Biomaterials (v.26, #7)

Calendar (I).

The influence of dispersant concentration on the pore morphology of hydroxyapatite ceramics for bone tissue engineering by L.A. Cyster; D.M. Grant; S.M. Howdle; F.R.A.J. Rose; D.J. Irvine; D. Freeman; C.A. Scotchford; K.M. Shakesheff (697-702).
There is a clinical need for synthetic scaffolds that will promote bone regeneration. Important factors include obtaining an optimal porosity and size of interconnecting windows whilst maintaining scaffold mechanical strength, enabling complete penetration of cells and nutrients throughout the scaffold, preventing the formation of necrotic tissue in the centre of the scaffold. To address this we investigated varying slip deflocculation in order to control the resulting porosity, pore size and interconnecting window size whilst maintaining mechanical strength. Hydroxyapatite (HA) porous ceramics were prepared using a modified slip casting process. Rheological measurements of the HA slips were used to identify deflocculation conditions which resulted in changes in the cell and window sizes of the resulting ceramics. Sintered ceramics were characterised by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Pore and window size distribution was determined by SEM. XRD analysis confirmed that the crystal structure remained HA after the sintering process. SEM showed that HA porous ceramics presented a highly interconnected porous network with average pore sizes ranging from 391±39 to 495±25 μm. The average window size varied from 73±5 to 135±7 μm. Pore diameters obtained were controllable in the range 200–500 μm. Window sizes were in the range 30–250 μm. The use of dispersant concentration allows pore and window size to be modified whilst maintaining control over porosity demonstrated by a porosity of 85% for seven different dispersant concentrations. The advantage of this approach allows the correlation between the rheological conditions of the slip and the resultant sintered ceramic properties. In particular, optimising the ceramic strength by controlling the agglomeration during the casting process.
Keywords: Hydroxyapatite scaffolds; Tissue engineering; Pore size; Window size;

The effect of backbone structure on polycation comb-type copolymer/DNA interactions and the molecular assembly of DNA by Yu-ichi Sato; Yuki Kobayashi; Takayuki Kamiya; Hiromitsu Watanabe; Toshihiro Akaike; Kenichi Yoshikawa; Atsushi Maruyama (703-711).
A series of comb-type copolymers comprised of various polycation backbones and dextran (Dex) side chains were prepared to study the DNA/copolymer interaction. While the cationic copolymers with a lower degree of dextran grafts maintained an ability to condense DNA molecules into a globule form those with a higher degree of dextran grafting interacted with DNA without inducing DNA condensation. The structural differences in cationic backbones diversely influenced DNA hybridization as evaluated by circular dichroism (CD) spectrometry and UV-melting analyses. The copolymer having a polyallylamine (PAA) backbone induced B→A-type transformation of DNA duplex, whereas the copolymers having either α-poly(l-lysine) (αPLL) or ε-poly(l-lysine) (εPLL) backbone induced B→C-type transformation. The PAA copolymer is the first example of the artificial polymer that induces B→A-type transformation under physiologically relevant condition. UV-melting analyses of DNA strands indicated that the αPLL copolymers showed the highest stabilization efficacy toward poly(dA)·poly(dT) duplex and poly(dA)·2poly(dT) triplex without affecting reversibility of inter DNA association. Melting temperatures (T m) of the triplex increased from 38°C to 99°C by the addition of the αPLL copolymer with an appropriate grafting degree. While the PAA copolymers had higher density of cationic groups along the backbone than αPLL copolymers, these copolymers moderately increased T m of the DNA triplex. The PAA copolymer caused considerable hysteresis in thermal melting/reassociation processes. Note that the εPLL copolymers increased T m of the DNA triplex and not the duplex, suggesting their potential as a triplex selective stabilizer. Chemical structures of the cationic backbones of the copolymers were characteristically affected on the copolymer/DNA interaction even if their backbones were surrounded by abundant side chains (>65 wt%) of dextran. The study suggested that tailor-made design of “functional polycounterion” is a strategy to engineer molecular assembling of DNA.
Keywords: DNA; Graft copolymer; Inter polyelectrolyte complex; Double helix;

Effects of incorporation of HA/ZrO2 into glass ionomer cement (GIC) by Y.W. Gu; A.U.J. Yap; P. Cheang; K.A. Khor (713-720).
Glass ionomer cements (GICs) are a class of bioactive cements that bond directly to bone. In this paper, a new bioactive hydroxyapatite (HA)/zirconia (ZrO2)-filled GIC composite was developed to improve the biocompatibility and bioactivity of the GICs with the surrounding bone and connective tissues. Nano-sized HA/30 wt% ZrO2 powders were heat treated at 700°C and 800°C for 3 h to elucidate the influence of the crystallinity of composite powders on the performance of HA/ZrO2-GICs. The effects of different volume percentages of HA/ZrO2 powders (4, 12, 28 and 40 vol%) substituted within GICs were investigated based on their microhardness, compressive strength and diametral tensile strength. The HA/ZrO2-GICs composite was soaked in distilled water for 1 day and 1 week before subjecting the samples to mechanical testing. Results showed that the glass and HA/ZrO2 particles were distributed uniformly in the GIC matrix. The substitution of highly crystalline HA/ZrO2 improved the mechanical properties of the HA/ZrO2-GICs due to the slow resorption rate for highly crystalline powders in distilled water. The mechanical properties of HA/ZrO2-GICs increased with increasing soak time due to the continuous formation of aluminium salt bridges, which improved the final strength of the cements. The compositions 4 and 12 vol% HA/ZrO2-GICs exhibited superior mechanical properties than the original GICs. The mechanical properties of HA/ZrO2-GICs were found to be much better than those of HA-GICs because ZrO2 has the attributes of high strength, high modulus, and is significantly harder than glass and HA particles. Furthermore, ZrO2 does not dissolve with increasing soaking time.
Keywords: Glass ionomer; Zirconia; Hydroxyapatite; Strength; Microhardness;

Aromatic diacids were synthesized from chlorinated triethylene or pentaethylene glycols and p-hydroxy benzoic acid. The diacids were acetylated with acetic anhydride to produce homopolymers of polyanhydrides for controlled release applications such as the stabilization of proteins and drugs. Adding ethylene glycol segments into the acid monomer allows tailoring of the hydrophobicity of the polyanhydrides, which in turn dictates the solubility of molecules within the polymer matrix and degradation rate of the polymer. The glycol containing polyanhydrides were characterized by NMR, GPC, DSC and dissolution testing. The release characteristics and mechanism of the new polyanhydrides were evaluated using hydrophilic and hydrophobic dyes.
Keywords: Polyanhydride; Controlled drug delivery; Degradation; Oligo ethylene glycol;

Characterization of aqueous dispersions of Fe3O4 nanoparticles and their biomedical applications by Fong-Yu Cheng; Chia-Hao Su; Yu-Sheng Yang; Chen-Sheng Yeh; Chiau-Yuang Tsai; Chao-Liang Wu; Ming-Ting Wu; Dar-Bin Shieh (729-738).
A newly developed non-polymer coated Fe3O4 nanoparticles showing well-dispersion were synthesized using Fe(II) and Fe(III) salt chemical coprecipitation with tetramethylammonium hydroxide (N(CH3)4OH) in an aqueous solution. Transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectrometer (FT-IR), X-ray photoelectron spectrometer (XPS) and superconducting quantum interference measurement device (SQUID) measurements were employed to investigate the iron oxide properties. The resulting iron oxide particles were manipulated to be as small as 9 nm diameter in size. Based on FT-IR and X-ray photoelectron spectrometer results, it is suggested that the surfaces of the magnetite (Fe3O4) particles are covered with hydroxide (–OH) groups incorporated with (CH3)4N+ through electrostatic interaction. The in vitro cytotoxicity test revealed that the magnetite particles exhibited excellent biocompatibility, suggesting that they may be further explored for biomedical applications. NMR measurements revealed significantly reduced water proton relaxation times T1 and T2. The MR images of the nanoparticles in water, serum, and whole blood were investigated using a 1.5 T clinical MR imager. Significant reduction of the background medium signal was achieved in the T2-weighted and the T2*-weighted sequence especially in the serum and whole blood. Combining the advantage of MRI signal contrast, the non-polymer-coated surface chemistry for distinct bioconjugation and the homogenous nanometer size for better controlled biodistribution, these preliminary experiments demonstrated the potential of the as-synthesized magnetite material in functional molecular imaging for biomedical research and clinical diagnosis.
Keywords: MRI; Nanoparticle; Cytotoxicity;

In vitro corrosion study by EIS of a nickel-free stainless steel for orthopaedic applications by G. Rondelli; P. Torricelli; M. Fini; R. Giardino (739-744).
The electrochemical impedance spectroscopy (EIS) technique was used for the study of the electrochemical behaviour of Ni-free austenitic stainless steel for orthopaedic applications. Experiments were carried out using four different test solutions: (i) phosphate-buffered saline (PBS), (ii) minimum essential medium (MEM), (iii) MEM + 10% fetal calf serum (FCS), (iv) MEM + 10% fetal calf serum + L929 fibroblast cell line (Cell). Bode-phase spectra showed the presence of two maxima and were fitted with an equivalent circuit characterized by two parallel combinations (Resistance, Constant Phase Element). The (R 1, CPE1) branch was assigned to the inner compact passive film and the (R 2, CPE2) branch to the external porous film. The resistance of the inner film R 1, here directly related to the material's uniform corrosion resistance, raised with the immersion time and increased in the following order: PBS<FCS≈Cell<MEM. In the same test condition the R 1 value of the Ni-free austenitic stainless steel is, as expected, lower than that of titanium.
Keywords: Stainless steel; Corrosion; In vitro test; Electrochemistry; Biocompatibility;

Stimulation of glutathione depletion, ROS production and cell cycle arrest of dental pulp cells and gingival epithelial cells by HEMA by Hsiao-Hua Chang; Ming-Kuang Guo; Frederick H. Kasten; Mei-Chi Chang; Guay-Fen Huang; Yin-Lin Wang; Ruey-Song Wang; Jiiang-Huei Jeng (745-753).
2-Hydroxy-ethyl methacrylate (HEMA) is the major component released from resin-modified glass ionomer cements and dental adhesives. Human tissues mainly affected by HEMA are oral epithelium and dental pulp. We treated human gingival epithelial S–G cells and pulp fibroblasts (HPF) with various concentrations of HEMA, to evaluate its effects on cell growth, cell cycle progression, intracellular glutathione (GSH) level and reactive oxygen species (ROS) production. HEMA-induced growth inhibition in HPF and S–G cells in a dose-dependent manner, which may be partially explained by induction of cell cycle perturbation. G2/M phase arrest was noted after exposure of HPF to 5 and 10 mm of HEMA, concomitant with glutathione depletion and ROS production. S-phase arrest occurred in S–G cells when treated with 2.5 and 5 mm, while at 10 mm a sub-G0/G1 peak was noted, indicating the potential induction of apoptosis. GSH depletion was marked in S–G cells only at concentrations of 5 and 10 mm, but excessive ROS production was noted at concentration of 1 mm and rose with dose increase between 1 and 5 mm, then lessened at 10 mm. This suggested that the increase of ROS in S–G cells was not mainly caused by GSH depletion. These results helped to define the mechanism of the cytotoxicity caused by HEMA.
Keywords: Apoptosis; Cell cycle; Glutathione; HEMA; Pulp cells; Gingival cells; Reactive oxygen species; Toxicity;

Effect of composition of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) on growth of fibroblast and osteoblast by Ya-Wu Wang; Fei Yang; Qiong Wu; Yin-chung Cheng; Peter H.F. Yu; Jinchun Chen; Guo-Qiang Chen (755-761).
Films made of poly (3-hydroxybutyrate) (PHB), poly(3-hydroxybutyrate- co-3-hydroxyhexanoate) (PHBHHx) consisting of 5%, 12% and 20% hydroxyhexanoate (HHx), respectively, were evaluated for biomedical application in comparison with poly (l-Lactide) (PLA). With the increase of HHx content in PHBHHx, the polymer surface properties changed accordingly. P(HB-co-20%-HHx) had the smoothest surface while PHB surface was most hydrophilic among the evaluated PHB and all the PHBHHx. All PHBHHx also showed strong protein affinity and biocompatibility. It was found that fibroblast and osteoblast had different responses to these polymers: fibroblast cells favored P(HB-co-20%-HHx), yet osteoblast cells preferred P(HB-co-12%-HHx). PHB and all PHBHHx appeared to have better biocompatibility for fibroblast and osteoblast compared with PLA. Polymers possessing diferent surface properties may help meet different cellular requirements. Combined with their good mechanical properties for elongation and adjustable biocompatibility, PHBHHx may meet the needs of growth requirements of different tissues and cells.
Keywords: Poly (3-hydroxybutyrate-co-3-hydroxyhexanoate); PHBHHx; PHB; Biocompatibility; Osteoblast; Fibroblast;

Laser surface modification of poly(ε-caprolactone) (PCL) membrane for tissue engineering applications by K.S. Tiaw; S.W. Goh; M. Hong; Z. Wang; B. Lan; S.H. Teoh (763-769).
Ultra-thin polycaprolactone (PCL) produced by bi-axial stretching was previously shown to have significant advantage for membrane tissue engineering. However, the permeability of the membrane needs to be enhanced. In this study, ablation experiments using femtosecond laser and excimer laser were carried out to modify the PCL surface. The use of the femtosecond laser produces neat drilled-through holes while the excimer laser is employed to produce blind-holes on the membrane. The modified surface of the membrane was studied and analyzed for different laser parameters (such as pulse energy and pulse repetition rate and characterized using several techniques that include optical microscopy, scanning electron microscopy and water contact angle measurements). Results showed that the morphological surface changes with different laser parameters, and the water contact angle decreases as the surface of the membrane is modified. The decrease in water contact angle suggests that surface of the membrane had become more hydrophilic than the non-laser treated membrane. The present study demonstrated that laser surface modification on the PCL can be achieved with high degree of success and precision. This paved the way for further enhancement in membrane tissue engineering.
Keywords: Poly(ε-caprolactone); Femtosecond laser; Excimer laser; Ablation; Surface modification; Wettability;

The influence of microchannels on neurite growth and architecture by Melissa J. Mahoney; Ruth R. Chen; Jian Tan; W. Mark Saltzman (771-778).
Microchannels were produced using a photolithographic technique to pattern polyimide walls (11 μm in height and 20–60 μm in width) onto a planar glass substrate. PC12 cells were seeded onto patterned surfaces. After 3 days of culture in NGF supplemented medium cells were viable and extended neurites. Culture in microchannels influenced the direction of neurite growth (θ Orientation) and the complexity of PC12 cell architecture including neurite length (L Neurite), the number of neurites emerging per cell (N Neurites), and the angle at which neurites emerged from the cell soma (θ Soma). In microchannels neurites oriented parallel to channel walls and the complexity of neuronal architecture was reduced. Both of these effects were strongest for cells located in channels 20–30 μm wide. Within each channel the magnitude of the effect on orientation and architecture was inversely proportional to the distance of the soma from the channel wall. Microtubule and actin filament mobility within the cytoplasm may underly effect on neurite orientation and cell architecture. By manipulating channel width the overall direction of neurite growth and the complexity of neuronal architecture was controlled. Results from these studies will be applied towards the development of biomaterials for microfluidic platforms and drug discovery studies and in neural regeneration research—two applications that would be significantly improved given the ability to control neurite orientation and the complexity of neuronal architecture.
Keywords: Neural cell; Nerve tissue engineering; Micropatterning; Biomimetic material;

Observation of osteogenic differentiation cascade of living mesenchymal stem cells on transparent hydroxyapatite ceramics by Noriko Kotobuki; Koji Ioku; Daisuke Kawagoe; Hirotaka Fujimori; Seishi Goto; Hajime Ohgushi (779-785).
The use of bioceramics and cultured cells for tissue engineering is a novel approach, which is available in a wide variety of clinical situations. The approach requires apparent verification of the cellular functions occurring on the ceramic surface, and these functions could be monitored by microscopic observation of the cultured living cells on the ceramic material. However, such observation is difficult due to the opaque nature of ordinary ceramics. To overcome this drawback, we used transparent hydroxyapatite (tHA) ceramics as a culture substrate and a transgenic rat having an enhanced green fluorescent protein (EGFP)-expressing gene as the cell source. Marrow mesenchymal stem cells (MSC) were obtained from the rat and cultured on both tHA ceramics and a tissue culture polystyrene (TCPS) dish. One hour after the cell seeding, many MSC had attached and showed initial cell spreading. The attachment and spreading were more obvious 5 h after the seeding. Following the culture in the osteogenic condition, the cells differentiated into osteoblasts, which fabricated bone matrix on the culture substrate. The phenomena were similarly observed on both the tHA ceramics and TCPS substrata. These results confirm the excellent properties of tHA ceramics, which support cell attachment, proliferation, and differentiation. Transparent materials make us know the biological usefulness of ceramics in tissue-engineering field.
Keywords: Observation; Mesenchymal stem cells (MSC); Transparent hydroxyapatite (tHA) ceramics;

Gentamicin supplementation of polyvinylidenfluoride mesh materials for infection prophylaxis by Karsten Junge; Raphael Rosch; Uwe Klinge; Carsten Krones; Bernd Klosterhalfen; Peter R. Mertens; Petra Lynen; Dagmar Kunz; Achim Preiß; Heidrun Peltroche-Llacsahuanga; Volker Schumpelick (787-793).
Hernia repair evolved from pure tissue repair to mesh repair due to decreased recurrence rates. However, concern exists about mesh-related infections occurring even several years after initial operation. Therefore, a polyvinylidenfluoride (PVDF) mesh material was constructed and surface modified by plasma-induced graft polymerization of acrylic acid (PVDF+PAAc). Antimicrobial treatment was sought by binding of gentamicin (PVDF+PAAc+Gentamicin). In vitro efficacy and cytotoxicity was measured by agar diffusion test, L929 cytotoxicity testing and by analyzing the amount of gentamicin release from the mesh surface. In vivo biocompatibility was evaluated in 45 Sprague–Dawley rats. 7, 21 and 90 days after mesh implantation the amount of inflammatory and connective tissue as well as the percentage of proliferating (Ki67) and apoptotic cells (TUNEL) were analyzed at the perifilamentary region. Agar diffusion tests showed sufficient local antimicrobiotic effects against the bacteria tested after 24 h of incubation. No signs of cytotoxicity could be identified by L929 testing. Furthermore, surface modification did not affect the in vivo biocompatibility. At the end of the observation period, no significant differences were found for the perifilamentary amount of inflammatory cells and connective tissue and the percentage of Ki67 and TUNEL positive stained cells. The presented data confirm that an antibiotic surface modification of PVDF mesh samples is feasible. By analyzing cytotoxicity in vitro as well as biocompatibility in vivo no side effects were observed.
Keywords: Mesh; Infection; Gentamicin; Surface modification; PVDF;

The effects of collagen fiber orientation on the flexural properties of pericardial heterograft biomaterials by Ali Mirnajafi; Jeremy Raymer; Michael J. Scott; Michael S. Sacks (795-804).
Improving cardiac valve bioprostheses (BHV) utilizing heterograft biomaterials requires a better understanding of their mechanical behavior. Flexure is a major mode of deformation for BHV leaflets during valve operation, inducing more complex deformation patterns within the tissue compared to tensile loads. In this study, we investigated the relation between collagen fiber preferred direction and the resulting flexural properties of native and glutaraldehyde-treated bovine pericardium. 20 mm×4 mm strips were cut from the presorted sheets of bovine pericardium and divided into four groups: two directions of collagen fiber orientation in two groups of native and chemically treated specimens. Specimens were flexed in two different directions using a three-point bending technique (ASAIO J. 45(1999)59) and their flexural mechanical response compared. Results indicated that: (1) the relationship between the applied flexing moment and change of curvature of specimens was non-linear in both native and chemically fixed groups, (2) there were no directional differences in flexural properties when the bovine pericardium is flexed towards either the epi-pericardial or visceral surfaces in both native and chemically fixed specimens, (3) native and chemically fixed bovine pericardium were stiffer when flexed perpendicular to local preferred collagen fiber direction, and (4) chemical fixation increased the flexural rigidity of bovine pericardium. Results of this study indicate that the flexural properties of bovine pericardium are dominated by inter-fiber cross-links as opposed to the stiffness of the collagen fibers themselves. These findings can be used to guide the development of novel chemical treatment methods that seek to optimize biomechanical properties of heterograft biomaterials.
Keywords: Pericardium; Bioprosthetic heart valves; Collagen orientation; Flexural properties; Heterograft biomaterials;

Calcium phosphate and fluorinated calcium phosphate coatings on titanium deposited by Nd:YAG laser at a high fluence by Daniela Ferro; Sergey M. Barinov; Jiulietta V. Rau; Roberto Teghil; Alessandro Latini (805-812).
Calcium phosphate coatings are known to enhance long-term fixation, reliability and promote osteointegration of cementless titanium-based implant devices. This study was aimed at the pulsed laser deposition of calcium phosphate coatings onto titanium using hydroxyapatite and hydroxyapatite–fluorapatite targets. The deposition was carried out at the high laser beam fluence conditions, about 12 J/cm2. The coatings were characterized with respect to their morphology, phase composition and hardness. X-ray energy dispersive analysis revealed the coatings retain their elemental composition, and fluoride content within the film is the same as in the initial target. However, unlike sintered targets, the deposited films contain no apatite-like phases. The hardness of the films, about 18 GPa, is surprisingly high compared to that of hydroxyapatite and hydroxyapatite–fluorapatite ceramic targets. The deposited coatings of 2.7–2.9 μm thickness have uniform and dense microstructure, containing the solidified droplets of the expulsed from the target phase. The uncommon structure and hardness of the films can be attributed to the melting and phase decomposition of the initial material in the laser plasma.
Keywords: Thin films; Calcium phosphate; Laser ablation;

Fibro-porous meshes made from polyurethane micro-fibers: effects of surface charge on tissue response by Joan E. Sanders; Sarah E. Lamont; Ari Karchin; Steven L. Golledge; Buddy D. Ratner (813-818).
The purpose of this research was to evaluate the influence of surface charge on fibrous encapsulation, cell nuclei density, and vessel ingrowth into small-fiber, fibro-porous, biomaterial meshes. Meshes electrospun from polyurethane with mean fiber diameters of 5.8 μm and mean fiber spacing of 64.9 μm were plasma coated with films of different relative surface charge: Hexafluoropropylene (HF) (neutral), N,N-dimethylaminoethyl methacrylate (NN) (positive charge), and methacrylic acid (MA) (negative charge). Samples were implanted in rat subcutaneous dorsum for 5 weeks then fibrous capsule presence around the implants, cell nuclei density, and vessel number were assessed. Results showed that within the resolution of the histological analysis methods used, no implant experienced fibrous encapsulation. There was no significant difference between cell nuclei density and coating for the four groups: uncoated, HF-coated, NN-coated, and MA-coated. HF-coated and NN-coated samples had lower vessel numbers than uncoated samples (p=0.055 and 0.032, respectively). MA-coated samples had vessel numbers not significantly different from uncoated polyurethane (slightly negatively charged) samples (p=0.879). The results suggest that negatively charged surfaces may facilitate vessel ingrowth into fibro-porous mesh biomaterials.
Keywords: Polyurethane; Fibrous tissue; Blood flow; Vessel ingrowth;

Synthesis and in vitro evaluation of a novel thiolated chitosan by Krum Kafedjiiski; Alexander H. Krauland; Martin H. Hoffer; Andreas Bernkop-Schnürch (819-826).
In order to achieve the same properties as chitosan–4-thio-butyl-amidine and to overcome at the same time its insufficient stability, the aim of this study was to evaluate the imidoester reaction of isopropyl-S-acetylthioacetimidate for the chemical modification of chitosan and to study the properties of the resulting chitosan–thioethylamidine (TEA) derivative. The thioalkylamidine substitute was introduced without the formation of N-substituted non-thiol products. The resulting conjugates exhibited 1.05±0.17% or 139.68±17.13 μmol immobilized free thiol groups per gram polymer and a total amount of reduced and oxidized thiol groups of 1.81±0.65% or 179.46±67.95 μmol/g polymer. By the immobilization of thiol groups mucoadhesion was strongly improved due to the formation of disulfide bonds with mucus glycoproteins. Chitosan–TEA was investigated regarding to its mucoadhesive properties via tensile studies and the rotating cylinder method. In tensile studies the total work of adhesion of chitosan–TEA was increased 3.3-fold in comparison to unmodified chitosan. Results from the rotating cylinder method showed an improvement ratio of 8.9 for chitosan–TEA compared with unmodified chitosan. In spite of the immobilization of thiol groups onto chitosan its swelling behavior in aqueous solutions was not significantly altered. Cumulative release studies out of matrix tablets comprising the chitosan–TEA and the model compound fluorescence labeled dextrane (FD4) demonstrated a controlled release over 3 h with a trend toward a pseudo-zero-order kinetic. Because of these features the new chitosan thioamidine conjugate might represent a promising new polymeric excipient for various drug delivery systems.
Keywords: Thiolated chitosan; Chitosan–thioethylamidine conjugates; Isopropyl-S-acetylthioacetimidate.HCl; Mucoadhesion;

Erratum to ‘Ordered growth of neurons on diamond’ by Christian G. Specht; Oliver A. Williams; Richard B. Jackman; Ralf Schoepfer (828).