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.

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.

Porous calcium phosphate-collagen composite microspheres for effective growth factor delivery and bone tissue regeneration.

Microspheres are beneficial for filling defects of various shapes and provide a large surface area for cell attachment. Porous microspheres have attracted particular attention because they can deliver cells and bioactive molecules such as growth factors. In this study, BCP-collagen composite microspheres were developed for growth factor delivery in bone regeneration. Firstly, porous biphasic calcium phosphate (BCP) microspheres were fabricated by applying a water-in-oil emulsion technique using camphene as a pore generator. Then, porous BCP-collagen composite microspheres were fabricated by repetitively dip coating the microspheres in a collagen solution to effectively deliver growth factor to bone defects. Characterization of the microspheres and in vitro studies were conducted to investigate the effect of collagen infiltration on bone regeneration. In addition, in vitro evaluation demonstrated the sustained bone morphogenetic protein-2 (BMP-2) delivery of the microspheres and the effect of cell differentiation, and in vivo assessment with rabbits revealed that the microspheres filled the defect well and that bone could be regenerated through the microspheres. Moreover, the composite system was more effective for bone regeneration than the bare BCP microspheres because of the drug retention of collagen. These findings indicate that the porous microspheres are effective for tissue regeneration by continuous growth factor delivery.

Bioactive and mechanically stable hydroxyapatite patterning for rapid endothelialization of artificial vascular graft.

Polymeric vascular grafts have been widely used in the vascular regeneration field because of their ease of application. However, synthetic polymer grafts have the severe problem of low biocompatibility, which may cause delayed endothelialization and hyperplasia. In this study, we fabricated a linear hydroxyapatite (HA) pattern on a silicon wafer and then transferred the pattern to a poly(L-lactic)-acid (PLLA) film for use as a tubular vascular graft. The HA pattern with its characteristic needle-like shape was successfully embedded into the PLLA. The HA-patterned PLLA film exhibited superior mechanical stability compared with that of a HA-coated PLLA film under bending, elongation, and in vitro circulation conditions, suggesting its suitability for use as a tubular vascular graft. In addition, the HA pattern guided rapid endothelialization by promoting proliferation of endothelial cells and their migration along the pattern. The hemocompatibility of the HA-patterned PLLA was also confirmed, with substantially fewer platelets adhered on its surface. Overall, in addition to good mechanical stability, the HA-patterned PLLA exhibited enhanced biocompatibility and hemocompatibility compared with pure PLLA.

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.

Reduced fibrous capsule formation at nano-engineered silicone surfaces via tantalum ion implantation.

Although the design of more biocompatible polymeric implants has been studied for decades, their intended functionality continues to be impaired by the response of the host tissue to foreign bodies at the tissue-implant interface. In particular, the formation and contracture of fibrous capsules prevent the intimate integration of an implant with surrounding tissues, which leads to structural deformation of the implants and persistent discomfort and pain. We report a new surface nano-engineered silicone implant that reduces fibrous capsule formation and improves the biocompatibility of it via sputtering-based plasma immersion ion implantation (S-PIII). This technique can introduce biologically compatible tantalum (Ta) on the silicone surface to produce a Ta-implanted skin layer (<60 nm thick) as well as generate either smooth (Smooth/Ta silicone) or nano-textured (Nano/Ta silicone) surface morphologies. The biologically inert chemical structure and strong hydrophobic surface characteristics of bare silicone are substantially ameliorated after Ta ion implantation. In particular, the Nano/Ta silicone implant's combination of surface nano-texturing as a physical cue and the Ta-implanted layer as a chemical cue was found to be very effective at achieving outstanding hydrophilicity and fibroblast affinity compared to the bare and Smooth/Ta silicone implants. In a mouse in vivo study conducted for 8 weeks, the Nano/Ta silicone implant inhibited fibrous capsule formation and contracture on its surface better than the bare silicone based on an analysis of the number of macrophages, myofibroblast differentiation and activation, collagen density, and thickness of fibrous capsules.

Enhanced Osseointegration Ability of Poly(lactic acid) via Tantalum Sputtering-Based Plasma Immersion Ion Implantation.

Poly(lactic acid) (PLA) is the most utilized biodegradable polymer in orthopedic implant applications because of its ability to replace regenerated bone tissue via continuous degradation over time. However, the poor osteoblast affinity for PLA results in a high risk of early implant failure, and this issue remains one of the most difficult challenges with this technology. In this study, we demonstrate the use of a new technique in which plasma immersion ion implantation (PIII) is combined with a conventional DC magnetron sputtering. This technique, referred to as sputtering-based PIII (S-PIII), makes it possible to produce a tantalum (Ta)-implanted PLA surface within 30 s without any tangible degradation or deformation of the PLA substrate. Compared to a Ta-coated PLA surface, the Ta-implanted PLA showed twice the surface roughness and substantially enhanced adhesion stability in dry and wet conditions. The strong hydrophobic surface properties and biologically relatively inert chemical structure of PLA were ameliorated by Ta S-PIII treatment, which produced a moderate hydrophilic surface and enhanced cell-material interactions. Furthermore, in an in vivo evaluation in a rabbit distal femur implantation model, Ta-implanted PLA demonstrated significantly enhanced osseointegration and osteogenesis compared with bare PLA. These results indicate that the Ta-implanted PLA has great potential for orthopedic implant applications.

Use of thioglycerol on porous polyurethane as an effective theranostic capping agent for bone tissue engineering.

Thiolated biodegradable polyurethane (TG-DPU) was synthesized using a one-pot reaction with thioglycerol adopted as a functionalized chain extender. After characterization of the chemical structure of TG-DPU using proton nuclear magnetic resonance spectroscopy, bone morphogenetic protein (BMP-2) was loaded in the TG-DPU under oxidative conditions to form disulfides between the free thiol of TG-DPU and BMP-2. The interaction between TG-DPU and BMP-2, so-called bioconjugates, was investigated using X-ray photoelectron spectroscopy analysis; the appearance of disulfide (S-S) linkage indicated the formation of a polymer/growth factor conjugate system. The covalently linked bioconjugates provided stability with minimal loss during the drug delivery with prolonged release performance in in vitro release tests. The effects of the drugs delivered by TG-DPU were also confirmed by in vitro alkaline phosphatase tests using pre-osteoblasts and in vivo bone regeneration tests. The drugs effectively induced cell differentiation and promoted mature bone recovery.

Hydroxyapatite Microspheres as an Additive to Enhance Radiopacity, Biocompatibility, and Osteoconductivity of Poly(methyl methacrylate) Bone Cement.

This study demonstrates the utility of hydroxyapatite (HA) microspheres as an additive to enhance the radiopaque properties, biocompatibility, and osteoconductivity of poly(methyl methacrylate) (PMMA)-based bone cements. HA microspheres were synthesized using spray drying. They had well-defined spherical shapes, thus allowing for the production of PMMA/HA composites with a very high HA content (20 vol % and 40 vol %). The uniform distribution of these HA microspheres in the PMMA matrix resulted in a remarkable increase in compressive modulus (p < 0.05), while preserving a reasonably high compressive strength. The PMMA/HA bone cements showed much higher radiopacity than PMMA containing BaSO4 as the additive. This was attributed to the high HA content up to 40 vol %. In addition, the biocompatibility and osteoconductivity of PMMA/HA bone cements were significantly enhanced compared to those of PMMA bone cements containing BaSO4, which were assessed using in vitro tests and in vivo animal experiments.

Multiscale porous titanium surfaces via a two-step etching process for improved mechanical and biological performance.

Titanium (Ti)-based dental implants with multiscale surface topography have attracted great attention as a promising approach to enhance fixation and long-term stability of the implants, through the synergistic effect of nano- and microscale surface roughness, for accelerated bone regeneration and improved mechanical interlocking. However, structural integrity and mechanical stability of the multiscale roughened Ti surface under deformation need to be considered because significant deformation of dental implants is often induced during the surgical operation. Therefore, in this study, a well-defined nanoporous structure was directly introduced onto micro-roughened Ti surfaces through target-ion induced plasma sputtering (TIPS) with a tantalum (Ta) target, following sand-blasted, large-grit and acid-etching (SLA). This two-step etching process successfully created multiscale surface roughness on Ti with a minimal change of the pre-formed microscale roughness. Moreover, TIPS allowed the Ti surface to possess good mechanical stability under deformation and improved hydrophilicity, through altering the surface chemistry of brittle and hydrophobic SLA-treated Ti without formation of the interface between nanoporous and microporous structures. The in vitro and in vivo tests confirmed that multiscale roughened Ti significantly enhanced osteoblast attachment, proliferation and differentiation, which eventually led to improved bone regeneration and osseointegration, compared to smooth and micro-roughened Ti.

Enhancement of osseointegration by direct coating of rhBMP-2 on target-ion induced plasma sputtering treated SLA surface for dental application.

Owing to the excellent bioactive properties of recombinant human bone morphogenetic proteins (rhBMPs), dentistry considers them as a fascinating adjuvant alternative for enhancing bone regeneration and bone-to-implant junction in the early implantation stages. However, stable loading and delivery efficiency of rhBMPs on the implant surfaces involve major concerns because of the harsh wearing condition under load during implantation. In this study, to achieve successful rhBMP-2 delivery, a nanoporous surface structure is introduced on the sandblasting with large grit and acid-etching (SLA)-treated titanium (Ti) surface via the tantalum (Ta) target-ion induced plasma sputtering (TIPS) technique. Unlike oxidation-induced surface nanoporous fabrications on a Ti surface, TIPS-treated surfaces provide excellent structural unity of the nanoporous structure with the substrate due to their etching-based fabrication mechanism. SLA/TIPS-treated Ti exhibits distinct nanoporous structures on the microscale surface geometry and better hydrophilicity compared with SLA-treated Ti. A sufficiently empty nanoporous surface structure combined with the hydrophilic property of SLA/TIPS-treated Ti facilitates the formation of a thick and uniform coating layer of rhBMP-2 on the surface without any macro- and microcoagulation. Compared with the SLA-treated Ti surface, the amount of coated rhBMP-2 increases up to 63% on the SLA/TIPS-treated Ti surface. As a result, the in vitro pre-osteoblast cell response of the SLA/TIPS-treated Ti surface, especially cell adhesion and differentiation behaviors, improves remarkably. A bone-regenerating direct comparison between the rhBMP-2-coated SLA-treated and SLA/TIPS-treated Ti is conducted on a defective dog mandible model. After 8 weeks of implantation surgery, SLA/TIPS-treated Ti with rhBMP-2 exhibits a better degree of contact area for the implanted bone, which mineralizes new bones around the implant. Quantitative results of bone-in-contact ratio and new bone volume also show significantly higher values for the SLA/TIPS-treated Ti with the rhBMP-2 specimen. These results confirm that an SLA/TIPS-treated surface is a suitable rhBMP-2 carrier for a dental implant to achieve early and strong osseointegration of Ti dental implants.