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Biodegradable polymers, such as poly(L-lactide) (PLLA), are very useful in many biomedical applications. However, their degradation by-products have been much of a concern as they are the sources of inflammatory reactions in the body. In this work, we suggest a novel composite system composed of PLLA and oligolactide-grafted magnesium hydroxide (Mg-OLA) that can overcome drawbacks caused by poor mechanical properties and inflammatory response of PLLA for biomedical applications. Mg-OLAs were synthesized by ring opening polymerization and the structure, morphology, pH change, thermal, and mechanical properties were analyzed using FTIR, SEM, pH meter, TGA, and UTM. In particular, the tensile strength and modulus of PLLA/Mg80-OLA20 (0–20 wt%) were higher than those of PLLA/magnesium hydroxide. The PLLA/Mg80-OLA20 composite was also very effective in neutralizing the acidic environment caused by the degradable by-product of the PLLA matrix. In vitro cell viability and the expression levels of COX-2 and IL-6 proteins in the PLLA composites were also evaluated. Cell viability increased to around 100% with increasing the amount of Mg80-OLA20 from 0 to 20 wt%. The expression levels of IL-6 and COX-2 were reduced dramatically when increasing the proportion of Mg80-OLA20 from 0 to 50 wt%. As a result, the incorporation of Mg-OLAs into the PLLA matrix could reinforce the mechanical properties as well as reduce the inflammatory response of the hybrid PLLA. Therefore, this hybrid composite system blending oligomer-grafted magnesium hydroxide in biodegradable polymers would be a promising strategy for avoiding current fatal problems in biomedical applications.

Biodegradable polymers have been extensively used in biomedical applications, ranging from regenerative medicine to medical devices. However, the acidic byproducts resulting from degradation can generate vigorous inflammatory reactions, often leading to clinical failure. We present an approach to prevent acid-induced inflammatory responses associated with biodegradable polymers, here poly(lactide- co-glycolide), by using oligo(lactide)-grafted magnesium hydroxide (Mg(OH)2) nanoparticles, which neutralize the acidic environment. In particular, we demonstrated that incorporating the modified Mg(OH)2 nanoparticles within degradable coatings on drug-eluting arterial stents efficiently attenuates the inflammatory response and in-stent intimal thickening by more than 97 and 60%, respectively, in the porcine coronary artery, compared with that of drug-eluting stent control. We also observed that decreased inflammation allows better reconstruction of mouse renal glomeruli in a kidney tissue regeneration model. Such modified Mg(OH)2 nanoparticles may be useful to extend the applicability and improve clinical success of biodegradable devices used in various biomedical fields.

Drug-eluting stents (DESs) are generally used in percutaneous coronary intervention. Paclitaxel (PTX) is widely used in DESs to suppress neointima, which causes restenosis. However, the PTX release profile is slow owing to its hydrophobic properties, resulting in negative effects on re-endothelialization in vessels. In this study, we assessed the effects of the controlled release of PTX particles of specific sizes on in-stent restenosis (ISR). PTX particle sizes were controlled by adjusting the evaporating temperature of the solvent from 25 to 80°C during ultrasonic coating, and DESs were prepared. The properties of prepared films and DESs were analyzed, and cell viability was assessed in vitro and in vivo. Poly(lactic-co-glycolic acid) (PLGA)/PTX500-loaded stents showed the most rapid release for 58 days, and smaller drug particles exhibited lower PTX release rates. In vivo, PLGA/PTX50-, PLGA/PTX250-, and PLGA/PTX500-loaded stents showed good efficacy for alleviating ISR as compared with bare metal stents and PLGA/PTX5-loaded stents. However, PLGA/PTX250- and PLGA/PTX500-loaded stents exhibited strut exposure and reduced recovery of the vascular compared with PLGA/PTX50-loaded stents. PTX drug particles of approximately 50 nm were most effective in vivo, and the control of particle size is a promising strategy for improving the performance of PTX-eluting stents. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2275-2283, 2018.

Drug-eluting stents (DESs) are generally used in percutaneous coronary intervention. Paclitaxel (PTX) is widely used in DESs to suppress neointima, which causes restenosis. However, the PTX release profile is slow owing to its hydrophobic properties, resulting in negative effects on re-endothelialization in vessels. In this study, we assessed the effects of the controlled release of PTX particles of specific sizes on in-stent restenosis (ISR). PTX particle sizes were controlled by adjusting the evaporating temperature of the solvent from 25 to 80°C during ultrasonic coating, and DESs were prepared. The properties of prepared films and DESs were analyzed, and cell viability was assessed in vitro and in vivo. Poly(lactic-co-glycolic acid) (PLGA)/PTX500-loaded stents showed the most rapid release for 58 days, and smaller drug particles exhibited lower PTX release rates. In vivo, PLGA/PTX50-, PLGA/PTX250-, and PLGA/PTX500-loaded stents showed good efficacy for alleviating ISR as compared with bare metal stents and PLGA/PTX5-loaded stents. However, PLGA/PTX250- and PLGA/PTX500-loaded stents exhibited strut exposure and reduced recovery of the vascular compared with PLGA/PTX50-loaded stents. PTX drug particles of approximately 50 nm were most effective in vivo, and the control of particle size is a promising strategy for improving the performance of PTX-eluting stents. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2275-2283, 2018.

Two kinds of magnesium hydroxide (Mg(OH)2) rods (Mg-Rod, 150 and 350 nm in size) and plates (Mg-PL, 60 and 300 nm) were prepared, and blended with poly(L-lactide) (PLLA) to obtain PLLA/Mg(OH)2 composites to investigate the effect of the shape and size of Mg(OH)2 particles. The structure, morphology, pH change, thermal and mechanical properties, cytotoxicity, and inflammation of Mg(OH)2 control and PLLA/Mg(OH)2 composites were evaluated. PLLA/Mg-Rod150 (30%) composite showed a 50% higher tensile strength and a 45% improved modulus as compared with PLLA/Mg-PL300 30% composite. Although Mg-Rods displayed similar cell viability (above 80%) as compared to Mg-PLs, the expression levels of TNF-α from Mg-PL60 gradually increased with increasing concentrations from 1 to 300 μg. This indicates that Mg-PL60 had a potential cytotoxicity due to endocytosis. In addition, the byproduct of PLLA/Mg-Rods composite was more effectively neutralized than that of the PLLA/Mg-PLs composite, but cell viability and the expression levels of TNF-α were similar. Therefore, the use of our PLLA/Mg-Rod composite system would be a promising strategy to prevent the current fatal problems in biomedical applications including biodegradable implants such as stents.

Poly(D,L-lactic-co-glycolic acid) (PLGA) has been widely used as a biodegradable polymer in the fabrication of porous polymer scaffolds, but it is hydrolyzed into acidic by-products such as glycolic acid and lactic acid in the human body. Magnesium hydroxide nanoparticles (Mg-NPs) were incorporated into a PLGA scaffold in order to neutralize the acidic environment caused by the hydrolysis of PLGA, thereby reducing the cytotoxicity and inflammatory response. In this study, three-dimensional porous scaffolds blended with 30% Mg-NP were fabricated using gas foaming (PLGA/Mg/NaHCO3), salt leaching (PLGA/Mg/NaCl), and freeze drying (PLGA/Mg/Ice), and their structures, morphologies, pH change, thermal properties, and mechanical properties were analyzed by Fourier transform infrared spectroscopy, scanning electron microscopy, pH meter, thermogravimetric analysis, and a universal testing machine. The porosity of the PLGA/Mg/Ice scaffold was higher at about 10-13 wt% than those of the PLGA/Mg/NaCl or PLGA/Mg/NaHCO3 scaffolds. The Mg-NP content of the PLGA/Mg/NaHCO3 scaffold remained lower than those of the other scaffolds at about 63%. As a result of this loss of Mg-NP, the PLGA/Mg/NaHCO3 scaffold was confirmed to have lower cell viability (about 70%) than the PLGA/Mg/Ice scaffold (about 100%), owing to the reduced neutralizing effect. Although the PLGA/Mg/Ice and PLGA/Mg/NaCl scaffolds showed similar cell viability, the NaCl of the PLGA/Mg/NaCl scaffold exhibited slight toxicity in the body. The expression level of interleukin-6 (IL-6) was significantly decreased in the PLGA/Mg/Ice scaffold than in the PLGA/Ice scaffold, but the PLGA/Mg/Ice scaffold exhibited an IL-6 expression level that was about 10% lower than that of the PLGA/Mg/ NaCl scaffold. Consequently, the addition of Mg-NP/Ice could conceivably reduce the expression level of IL-6 in PLGA scaffolds. This anti-inflammatory PLGA/Mg/Ice scaffold is therefore expected to show great promise when used as a template in tissue engineering. Open image in new window