Archive of Medical Research

Studies of the cellular uptake of hydrogel nanospheres and microspheres by phagocytes, vascular endothelial cells, and smooth muscle cells.

Intensive research efforts have been placed on the development of nanospheres for targeted drug delivery for treating a variety of diseases, including coronary restenosis, cancer, and inflammatory reactions. Although most of these drug-bearing spheres are delivered via intravenous administration, little is known about the effect of sphere physical characteristics on the responses of vascular and blood cells. To find the answer, this work was aimed to investigate the cellular uptake of nanosized (100 nm) and microsized hydrogel spheres (1 mum) made of poly(N-isopropylacrylamide) by vascular cells and phagocytes under various flow conditions in vitro. We found that the cellular uptake of nanospheres depended on incubation times and sphere concentrations as well as on the introduced shear stress levels of the medium. Measurements of the intracellular-released fluorescence and confocal fluorescence microscopy revealed that nanospheres were internalized by endothelial cells and smooth muscle cells more than microspheres, whereas microspheres were rapidly taken up by phagocytes, especially at high concentration. Our results strongly suggest that hydrogel nanospheres are more effective as an intravascular delivery system compared to microspheres in the terms of vascular cellular uptake and biocompatibility. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008.

Nguyen KT, Shukla KP, Moctezuma M, Braden AR, Zhou J, Hu Z, Tang L.

Department of Bioengineering, The University of Texas at Arlington, Arlington, Texas 76019.

Electrosynthesis of hydrogel films on metal substrates for the development of coatings with tunable drug delivery performances.

Novel polyacrylates-based hydrogel thin films were prepared by electrochemical polymerization, a new method to obtain hydrogels directly onto metal substrates. 2-Hydroxy-ethyl-methacrylate (HEMA), a macromer poly (ethylene-glycol diacrylate) (PEGDA) and PEGDA copolymerized with acrylic acid (AA) were used to obtain hydrogels. The electrosynthesized coatings were characterized by X-ray photoelectron spectroscopy, to assess their surface chemical composition, and by water content determination measurements, to characterize the swelling behavior. In particular, quartz crystal microbalance with dissipation monitoring was used to evaluate the pH-dependency of the swelling for AA-containing hydrogels. Moreover, a model protein (bovine serum albumin) and a model drug (caffeine) were entrapped within the hydrogel coatings during electrosynthesis, to examine the release performances and mechanisms of the electrosynthesized hydrogels. It was observed that all the examined polymers showed significant release properties and, in particular, AA-containing hydrogel films confirmed a strong pH-dependence as expected. These coatings seem to be promising in orthopedic field for in situ drug delivery applications. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008.

De Giglio E, Cometa S, Satriano C, Sabbatini L, Zambonin PG.

Department of Chemistry, University of Bari, Via E. Orabona 4 I‐70126 Bari, Italy.

Enhancing neurite outgrowth from primary neurones and neural stem cells using thermoresponsive hydrogel scaffolds for the repair of spinal cord injury.

In this study, thermoresponsive xyloglucan hydrogel scaffolds were investigated as candidates for neural tissue engineering of the spinal cord. The hydrogels were optimized to provide similar mechanical properties to that of native spinal cord, although also being functionalized through the immobilization of poly-D-lysine to promote neurone adhesion and neurite outgrowth. Under 2D and 3D culture conditions, xyloglucan scaffolds supported the differentiation of primary cortical neurones. Furthermore, functionalization provided a means of controlling and optimizing the cell diameter, number, migration and the neurite density, and the direction of growth. The interaction of neural stem cells (NSCs) was also investigated on the xyloglucan scaffolds in vitro. The survival of the NSCs and the axonal extensions on the scaffolds were similar to that of the primary cortical neurones. These findings suggest that xyloglucan-based materials are suitable for providing a neurotrophic milieu. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008.

Nisbet DR, Moses D, Gengenbach TR, Forsythe JS, Finkelstein DI, Horne MK.

Department of Materials Engineering, Division of Biological Engineering, Monash University, Victoria 3800, Australia.

Poly(ethylene imine)-g-chitosan using EX-810 as a spacer for nonviral gene delivery vectors.

Polyelectrolyte complexes have been widely studied as gene carriers in recent years. In this study, poly (ethylene imine) was grafted onto chitosan (PEI-g-CHI) as a nonviral gene carrier in order to improve the water solubility as well as the inherent transfection efficiency of chitosan. We present a novel method to conjugate the amine or hydroxyl groups of chitosan (CHI) and the amine groups of PEI through opening the epoxide rings of ethylene glycol diglycidyl ether (EX-810), which also brings the merits as mentioned in PEGylation chemistry. The degree of substitution of PEI onto CHI was characterized by NMR. The preliminarily cellular mechanisms, from the cellular entry to the endosomal release, were investigated by the correlations among the physicochemical properties of the DNA-polymer complexes, the buffering capacity of the modified polymer, the cytotoxicity, and the efficiency of the transgene expression. The cytotoxicity assayed by MTT shows that cell viability of PEI-g-CHI is higher than CHI especially noticeable at high concentrations using human kidney 293T cells. The efficiency of transgene expression and the amount of intracellular plasmid were monitored using green fluorescent protein (GFP) and visualized by fluorescence microscopy. The transfection efficiency of PEI-g-CHI/DNA polyplex is significantly better than CHI/DNA polyplex when using the weight ratios higher than 2.5. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008.

Lou YL, Peng YS, Chen BH, Wang LF, Leong KW.

Faculty of Medicinal and Applied Chemistry, School of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan 80708, Republic of China.

Evaluation of the mechanical properties of posterolateral structures and supporting posterolateral instability of the knee.

The objectives of this study are to evaluate the contributions of the popliteofibular ligament (PFL), the popliteus tendon (PT), and the lateral (fibular) collateral ligament (LCL) to the posterolateral stability of the knee by changing the sequence of selective transection. Twelve fresh-frozen cadaveric knees were divided into two groups. Group 1 has a cutting sequence as follows: PFL, PT, LCL. Group 2 has a cutting sequence as follows: PT, PFL, LCL. Each specimen was mounted on the apparatuses using the Ilizarov external fixator for measuring external rotatory and varus laxities at every 30 degrees from 0 degrees to 90 degrees of knee flexion. In both groups, there was no significant difference between the PFL and PT in the increment of respective external rotatory laxity after transection at each knee flexion angle, except 0 degrees in group 2. The transection of the LCL significantly increased the external rotation laxity at 0 degrees and 30 degrees . Varus instability was increased significantly only after cutting the LCL at every knee flexion angle. In conclusion, both the PFL and PT equally contribute to the external rotatory stability. The LCL also contributes to the external rotatory stability at early range of knee flexion. The LCL is a main structure for varus stability in the knee. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Chun YM, Kim SJ, Kim HS.

Department of Orthopaedic Surgery, Anthroscopy and Joint Research Institute, Yonsei University College of Medicine, CPO Box 8044, 134, Shinchon‐dong, Seodaemun‐gu, Seoul 120‐752, Korea.

Interview with President Shirley Tilghman (Princeton University).

Catalytic Synthesis of beta(3)-Amino Acid Derivatives from alpha-Amino Acids.

Byrne CM, Church TL, Kramer JW, Coates GW.

Department of Chemistry and Chemical Biology, Cornell University, Baker Laboratory, Ithaca, NY 14853-1301, USA, Fax: (+1) 607-255-4137.

Protection by Conformationally Restricted Mobility: First Solid-Phase Synthesis of Triostin A.

Tulla-Puche J, Marcucci E, Fermin M, Bayó-Puxan N, Albericio F.

Institute for Research in Biomedicine, Barcelona Science Park, Josep Samitier 1, 08028 Barcelona, Spain, Fax: (+34) 93-403-7126.

Copper-Catalyzed Asymmetric Propargylic Substitution Reactions of Propargylic Acetates with Amines.

Hattori G, Matsuzawa H, Miyake Y, Nishibayashi Y.

Institute of Engineering Innovation, School of Engineering, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo, 113-8656, Japan, Fax: (+81) 3-5841-1175 http://park.itc.u-tokyo.ac.jp/nishiba/

Implications of a Carboxylate-Bound C-Cluster Structure of Carbon Monoxide Dehydrogenase.

Lindahl PA.

Department of Chemistry and, Department of Biochemistry/Biophysics, Texas A&M University, College Station, TX 77843-3255, USA, Fax: (+1) 979-845-4719.