Titanium Scaffolds Research Articles

A preliminary study on the mechanical characteristics of the titanium scaffolds with three-dimensional mesh structure fabricated by electron beam melting

Objective: To examine the biomechanical properties of three-dimensional(3D) printed electron beam melting(EBM) Ti-6Al-4V mesh as scaffold for mandibular repairment. Methods: We fabricated Ti-6Al-4V samples of different structures with strut, sheet and 3D mesh scaffolds(a controllable diameter 0.35, 0.50, 0.70 mm, distribution density: intensive sparse) by EBM process. The mechanical properties of these structures were examined by X-ray energy dispersive spectrum(EDS), uniaxial tensile test, three-point bending test, under compression load and compared with their different microstructure and mechanical properties. Results: Compressive deformation behavior of these cellular structures exhibited brittle character that had a typical irregular plateau region in the stress-strain curves. The mesh of larger diameter(d=0.70 mm) showed higher specific strength than the meshs of small diameter(d=0.35 mm) did, and the other 3D mesh under the same condition showed identical specific stiffness. Conclusions: EBM was successfully used to fabricate novel 3D mesh Ti-6Al-4V structures for applications. By optimizing the buckling and bending deformation, Ti-6Al-4V cellular solids with high strength, low modulus. Furthermore, the results of mechanical property and chemistry composition showed that the scaffold could completely satisfy the requirement of hard tissue repairment.

Incorporating simvastatin/poloxamer 407 hydrogel into 3D-printed porous Ti6Al4V scaffolds for the promotion of angiogenesis, osseointegration and bone ingrowth

Three-dimensional porous titanium alloys printed via electron beam melting have low stiffness similar to that of cortical bone and are promising scaffolds for orthopedic applications. However, the bio-inert nature of titanium alloy is poorly compatible with bone ingrowth. We previously observed that simvastatin/poloxamer 407 thermosensitive hydrogel induces endogenous angiogenic/osteogenic growth factors and promotes angiogenesis and osteogenesis, but the mechanical properties of this hydrogel are poor. The purpose of this study was to construct 3D-printed porous titanium scaffolds (pTi scaffolds) filled with simvastatin/hydrogel and evaluate the effects of this composite on osseointegration, bone ingrowth and neovascularization using a tibial defect rabbit model. Four and eight weeks after implantation, the bone volume, bone mineral density, mineral apposition rate, and push-in maximum force of the pTi scaffolds filled with simvastatin/hydrogel were significantly higher than those without simvastatin (p < 0.05). Moreover, filling with simvastatin/hydrogel significantly enhanced vascularization in and around the pTi scaffolds, and a significant correlation was observed between the volume of new bone and neovascularization (p < 0.01). In conclusion, incorporating simvastatin/poloxamer 407 hydrogel into pTi scaffolds significantly improves neovascularization, osseointegration and bone ingrowth.

Titanium-niobium pentoxide composites for biomedical applications

The strength of titanium scaffolds with the introduction of high porosity decreases dramatically and may become inadequate for load bearing in biomedical applications. To simultaneously meet the requirements of biocompatibility, low elastic modulus and appropriate strength for orthopedic implant materials, it is highly desirable to develop new biocompatible titanium based materials with enhanced strength. In this study, we developed a niobium pentoxide (Nb2O5) reinforced titanium composite via powder metallurgy for biomedical applications. The strength of the Nb2O5 reinforced titanium composites (Ti-Nb2O5) is significantly higher than that of pure titanium. Cell culture results revealed that the Ti-Nb2O5 composite exhibits excellent biocompatibility and cell adhesion. Human osteoblast-like cells grew and spread healthily on the surface of the Ti-Nb2O5 composite. Our study demonstrated that Nb2O5 reinforced titanium composite is a promising implant material by virtue of its high mechanical strength and excellent biocompatibility.

Characterization of the porous structures of the green body and sintered biomedical titanium scaffolds with micro-computed tomography

The present research was aimed at gaining an understanding of the porous structure changes from the green body through water leaching and sintering to titanium scaffolds. Micro-computed tomography (micro-CT) was performed to generate 3D models of titanium scaffold preforms containing carbamide space-holding particles and sintered scaffolds containing macro- and micro-pores. The porosity values and structural parameters were determined by means of image analysis. The result showed that the porosity values, macro-pore sizes, connectivity densities and specific surface areas of the titanium scaffolds sintered at 1200°C for 3h did not significantly deviate from those of the green structures with various volume fractions of the space holder. Titanium scaffolds with a maximum specific surface area could be produced with an addition of 60–65vol% carbamide particles to the matrix powder. The connectivity of pores inside the scaffold increased with rising volume fraction of the space holder. The shrinkage of the scaffolds prepared with >50vol% carbamide space holder, occurring during sintering, was caused by the reductions of macro-pore sizes and micro-pore sizes as well as the thickness of struts. In conclusion, the final porous structural characteristics of titanium scaffolds could be estimated from those of the green body.

Influence of Microarchitecture on Osteoconduction and Mechanics of Porous Titanium Scaffolds Generated by Selective Laser Melting

Bone regeneration is naturally based on bone forming cells, osteoinduction by diverse growth factors, and osteoconduction. The latter one used as term in this study is the ingrowth of bone in 3D structures, which leads to an optimal case in creeping substitution of the scaffold by newly formed bone. Autologous bone is still the gold standard for bone substitutes. In most cases, newly developed bone substitutes consist of calcium phosphate, since hydroxyapatite is the main component of bone and mimics cancellous bone in microstructure. In this study, we wanted to elucidate the optimal microarchitecture for osteoconduction and determine compression strength and Young's Modulus of the selected architectures. Selective laser melting of titanium was used as tool to generate diverse architectures in a repetitive and precise way. To link 3D scaffold architecture to biological readouts, bone ingrowth, bone to implant contact, and defect bridging of noncritical-sized defects in the calvarial bone of rabbits were determined. In this series, 5 different microarchitectures were tested with pore sizes ranging from 700 to 1300 μm and constrictions between 290 and 700 μm. To our surprise, all microstructures showed the same biological response of excellent osteoconduction. However, the mechanical yield strength of these structures differed by the factor of three and reached up to three times the strength of cancellous bone at a porosity of 72.3–88.4%. These results suggest that the microarchitecture of bone substitutes can be optimized toward mechanical strength in a wide range of constrictions and pore sizes without having a negative influence on osteoconduction.

Antibacterial Behavior of Additively Manufactured Porous Titanium with Nanotubular Surfaces Releasing Silver Ions.

Additive manufacturing (3D printing) has enabled fabrication of geometrically complex and fully interconnected porous biomaterials with huge surface areas that could be used for biofunctionalization to achieve multifunctional biomaterials. Covering the huge surface area of such porous titanium with nanotubes has been already shown to result in improved bone regeneration performance and implant fixation. In this study, we loaded TiO2 nanotubes with silver antimicrobial agents to equip them with an additional biofunctionality, i.e., antimicrobial behavior. An optimized anodizing protocol was used to create nanotubes on the entire surface area of direct metal printed porous titanium scaffolds. The nanotubes were then loaded by soaking them in three different concentrations (i.e., 0.02, 0.1, and 0.5 M) of AgNO3 solution. The antimicrobial behavior and cell viability of the developed biomaterials were assessed. As far as the early time points (i.e., up to 1 day) are concerned, the biomaterials were found to be extremely effective in preventing biofilm formation and decreasing the number of planktonic bacteria particularly for the middle and high concentrations of silver ions. Interestingly, nanotubes not loaded with antimicrobial agents also showed significantly smaller numbers of adherent bacteria at day 1, which may be attributed to the bactericidal effect of high aspect ratio nanotopographies. The specimens with the highest concentrations of antimicrobial agents adversely affected cell viability at day 1, but this effect is expected to decrease or disappear in the following days as the rate of release of silver ions was observed to markedly decrease within the next few days. The antimicrobial effects of the biomaterials, particularly the ones with the middle and high concentrations of antimicrobial agents, continued until 2 weeks. The potency of the developed biomaterials in decreasing the number of planktonic bacteria and hindering the formation of biofilms make them promising candidates for combating peri-operative implant-associated infections.

Osteoinductive Activity of 3D-modeling Titanium Scaffold with BMP

Osteoinductive Activity of 3D-modeling Titanium Scaffold with BMP

Digital modeling for the individual mandibular 3D mesh scaffold based on 3D printing technology

To investigate an ideal modeling method of designing 3D mesh scaffold substitutes based on tissue engineering to restore mandibular bone defects. By analyzing the theoretical model from titanium scaffolds fabricated by 3D printing, the feasibility and effectiveness of the proposed methodology were verified. Based on the CT scanned data of a subject, the Mimics 15.0 and Geomagic studio 12.0 reverse engineering software were adopted to generate surface model of mandibular bone and the defect area was separated from the 3D model of bone. Then prosthesis was designed via mirror algorithm, in which outer shape was used as the external shape of scaffold. Unigraphics software NX 8.5 was applied on Boolean calculation of subtraction between prosthesis and regular microstructure structure and ANSYS 14.0 software was used to design the inner construction of 3D mesh scaffolds. The topological structure and the geometrical parameters of 3D mesh titanium scaffolds were adjusted according to the aim of optimized structure and maximal strength with minimal weight. The 3D mesh scaffolds solid model through two kinds of computer-aided methods was input into 3D printing equipment to fabricate titanium scaffolds. Individual scaffolds were designed successfully by two modeling methods. The finite element optimization made 10% decrease of the stress peak and volume decrease of 43%, and the porosity increased to 76.32%. This modeling method was validated by 3D printing titanium scaffold to be feasible and effective. 3D printing technology combined with finite element topology optimization to obtain the ideal mandibular 3D mesh scaffold is feasible and effective.

Construction of surface HA/TiO2 coating on porous titanium scaffolds and its preliminary biological evaluation

A simple approach to fabricating hydroxyxapatite/titanium dioxide (HA/TiO2) coating on porous titanium (Ti) scaffolds was developed in the present study. Surface TiO2 layer was firstly formed on porous Ti scaffolds with multi-scale pores by acid-alkali (AA) treatment. The outer HA layer was then formed on the TiO2 layer by subsequent pulse electrochemical deposition (ED) technique. All the three main process parameters, i.e. deposition times, current density and mass transfer mode affected the properties of the HA coating notably. Under the conditions of 90 deposition cycles, −10mA/cm2 of pulse current density and stirring, a thin layer of homogeneous and nanorod-like HA sediments was formed on the substrate surface of porous Ti scaffolds. The results of protein adsorption and cellular experiments showed that compared to the single TiO2 surface, the HA/TiO2 surface allowed more adsorption of serum proteins and further enhanced the alkaline phosphatase (ALP) activity of MC3T3-E1 osteoblasts.

Ti scaffolds with tailored porosities and mechanical properties using porous polymer templates

This study proposes a simple, useful approach to produce three-dimensionally macrochanneled titanium (Ti) scaffolds with tailored porosities and mechanical properties using porous polylactic acid (PLA) templates that can be prepared by conventional solid freeform fabrication (SFF) technique. Specifically, methylcellulose (MC) polymer was used as a binder since it could effectively bind coarse Ti particles and remain chemically stable inert in organic solvents used to dissolve PLA polymer. A Ti slurry-filled PLA was immersed in chloroform to remove the PLA template, followed by sintering at 1300°C for 3h in a vacuum. The use of a relatively small amount of a MC binder and removal of the PLA template in solvent enabled the construction of straight Ti frameworks and macrochannels in a 3-D periodic pattern without severe impurity contamination. This tightly controlled porous structure enabled the achievement of high compressive strengths without a catastrophic failure, while the compressive strength increased from ~72MPa to 121MPa with a decrease in overall porosity from ~75vol% to ~67vol%. In addition, the porous Ti scaffolds showed good biocompatibility, which was assessed by in vitro cell tests in terms of attachment, proliferation, and differentiation of MC3T3-E1 cells.

Titanium scaffold osteogenesis in healthy and osteoporotic rats is improved by the use of low-level laser therapy (GaAlAs).

The present study aimed to assess the effects of low-level laser therapy (GaAlAs) on the bone repair process within titanium scaffolds in the femurs of healthy and osteoporotic rats. Fifty-six rats were divided into four groups: group Sh: SHAM animals that received scaffolds; group LSh: SHAM animals that received scaffolds and were subjected to laser therapy; group OV: ovarietomized (OVX) animals that received scaffolds; and group LOV: OVX animals that received scaffolds and were subjected to laser therapy. Thirty days following ovariectomy or sham surgery, scaffolds were implanted in the left femurs of all animals in the study. Immediately after opening the surgical site, the inner part of the surgical cavity was stimulated with low-level laser (GaAlAs). In addition to this procedure, the laser group was also subjected to sessions of low-level laser therapy (LLLT) at 48-h intervals, with the first session performed immediately after surgery. The rats were sacrificed at 2 and 6weeks, time in which femur fragments were submitted for histological and histomorphometric examination, and skin tissue above the scaffold was submitted to histological analysis. At the end of the study, greater bone formation was observed in the animals submitted to LLLT. At 2 and 6weeks, statistically significant differences were observed between LSh and Sh groups (p = 0.009 and 0.0001) and LOV and OV (p = 0.0001 and 0.0001), respectively. No statistical difference was observed when assessing the estrogen variable. On the basis of our methodology and results, we conclude that LLLT improves and accelerates bone repair within titanium scaffolds in both ovariectomized and healthy rats, when compared to animals not subjected to radiation.

Rapid direct deposition of TiH2 paste for porous Ti scaffolds with tailored porous structures and mechanical properties

We herein demonstrate the utility of the rapid direct deposition of a titanium hydride (TiH2) paste for the production of porous titanium (Ti) scaffolds with tailored porous structures and mechanical properties. In particular, methylcellulous (MC) polymer was used as the binder, since it can rapidly solidify in acetone through solvent extraction, thus enabling deposited green filaments to have high structural integrity. In addition, TiH2 powder was used as the Ti source because of its smaller particle size than commercial Ti powder and conversion to Ti metal through a two-step dehydrogenation process. The uses of fine TiH2 powder and MC binder allowed for the creation of three−dimensionally interconnected periodic macrochannels with sizes of ∼165 ± 14 × 167 ± 25 μm. The produced Ti scaffold had a porosity of ∼42 ± 7 vol % and a reasonably high compressive strength of 48 ± 15 MPa. In addition, the porosity and mechanical properties of porous Ti scaffolds could be tailored simply by adjusting the initial distances between deposited green TiH2/MC filaments. All of the porous Ti scaffolds produced with various porosities showed good in vitro biocompatibility.

Porous titanium scaffolds with injectable hyaluronic acid-DBM gel for bone substitution in a rat critical-sized calvarial defect model.

Demineralized bone matrix (DBM) is an allograft bone substitute used for bone repair surgery to overcome drawbacks of autologous bone grafting, such as limited supply and donor-site comorbidities. In view of different demineralization treatments to obtain DBM, we examined the biological performance of two differently demineralized types of DBM, i.e. by acidic treatment using hydrochloric acid (HCl) or treatment with the chelating agent ethylene diamine tetra-acetate (EDTA). First, we evaluated the osteo-inductive properties of both DBMs by implanting the materials subcutaneously in rats. Second, we evaluated the effects on bone formation by incorporating DBM in a hyaluronic acid (HA) gel to fill a porous titanium scaffold for use in a critical-sized calvarial defect model in 36 male Wistar rats. These porous titanium scaffolds were implanted empty or filled with HA gel containing either DBM HCl or DBM EDTA. Ectopically implanted DBM HCl and DBM EDTA did not induce ectopic bone formation over the course of 12weeks. For the calvarial defects, mean percentages of newly formed bone at 2weeks were significantly higher for Ti-Empty compared to Ti-HA+DBM HCl, but not compared to Ti-HA+DBM EDTA. Significant temporal bone formation was observed for Ti-Empty and Ti-HA+DBM HCl, but not for Ti-HA+DBM EDTA. At 8weeks there were no significant differences in values of bone formation between the three experimental constructs. In conclusion, these results showed that, under the current experimental conditions, neither DBM HCl nor DBM EDTA possess osteo-inductive properties. Additionally, in combination with an HA gel loaded in a porous titanium scaffold, DBM HCl and DBM EDTA showed similar amounts of new bone formation after 8weeks, which were lower than using the empty porous titanium scaffold. Copyright © 2016 John Wiley & Sons, Ltd.

An improved polymeric sponge replication method for biomedical porous titanium scaffolds

Biomedical porous titanium (Ti) scaffolds were fabricated by an improved polymeric sponge replication method. The unique formulations and distinct processing techniques, i.e. a mixture of water and ethanol as solvent, multiple coatings with different viscosities of the Ti slurries and centrifugation for removing the extra slurries were used in the present study. The optimized porous Ti scaffolds had uniform porous structure and completely interconnected macropores (~365.1μm). In addition, two different sizes of micropores (~45.4 and ~6.2μm) were also formed in the skeleton of the scaffold. The addition of ethanol to the Ti slurry increased the compressive strength of the scaffold by improving the compactness of the skeleton. A compressive strength of 83.6±4.0MPa was achieved for a porous Ti scaffold with a porosity of 66.4±1.8%. Our cellular study also revealed that the scaffolds could support the growth and proliferation of mesenchymal stem cells (MSCs).

Post Processing and Biological Evaluation of the Titanium Scaffolds for Bone Tissue Engineering.

Nowadays, post-surgical or post-accidental bone loss can be substituted by custom-made scaffolds fabricated by additive manufacturing (AM) methods from metallic powders. However, the partially melted powder particles must be removed in a post-process chemical treatment. The aim of this study was to investigate the effect of the chemical polishing with various acid baths on novel scaffolds’ morphology, porosity and mechanical properties. In the first stage, Magics software (Materialise NV, Leuven, Belgium) was used to design a porous scaffolds with pore size equal to (A) 200 µm, (B) 500 µm and (C) 200 + 500 µm, and diamond cell structure. The scaffolds were fabricated from commercially pure titanium powder (CP Ti) using a SLM50 3D printing machine (Realizer GmbH, Borchen, Germany). The selective laser melting (SLM) process was optimized and the laser beam energy density in range of 91–151 J/mm3 was applied to receive 3D structures with fully dense struts. To remove not fully melted titanium particles the scaffolds were chemically polished using various HF and HF-HNO3 acid solutions. Based on scaffolds mass loss and scanning electron (SEM) observations, baths which provided most uniform surface cleaning were proposed for each porosity. The pore and strut size after chemical treatments was calculated based on the micro-computed tomography (µ-CT) and SEM images. The mechanical tests showed that the treated scaffolds had Young’s modulus close to that of compact bone. Additionally, the effect of pore size of chemically polished scaffolds on cell retention, proliferation and differentiation was studied using human mesenchymal stem cells. Small pores yielded higher cell retention within the scaffolds, which then affected their growth. This shows that in vitro cell performance can be controlled to certain extent by varying pore sizes.

Customized Osteomesh Cranioplasty

Cranioplasty, one of the oldest surgical procedures used to repair cranial defects, has undergone many revolutionary changes over time to find the ideal material to improve patient outcome. The surgical challenge in repairing large calvarial defects is known to craniofacial surgeons. Ongoing researches on various cranioplasty materials continue with the help of recent technology. Stem cell experiments and development of morphogenic proteins are expected to take the lead in future. With the aid of Computer Aided Designing technology, all currently used alloplastic materials can be custom made for even large skull defect. We present a case of young female patient following trauma underwent craniotomy and complicated with bone graft loss. Patient initially underwent cranioplasty using a PMMA implant, inspite of its excellent tensile strength was not proven to be effective it sustained fracture and got exposed. A customized osteomesh of polycaprolactone (PCL) with a titanium scaffold with bone morphogenic protein (BMP) was impregnated with stem cells was used in cranioplasty. This aided in osseoinduction, which was later proved by imaging. Empirically, there has been no ideal material for cranioplasty; however, materials that are strong, resistant to infection, radiolucent, inexpensive, and able to reincorporate with a patient's craniotomy defect will offer the greatest advantages for such patients and hence PCL with such qualities proves to be a good alternative. Keywords: Cranioplasty, Composite graft, Osteomesh, Stem cells.

The effect of pore structure on the mechanical properties of titanium scaffolds

In the present research, a porous titanium scaffold was prepared by powder metallurgy route. The effect of cold compaction pressure on the morphology and sizes of the pores was investigated by scanning electron microscope (SEM) and optical microscope (OM). The mechanical properties of the porous titanium scaffold were evaluated using compression test. The results indicated that the morphology of macro pores and the amount of micro pores in the struts affected the mechanical properties of porous titanium scaffold. The presence of micro pores in struts made large differences between the experimental results and analytically calculated values of the plateau stress of porous titanium scaffold.

Bone ingrowth of various porous titanium scaffolds produced by a moldless and space holder technique: an in vivo study in rabbits

Porous titanium has long been desired as a bone substitute material because of its ability to reduce the stress shielding in supporting bone. In order to achieve the various pore structures, we have evolved a moldless process combined with a space holder technique to fabricate porous titanium. This study aims to evaluate which pore size is most suitable for bone regeneration using our process. The mixture comprising Ti powder, wax binder and PMMA spacer was prepared manually at 70 °C which depended on the mixing ratio of each group. Group 1 had an average pore size of 60 μm, group 2 had a maximum pore size of 100 μm, group 3 had a maximum pore size of 200 μm and group 4 had a maximum pore size of 600 μm. These specimens were implanted into rabbit calvaria for three and 20 weeks. Thereafter, histomorphometrical evaluation was performed. In the histomorphometrical evaluation after three weeks, the group with a 600 μm pore size showed a tendency to greater bone ingrowth. However, after 20 weeks the group with a pore size of 100 μm showed significantly greater bone ingrowth than the other groups. This study suggested that bone regeneration into porous titanium scaffolds is pore size-dependent, while bone ingrowth was most prominent for the group with 100 μm-sized pores after 20 weeks in vivo.

Influence of pore size of porous titanium fabricated by vacuum diffusion bonding of titanium meshes on cell penetration and bone ingrowth

The present work assesses the potential of three-dimensional (3D) porous titanium (pore size of 188–390μm and porosity of 70%) fabricated by vacuum diffusion bonding of titanium meshes for applications in bone engineering. Rat bone marrow mesenchymal stem cells were used to investigate the proliferation and differentiation of cells on titanium scaffolds with different pore sizes at day 7, day 14 and day 21 based on DNA contents, alkaline phosphatase (ALP) activity, collagen (COL) secretion and osteogenic gene expressions including ALP, COL-1, bone morphogenetic protein-2 (BMP-2), osteopontin (OPN), runt-related transcription factor 2 (RUNX2), using smooth solid titanium plate as reference material. The rabbit models with distal femoral condyles defect were used to investigate the bone ingrowth into the porous titanium. All samples were subjected to Micro-CT and histological analysis after 4 and 12weeks of healing. A one-way ANOVA followed by Tukey post hoc tests was used to analyze the data. It was found that the differentiation stage of cells on the porous titanium delayed compared with the smooth solid titanium plate and Ti 188 was more inclined to promote cell differentiation at the initial stage (day 14) while cell proliferation (day 1, 4, 7, 10, 14 and 21) and bone ingrowth (4 and 12weeks) were biased to Ti 313 and Ti 390. The study indicates that the hybrid porous implant design which combines the advantages of different pore sizes may be meaningful and promising for bone defect restoration. Statement of SignificanceOne of the significant challenges in bone defect restoration is the integration of biomaterials and surrounding bone tissue. Porous titanium may be a promising choice for bone ingrowth and mineralization with appropriate mechanical and biological properties. In this study, based on porous titanium fabricated by vacuum diffusion bonding of titanium meshes, we have evaluated the influence of various pore sizes on rat bone marrow mesenchymal stem cells (rBMMSCs) penetration in vitro and bone ingrowth in vivo. It was interesting that we found the proliferation and differentiation abilities of rBMMSCs, as well as bone ingrowth were related to different pore sizes of such porous scaffolds. The results may provide guidance for porous titanium design for bone defect restoration.

Titanium scaffolds with multi-scale porosity obtained by controlled chemical and electrochemical treatments of porous solids from PM space holder technique

Titanium scaffolds with multi-scale porosity obtained by controlled chemical and electrochemical treatments of porous solids from PM space holder technique