3D-printed versatile biliary stents with nanoengineered surface for anti-hyperplasia and antibiofilm formation.

Biliary strictures are characterized by the narrowing of the bile duct lumen, usually caused by surgical biliary injury, cancer, inflammation, and scarring from gallstones. Endoscopic stent placement is a well-established method for the management of biliary strictures. However, maintaining optimal mechanical properties of stents and designing surfaces that can prevent stent-induced tissue hyperplasia and biofilm formation are challenges in the fabrication of biodegradable biliary stents (BBSs) for customized treatment. This study proposes a novel approach to fabricating functionalized polymer BBSs with nanoengineered surfaces using 3D printing. The 3D printed stents, fabricated from bioactive silica poly(ε-carprolactone) (PCL) via a sol-gel method, exhibited tunable mechanical properties suitable for supporting the bile duct while ensuring biocompatibility. Furthermore, a nanoengineered surface layer was successfully created on a sirolimus (SRL)-coated functionalized PCL (fPCL) stent using Zn ion sputtering-based plasma immersion ion implantation (S-PIII) treatment to enhance the performance of the stent. The nanoengineered surface of the SRL-coated fPCL stent effectively reduced bacterial responses and remarkably inhibited fibroblast proliferation and initial burst release of SRL in vitro systems. The physicochemical properties and biological behaviors, including in vitro biocompatibility and in vivo therapeutic efficacy in the rabbit bile duct, of the Zn-SRL@fPCL stent demonstrated its potential as a versatile platform for clinical applications in bile duct tissue engineering.

Photonic control of ligand nanospacing in self-assembly regulates stem cell fate.

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo+ self-assembly composed of azobenzene derivatives (Azo+) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis-Azo+-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of "closely nanospaced" ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo, including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo+ molecules and loaded molecules. Conversely, visible light induces trans-Azo+ formation that facilitates cation-π interactions, thereby deflating self-assembly with "closely nanospaced" ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of "distantly nanospaced" ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.

A strategy for enhancing bioactivity and osseointegration with antibacterial effect by incorporating magnesium in polylactic acid based biodegradable orthopedic implant.

Biodegradable orthopedic implants are essential for restoring the physiological structure and function of bone tissue while ensuring complete degradation after recovery. Polylactic acid (PLA), a biodegradable polymer, is considered a promising material due to its considerable mechanical properties and biocompatibility. However, further improvements are necessary to enhance the mechanical strength and bioactivity of PLA for reliable load-bearing orthopedic applications. In this study, a multifunctional PLA-based composite was fabricated by incorporating tricalcium phosphate (TCP) microspheres and magnesium (Mg) particles homogenously at a volume fraction of 40 %. This approach aims to enhance mechanical strength, accelerate pore generation, and improve biological and antibacterial performance. Mg content was incorporated into the composite at varying values of 1, 3, and 5 vol% (referred to as PLA/TCP-1 Mg, PLA/TCP-3 Mg, and PLA/TCP-5 Mg, respectively). The compressive strength and stiffness were significantly enhanced in all composites, reaching 87.7, 85.9, and 84.1 MPa, and 2.7, 3.0, and 3.1 GPa, respectively. The degradation test indicated faster elimination of the reinforcers as the Mg content increased, resulting in accelerated pore generation to induce enhanced osseointegration. Because PLA/TCP-3 Mg and PLA/TCP-5 Mg exhibited cracks in the PLA matrix due to rapid corrosion of Mg forming corrosion byproducts, to optimize the Mg particle content, PLA/TCP-1 Mg was selected for further evaluation. As determined by in vitro biological and antibacterial testing, PLA/TCP-1 Mg showed enhanced bioactivity with pre-osteoblast cells and exhibited antibacterial properties by suppressing bacterial colonization. Overall, the multifunctional PLA/TCP-Mg composite showed improved mechanobiological performance, making it a promising material for biodegradable orthopedic implants.

Self-Expandable Electrode Based on Chemically Polished Nickel-Titanium Alloy Wire for Treating Endoluminal Tumors Using Bipolar Irreversible Electroporation.

The application of irreversible electroporation (IRE) to endoluminal organs is being investigated; however, the current preclinical evidence and optimized electrodes are insufficient for clinical translation. Here, a novel self-expandable electrode (SE) made of chemically polished nickel-titanium (Ni-Ti) alloy wire for endoluminal IRE is developed in this study. Chemically polished heat-treated Ni-Ti alloy wires demonstrate increased electrical conductivity, reduced carbon and oxygen levels, and good mechanical and self-expanding properties. Bipolar IRE using chemically polished Ni-Ti wires successfully induces cancer cell death. IRE-treated potato tissue shows irreversibly and reversibly electroporated areas containing dead cells in an electrical strength-dependent manner. In vivo study using an optimized electric field strength demonstrates that endobiliary IRE using the SE evenly induces well-distributed mucosal injuries in the common bile duct (CBD) with the overexpression of the TUNEL, HSP70, and inflammatory cells without ductal perforation or stricture formation. This study demonstrates the basic concept of the endobiliary IRE procedure, which is technically feasible and safe in a porcine CBD as a novel therapeutic strategy for malignant biliary obstruction. The SE is a promising electrical energy delivery platform for effectively treating endoluminal organs.

Antibacterial PLA/Mg composite with enhanced mechanical and biological performance for biodegradable orthopedic implants.

Biodegradability, bone-healing rate, and prevention of bacterial infection are critical factors for orthopedic implants. Polylactic acid (PLA) is a good candidate biodegradable material; however, it has insufficient mechanical strength and bioactivity for orthopedic implants. Magnesium (Mg), has good bioactivity, biodegradability, and sufficient mechanical properties, similar to that of bone. Moreover, Mg has an inherent antibacterial property via a photothermal effect, which generates localized heat, thus preventing bacterial infection. Therefore, Mg is a good candidate material for PLA composites, to improve their mechanical and biological performance and add an antibacterial property. Herein, we fabricated an antibacterial PLA/Mg composite for enhanced mechanical and biological performance with an antibacterial property for application as biodegradable orthopedic implants. The composite was fabricated with 15 and 30 vol% of Mg homogeneously dispersed in PLA without the generation of a defect using a high-shear mixer. The composites exhibited an enhanced compressive strength of 107.3 and 93.2 MPa, and stiffness of 2.3 and 2.5 GPa, respectively, compared with those of pure PLA which were 68.8 MPa and 1.6 GPa, respectively. Moreover, the PLA/Mg composite at 15 vol% Mg exhibited significant improvement of biological performance in terms of enhanced initial cell attachment and cell proliferation, whereas the composite at 30 vol% Mg showed deteriorated cell proliferation and differentiation because of the rapid degradation of the Mg particles. In turn, the PLA/Mg composites exerted an antibacterial effect based on the inherent antibacterial property of Mg as well as the photothermal effect induced by near-infrared (NIR) treatment, which can minimize infection after implantation surgery. Therefore, antibacterial PLA/Mg composites with enhanced mechanical and biological performance may be a candidate material with great potential for biodegradable orthopedic implants.

3D-Printed Functional Hydrogel by DNA-Induced Biomineralization for Accelerated Diabetic Wound Healing.

Chronic wounds in diabetic patients are challenging because their prolonged inflammation makes healing difficult, thus burdening patients, society, and health care systems. Customized dressing materials are needed to effectively treat such wounds that vary in shape and depth. The continuous development of 3D-printing technology along with artificial intelligence has increased the precision, versatility, and compatibility of various materials, thus providing the considerable potential to meet the abovementioned needs. Herein, functional 3D-printing inks comprising DNA from salmon sperm and DNA-induced biosilica inspired by marine sponges, are developed for the machine learning-based 3D-printing of wound dressings. The DNA and biomineralized silica are incorporated into hydrogel inks in a fast, facile manner. The 3D-printed wound dressing thus generates provided appropriate porosity, characterized by effective exudate and blood absorption at wound sites, and mechanical tunability indicated by good shape fidelity and printability during optimized 3D printing. Moreover, the DNA and biomineralized silica act as nanotherapeutics, enhancing the biological activity of the dressings in terms of reactive oxygen species scavenging, angiogenesis, and anti-inflammation activity, thereby accelerating acute and diabetic wound healing. These bioinspired 3D-printed hydrogels produce using a DNA-induced biomineralization strategy are an excellent functional platform for clinical applications in acute and chronic wound repair.

Accelerated biodegradation of iron-based implants via tantalum-implanted surface nanostructures.

In recent years, pure iron (Fe) has attracted significant attention as a promising biodegradable orthopedic implant material due to its excellent mechanical and biological properties. However, in physiological conditions, Fe has an extremely slow degradation rate with localized and irregular degradation, which is problematic for practical applications. In this study, we developed a novel combination of a nanostructured surface topography and galvanic reaction to achieve uniform and accelerated degradation of an Fe implant. The target-ion induced plasma sputtering (TIPS) technique was applied on the Fe implant to introduce biologically compatible and electrochemically noble tantalum (Ta) onto its surface and develop surface nano-galvanic couples. Electrochemical tests revealed that the uniformly distributed nano-galvanic corrosion cells of the TIPS-treated sample (nano Ta-Fe) led to relatively uniform and accelerated surface degradation compared to that of bare Fe. Furthermore, the mechanical properties of nano Ta-Fe remained almost constant during a long-term in vitro immersion test (~40 weeks). Biocompatibility was also assessed on surfaces of bare Fe and nano Ta-Fe using in vitro osteoblast responses through direct and indirect contact assays and an in vivo rabbit femur medullary cavity implantation model. The results revealed that nano Ta-Fe not only enhanced cell adhesion and spreading on its surface, but also exhibited no signs of cellular or tissue toxicity. These results demonstrate the immense potential of Ta-implanted surface nanostructures as an effective solution for the practical application of Fe-based orthopedic implants, ensuring long-term biosafety and clinical efficacy.

Freeform 3D printing of vascularized tissues: Challenges and strategies.

In recent years, freeform three-dimensional (3D) printing has led to significant advances in the fabrication of artificial tissues with vascularized structures. This technique utilizes a supporting matrix that holds the extruded printing ink and ensures shape maintenance of the printed 3D constructs within the prescribed spatial precision. Since the printing nozzle can be translated omnidirectionally within the supporting matrix, freeform 3D printing is potentially applicable for the fabrication of complex 3D objects, incorporating curved, and irregular shaped vascular networks. To optimize freeform 3D printing quality and performance, the rheological properties of the printing ink and supporting matrix, and the material matching between them are of paramount importance. In this review, we shall compare conventional 3D printing and freeform 3D printing technologies for the fabrication of vascular constructs, and critically discuss their working principles and their advantages and disadvantages. We also provide the detailed material information of emerging printing inks and supporting matrices in recent freeform 3D printing studies. The accompanying challenges are further discussed, aiming to guide freeform 3D printing by the effective design and selection of the most appropriate materials/processes for the development of full-scale functional vascularized artificial tissues.

Ultra-wide band (O to L) photonic integrated polymer cross-bar switch matrix.

We present an ultra-wide band photonic integrated 4×4 polymer cross-bar switch matrix based on total internal reflection and the thermo-optic effect. The photonic integrated polymer switch owns low insertion loss, low power consumption, wavelength, and polarization-independent operation for all switching paths. The experimental results show ultra-wide band (O- to L-band) operation with fiber-to-fiber insertion losses ranging from -3.7 to -6.5dB, 0.1 to 0.6 dB polarization-dependent losses, switching the on-off ratio above 36 dB on average, and 25 mW power consumption per path. Error-free operation with a power penalty <0.2dB at 1 E-9 bit error rate (BER) for ultra-wide band non-return-to-zero on-off keying (NRZ-OOK) wavelength-division multiplexing (WDM) switched signals at 10, 25, 40, and 50 Gbit/s, and 510 Gbps dual polarization 64-QAM switched data with a negligible penalty were measured.

Nano-Topographical Control of Ti-Nb-Zr Alloy Surfaces for Enhanced Osteoblastic Response.

Nano-scale surface roughening of metallic bio-implants plays an important role in the clinical success of hard tissue reconstruction and replacement. In this study, the nano-topographical features of titanium-niobium-zirconium (TNZ) alloy surfaces were controlled by using the target-ion induced plasma sputtering (TIPS) technique to improve the in vitro osteoblastic response. The TIPS technique is a novel strategy for etching the surface of metallic bio-implants using bombardment of target metal cations, which were accelerated by an extremely high negative bias voltage applied to the substrates. The nano-topography of the TNZ surfaces was successfully controlled by modulating experimental variables (such as the ion etching energy and the type of substrate or target materials) of TIPS. As a result, various nanopatterns (size: 10-210 nm) were fabricated on the surface of the TNZ alloys. Compared with the control group, experimental groups with nanopattern widths of ≥130 nm (130 and 210 nm groups) exhibited superior cell adhesion, proliferation, and differentiation. Our findings demonstrate that TIPS is a promising technology that can impart excellent biological functions to the surface of metallic bio-implants.

Bifunctional poly (l-lactic acid)/hydrophobic silica nanocomposite layer coated on magnesium stents for enhancing corrosion resistance and endothelial cell responses.

Biodegradable magnesium (Mg)-based vascular stents can overcome the limitations of conventional permanent metallic stents, such as late in-stent restenosis and thrombosis, but still have difficulty retarding degradation while providing adequate mechanical support to the blood vessel. We incorporated silica nanoparticles surface-functionalized with hexadecyltrimethoxysilane (mSiNP) into a poly (l-lactic acid) (PLLA) coating as a physical barrier to disturb the penetration of the corrosive medium as well as a bioactive source that releases silicon ions capable of stimulating endothelial cells. The corrosion resistance and biocompatibility of this bifunctional PLLA/mSiNP nanocomposite coating were investigated using different weight ratios of mSiNP. The nanocomposite coating containing more than 10 wt% of the mSiNP (PLLA/10mSiNP and PLLA/20mSiNP) significantly delayed the corrosion of the Mg substrate and exhibited favorable endothelial cell responses, compared to the pure PLLA coating. Specifically, the calculated corrosion rates of PLLA/10mSiNP and PLLA/20mSiNP decreased by half, indicating the durability of the coating after immersion in simulated body fluid for 12 days. Based on the in vitro cellular response, the incorporation of the mSiNPs into the PLLA coating significantly improved the endothelial cell responses to the Mg substrate, showing better initial cell surface coverage, migration, and proliferation rate than those of pure PLLA. These results indicate that the PLLA/mSiNP nanocomposite coatings have significant potential to improve the corrosion resistance and vascular compatibility of biodegradable Mg-based vascular stents.

Design and Usability Evaluations of a 3D-Printed Implantable Drug Delivery Device for Acute Liver Failure in Preclinical Settings.

Acute liver failure (ALF) requiring liver transplantation is a disease that occurs due to rapid hepatocellular dysfunction. As liver transplantation has various limitations, including donor scarcity, high cost, and immuno-incompatibility, continuous local delivery of biopharmaceuticals to the liver tissue can be a promising ALF treatment option. Here, the in vivo safety and usability of a 3D-printed implantable drug delivery device for effective ALF treatment is evaluated. The implantable reservoir consists of a 3D-printed container and a semipermeable membrane for repeated administrations of drugs, specifically to the liver tissue. The physical stability and function of the 3D-printed reservoir are confirmed by the mechanical properties and in vitro drug release test, respectively. In mice implanted with the reservoir system, mortality, weight changes, clinical signs, hematological and serum biochemical changes, and organ weight changes are not observed, suggesting no foreign body reaction. The usability of the reservoir system is further evaluated using an ALF model of 70% hepatectomized mice treated with N-acetylcysteine through the system, showing cell-specific regeneration and significant liver injury alleviation. Overall, the 3D-printed reservoir system is safe for studying the therapeutic potential of ALF treatment, and it can be used for the delivery of various active pharmaceutical ingredients.

Construction of tantalum/poly(ether imide) coatings on magnesium implants with both corrosion protection and osseointegration properties.

Poly(ether imide) (PEI) has shown satisfactory corrosion protection capability with good adhesion strength as a coating for magnesium (Mg), a potential candidate of biodegradable orthopedic implant material. However, its innate hydrophobic property causes insufficient osteoblast affinity and a lack of osseointegration. Herein, we modify the physical and chemical properties of a PEI-coated Mg implant. A plasma immersion ion implantation technique is combined with direct current (DC) magnetron sputtering to introduce biologically compatible tantalum (Ta) onto the surface of the PEI coating. The PEI-coating layer is not damaged during this process owing to the extremely short processing time (30 s), retaining its high corrosion protection property and adhesion stability. The Ta-implanted layer (roughly 10-nm-thick) on the topmost PEI surface generates long-term surface hydrophilicity and favorable surface conditions for pre-osteoblasts to adhere, proliferate, and differentiate. Furthermore, in a rabbit femur study, the Ta/PEI-coated Mg implant demonstrates significantly enhanced bone tissue affinity and osseointegration capability. These results indicate that Ta/PEI-coated Mg is promising for achieving early mechanical fixation and long-term success in biodegradable orthopedic implant applications.

Powder based additive manufacturing for biomedical application of titanium and its alloys: a review.

Powder based additive manufacturing (AM) technology of Ti and its alloys has received great attention in biomedical applications owing to its advantages such as customized fabrication, potential to be cost-, time-, and resource-saving. The performance of additive manufactured implants or scaffolds strongly depends on various kinds of AM technique and the quality of Ti and its alloy powders. This paper has specifically covered the process of commonly used powder-based AM technique and the powder production of Ti and its alloy. The selected techniques include laser-based powder bed fusion of metals (PBF-LB/M), electron beam powder bed fusion of metals (PBF-EB/M), and directed energy deposition utilized in the production of the biomaterials are discussed as well as the powder fed system of binder jetting. Moreover, titanium based powder production methods such as gas atomization, plasma atomization, and plasma rotating electrode process are also discussed.

Enhanced Bioactivity of Micropatterned Hydroxyapatite Embedded Poly(L-lactic) Acid for a Load-Bearing Implant.

Poly(L-lactic) acid (PLLA) is among the most promising polymers for bone fixation, repair, and tissue engineering due to its biodegradability and relatively good mechanical strength. Despite these beneficial characteristics, its poor bioactivity often requires incorporation of bioactive ceramic materials. A bioresorbable composite made of PLLA and hydroxyapatite (HA) may improve biocompatibility but typically causes deterioration in mechanical properties, and bioactive coatings inevitably carry a risk of coating delamination. Therefore, in this study, we embedded micropatterned HA on the surface of PLLA to improve bioactivity while eliminating the risk of HA delamination. An HA pattern was successfully embedded in a PLLA matrix without degeneration of the matrix's mechanical properties, thanks to a transfer technique involving conversion of Mg to HA. Furthermore, patterned HA/PLLA's biological response outperformed that of pure PLLA. These results confirm patterned HA/PLLA as a candidate for wide acceptance in biodegradable load-bearing implant applications.

3D Freeform Printing of Nanocomposite Hydrogels through in situ Precipitation in Reactive Viscous Fluid.

Composite hydrogels have gained great attention as three-dimensional (3D) printing biomaterials because of their enhanced intrinsic mechanical strength and bioactivity compared to pure hydrogels. In most conventional printing methods for composite hydrogels, particles are preloaded in ink before printing, which often reduces the printability of composite ink with little mechanical improvement due to poor particle-hydrogel interaction of physical mixing. In contrast, the in situ incorporation of nanoparticles into a hydrogel during 3D printing achieves uniform distribution of particles with remarkable mechanical reinforcement, while precursors dissolved in inks do not influence the printing process. Herein, we introduced a "printing in liquid" technique coupled with a hybridization process, which allows 3D freeform printing of nanoparticle-reinforced composite hydrogels. A viscoplastic matrix for this printing system provides not only support for printed hydrogel filaments but also chemical reactants to induce various reactions in printed objects for in situ modification. Nanocomposite hydrogel scaffolds were successfully fabricated through this 3D freeform printing of hyaluronic acid (HAc)-alginate (Alg) hydrogel inks through a two-step crosslinking strategy. The first ionic crosslinking of Alg provided structural stability during printing, while the secondary crosslinking of photo-curable HAc improved the mechanical and physiological stability of the nanocomposite hydrogels. For in situ precipitation during 3D printing, phosphate ions were dissolved in the hydrogel ink and calcium ions were added to the viscoplastic matrix. The composite hydrogels demonstrated a significant improvement in mechanical strength, biostability, as well as biological performance compared to pure HAc. Moreover, the multi-material printing of composites with different calcium phosphate contents was achieved by adjusting the ionic concentration of inks. Our method greatly accelerates the 3D printing of various functional or hybridized materials with complex geometries through the design and modification of printing materials coupled with in situ post-printing functionalization and hybridization in reactive viscoplastic matrices.

Preliminary Characterization of Glass/Alumina Composite Using Laser Powder Bed Fusion (L-PBF) Additive Manufacturing.

Powder bed fusion (PBF) additive manufacturing (AM) is currently used to produce high-efficiency, high-density, and high-performance products for a variety of applications. However, existing AM methods are applicable only to metal materials and not to high-melting-point ceramics. Here, we develop a composite material for PBF AM by adding Al2O3 to a glass material using laser melting. Al2O3 and a black pigment are added to a synthesized glass frit for improving the composite strength and increased laser-light absorption, respectively. Our sample analysis shows that the glass melts to form a composite when the mixture is laser-irradiated. To improve the sintering density, we heat-treat the sample at 750 °C to synthesize a high-density glass frit composite. As per our X-ray diffraction (XRD) analysis to confirm the reactivity of the glass frit and Al2O3, we find that no reactions occur between glass and crystalline Al2O3. Moreover, we obtain a high sample density of ≥95% of the theoretical density. We also evaluate the composite's mechanical properties as a function of the Al2O3 content. Our approach facilitates the manufacturing of ceramic 3D structures using glass materials through PBF AM and affords the benefits of reduced process cost, improved performance, newer functionalities, and increased value addition.

Improved cell viability for large-scale biofabrication with photo-crosslinkable hydrogel systems through a dual-photoinitiator approach.

Biofabrication with various hydrogel systems allows the production of tissue or organ constructs in vitro to address various challenges in healthcare and medicine. In particular, photocrosslinkable hydrogels have great advantages such as excellent spatial and temporal selectivity and low processing cost and energy requirements. However, inefficient polymerization kinetics of commercialized photoinitiators upon exposure to UV-A radiation or visible light increase processing time, often compromising cell viability. In this study, we developed a hydrogel crosslinking system which exhibited efficient crosslinking properties and desired mechanical properties with high cell viability, through a dual-photoinitiator approach. Through the co-existence of Irgacure 2959 and VA-086, the overall crosslinking process was completed with a minimal UV dosage during a significantly reduced crosslinking time, producing mechanically robust hydrogel constructs, while most encapsulated cells within the hydrogel constructs remained viable. Moreover, we fabricated a large PEGDA hydrogel construct with a single microchannel as a proof of concept for hydrogels with vasculature to demonstrate the versatility of the system. Our dual-photoinitiator approach allowed the production of this photocrosslinkable hydrogel system with microchannels, significantly improving cell viability and processing efficiency, yet maintaining good mechanical stability. Taken together, we envision the concurrent use of photoinitiators, Irgacure 2959 and VA-086, opening potential avenues for the utilization of various photocrosslinkable hydrogel systems in perfusable large artificial tissue for in vivo and ex vivo applications with improved processing efficiency and cell viability.

Ta ion implanted nanoridge-platform for enhanced vascular responses.

Bare metal stents are commonly used in interventional cardiology; they provide successful treatment because of their excellent mechanical properties, expandability ratios, and flexibility. However, their insufficient vascular affinity can induce the development of neointimal hyperplasia following arterial injury and subsequent smooth muscle cell overgrowth in the lumen of a stented vessel. Nanoengineering of the bare metal stent surface is a valuable strategy for eliciting favorable vascular responses. In this study, we introduce a target-ion-induced plasma sputtering (TIPS) technique to fabricate a platform with a favorable endothelial environment. This technique enables the simple single-step production of a Ta-implanted nanoridged surface on a stent with a complex 3D geometry that shows a clear tendency to become oriented parallel to the direction of blood flow. Moreover, the nanoridges developed show good structural integrity and mechanical stability, resulting in apparently stable morphologies under high strain rates. In vitro cellular responses to the Co-Cr, such as endothelialization, platelet activation, and blood coagulation, are considerably altered after TIPS treatment; endothelium formation is rapid and surface thrombogenicity is low. An in vivo rabbit iliac artery model is used to confirm that the nanoridged surface facilitates rapid re-endothelialization and limits the formation of neointima compared to the bare stent. These results indicate that the Ta ion implanted nanoridge platform fabricated using the TIPS technique has immense potential as a solution for in-stent restenosis and ensuring the long-term patency of bare metal stents.

Enhanced bioactivity of titanium-coated polyetheretherketone implants created by a high-temperature 3D printing process.

Polyetheretherketone (PEEK), one of the potential alternatives to metallic materials for implants, necessarily involves high temperature process conditions to be three-dimensionally (3D) printed. We developed a 3D printing setup equipped with thermally stabilized modules of the printing nozzle and building chamber, by which the PEEK implants could be successfully manufactured. Under optimized printing conditions, the maximal mechanical strength of the 3D printed sample attained over 80% of the original bulk property of PEEK. To enhance the interfacial biocompatibility, the as-printed implants were postprocessed with titanium (Ti) sputtering. The Ti-coated surfaces were evaluated through characterization studies of x-ray diffraction spectra, microscopic topographies, and wetting properties. For the in vitro tests, preosteoblasts were cultured on the developed PEEK-Ti structures and evaluated in terms of cell adhesion, proliferation, and osteogenic differentiation. In addition, the bone regeneration capability of the PEEK-Ti implants was confirmed by animal experiments using a rabbit tibia defect model for a period of 12 weeks. In the overall in vitro and in vivo tests, we confirmed the superior bioactivities of the Ti-modified and 3D printed interface by comparisons between the samples of machined and printed samples with or without Ti coating. Taken together, the comprehensive manufacturing approaches that involve 3D printing and biocompatible postprocessing are expected to have universal applicability in a wide range of bone tissue engineering.