In Vivo Degradation Studies of PGA-PLA Block Copolymer and Their Histochemical Analysis for Spinal-Fixing Application.

Polylactic acid (PLA) and polyglycolic acid (PGA) are well-known medical-implant materials. Under the consideration of the limitations of degradable polymeric materials, such as weak mechanical strength and by-product release through the biodegradation process under in vivo environments, PLA-PGA block copolymer is one of the effective alternative implant materials in the clinical field. In our previous study, two types of extremely effective PGA-PLA copolymers (multi/tri-block PGA-PLA copolymers) were synthesized. These synthesized block copolymers could overcome aforementioned issues and also showed good biocompatibility. In this study, the PGA-PLA block copolymers with large molecular weight were synthesized under the same chemical scheme, and their bio durability was confirmed through the in vivo degradation behavior and histochemical analyses (by hematoxylin and eosin and immune staining) in comparison with commercial PLGA random copolymer (medical grade). Specimens for the degradation test were investigated by SEM and X-ray diffractometer (XRD). As a result, the synthesized PGA-PLA block copolymer showed good biocompatibility and had a controlled biodegrading rate, making it suitable for use in resorbable spinal-fixation materials.

Advances in the development of hemostatic biomaterials for medical application.

BACKGROUND: Medical hemostatic biological materials are necessary for the development of the process of preventing and stopping damaged intravascular bleeding. In the process, some red blood cells and white blood cells are trapped in nets. The resulting plug is called a blood clot. This is often a good step in wound healing, but separation of blood clots from blood vessel walls can cause serious health problems. MAIN BODY: The advance in the development of hemostatic biomaterials is necessary for biomedical application. Firstly, the historical background of artificial hemostasis has been included and the current research of hemostasis has been included in more detail. Secondly, the current research of hemostasis has been included on the oxidized cellulose-based hemostatic biomaterials such as starch based on composite cross-linking hemostatic networks, hemostatic materials on NHS-esters, hemostatic agent from local materials and biomaterials for hemostatic management. Thirdly, polysaccharide hemostatic materials, bio-inspired adhesive catechol-conjugated chitosan, mesoporous silica and bioactive glasses for improved hemostasis, minimally invasive hemostatic biomaterials and chitosan-base materials for hemostatic application have been included. Fourthly, the biological properties of natural hemostatic agent by plasma technology and the hemostatic agents based on gelatin-microbial transglutaminase mixes have been also included. CONCLUSION: Current research on hemostasis includes hemostatic biomaterials such as cellulose-based hemostatic starch based on a complex cross-linked hemostatic network. It also includes polysaccharide hemostatic materials, biomimetic adhesive catechol-binding chitosan, mesoporous silica or physiologically active glass for hemostatic improvement, minimally invasive hemostatic chitosan-based materials, and gelatin-microbial transglutaminase-based hemostatic agents. Future studies should focus on modular combination of hemostatic imitation and reinforcement mechanisms of different materials and technologies to find the optimal system to promote and strengthen active platelet or platelet imitation aggregation in bleeding sites. The second optionally increases the production of thrombin and fiber formation at the site. Third, the formed fibrin biopolymer network has strengthened to reduce thrombosis and amplify hemostasis.

Hemostatic Patches Based on Crosslinked Chitosan Films Applied in Interventional Procedures.

In this study, we manufactured biocompatible hemostatic crosslinked chitosan (CS) patches and analyzed their physicochemical and biological properties for femoral arterial puncture applications. CS is a representative hemostatic material but has some drawbacks, such as swelling, shrinkage, and brittleness. Thus, it was crosslinked via a 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) coupling reaction and a nucleophilic addition reaction with citric acid (CA), glutaraldehyde (GTA), and genipin (GP) to remedy its shortcomings. The CSCA (crosslinked CS with CA/EDC), CSGTA (crosslinked CS with GTA), and CSG (crosslinked CS with GP) films showed low swelling degrees and good mechanical properties (excluding CSCA) compared with those of neat CS films. Additionally, every crosslinked CS film coated with thrombin (TB-CS) showed enhanced hemostatic ability in the whole blood clotting and activated partial thromboplastin time tests. Furthermore, the CSCA, CSGTA, and CSGP were nontoxic in an in vitro cell cytotoxicity test (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay) using L-929 mouse fibroblasts cells.

Mechanical Properties and Bioactivity of Polyetheretherketone/Hydroxyapatite/Carbon Fiber Composite Prepared by the Mechanofusion Process.

The main obstacles in the melt-processing of hydroxyapatite (HA) and carbon fiber (CF) reinforced polyetheretherketone (PEEK) composite are the high melting temperature of PEEK, poor dispersion of HA nanofillers, and poor processability due to high filler content. In this study, we prepared PEEK/HA/CF ternary composite using two different non-melt blending methods; suspension blending (SUS) in ethanol and mechanofusion process (MF) in dry condition. We compared the mechanical properties and bioactivity of the composite in a spinal cage application in the orthopedic field. Results showed that the PEEK/HA/CF composite made by the MF method exhibited higher flexural and compressive strengths than the composite prepared by the SUS method due to the enhanced dispersibility of HA nanofiller. On the basis of in vitro cell compatibility and cell attachment tests, PEEK/HA/CF composite by mechanofusion process showed an improvement in in vitro bioactivity and osteo-compatibility.

In Vitro and In Vivo Biosafety Analysis of Resorbable Polyglycolic Acid-Polylactic Acid Block Copolymer Composites for Spinal Fixation.

Herein, spinal fixation implants were constructed using degradable polymeric materials such as PGA-PLA block copolymers (poly(glycolic acid-b-lactic acid)). These materials were reinforced by blending with HA-g-PLA (hydroxyapatite-graft-poly lactic acid) and PGA fiber before being tested to confirm its biocompatibility via in vitro (MTT assay) and in vivo animal experiments (i.e., skin sensitization, intradermal intracutaneous reaction, and in vivo degradation tests). Every specimen exhibited suitable biocompatibility and biodegradability for use as resorbable spinal fixation materials.

Novel PEEK Copolymer Synthesis and Biosafety - I: Cytotoxicity Evaluation for Clinical Application.

In this research, we synthesized novel polyetheretherketone (PEEK) copolymers and evaluated the biosafety and cytotoxicity of their composites for spinal cage applications in the orthopedic field. The PEEK copolymers and their composites were prepared through a solution polymerization method using diphenyl sulfone as a polymerization solvent. The composite of PEEK copolymer showed good mechanical properties similar to that of natural bone, and also showed good thermal characteristics for the processing of clinical use as spine cage. The results of an in vitro cytotoxicity test did not show any evidence of a toxic effect on the novel PEEK composite. On the basis of these cytotoxicity test results, the PEEK composite also proved its in vitro biosafety for application to an implantable spine cage.

In-vitro toxicity study of poly(alkylphenol) as vulcanizing agent.

In this study, cytotoxicity of various novel poly(alkylpehnol) derivatives which, one of constituent for vulcanizing agent, could be adjusted in medical elastic rubber applications were investigated under various conditions of cytotoxicity test. By MTT-assay which according to ISO 10993-5 regulation, we could figure out cell viability of mouse fibroblast in various sample conditions. Furthermore, by Live & Dead Cell assay, we could get colorimetric cell viability via fluorescence images.

Stability study of docetaxel solution (0.9%, saline) using Non-PVC and PVC tubes for intravenous administration.

BACKGROUND: Di-2-ethylhexyl phthalate (DEHP) are added to poly(vinyl chloride)(PVC) infusion tubes as a plasticizer to ensure tube flexibility. In addition to previously reported disadvantages of DEHP, released DEHP molecules from PVC tubes can easily interact with surfactants in anticancer drug solutions (i.e., polysorbate 80 for Taxotere®-Inj) and reduce the solubility of docetaxel in aqueous solution during anticancer drug administration. RESULTS: In this study, we investigated the in vitro stability of docetaxel in a 0.9% saline solution under an intravenous administration condition using a PVC tube (high DEHP content) and non-PVC infused tube. CONCLUSION: The docetaxel solution circulating through the non-PVC tube had better solution stability than through the PVC tube(high DEHP content).

Biodegradable and elastomeric poly(glycerol sebacate) as a coating material for nitinol bare stent.

We synthesized and evaluated biodegradable and elastomeric polyesters (poly(glycerol sebacate) (PGS)) using polycondensation between glycerol and sebacic acid to form a cross-linked network structure without using exogenous catalysts. Synthesized materials possess good mechanical properties, elasticity, and surface erosion biodegradation behavior. The tensile strength of the PGS was as high as 0.28 ± 0.004 MPa, and Young's modulus was 0.122 ± 0.0003 MPa. Elongation was as high as 237.8 ± 0.64%, and repeated elongation behavior was also observed to at least three times the original length without rupture. The water-in-air contact angles of the PGS surfaces were about 60°. We also analyzed the properties of an electrospray coating of biodegradable PGS on a nitinol stent for the purpose of enhancing long-term patency for the therapeutic treatment of varicose veins disease. The surface morphology and thickness of coating layer could be controlled by adjusting the electrospraying conditions and solution parameters.

Nanosized polyamidoamine (PAMAM) dendrimer-induced apoptosis mediated by mitochondrial dysfunction.

Nano-materials are currently being used in a variety of fields. One of the concerns associated with their use is their potential to harm human health. In an attempt to identify genes expressed differently in human lung cells (WI-26 VA4) exposed to nanosized (45 nm in diameter) PAMAM (polyamidoamine) dendrimers, we observed down-regulation of mitochondrial DNA-encoded genes involved in the maintenance of mitochondrial membrane potential. Down-regulation of gene expression was confirmed by semi-quantitative RT-PCR. Dendrimers were shown to colocalize with mitochondria and cause the release of cytochrome C. Mitochondrial membrane potential was disrupted and the viability of cells was decreased in the presence of dendrimers. Activation of caspases 3 and 9 was increased. Apoptosis was observed by annexin V/propidium iodide staining and DNA fragmentation. In summary, nanosized dendrimers damaged mitochondria resulting in apoptosis.

Control over micro-fluidity of liposomal membranes by hybridizing metal nanoparticles.

This study introduces a facile method to hybridize metal nanoparticles with lipid vesicles, which allows us to control over their membrane micro-fluidity. We have fabricated these hybrid liposomes by directly hybridizing metal nanoparticles with lipid bilayers solely consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC). For this, we have used the dehydration and rehydration method. Characterizing their morphology and micro-fluidity, in which we have used electron microscopy and fluorescence anisotropy spectroscopy, enables us to demonstrate that metal nanoparticles with different surface properties create interactions with either phosphorus end groups or hydrophobic tails of DPPC, thereby resulting in decrease in micro-fluidity of the assembled lipid membranes, especially for the hydrophobic layers. Our approach to hybridize metal nanoparticles in between lipid layers offers a flexible means that allows us to obtain a liposome system with more controllable membrane properties.

Quantitative characterization of degradation behaviors of antioxidants stabilized in lipid particles.

This study describes a flexible approach that allows us to characterize the long-term stability of antioxidants by using a thermodynamically extended Arrhenius equation. We use retinol, Vitamin A, as a model antioxidant and its degradation behaviors are characterized for both stabilized and non-stabilized systems; in this study, by using a fluid bed technique, we immobilize the retinol in lipid particles, thus increasing its thermal stability in complex formulations, such as aqueous polymer gels and emulsions. Our approach demonstrates that the degradation behaviors of the retinol show a functional relationship with temperature and time, which makes it possible to use the Arrhenius approach. This result allows us to precisely characterize the stability of antioxidants in complex formulations for long time.