Exposure Levels and Contributing Factors of Various Arsenic Species and Their Health Effects on Korean Adults.

Arsenic is a human carcinogen. Data on urinary arsenic species analyses of Koreans are limited. This study evaluated the arsenic exposure level, contributing factors, and health effects in Korean adults. Dietary intake information and urine samples were obtained from 2044 participants. Arsenic exposure was assessed based on urinary concentrations of arsenic species, such as inorganic arsenic, As(III) and As(V), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and arsenobetaine (AsB), using high-performance liquid chromatography with inductively coupled plasma mass spectrometry, followed by determination of biomarkers, malondialdehyde and c-peptide. The geometric mean concentrations were 30.9 µg/L for the sum of inorganic arsenic and their metabolites, and 84.7 µg/L for the total sum of arsenic measured. Urinary concentrations of arsenic species were influenced by age, inhabitant area (inland or coastal), and seafood intake, which was positively correlated with inorganic arsenic, DMA, and AsB. Rice intake was positively correlated with inorganic arsenic and its metabolites but not with AsB. Additionally, malondialdehyde and c-peptide levels were significantly associated with urinary concentrations of various arsenic species. Seafood and rice are major sources of organic/inorganic arsenic exposure in Korean adults; however, it is necessary to evaluate whether their overconsumption could have a potentially detrimental effect on human health.

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.

Stable sol-gel hydroxyapatite coating on zirconia dental implant for improved osseointegration.

Aside from being known for its excellent mechanical properties and aesthetic effect, zirconia has recently attracted attention as a new dental implant material. Many studies have focused on hydroxyapatite (HA) coating for obtaining improved biocompatibility, however the coating stability was reduced by a byproduct produced during the high-temperature sintering process. In this study, to overcome this problem, we simply coated the zirconia surface with a sol-gel-derived hydroxyapatite (HA) layer and then sintered it at a varied temperature (<1000 °C). The surface showed a nanoporous structure, and there was no crystalline phase other than HA and zirconia when the sintering temperature was 800 °C. The adhesion strength of the HA layer (>40 MPa) was also appropriate as a dental implant application. In addition, in vitro cell experiments using a preosteoblast cell line revealed that the HA-coated zirconia surface acts as a preferable surface for cell attachment and proliferation than bare zirconia surface. In vivo animal experiments also demonstrated that the osteoconductivity of zirconia were dramatically enhanced by HA coating, which was comparable to that of Ti implant. These results suggest that the sol-gel-based HA-coated zirconia has a great potential for use as a dental implant material.

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.

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.

PLLA Membrane with Embedded Hydroxyapatite Patterns for Improved Bioactivity and Efficient Delivery of Growth Factor.

Poly(l-lactic) acid (PLLA) is widely used in guided bone regeneration membranes due to its mechanical properties and biodegradability. However, the lack of biocompatibility is a serious disadvantage. Herein, the biocompatibility of PLLA is improved by patterning hydroxyapatite (HA) loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) under it. The HA is obtained by preparing a magnesium pattern via photolithography and hydrothermal converting. After loading rhBMP-2, the pattern is transferred to PLLA. The pattern is tightly embedded in the PLLA and retained its original position after mechanical stimuli. Fluorescence images allow to assess the protein adsorption and gradual release in a controlled manner. The amount of released rhBMP-2 is overwhelmingly large when loaded under HA because of its large surface area. Osteogenic differentiation supports the synergistic effect of HA and rhBMP-2 to improve the biocompatibility. Moreover, in vivo experiments demonstrate that the synergistic effect positively affects the healing rate of bone.

Tantalum-coated polylactic acid fibrous membranes for guided bone regeneration.

Guided bone regeneration (GBR) membrane is necessary to reconstruct the defect bone tissue by defending penetration of soft tissues. Polylactic acid (PLA) attracts much attention to utilize as a GBR membrane because it has relatively high mechanical strength and biodegradability. However, the poor osteoconductivity of PLA is a major concern. The aim of this study is to improve the osteoconductivity of fibrous, electrospun, PLA guided bone regeneration membranes by coating the fiber surface with highly biocompatible tantalum (Ta). Ta coating of electrospun PLA membrane was created through sputtered Ta ions surrounding the PLA fibers. The Ta-coated PLA (Ta-PLA) membranes remain a randomly aligned fibrous structure with no defects caused by sputtering. The chemical composition of Ta-PLA membrane indicates Ta coating was well deposited on PLA fibers. Although the mechanical strength of Ta-PLA was reduced compared with bare PLA membrane, the Ta coating layer does not readily delaminate from the single PLA fiber surface due to its cladded structure which indicates that the Ta coating has high mechanical stability on PLA fibers. In vitro cell tests demonstrate that the attachment, proliferation, and differentiation of preosteoblasts are significantly promoted on the Ta-PLA membranes compared to bare PLA. In an in vivo animal test, most calvarial defects in the Ta-PLA group are covered with newly formed bone within six weeks, while the defects in the bare PLA group are rarely covered. Furthermore, the degree of bone healing in the Ta-PLA group is comparable to healing observed on collagen membranes, which are highly bioactive materials. These results indicate the superior osteoconductivity of Ta-PLA will make it particularly useful as a guided bone regeneration membrane.

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.

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.

In vitro and in vivo evaluation of polylactic acid-based composite with tricalcium phosphate microsphere for enhanced biodegradability and osseointegration.

A biodegradable polylactic acid composite containing tricalcium phosphate microsphere was fabricated. The composite exhibited enhanced biocompatibility and a well-interconnected porous structure that enabled tissue ingrowth after degradation. The tricalcium phosphate microspheres had an average size of 106 ± 43 µm and were incorporated into the polylactic acid matrix using a high-shear mixer. The resulting bioactivity and hydrophilicity were enhanced to levels comparable to those of a polylactic acid composite containing tricalcium phosphate powder, which is a well-known material used in the medical field. An accelerated 30-day degradation test in HCl revealed successful generation of an open porous structure with ∼98% interconnectivity in the polylactic acid-tricalcium phosphate microsphere composite, demonstrating the potential of this material to induce enhanced osseointegration in the later stage of bone regeneration. The early stage osseointegration was also evaluated by implanting the composite in vivo using a rabbit femoral defect model. After 16 weeks of implantation, the bone-to-implant contact ratio of the polylactic acid-tricalcium phosphate microsphere composite was enhanced owing to tissue ingrowth through the generated pores near the surface.

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.

Calcium Phosphate-Collagen Scaffold with Aligned Pore Channels for Enhanced Osteochondral Regeneration.

This study reports the development of a bilayered scaffold with aligned channels produced via a sequential coextrusion and unidirectional freezing process to facilitate upward bone-marrow stem-cell migration. The biomimetic scaffold with collagen and biphasic calcium phosphate (BCP) layers is successfully fabricated with matching of the cartilage and bone layers. The aligned structure results in an enhancement of the compressive strength, and the channels enable tight anchoring of the collagen layers on the BCP scaffolds compared with a randomly structured porous scaffold. An in vitro evaluation demonstrates that the aligned channels guide the cells to attach on the surface in highly stretched shapes and migrate upward faster than the random structure. In addition, in vivo assessment reveals that the aligned channels yield superior osteochondral tissue regeneration compared with the random structure. Moreover, the channel diameter greatly affects the tissue regeneration, and the scaffold with a channel diameter of ≈270 µm exhibits the optimal regeneration because of sufficient nutrient supply and adequate tissue ingrowth. These findings indicate that the introduction of aligned channels to a bilayered scaffold provides an effective approach for osteochondral tissue regeneration.