Intra-tumor ROS amplification by melatonin interferes in the apoptosis-autophagy-inflammation-EMT collusion in the breast tumor microenvironment.

Epidemiological as well as experimental studies have established that the pineal hormone melatonin has inhibitory effects on different types of cancers. Several mechanisms have been proposed for the anticancer activities of melatonin, but the fundamental molecular pathways still require clarity. We developed a mouse model of breast cancer using Ehrlich's ascites carcinoma (injected in the 4th mammary fat pad of female Swiss albino mice) and investigated the possibility of targeting the autophagy-inflammation-EMT colloquy to restrict breast tumor progression using melatonin as intervention. Contrary to its conventional antioxidant role, melatonin was shown to augment intracellular ROS and initiate ROS-dependent apoptosis in our system, by modulating the p53/JNK & NF-κB/pJNK expressions/interactions. Melatonin-induced ROS promoted SIRT1 activity. Interplay between SIRT1 and NF-κB/p65 is known to play a pivotal role in regulating the crosstalk between autophagy and inflammation. Persistent inflammation in the tumor microenvironment and subsequent activation of the IL-6/STAT3/NF-κB feedback loop promoted EMT and suppression of autophagy through activation of PI3K/Akt/mTOR signaling pathway. Melatonin disrupted NF-κB/SIRT1 interactions blocking IL-6/STAT3/NF-κB pathway. This led to reversal of pro-inflammatory bias in the breast tumor microenvironment and augmented autophagic responses. The interactions between p62/Twist1, NF-κB/Beclin1 and NF-κB/Slug were altered by melatonin to strike a balance between autophagy, inflammation and EMT, leading to tumor regression. This study provides critical insights into how melatonin could be utilized in treating breast cancer via inhibition of the PI3K/Akt/mTOR signaling and differential modulation of SIRT1 and NF-κB proteins, leading to the establishment of apoptotic and autophagic fates in breast cancer cells.

Additively Manufactured SiO2 and Cu-Added Ti Implants for Synergistic Enhancement of Bone Formation and Antibacterial Efficacy.

Commercially pure titanium (CpTi), a bioinert metal, is used as an implant material at low load-bearing sites and as a porous coating on Ti6Al4V at high load-bearing sites. There is an unmet need for metallic biomaterials to improve osseointegration and inherent antimicrobial resistance. In this study, we have added 1 wt % SiO2 and 3 wt % Cu to the CpTi matrix and processed via metal additive manufacturing (AM). Si4+ ions promote angiogenesis and osteogenesis. CpTi-SiO2 composition exhibited 4.5 times higher bone formation at the bone-implant interface over CpTi in an in vivo study with a rat distal femur model. In vitro bacterial studies with Gram-positive Staphylococcus aureus bacterium revealed 85% antibacterial efficacy by CpTi-SiO2-3Cu than CpTi. CpTi-SiO2-3Cu did not show any inflammatory markers in vivo, indicating the absence of cytotoxicity, but displayed delayed osseointegration compared to CpTi-SiO2. CpTi-SiO2-3Cu displayed 3-fold higher mineralized bone formation than CpTi. Our results emphasize the synergistic effect of SiO2 and Cu addition in CpTi, promoting enhanced early stage osseointegration and inherent antibacterial efficacy, contributing toward implant longevity and stability in vivo.

Enhanced osteogenesis and bactericidal performance with additively manufactured MgO and Cu-added CpTi for load-bearing implants.

Titanium, being the ultimate choice of metallic material for implant applications, its bio-inertness causes delayed bone-tissue integration at the implant site and prevents expedited healing for the patient. This can cause a severe issue for patients with immunocompromised bone health. Infections at the implant site are another concern; titanium does not offer inherent antimicrobial properties. Current strategies addressing the issues above include using cemented implants as a coating on Ti6Al4V bulk material for orthopedic applications. Roadblock arises with coating failure due to weak interfacial bond at the Ti-cement interface, resulting in revision surgeries. We have added osteogenic MgO and antibacterial Cu to CpTi and processed them using metal additive manufacturing (AM) to address these issues. Mg, an essential trace element in the body, has been proven to enhance osseointegration in vivo. Cu has been popular for its bactericidal capabilities. With 1 wt.% of MgO addition in the CpTi matrix, we have observed a four-fold increase in the mineralized bone formation at the bone-implant interface in vivo. The presence of 3 wt.% of Cu showed no cytotoxicity markers, and adding Cu to CpTi-MgO chemical makeup showed similar in vivo performance to CpTi-MgO. In vitro bacterial studies with gram-positive Staphylococcus aureus bacteria showed 81% bacterial efficiency displayed by CpTi-MgO-Cu at the end of 72 h of culture. Our findings highlight the synergistic benefits of CpTi-MgO-Cu, which exhibit superior early-stage osseointegration and antimicrobial capabilities.

Vitamin C and E supplementation and high intensity interval training induced changes in lipid profile and haematological variables of young males.

High intensity interval training (HIIT) causes oxidative stress and haematological alteration. Present study was aimed to evaluate the effect of 8 weeks' supplementation of vitamin C and E on HIIT induced changes in lipid profile parameters and haematological variables. Hundred six male adolescent players were randomly assigned into five age-matched groups, i.e., Control (no exercise+placebo), HIIT (placebo), HIIT â€‹+ â€‹vitamin-C (1 000 â€‹mg/day), HIIT â€‹+ â€‹vitamin-E 400 IU/day) and combined HIIT â€‹+ â€‹vitamin C and E. Morning and evening sessions (90 â€‹min) of HIIT included 4 phases (15 â€‹min each) with 3 sets (4 â€‹min each). Each 4 â€‹min HIIT set consisted of 2 â€‹min intense sprint workout (90%-95% of heart rate maximum [HRmax]) followed by 1 â€‹min active recovery (60%-70% HRmax) followed by 1 â€‹min of complete rest (1:1 work-rest ratio). Lipid profile parameters, haematological variables, endurance capacity and vertical jump were evaluated by standard protocols. Significant decrease in body weight, fat%, total cholesterol, triglyceride, Total Cholesterol/High Density Lipoprotein-Cholesterol and significant increase in High Density Lipoprotein-Cholesterol, maximal oxygen consumption, vertical jump were observed for all four intervention groups. White blood cell count, red blood cell count, haemoglobin percentage and haematocrit values were significantly decreased while platelet count and platelet-to-leukocyte ratio (PLR) ratio were increased significantly only for HIIT group. Blood level of tocopherol and ascorbic acid was significantly increased (values were within the normal range) in all the respective vitamin supplemented groups. Supplementation of vitamin C and E secures health protection with suppressed haemolysis and improved inflammatory blood variables with enhanced explosive leg strength and lipid profile parameters without any concomitant change in endurance capacity.

Porous metal implants: processing, properties, and challenges.

Porous and functionally graded materials have seen extensive applications in modern biomedical devices-allowing for improved site-specific performance; their appreciable mechanical, corrosive, and biocompatible properties are highly sought after for lightweight and high-strength load-bearing orthopedic and dental implants. Examples of such porous materials are metals, ceramics, and polymers. Although, easy to manufacture and lightweight, porous polymers do not inherently exhibit the required mechanical strength for hard tissue repair or replacement. Alternatively, porous ceramics are brittle and do not possess the required fatigue resistance. On the other hand, porous biocompatible metals have shown tailorable strength, fatigue resistance, and toughness. Thereby, a significant interest in investigating the manufacturing challenges of porous metals has taken place in recent years. Past research has shown that once the advantages of porous metallic structures in the orthopedic implant industry have been realized, their biological and biomechanical compatibility-with the host bone-has been followed up with extensive methodical research. Various manufacturing methods for porous or functionally graded metals are discussed and compared in this review, specifically, how the manufacturing process influences microstructure, graded composition, porosity, biocompatibility, and mechanical properties. Most of the studies discussed in this review are related to porous structures for bone implant applications; however, the understanding of these investigations may also be extended to other devices beyond the biomedical field.

3D printed silicon nitride, alumina, and hydroxyapatite ceramic reinforced Ti6Al4V composites - Tailored microstructures to enhance bio-tribo-corrosion and antibacterial properties.

This study utilized directed energy deposition (DED) as a metal additive manufacturing (AM) technique to create ceramic-reinforced composites of Ti6Al4V (Ti64) with hydroxyapatite (HA), alumina (Al2O3), and silicon nitride (Si3N4). The resulting composites had tailored microstructures designed to improve bio-tribological and antibacterial properties simultaneously. A total of 5-wt % ceramic reinforcement were used in Ti64 in four different composites - (1) only Si3N4 (5S), (2) only Al2O3 (5A), (3) 3 wt % Si3N4 and 2 wt% HA (32SH) and (4) 3 wt % Al2O3 and 2 wt% HA (32AH). Microstructural observations revealed that martensite transformation between α and ß-Ti in composites resulted in compressive residual stress at the matrix. Coherency is observed between the ceramic particles and Ti64 matrix, preventing cracking, debonding, or porosity. Vicker's hardness of the composite samples increases by 50% over the Ti64 matrix. Various strengthening mechanisms are discussed in detail, representing the reason behind the reduction of compound wear in 5S and 5A composites. Si3N4-added composites demonstrated an antibacterial response against gram-positive Staphylococcus aureus. The multifunctional performance of ceramic-reinforced Ti64 composites makes them suitable for articulating biomedical devices such as femoral heads in hip implants.

Radial bimetallic structures via wire arc directed energy deposition-based additive manufacturing.

Bimetallic wire arc additive manufacturing (AM) has traditionally been limited to depositions characterized by single planar interfaces. This study demonstrates a more complex radial interface concept, with in situ mechanical interlocking and as-built properties suggesting a prestressed compressive effect. A 308 L stainless core is surrounded by a mild steel casing, incrementally maintaining the interface throughout the Z-direction. A small difference in the thermal expansion coefficient between these steels creates residual stresses at their interface. X-ray diffraction analysis confirms phase purity and microstructural characterization reveals columnar grain growth independent of layer transitions. Hardness values are consistent with thermal dissipation characteristics, and the compressive strength of the bimetallic structures shows a 33% to 42% improvement over monolithic controls. Our results demonstrate that biomimetic radial bimetallic variation is feasible with improved mechanical response over monolithic compositions, providing a basis for advanced structural design and implementation using arc-based metal AM.

Attenuation of sodium arsenite mediated ovarian DNA damage, follicular atresia, and oxidative injury by combined application of vitamin E and C in post pubertal Wistar rats.

Arsenic being a toxic metalloid ubiquitously persists in environment and causes several health complications including female reproductive anomalies. Epidemiological studies documented birth anomalies due to arsenic exposure. Augmented reactive oxygen species (ROS) generation and quenched antioxidant pool are foremost consequences of arsenic threat. On the contrary, Vitamin E (VE) and C (VC) are persuasive antioxidants and conventionally used in toxicity management. Present study was designed to explore the extent of efficacy of combined VE and VC (VEC) against Sodium arsenite (NaAsO2) mediated ovarian damage. Thirty-six female Wistar rats were randomly divided into three groups (Grs) and treated for consecutive 30 days; Gr I (control) was vehicle fed, Gr II (treated) was gavaged with NaAsO2 (3 mg/kg/day), Gr III (supplement) was provided with VE (400 mg/kg/day) & VC (200 mg/kg/day) along with NaAsO2. Marked histological alterations were evidenced by disorganization in oocyte, granulosa cells and zona pellucida layers in treated group. Considerable reduction of different growing follicles along with increased atretic follicles was noted in treated group. Altered activities ofΔ5 3ß-Hydroxysteroid dehydrogenase and 17ß-Hydroxysteroid dehydrogenase accompanied by reduced luteinizing hormone, follicle-stimulating hormone and estradiol levels were observed in treated animals. Irregular estrous cyclicity pattern was also observed due to NaAsO2 threat. Surplus ROS production affected ovarian antioxidant strata as evidenced by altered oxidative stress markers. Provoked oxidative strain further affects DNA status of ovary. However, supplementation with VEC caused notable restoration from such disparaging effects of NaAsO2 toxicities. Antioxidant and antiapoptotic attributes of those vitamins might be liable for such restoration.

Design and manufacturing of patient-specific Ti6Al4V implants with inhomogeneous porosity.

Stress shielding remains a challenge in orthopaedic implants, including total hip arthroplasty. Recent development in printable porous implants offers improved patient-specific solutions by providing adequate stability and reducing stress shielding possibilities. This work presents an approach for designing patient-specific implants with inhomogeneous porosity. A novel group of orthotropic auxetic structures is introduced, and their mechanical properties are computed. These auxetic structure units were distributed at different locations on the implant along with optimized pore distribution to achieve optimum performance. A computer tomography (CT) based finite element (FE) model was used to evaluate the performance of the proposed implant. The optimized implant and the auxetic structures were manufactured using laser powder bed-based laser metal additive manufacturing. Validation was done by comparing FE results with experimentally measured directional stiffness and Poisson's ratio of the auxetic structures and strain on the optimized implant. The correlation coefficient for the strain values was within a range of 0.9633-0.9844. Stress shielding was mainly observed in Gruen zones 1, 2, 6, and 7. The average stress shielding on the solid implant model was 56%, reduced to 18% when the optimized implant was used. This significant reduction in stress shielding can decrease the risk of implant loosening and create an osseointegration-friendly mechanical environment on the surrounding bone. The proposed approach can be effectively applied to the design of other orthopaedic implants to minimize stress shielding.

Improving Biocompatibility for Next Generation of Metallic Implants.

The increasing need for joint replacement surgeries, musculoskeletal repairs, and orthodontics worldwide prompts emerging technologies to evolve with healthcare's changing landscape. Metallic orthopaedic materials have a shared application history with the aerospace industry, making them only partly efficient in the biomedical domain. However, suitability of metallic materials in bone tissue replacements and regenerative therapies remains unchallenged due to their superior mechanical properties, eventhough they are not perfectly biocompatible. Therefore, exploring ways to improve biocompatibility is the most critical step toward designing the next generation of metallic biomaterials. This review discusses methods of improving biocompatibility of metals used in biomedical devices using surface modification, bulk modification, and incorporation of biologics. Our investigation spans multiple length scales, from bulk metals to the effect of microporosities, surface nanoarchitecture, and biomolecules such as DNA incorporation for enhanced biological response in metallic materials. We examine recent technologies such as 3D printing in alloy design and storing surface charge on nanoarchitecture surfaces, metal-on-metal, and ceramic-on-metal coatings to present a coherent and comprehensive understanding of the subject. Finally, we consider the advantages and challenges of metallic biomaterials and identify future directions.

In vivo biocompatibility of SrO and MgO doped brushite cements.

The addition of dopants in biomaterials has emerged as a critical regulator of bone formation and regeneration due to their imminent role in the biological process. The present work evaluated the role of strontium (Sr) and magnesium (Mg) dopants in brushite cement (BrC) on in vivo bone healing performance in a rabbit model. Pure, 1 wt% SrO (Sr-BrC), 1 wt% MgO (Mg-BrC), and a binary composition of 1.0 wt% SrO + 1.0 wt% MgO (Sr + Mg-BrC) BrCs were implanted into critical-sized tibial defects in rabbits for up to 4 months. The in vivo bone healing of three doped and pure BrC samples was examined and compared using sequential radiological examination, histological evaluations, and fluorochrome labeling studies. The results indicated excellent osseous tissue formation for Sr-BrC and Sr + Mg-BrC and moderate bone regeneration for Mg-BrC compared to pure BrC. Our findings indicated that adding small amounts of SrO, MgO, and binary dopants to the BrC can significantly influence new bone formation for bone tissue engineering.

Fatigue behavior of additively manufactured Ti3Al2V alloy.

This study measured the tensile, compression, and fatigue behavior of additively manufactured Ti3Al2V as a function of build orientation. Ti3Al2V alloy was prepared by mixing commercially pure titanium (CpTi) and Ti6Al4V in 1:1 wt. ratio. Laser powder bed fusion (L-PBF) based additive manufacturing (AM) technique was used to fabricate the samples. Tensile tests resulted in an ultimate strength of 989 ± 8 MPa for Ti3Al2V. Ti6Al4V 90° orientation samples showed a compressive yield strength of 1178 ± 33 MPa, and that for Ti3Al2V 90° orientation was 968 ± 24 MPa. Varying the build orientation to account for anisotropy, Ti32-45° and Ti32-0° displayed similar compressive yield strength values of 1071 ± 16 and 1051± 18 MPa, respectively, higher than Ti32-90°. Fatigue loading revealed an endurance limit (10 million cycles) of 250 MPa for Ti6Al4V and 219 MPa for Ti3Al2V built at 90° orientations. The effect of the build orientation was significant under fatigue loading; Ti3Al2V built at 45° displayed an endurance limit of 387.5 MPa, and 0° showed 512 MPa; more than two-fold increment in endurance limit was observed. Our results show the potential of Ti3Al2V alloy for orthopedic devices, replacing Ti6Al4V alloy, particularly in load-bearing applications.

Plasma sprayed fluoride and zinc doped hydroxyapatite coated titanium for load-bearing implants.

Titanium (Ti) alloys show excellent fatigue and corrosion resistance, high strength to weight ratio, and no toxicity; however, poor osseointegration ability of Ti may lead to implant loosening in vivo. Plasma spraying of hydroxyapatite [HA, Ca10 (PO4)6 (OH)2] coating on Ti surfaces is commercially used to enhance osseointegration and the long-term stability of these implants. The biological properties of HA can be improved with the addition of both cationic and anionic dopants, such as zinc ions (Zn2+) and fluoride (F-). However, the hygroscopic nature of fluoride restricts its utilization in the radiofrequency (RF) plasma spray process. In addition, the amount of doping needs to be optimized to ensure cytocompatibility. We have fabricated zinc and fluoride doped HA-coated Ti6Al4V (Ti64) to mitigate these challenges using compositional and parametric optimizations. The RF induction plasma spraying method is utilized to prepare the coatings. Multiple parametric optimizations with amplitude and frequency during the processing result in coating thicknesses between 80 and 145 µm. No adverse effects on the adhesion properties of the coating are noticed because of doping. The antibacterial efficacy of each composition is tested against S. aureus for 24, 48, and 72 h, and showed that the addition of zinc oxide and calcium fluoride to HA leads to nearly 70 % higher antibacterial efficacy than pure HA-coated samples. The addition of osteogenic Zn2+and F- leads to 1.5 times higher osteoblast viability for the doped samples than pure HA-coated samples after 7-days of cell culture. Zn2+ and F- doped HA-coated Ti64 with simultaneous improvements in anti-bacterial efficacy and in vitro biocompatibility can find application in load-bearing implants, particularly in revision surgeries and immune-compromised patients.

Translation of 3D printed materials for medical applications.

During the past 30 years, 3D printing (3DP) technologies significantly influenced the manufacturing world, including innovation in biomedical devices. This special issue reviews recent advances in translating 3DP biomaterials and medical devices for metallic, ceramic, and polymeric devices, as well as bioprinting for organ and tissue engineering, along with regulatory issues in 3DP biomaterials. In our introductory article, besides introducing selected 3DP processes for biomaterials, current challenges and growth opportunities are also discussed. Finally, it highlights a few success stories for the 3D printed biomaterials for medical devices. We hope these articles will educate engineers, scientists, and clinicians about recent developments in translational 3DP technologies.

Additive manufacturing of Ti-Ni bimetallic structures.

Bimetallic structures of nickel (Ni) and commercially pure titanium (CP Ti) were manufactured in three different configurations via directed energy deposition (DED)-based metal additive manufacturing (AM). To understand whether the bulk properties of these three composites are dominated by phase formation at the interface, their directional dependence on mechanical properties was tested. X-ray diffraction (XRD) pattern confirmed the intermetallic NiTi phase formation at the interface. Microstructural gradient observed at the heat-affected zone (HAZ) areas. The longitudinal samples showed about 12% elongation, while the same was 36% for the transverse samples. During compressive deformation, strain hardening from dislocation accumulation was observed in the CP Ti and transverse samples, but longitudinal samples demonstrated failures similar to a brittle fracture at the interface. Transverse samples also showed shear band formation indicative of ductile failures. Our results demonstrate that AM can design innovative bimetallic structures with unique directional mechanical properties.

Influence of strut-size and cell-size variations on porous Ti6Al4V structures for load-bearing implants.

Mechanical properties of porous metal coatings in load-bearing implants play a critical role in determining the in vivo lifetime. However, there is a knowledge gap in measuring the shear strength of porous metal coatings at the porous-dense interface. This study evaluated pore morphology dependence and strut-size on compression, shear deformation, and in vitro response of additively manufactured porous Ti6Al4V structures. Selective laser melting (SLM)-based additive manufacturing (AM) technique was used to process two types of structures with honeycomb cell design-one with constant cell-size of ∼470 µm with mean strut-size varying from 92 to 134 µm, and denoted as strut-size variation (SSV); and the other with a constant strut-size of ∼135 µm with mean cell-size varying from 580 to 740 µm, denoted as cell-size variation (CSV). It was observed that under compressive loading, changes in elastic modulus were more sensitive to variations in strut-size over cell-size. Under shear loading at the porous-dense interface, strength enhancement and material hardening were observed in both SSV and CSV samples due to pore-collapsing. Our results show that for hexagonal cell designs, shear behavior is more sensitive to variations in cell-size over strut-size, although elastic modulus is more sensitive to changes in strut-size for porous metallic structures. From in vitro hFOB analysis, it was observed that pore size of 670 µm demonstrated the highest osteoblast cell viability among porous structures with evidence of pore-bridging by cells. P. aeruginosa bacterial culture showed that bacterial cell viability was higher for porous structures than dense Ti, with evidence of pore-bridging by bacterial cells.

Designing high-temperature oxidation-resistant titanium matrix composites via directed energy deposition-based additive manufacturing.

Composite material development via laser-based additive manufacturing offers many exciting advantages to manufacturers; however, a significant challenge exists in our understanding of process-property relationships for these novel materials. Herein we investigate the effect of input processing parameters towards designing an oxidation-resistant titanium matrix composite. By adjusting the linear input energy density, a composite feedstock of titanium-boron carbide-boron nitride (5 wt% overall reinforcement) resulted in a highly reinforced microstructure composed of borides and carbides and nitrides, with variable properties depending on the overall input energy. Crack-free titanium-matrix composites with hardness as high as 700 ± 17 HV0.2/15 and 99.1% relative density were achieved, with as high as a 33% decrease in oxidation mass gain in the air relative to commercially pure titanium at 700 °C for 50 h. Single-tracks and bulk samples were fabricated to understand the processing characteristics and in situ reactions during processing. Our results indicate that input processing parameters can play a significant role in the oxidation resistance of titanium matrix composites and can be exploited by manufacturers for improving component performance and high temperature designs.

Biotribocorrosion of 3D-Printed silica-coated Ti6Al4V for load-bearing implants.

Laser-based 3D Printing was utilized to deposit a silica (SiO2) coating on the surface of Ti6Al4V (Ti64) alloy for implementation onto articulating surfaces of load-bearing implants. The surface laser melting (SLM) technique was implemented in 1, and 2 laser passes (1LP and 2LP) after SiO2 deposition to understand the influence of remelting on the coating's hardness and tribological performance. It was observed that compositional and microstructural features increased the cross-sectional hardness. Wear rate was observed to decrease from 2.9×10-4 in the Ti64 to 5.2 ×10-6, 3.8×10-6, and 2.1×10-7 mm3/Nm for the as-processed or zero laser-pass (0LP), 1LP, and 2LP, respectively. Coated samples displayed a positive shift in open-circuit potential (OCP) during linear wear by displaying a 368, 85, and 613 mV increase compared to Ti64 for 0LP, 1LP, and 2LP, respectively. Our results showed promising tribological performance of SiO2 coated Ti6Al4V for articulating surfaces of load-bearing implants.

Influence of random and designed porosities on 3D printed tricalcium phosphate-bioactive glass scaffolds.

Calcium phosphate (CaP)-based ceramics are a popular choice for bone-graft applications due to their compositional similarities with bone. Similarly, Bioactive glass (BG) is also common for bone tissue engineering applications due to its excellent biocompatibility and bone binding ability. We report tricalcium phosphate (TCP)-BG (45S5 BG) composite scaffolds using conventional processing and binder jetting-based 3D printing (3DP) technique. We hypothesize that BG's addition in TCP will enhance densification via liquid phase sintering and improve mechanical properties. Further, BG addition to TCP should modulate the dissolution kinetics in vitro. This work's scientific objective is to understand the influence of random vs. designed porosity in TCP-BG ceramics towards variations in compressive strength and in vitro biocompatibility. Our findings indicate that a 5 wt % BG in TCP composite shows a compressive strength of 26.7 ± 2.7 MPa for random porosity structures having a total porosity of ~47.9%. The same composition in a designed porosity structure shows a compressive strength of 21.3 ± 2.9 MPa, having a total porosity of ~54.1%. Scaffolds are also tested for their dissolution kinetics and in vitro bone cell materials interaction, where TCP-BG compositions show favorable bone cell materials interactions. The addition of BG enhances a flaky hydroxycarbonate apatite (HCA) layer in 8 weeks in vitro. Our research shows that the porous TCP- BG scaffolds, fabricated via binder jetting method with enhanced mechanical properties and dissolution properties can be utilized in bone graft applications.

3D Printing in alloy design to improve biocompatibility in metallic implants.

3D Printing (3DP) or additive manufacturing (AM) enables parts with complex shapes, design flexibility, and customization opportunities for defect specific patient-matched implants. 3DP or AM also offers a design platform that can be used to innovate novel alloys for application-specific compositional modifications. In medical applications, the biological response from a host tissue depends on a biomaterial's structural and compositional properties in the physiological environment. Application of 3DP can pave the way towards manufacturing innovative metallic implants, combining structural variations at different length scales and tailored compositions designed for specific biological responses. This study shows how 3DP can be used to design metallic alloys for orthopedic and dental applications with improved biocompatibility using in vitro and in vivo studies. Titanium (Ti) and its alloys are used extensively in biomedical devices due to excellent fatigue and corrosion resistance and good strength to weight ratio. However, Ti alloys' in vivo biological response is poor due to its bioinert surface. Different coatings and surface modification techniques are currently being used to improve the biocompatibility of Ti implants. We focused our efforts on improving Ti's biocompatibility via a combination of tantalum (Ta) chemistry in Ti, the addition of designed micro-porosity, and nanoscale surface modification to enhance both in vitro cytocompatibility and early stage in vivo osseointegration, which was studied in rat and rabbit distal femur models.