Ti Scaffolds Research Articles

Effect of acid-etching 3D printed Ti templates on mechanical properties and corrosion resistance of Mg alloy scaffolds with different pore geometries

Segmental bone defect repair currently remains a major challenge in orthopedic clinics. In this study, to match different implantation positions, different pore geometries (P, G and Do) of Mg alloy scaffolds were designed and prepared by infiltration casting with the acid-etching treated Ti scaffold as the templates. The results showed that the acid-etching treatment for Ti templates resulted in a smoother surface of the Mg alloy scaffolds with improving the mechanical properties and corrosion resistance. Both experiments and simulations showed that the P scaffold had the highest mechanical properties, with yield strength and elastic modulus up to 26.7±2.1 MPa and 327.1±16.2 MPa, respectively. And the P scaffold had the best corrosion resistance after cleaning the Ti template, with a degradation rate of 0.34±0.17 mm/y at 228 h. In vitro cellular experiments showed good cytocompatibility on the surface of all three scaffolds.

3D-ink-extruded titanium scaffolds with porous struts and bioactive supramolecular polymers for orthopedic implants

Porous titanium addresses the longstanding orthopedic challenges of aseptic loosening and stress shielding. This work expands on the evolution of porous Ti with the manufacturing of hierarchically porous, low stiffness, ductile Ti scaffolds via direct-ink write (DIW) extrusion and sintering of inks containing Ti and NaCl particles. Scaffold macrochannels were filled with a subtherapeutic dose of recombinant bone morphogenetic protein-2 (rhBMP-2) alone or co-delivered within a bioactive supramolecular polymer slurry (SPS) composed of peptide amphiphile nanofibrils and collagen, creating four treatment conditions (Ti struts: microporous vs. fully dense; BMP-2 alone or with SPS). The BMP-2-loaded scaffolds were implanted bilaterally across the L4 and L5 transverse processes in a rat posterolateral lumbar fusion model. In-vivo bone growth in these scaffolds is evaluated with synchrotron X-ray computed microtomography (µCT) to study the effects of strut microporosity and added biological signaling agents on the bone formation response. Optical and scanning electron microscopy confirms the ∼100 µm space-holder micropore size, high-curvature morphology, and pore fenestrations within the struts. Uniaxial compression testing shows that the microporous strut scaffolds have low stiffness and high ductility. A significant promotion in bone formation was observed for groups utilizing the SPS, while no significant differences were found for the scaffolds with the incorporation of micropores. Statement of significanceBy 2050, the anticipated number of people aged 60 years and older worldwide is anticipated to double to 2.1 billion. This rapid increase in the geriatric population will require a corresponding increase in orthopedic surgeries and more effective materials for longer indwelling times. Titanium alloys have been the gold standard of bone fusion and fixation, but their use has longstanding limitations in bone-implant stiffness mismatch and insufficient osseointegration. We utilize 3D-printing of titanium with NaCl space holders for large- and small-scale porosity and incorporate bioactive supramolecular polymers into the scaffolds to increase bone growth. This work finds no significant change in bone ingrowth via space-holder-induced microporosity but significant increases in bone ingrowth via the bioactive supramolecular polymers in a rat posterolateral fusion model.

3D-printed titanium scaffolds loaded with gelatin hydrogel containing strontium-doped silver nanoparticles promote osteoblast differentiation and antibacterial activity for bone tissue engineering.

Bone tissue engineering offers a promising alternative to stimulate the regeneration of damaged tissue, overcoming the limitations of conventional autografts and allografts. Recently, titanium alloy (Ti) implants have garnered significant attention for treating critical-sized bone defects, especially with the advancement of 3D printing technology. Although Ti alloys have impressive versatility, their lack of cellular adhesion, osteogenic and antibacterial properties are significant factors that contribute to their failure. Hence, to overcome these obstacles, this study aimed to incorporate osteoinductive and antibacterial cue-loaded hydrogels into 3D-printed Ti (3D-Ti) scaffolds. 3D-Ti scaffolds were synthesized using the direct metal laser sintering method and loaded with a gelatin (Gel) hydrogel containing strontium-doped silver nanoparticles (Sr-Ag NPs). Compared with Ag NPs, Sr-doped Ag NPs increased the expression of Runx2 mRNA, which is a key bone transcription factor. We subjected the bioactive 3D-hybrid scaffolds (3D-Ti/Gel/Sr-Ag NPs) to physicochemical and material characterization, followed by cytocompatibility and osteogenic evaluation. The microporous and macroporous topographies of the scaffolds with Sr-Ag NPs showed increased Runx2 expression and matrix mineralization, with potent antibacterial properties. Therefore, the 3D-Ti scaffolds incorporated with Sr-Ag NP-loaded Gel hydrogels favored osteoblast differentiation and antibacterial activity, indicating their potential for orthopedic applications.

Microstructure development of Ti scaffold by laser powder bed fusion with chemical polishing and its mechanical properties, biocompatibility

AbstractTitanium (Ti) dental scaffolds are widely used in dental prosthetics due to their excellent mechanical properties and biocompatibility. However, conventional Ti scaffolds manufactured through machining often do not fit perfectly with the bone defect site. Laser powder bed fusion (LPBF) technology enables the personalised manufacturing of custom‐made Ti scaffolds. A custom‐made Ti scaffold was prepared using LPBF and its surface roughness was improved through chemical polishing. To enhance the surface roughness, a nitric acid mixed solution with a specific composition of HF: HNO3:C3H6O3 = 2:2:3 was used. The polishing mechanism was investigated by adjusting the F/Ti ratio to control the formation and dissolution of the oxide film. As a result, the surface of the Ti scaffold after polishing exhibited a smooth and flat appearance compared to the LPBF part, with a reduced surface roughness (Ra) of 1.23 ± 0.19 μm. The custom‐made Ti scaffold also demonstrated favourable mechanical properties, with a bending strength of 335.18 ± 33.62 MPa and stiffness of 2.13 ± 0.21 GPa. Furthermore, in vitro cell tests confirmed the excellent biocompatibility of the custom‐made Ti scaffold. The authors present a feasible strategy for the further clinical application of custom‐made Ti scaffolds, offering enhanced surface properties and addressing the limitations of conventional machining methods.

Highly biologically functional magnesium silicate-coated 3D printed round pore-shaped titanium scaffold alters exosomal miRNA expression to promote osteogenic differentiation for bone defect repair

Bone defects are a serious condition that has a significant impact on the function and quality of life of the patient. In severe bone defects, restoring the structure and function of bone tissue is a complex task, and titanium (Ti) implants designed with superior performance can be an alternative. In this study, in order to develop a Ti implant that effectively promotes osseointegration and new bone ingrowth, 3D printing-based magnesium silicate (MgSiO3)-coated round pore-shaped Ti scaffold (S-R/MgSi) was fabricated by standardizing pore size and porosity and designing different pore shapes and selecting the optimal pore shape (round) as well as subsequent hydrothermal synthesis to finally form MgSiO3 coating. The experimental results of Ti scaffolds with different pore shapes showed that S-R is optimal for promoting osteogenic differentiation. After S-R was coated with MgSiO3, S-R/MgSi enhanced the adhesion, proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), as well as regulated angiogenesis. In vivo studies, S-R/MgSi significantly promoted new bone ingrowth and was effective in repairing bone defects. Following the mechanism exploration, it was found that exosomes secreted by BMSCs co-cultured with S-R/MgSi (Exo_S-R/MgSi) were more able to promote the osteogenic differentiation of BMSCs. In conclusion, this study not only successfully prepared a new type of Ti implant with superior ability to promote new bone ingrowth, but also provided a new explanation for the mechanism of scaffold surface chemistry affecting osteogenesis from the viewpoint of scaffold surface coating affecting the amount and function of cellular exosome secretion.

Complete Removal of Residual Particles and Realization of Mechanical Properties to Improve Osseointegration in Additively Manufactured Ti6Al4 V Scaffolds through Flowing Acid Etching.

Massive unmelted Ti6Al4 V (Ti64) particles presented across all surfaces of additively manufactured Ti64 scaffolds significantly impacted the designed surface topography, mechanical properties, and permeability, reducing the osseointegration of the scaffolds. In this study, the proposed flowing acid etching (FAE) method presented high efficiency in eliminating Ti64 particles and enhancing the surface modification capacity across all surfaces of Ti64 scaffolds. The Ti64 particles across all surfaces of the scaffolds were completely removed effectively and evenly. The surface topography of the scaffolds closely resembled the design after the 75 s FAE treatment. The actual elastic modulus of the treated scaffolds (3.206 ± 0.040 GPa) was closer to the designed value (3.110 GPa), and a micrometer-scale structure was constructed on the inner and outer surfaces of the scaffolds after the 90 s FAE treatment. However, the yield strength of scaffolds was reduced to 89.743 ± 0.893 MPa from 118.251 ± 0.982 MPa after the 90 s FAE treatment. The FAE method also showed higher efficiency in decreasing the roughness and enhancing the hydrophilicity and surface energy of all of the surfaces. The FAE treatment improved the permeability of scaffolds efficiently, and the permeability of scaffolds increased to 11.93 ± 0.21 × 10-10 mm2 from 8.57 ± 0.021 × 10-10 mm2 after the 90 s FAE treatment. The treated Ti64 scaffolds after the 90 s FAE treatment exhibited optimized osseointegration effects in vitro and in vivo. In conclusion, the FAE method was an efficient way to eliminate unmelted Ti64 particles and obtain ideal surface topography, mechanical properties, and permeability to promote osseointegration in additively manufactured Ti64 scaffolds.

Mechanical, bioactive, and long-lasting antibacterial properties of a Ti scaffold with gradient pores releasing iodine ions

The ideal bone implant would effectively prevent aseptic as well as septic loosening by minimizing stress shielding, maximizing bone ingrowth, and preventing implant-associated infections. Here, a novel gradient-pore-size titanium scaffold was designed and manufactured to address these requirements. The scaffold features a larger pore size (900 μm) on the top surface, gradually decreasing to small sizes (600 μm to 300 μm) towards the center, creating a gradient structure. To enhance its functionality, the additively manufactured scaffolds were biofunctionalized using simple chemical and heat treatments so as to incorporate calcium and iodine ions throughout the surface. This unique combination of varying pore sizes with a biofunctional surface provides highly desirable mechanical properties, bioactivity, and notably, long-lasting antibacterial activity. The target mechanical aspects, including low elastic modulus, high compression, compression-shear, and fatigue strength, were effectively achieved. Furthermore, the biofunctional surface exhibits remarkable in vitro bioactivity and potent antibacterial activity, even under conditions specifically altered to be favorable for bacterial growth. More importantly, the integration of small pores alongside larger ones ensures a sustained high release of iodine, resulting in antimicrobial activity that persisted for over three months, with full eradication of the bacteria. Taken together, this gradient structure exhibits obvious superiority in combining most of the desired properties, making it an ideal candidate for orthopedic and dental implant applications.

Characterization of infiltration process of AZ91E alloy in Ti64 scaffolds

Characterization of infiltration process of AZ91E alloy in Ti64 scaffolds

Enhanced antimicrobial properties and bioactivity of 3D-printed titanium scaffolds by multilayer bioceramic coating for large bone defects

The restoration of large bone defects caused by trauma, tumor resection, or infection is a major clinical problem in orthopedics and dentistry because postoperative infections, corrosion, and limited osteointegration of metal implants can lead to loosening of the implant. The aim of this study was to improve the surface properties of a 3D-printed (electron beam melting) Ti6Al4V-based macroporous scaffold by multilayer coating with bioactive silicate glasses (BAGs) and hydroxyapatite doped with a silver (AgHAP) or AgHAP additionally sonochemically modified with ZnO (ZnO-AgHAP). The coated scaffolds AgHAP_BAGs_Ti and ZnO-AgHAP_BAGs_Ti enhanced cytocompatibility in L929 and MRC5 cell lines and expressed bioactivity in simulated body fluid. A lower release of vanadium ions in coated samples compared to bare Ti scaffold indicates decreased dissolution of Ti alloy in coated samples. The coated samples reduced growth of Escherichia coli and Staphylococcus aureus for 4–6 orders of magnitude. Therefore, the 3D-printed Ti-based scaffolds coated with BAGs and (ZnO-)AgHAP have great potential for application as a multifunctional implant with antibacterial properties for the restoration of defects in load-bearing bones.

Evolution from Bioinert to Bioresorbable: In Vivo Comparative Study of Additively Manufactured Metal Bone Scaffolds.

Additively manufactured scaffolds offer significant potential for treating bone defects, owing to their porous, customizable architecture and functionalization capabilities. Although various biomaterials have been investigated, metals - the most successful orthopedic material - have yet to yield satisfactory results. Conventional bio-inert metals, such as titanium (Ti) and its alloys, are widely used for fixation devices and reconstructive implants, but their non-bioresorbable nature and the mechanical property mismatch with human bones limit their application as porous scaffolds for bone regeneration. Advancements in additive manufacturing have facilitated the use of bioresorbable metals, including magnesium (Mg), zinc (Zn), and their alloys, as porous scaffolds via Laser Powder Bed Fusion (L-PBF) technology. This in vivo study presents a comprehensive, side-by-side comparative analysis of the interactions between bone regeneration and additively manufactured bio-inert/bioresorbable metal scaffolds, as well as their therapeutic outcomes. The research offers an in-depth understanding of the metal scaffold-assisted bone healing process, illustrating that Mg and Zn scaffolds contribute to the bone healing process in distinct ways, but ultimately deliver superior therapeutic outcomes compared to Ti scaffolds. These findings suggest that bioresorbable metal scaffolds hold considerable promise for the clinical treatment of bone defects in the near future.

Potential assessment in laser powder bed fusion of bionic porous Ti scaffolds concerning compressive behavior, porosity, and surface roughness

The fabrication of cellular structures with biocompatible materials for implants has increased in recent years because of human aging and traffic road accidents. Laser powder bed fusion or Selective laser melting (SLM) can fabricate various load-bearing implants with mass customization in design and manufacturing. This work involves a manufacturability study in selective laser melting of biomedical Ti alloy implant plug for Osteoarthritis patients. The investigation involved the control variables like laser power (175,185,195) watt, scanning speed (1100,1250,1400) mm/s, and hatch spacing (0.065,0.0725,0.08) mm alongwith output responses such as Compressive yield strength, Elastic modulus, porosity, and surface roughness. The experiments were performed using Box Behnken design in Response surface modelling for collaborative optimization. The results were explicitly explained with an in-depth process physics supported with Characterization involving Scanning electron microscopy, Electro-dispersive spectroscopy, X-ray diffraction, micro-computed tomography, optical profilometry analyses, and process schematics. The optimal setting with laser power (195 W), scanning speed (1100 mm/s), and hatch spacing (0.068 mm) yielded high compressive yield strength (22.41 MPa), near trabecular bone Elastic modulus (0.891GPa), controlled porosity formation (29.32 %), and optimal surface roughness (3.647 μm). Topography resulted in a prominent lack of fusion pores because of low energy density levels, whereas the optimal settings produced around 15 % improvement from design of experiments data.

Functionalization of 3D-Printed Titanium Scaffolds with Elastin-like Recombinamers to Improve Cell Colonization and Osteoinduction.

The 3D printing of titanium (Ti) offers countless possibilities for the development of personalized implants with suitable mechanical properties for different medical applications. However, the poor bioactivity of Ti is still a challenge that needs to be addressed to promote scaffold osseointegration. The aim of the present study was to functionalize Ti scaffolds with genetically modified elastin-like recombinamers (ELRs), synthetic polymeric proteins containing the elastin epitopes responsible for their mechanical properties and for promoting mesenchymal stem cell (MSC) recruitment, proliferation, and differentiation to ultimately increase scaffold osseointegration. To this end, ELRs containing specific cell-adhesive (RGD) and/or osteoinductive (SNA15) moieties were covalently attached to Ti scaffolds. Cell adhesion, proliferation, and colonization were enhanced on those scaffolds functionalized with RGD-ELR, while differentiation was promoted on those with SNA15-ELR. The combination of both RGD and SNA15 into the same ELR stimulated cell adhesion, proliferation, and differentiation, although at lower levels than those for every single moiety. These results suggest that biofunctionalization with SNA15-ELRs could modulate the cellular response to improve the osseointegration of Ti implants. Further investigation on the amount and distribution of RGD and SNA15 moieties in ELRs could improve cell adhesion, proliferation, and differentiation compared to the present study.

Additive manufacturing of multi-morphology graded titanium scaffolds for bone implant applications

• Multi-morphology graded Ti scaffolds with different porosities were designed and characterized systematically. • Hybridized gradients design enhances mechanical and biological performances of scaffolds simultaneously. • Higher strength, appropriate permeability and elastic modulus, and excellent cytocompatibility make PG50 an promising orthopedic implant. Porous Titanium scaffolds have attracted widespread attention as bone implants for avoiding the stress shielding effect and promoting bone-in-growth. In this study, multi-morphology graded scaffolds hybridized by Primitive and Gyroid structures with porosity of 50%, 60%, and 70% were designed (denoted as PG50, PG60, and PG70, respectively) and fabricated by selective laser melting. The simulation results showed that the maximum von–Mises stress of hybridized scaffolds increased from 504.22 to 884.24 MPa with porosity. The permeability and average pore size of multi-morphology PG50, PG60, and PG70 were in the range of 3.58 × 10 –9 – 5.50 × 10 –9 m 2 and 568.1 – 758.4 μm, respectively. The microstructure of multi-morphology graded scaffolds consisted of a fully martensitic α′ phase. Tested permeabilities of PG50 and PG60 were 3.27 × 10 –9 and 4.35 × 10 –9 m 2 , respectively, which were within the range of human bone (0.01 – 12.1 × 10 –9 m 2 ). Elastic modulus and compressive yield strength of PG50 and PG60 ranged within 5.93 – 9.86 and 180.06 – 257.08 MPa, respectively. Therein, the PG50 not only exhibited a similar elastic modulus compared to human cortical bone (10.1 GPa) but also had higher strength (257.08 vs 131 MPa). The results of in vitro biocompatibility assay showed that PG50 and PG60 have better cytocompatibility than mono-morphology scaffolds with the same porosity. Taken together, PG50 is promising to be used for the restoration of bone defects due to its excellent mechanical properties, appropriate permeability, and good cytocompatibility.

Micron/Submicron Scaled Hierarchical Ti Phosphate/Ti Oxide Hybrid Coating on 3D Printed Scaffolds for Improved Osteointegration.

Three-dimensional (3D) printed implants have attracted substantial attention in the field of personalized medicine, but negative impacts on mechanical properties or initial osteointegration have limited their application. To address these problems, we prepared hierarchical Ti phosphate/Ti oxide (TiP-Ti) hybrid coatings on 3D printed Ti scaffolds. The surface morphology, chemical composition, and bonding strength of the scaffolds were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), contact angle measurement, X-ray diffraction (XRD), and scratch test. In vitro performance was analyzed by colonization and proliferation of rat bone marrow mesenchymal stem cells (BMSCs). In vivo osteointegration of the scaffolds in rat femurs was assessed by micro-CT and histological analyses. The results demonstrated improved cell colonization and proliferation as well as excellent osteointegration obtained by incorporation of our scaffolds with the novel TiP-Ti coating. In conclusion, micron/submicron scaled Ti phosphate/Ti oxide hybrid coatings on 3D printed scaffolds have promising potential in future biomedical applications.

Effect of Interbody Implants on the Biomechanical Behavior of Lateral Lumbar Interbody Fusion: A Finite Element Study

Porous titanium interbody scaffolds are growing in popularity due to their appealing advantages for bone ingrowth. This study aimed to investigate the biomechanical effects of scaffold materials in both normal and osteoporotic lumbar spines using a finite element (FE) model. Four scaffold materials were compared: Ti6Al4V (Ti), PEEK, porous titanium of 65% porosity (P65), and porous titanium of 80% porosity (P80). In addition, the range of motion (ROM), endplate stress, scaffold stress, and pedicle screw stress were calculated and compared. The results showed that the ROM decreased by more than 96% after surgery, and the solid Ti scaffold provided the lowest ROM (1.2-3.4% of the intact case) at the surgical segment among all models. Compared to solid Ti, PEEK decreased the scaffold stress by 53-66 and the endplate stress by 0-33%, while porous Ti decreased the scaffold stress by 20-32% and the endplate stress by 0-32%. Further, compared with P65, P80 slightly increased the ROM (<0.03°) and pedicle screw stress (<4%) and decreased the endplate stress by 0-13% and scaffold stress by approximately 18%. Moreover, the osteoporotic lumbar spine provided higher ROMs, endplate stresses, scaffold stresses, and pedicle screw stresses in all motion modes. The porous Ti scaffolds may offer an alternative for lateral lumbar interbody fusion.

Functionalized 3D-printed porous titanium scaffold induces in situ vascularized bone regeneration by orchestrating bone microenvironment

Titanium (Ti) and its alloys have been extensively explored for treating load-bearing bone defects. However, high-stress shielding, weak osteogenic activity, and insufficient vascularization remain key challenges for the long-term clinical outcomes of Ti-based implants. Herein, inspired by structural and functional cues of bone regeneration, a silicon-doped nano-hydroxyapatite (nSiHA)/titanium dioxide (TiO2) composite coating with a hierarchical micro/nano-network structure is constructed on the surface of a 3D-printed porous Ti scaffold via a combined strategy of acid-alkali (AA) treatment and electrochemical deposition technique, which not only endows the scaffold with excellent osteoinduction ability but can also effectively immobilize and release vascular endothelial growth factor (VEGF). The results of the in vitro cell experiments show that the functionalized Ti scaffold significantly promotes osteogenesis in bone marrow mesenchymal stem cells (BMSCs) and angiogenesis in human umbilical vein endothelial cells (HUVECs) by activating the extracellular signal-regulated protein kinase (ERK) and HIF-1α signaling pathways. After being implanted into a rat femoral condyle defect model, the functionalized Ti scaffold can induce in situ vascularized bone regeneration by orchestrating the two coupled processes of angiogenesis and osteogenesis. These findings indicate that the functionalized Ti scaffold has great potential in bone tissue regeneration and is a promising candidate for load-bearing bone defect repair.

BE A SOFTY: ENHANCED BONE FORMATION IN OPTIMIZED, LOW-STIFFNESS 3D-PRINTED TITANIUM IMPLANTS. AN IN VIVO TIBIAL OSTEOTOMY STUDY

Introduction: The mechanobiology and response of bone formation to strain under physiological loading is well established, however investigation into exceedingly soft scaffolds relative to cancellous bone is limited. In this study we designed and 3D printed mechanically-optimised low-stiffness implants, targeting specific strain ranges inducing bone formation and assessed their biological performance in a pre-clinical in vivo load-bearing tibial tuberosity advancement (TTA) model. The TTA model provides an attractive pre-clinical framework to investigate implant osseointegration within an uneven loading environment due to the dominating patellar tendon force.A knee finite element model from ovine CT data was developed to determine physiological target strains from simulated TTA surgery. We 3D printed low-stiffness Ti wedge osteotomy implants with homogeneous stiffness of 0.8 GPa (Ti1), 0.6 GPa (Ti2) and a locally-optimised design with a 0.3 GPa cortex and soft 0.1 GPa core (Ti3), for implantation in a 12-week ovine tibial advancement osteotomy (9mm). We quantitatively assessed bone fusion, bone area, mineral apposition rate and bone formation rate.Optimised Ti3 implants exhibited evenly high strains throughout, despite uneven wedge osteotomy loading. We demonstrated that higher strains above 3.75%, led to greater bone formation. Histomorphometry showed uniform bone ingrowthin optimised Ti3 compared to homogeneous designs (Ti1 and Ti2), and greater bone-implant contact. The greatest bone formation scores were seen in Ti3, followed by Ti2 and Ti1.Results from our study indicate lower stiffness and higher strain ranges than normally achieved in Ti scaffolds stimulate early bone formation. By accounting for loading environments through rational design, implants can be optimised to improve uniform osseointegration. Design and 3D printing of exceedingly soft titanium orthopaedic implants enhance strain induced bone formation and have significant importance in future implant design for knee, hip arthroplasty and treatment of large load-bearing bone defects.

Bi-continuous Mg-Ti interpenetrating-phase composite as a partially degradable and bioactive implant material

Mg (and Mg alloys) and Ti (and Ti alloys) are two important classes of metallic implant materials which are respectively completely degradable and non-degradable after implantation. Making composites composed of them offers the promise for combining their property advantages for bone repair. Here, we present a Mg-Ti composite fabricated by pressureless infiltration of pure Mg melt into 3D printed Ti scaffold, and demonstrate a potential of the composite for use as new partially degradable and bioactive implant materials. The composite has such architecture that the Mg and Ti phases are topologically bi-continuous and mutually interspersed in 3D space, and exhibits several advantages over its constituents, such as higher strengths than as-cast pure Mg and Ti scaffold along with lower Young's modulus than dense Ti. Additionally, the degradation of Mg phase may induce the formation and ingrowth of new bone tissues into the Ti scaffold to form mechanical interlocking between them; in this process, the Ti scaffold provides constant support and Young's modulus adaptively decreases toward that of bone. Despite the accelerated corrosion than pure Mg, the composite remains non-cytotoxic and does not cause obvious adverse reactions after implantation as revealed by in vitro and in vivo experiments. This study may offer a new possibility for combining mechanical durability and bioactivity in implant materials, and allow for customized and targeted design of the implant.

Structural and antibacterial studies of novel ZnO and ZnxMn(1−x)O nanostructured titanium scaffolds for biomedical applications

In the biomedical field, the demand for the development of broad-spectrum biomaterials able to inhibit bacterial growth is constantly increasing. Chronic infections represent the most serious and devastating complication related to the use of biomaterials. This is particularly relevant in the orthopaedic field, where infections can lead to implant loosening, arthrodesis, amputations and sometimes death. Antibiotics are the conventional approach for implanted-associated infections, but they have the limitation of increasing antibiotic resistance, a critical worldwide healthcare issue. In this context, the development of anti-infective biomaterials and infection-resistant surfaces can be considered the more effective strategy to prevent the implant colonisation and biofilm formation by bacteria, so reducing the occurrence of implant-associated infections. In the last years, inorganic nanostructures have become extremely appealing for chemical modifications or coatings of Ti surfaces, since they do not generate antibiotic resistance issues and are featured by superior stability, durability, and full compatibility with the sterilization process. In this work, we present a simple, rapid, and cheap chemical nanofunctionalization of titanium (Ti) scaffolds with colloidal ZnO and Mn-doped ZnO nanoparticles (NPs), prepared by a sol-gel method, exhibiting antibacterial activity. ZnO NPs and ZnxMn(1−x)O NPs formation with a size around 10–20nm and band gap values of 3.42 eV and 3.38 eV, respectively, have been displayed by characterization studies. UV–Vis, fluorescence, and Raman investigation suggested that Mn ions acting as dopants in the ZnO lattice. Ti scaffolds have been functionalized through dip coating, obtaining ZnO@Ti and ZnxMn(1−x)O@Ti biomaterials characterized by a continuous nanostructured film. ZnO@Ti and ZnxMn(1−x)O@Ti displayed an enhanced antibacterial activity against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Pseudomonas aeruginosa (P. aeruginosa) bacterial strains, compared to NPs in solution with better performance of ZnxMn(1−x)O@Ti respect to ZnO@Ti. Notably, it has been observed that ZnxMn(1−x)O@Ti scaffolds reach a complete eradication for S. aureus and 90 % of reduction for P. aeruginosa. This can be attributed to Zn2+ and Mn2+ metal ions release (as observed by ICP MS experiments) that is also maintained over time (72 h). To the best of our knowledge, this is the first study reported in the literature describing ZnO and Mn-doped ZnO NPs nanofunctionalized Ti scaffolds with improved antibacterial performance, paving the way for the realization of new hybrid implantable devices through a low-cost process, compatible with the biotechnological industrial chain method.

Combined Effects of Polydopamine-Assisted Copper Immobilization on 3D-Printed Porous Ti6Al4V Scaffold for Angiogenic and Osteogenic Bone Regeneration

Numerous studies have demonstrated that biological compounds and trace elements such as dopamine (DA) and copper ions (Cu) could be modified onto the surfaces of scaffolds using a one-step immersion process which is simple, inexpensive and, most importantly, non-cytotoxic. The development and emergence of 3D printing technologies such as selective laser melting (SLM) have also made it possible for us to fabricate bone scaffolds with precise structural designs using metallic compounds. In this study, we fabricated porous titanium scaffolds (Ti) using SLM and modified the surface of Ti with polydopamine (PDA) and Cu. There are currently no other reported studies with such a combination for osteogenic and angiogenic-related applications. Results showed that such modifications did not affect general appearances and microstructural characteristics of the porous Ti scaffolds. This one-step immersion modification allowed us to modify the surfaces of Ti with different concentrations of Cu ions, thus allowing us to fabricate individualized scaffolds for different clinical scenarios. The modification improved the hydrophilicity and surface roughness of the scaffolds, which in turn led to promote cell behaviors of Wharton’s jelly mesenchymal stem cells. Ti itself has high mechanical strength, therefore making it suitable for surgical handling and clinical applications. Furthermore, the scaffolds were able to release ions in a sustained manner which led to an upregulation of osteogenic-related proteins (bone alkaline phosphatase, bone sialoprotein and osteocalcin) and angiogenic-related proteins (vascular endothelial growth factor and angiopoietin-1). By combining additive manufacturing, Ti6Al4V scaffolds, surface modification and Cu ions, the novel hybrid 3D-printed porous scaffold could be fabricated with ease and specifically benefited future bone regeneration in the clinic.