from the β-TCP phase, which can elevate the local pH and disrupt bacterial membrane integrity.\u003c/p\u003e\u003cp\u003eThe ZOI findings validate the role of TCP in imparting intrinsic antimicrobial behavior to the Ti-Zr matrix, supporting its potential as a multifunctional dental implant material. Safi et al.(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e) and Stipniece et al.(\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e) highlighted that the antimicrobial effect of TCP largely stems from ion release and membrane disruption, which is further enhanced in hybrid metal\u0026ndash;ceramic composites due to prolonged ion exchange. The Ti- 15Zr- 25TCP combination leverages both these effects, offering a synergistic enhancement over ceramic coatings alone. Notably, while a higher TCP content enhanced the antimicrobial action, compositions beyond 25 wt. % slightly compromised mechanical stability. Therefore, Ti-15Zr-25TCP presents the most optimal balance between antibacterial effect and structural performance. These results confirm that the developed composite provides superior antibacterial performance compared to conventional implant materials studied in literature, while retaining mechanical integrity and cytocompatibility.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e3.2 Cell Viability\u003c/h2\u003e\u003cp\u003eAccording to the quantitative analyses of the MTT assay results for the Ti\u0026ndash;15Zr\u0026ndash;xTCP composites, there was a clear trend of cell viability with respect to the TCP amount. The highest viability among all compositions was for Ti\u0026ndash;15Zr\u0026ndash;25TCP (96.27%), a value close to that of the control (100%) as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. This is significantly greater than the value obtained for the traditional Ti-Zr alloys that usually attain an 85% viability in MG-63 cell test (Bosco et al. (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). It is also higher than that reported for cement-coated zirconia and other conventional Ti implants (67). As presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, the lowest viability was observed for Ti\u0026ndash;15Zr\u0026ndash;5TCP (48.89%), demonstrating scarce cytocompatibility at the lower percentage of TCP. The cell viability gradually increased with the increase of TCP content, for example, the cell viabilities of Ti\u0026ndash;15Zr\u0026ndash;20TCP and Ti\u0026ndash;15Zr\u0026ndash;30TCP were 81.93% and 94.96%, respectively. Apart form 5 and 10 wt.% of TCP, All other formulations exhibited cell viability exceeding 70% -a standard specified by ISO 10993-5 for cytocompatibility, to indicate that the materials are nontoxic.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThese results also matched what was seen when looking at the shape of MG-63 cells under a microscope (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The groups without TCP and with 35TCP (Pictures A and F) looked normal, with healthy, long cells that stuck well and were alive. Compared to the group with no TCP (Picture A), the cells with 5TCP and 10TCP (Pictures B and C) were a bit smaller, and the cells with 15TCP and 20TCP (Pictures D and E) looked somewhat different, which lined up with them not living as well. What we saw with our eyes backs up the different levels of cell death and further proves the numbers we got.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003ePrevious works on surfaces with more TCP has discovered that cells usually live between 70\u0026ndash;90% of the time, and this greatly depends on how much TCP is present and how quickly ions are released (31,67). The information in this research shows that cells live very well when there isn't much TCP and do great with 35TCP, which suggests that the TCP helping bone grow and the strong Ti\u0026ndash;Zr mix on the surface might work well together. This matched what Bajantri et al. found in their research (67), where they said that MG-63 cells lived up to about 90% of the time on implant surfaces covered in ceramic. The mix we have now is even better than that, showing that it could be very useful for putting inside the body for medical reasons.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCytocompatibility evaluation of Ti\u0026ndash;15Zr\u0026ndash;xTCP composites using MG-63 cells.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eMG-63\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eControl (0)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"7\" nameend=\"c9\" namest=\"c3\"\u003e\u003cp\u003ewt.% of TCP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5TCP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10TCP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15TCP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e20TCP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e25TCP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003e30TCP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003e35TCP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSample\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBlank\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.033\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.504\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.682\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.745\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.848\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.968\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.982\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.996\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.033\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.506\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.685\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.748\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.851\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.971\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.985\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.998\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.038\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.508\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.684\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.749\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.846\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.969\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.981\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.992\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAve\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.035\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.506\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.684\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.747\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.848\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.969\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.983\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.996\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e% Diff\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eViability (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e48.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e66.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e72.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e81.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e93.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e94.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e96.27\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e3.3 Hemocompatibility\u003c/h2\u003e\u003cp\u003eHemolysis testing, performed in compliance with ISO 10993-4 and ASTM F756-17 standards, demonstrated that all Ti-15Zr-xTCP samples-maintained Hemolysis levels below the 5% threshold, classifying them as non-haemolytic. The Ti-15Zr-5TCP and Ti- 15Zr- 25TCP samples exhibited the lowest Hemolysis rate of 3.2% and 3.15% respectivily as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e, indicating excellent blood compatibility with minimal red blood cell membrane disruption. These values are lower than those reported by Brunello et al.(\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e) ,who observed\u0026thinsp;~\u0026thinsp;4.5% Hemolysis in zirconium nitride-coated titanium abutments, and are comparable to cobalt-deposited titanium discs which showed Hemolysis rates between 3\u0026ndash;4% (\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e). These results confirm the safety of these composites for temporary or incidental blood contact during implant placement and reinforce their suitability for biomedical applications which are blood compatibility is a crucial criterion. Similar conclusions were drawn by Xie et al.(\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e), where Fe/Zn-modified TCP materials showed comparable hemocompatibility but lacked the added mechanical robustness offered by the Ti-Zr matrix in the present work.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003e3.4 Comparison of experimental results to selected literatures\u003c/h2\u003e\u003cp\u003eA comparative analysis of Ti\u0026ndash;15Zr\u0026ndash;35TCP with previously reported biomaterials is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e, focusing on three critical biological parameters such as zone of inhibition, Hemolysis percentage, and cell viability. The proposed composite shows excellent biocompatibility with the highest cell viability (96%) and the lowest Hemolysis rate (3.91%), outperforming many earlier materials. Additionally, it exhibits the largest zone of inhibition (14 mm), indicating superior antibacterial properties. These results suggest that the Ti\u0026ndash;15Zr\u0026ndash;35TCP composite not only supports osteoblast proliferation but also provides an effective defense against microbial colonization, making it a promising candidate for long-term dental and orthopedic applications.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study demonstrated that incorporating β-tricalcium phosphate (TCP) into Ti-15Zr via powder metallurgy significantly enhances antibacterial activity and cytocompatibility while retaining adequate mechanical stability. A clear trend of increasing antibacterial efficacy with higher TCP content was observed, with the Ti\u0026ndash;15Zr\u0026ndash;35TCP composite exhibiting the most favorable performance, including the widest inhibition zone (~\u0026thinsp;14 mm), highest cell viability (~\u0026thinsp;96%), and low hemolysis (~\u0026thinsp;3.91%). These findings highlight Ti\u0026ndash;15Zr\u0026ndash;35TCP as a promising candidate for biomedical implant applications. Future work will focus on advanced mechanical characterizations, including fatigue and wear resistance, as well as in vivo studies to validate long-term biological performance and clinical applicability.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors gratefully acknowledge the management of Thiagarajar College of Engineering, Madurai, for providing constant support and access to the Metallurgy Laboratory, Department of Mechanical Engineering facilities to conduct this research. The authors also extend their sincere thanks to the management of The American College, Madurai, for their support and for providing access to the Microbiology Laboratory facilities used in this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of conflicting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) received no financial support for the research, authorship, and/or publication of this article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePye AD, Lockhart DEA, Dawson MP, Murray CA, Smith AJ. 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Kukiattrakoon B, editor. International Journal of Dentistry. 2022 Jan 20;2022:1\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eTian X, Zhang P, Xu J. Incorporating zinc ion into titanium surface promotes osteogenesis and osteointegration in implantation early phase. J Mater Sci: Mater Med [Internet]. 2023 Nov 2 [cited 2025 Jul 9];34(11). Available from: https://link.springer.com/10.1007/s10856-023-06751-1\u003c/li\u003e\n\u003cli\u003eKhaskhoussi A, Calabrese L, Curr\u0026ograve; M, Ientile R, Bouaziz J, Proverbio E. Effect of the Compositions on the Biocompatibility of New Alumina\u0026ndash;Zirconia\u0026ndash;Titania Dental Ceramic Composites. Materials. 2020 Mar 18;13(6):1374. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"biomedical-materials-and-devices","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Biomedical Materials \u0026 Devices](https://link.springer.com/journal/44174)","snPcode":"44174","submissionUrl":"https://submission.springernature.com/new-submission/44174/3","title":"Biomedical Materials \u0026 Devices","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Antibacterial activity, Biocompatibility, Dental implants, Hemolysis, Powder metallurgy, Zone of inhibition","lastPublishedDoi":"10.21203/rs.3.rs-7729902/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7729902/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe growing clinical demand for durable and biologically safe dental implants has accelerated the development of novel material systems that address both mechanical and biological challenges. One major limitation of conventional titanium-based implants is their insufficient antibacterial activity, which increases the risk of postoperative infections and implant failure. In this study, titanium\u0026ndash;zirconium\u0026ndash;β-tricalcium phosphate (Ti\u0026ndash;15Zr\u0026ndash;xTCP, x\u0026thinsp;=\u0026thinsp;5, 10, 15, 20, 25, 30, 35 wt.%) composites were fabricated via powder metallurgy for testing to overcome this drawback. The objective was to enhance antibacterial properties while preserving biocompatibility. In vitro analyses confirmed that all compositions were non-hemolytic (\u0026lt;\u0026thinsp;5%). Antibacterial efficiency, assessed by the zone of inhibition, improved with increasing TCP content, with the 35 wt.% group exhibiting the largest inhibition zone of 14mm. This composition also demonstrated the highest MG-63 cell viability (96.27%) and supported favorable osteoblastic morphology. These findings suggest that Ti\u0026ndash;15Zr\u0026ndash;xTCP composites with 35 wt.% TCP offer an effective balance of antibacterial activity, cytocompatibility, and mechanical integrity, making them strong candidates for next-generation dental implants.\u003c/p\u003e","manuscriptTitle":"Biocompatibility Evaluation of Novel Ti-15Zr-TCP composite fabricated by powder metallurgy to enhance the antibacterial performance for dental implant application","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-10 13:10:40","doi":"10.21203/rs.3.rs-7729902/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-16T18:53:34+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-26T18:41:59+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-14T07:57:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-09T11:12:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"23358071734934547053317979469943939616","date":"2025-10-04T13:20:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"271983156968099977640237631121272532657","date":"2025-10-02T01:46:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"153100478193772288067606561516176248866","date":"2025-10-01T10:10:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-29T09:52:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-29T08:17:10+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-29T08:16:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"Biomedical Materials \u0026 Devices","date":"2025-09-27T17:24:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"biomedical-materials-and-devices","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Biomedical Materials \u0026 Devices](https://link.springer.com/journal/44174)","snPcode":"44174","submissionUrl":"https://submission.springernature.com/new-submission/44174/3","title":"Biomedical Materials \u0026 Devices","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"9616e6c6-313f-4958-95f5-a95ba7627509","owner":[],"postedDate":"October 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-07T08:39:33+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-10 13:10:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7729902","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7729902","identity":"rs-7729902","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}