Friction reducing ability of a poly-l-lysine and dopamine modified hyaluronan coating for polycaprolactone cartilage resurfacing implants

Frictional properties of cartilage resurfacing implants should be sufficiently low to limit damaging of the opposing cartilage during articulation. The present study determines if native lubricious molecule proteoglycan 4 (PRG4) can adsorb onto a layer-by-layer bioinspired coating composed of poly-l-lysine (PLL) and dopamine modified hyaluronic acid (HADN) and thereby can reduce the friction between implant and articular cartilage. An ELISA was developed to quantify the amount of immobilized human recombinant (rh)PRG4 after exposure to the PLL-HADN coating. The effect on lubrication was evaluated by comparing the coefficient of friction (CoF) of bare polycaprolactone (PCL) disks to that of PLL-HADN coated PCL disks while articulated against cartilage using a ring-on-disk geometry and a lubricant solution consisting of native synovial fluid components including rhPRG4. The PLL-HADN coating effectively immobilized rhPRG4. The surface roughness of PCL disks significantly increased while the water contact angle significantly decreased after application of the coating. The average CoF measured during the first minute of bare PCL against cartilage exceeded twice the CoF of the PLL-HADN coated PCL against cartilage. After 60 min, the CoF reached equilibrium values which were still significantly higher for bare PCL compared to coated PCL. The present study demonstrated that PCL can effectively be coated with PLL-HADN. Additionally, this coating reduces the friction between PCL and cartilage when a PRG4-rich lubricant is used, similar to the lubricating surface of native cartilage. This makes PLL-HADN coating a promising application to improve the clinical success of PCL-based cartilage resurfacing implants.</p

Introducing Hyaluronic Acid into Supramolecular Polymers and Hydrogels

[Abstract] The use of supramolecular polymers to construct functional biomaterials is gaining more attention due to the tunable dynamic behavior and fibrous structures of supramolecular polymers, which resemble those found in natural systems, such as the extracellular matrix. Nevertheless, to obtain a biomaterial capable of mimicking native systems, complex biomolecules should be incorporated, as they allow one to achieve essential biological processes. In this study, supramolecular polymers based on water-soluble benzene-1,3,5-tricarboxamides (BTAs) were assembled in the presence of hyaluronic acid (HA) both in solution and hydrogel states. The coassembly of BTAs bearing tetra(ethylene glycol) at the periphery (BTA-OEG4) and HA at different ratios showed strong interactions between the two components that led to the formation of short fibers and heterogeneous hydrogels. BTAs were further covalently linked to HA (HA-BTA), resulting in a polymer that was unable to assemble into fibers or form hydrogels due to the high hydrophilicity of HA. However, coassembly of HA-BTA with BTA-OEG4 resulted in the formation of long fibers, similar to those formed by BTA-OEG4 alone, and hydrogels were produced with tunable stiffness ranging from 250 to 700 Pa, which is 10-fold higher than that of hydrogels assembled with only BTA-OEG4. Further coassembly of BTA-OEG4 fibers with other polysaccharides showed that except for dextran, all polysaccharides studied interacted with BTA-OEG4 fibers. The possibility of incorporating polysaccharides into BTA-based materials paves the way for the creation of dynamic complex biomaterials.The authors acknowledge the ICMS Animation Studio for providing the artwork. S.V.-A. and G.M. acknowledge the funding received by Gravitation Program “Materials Driven Regeneration,” funded by the Netherlands Organization for Scientific Research (024.003.013). J.M. acknowledges a Marie Skłodowska-Curie postdoctoral fellowship (794016) for financial support. G.M. acknowledges the funding received by the Swiss National Science Foundation (SNSF “Early PostDoc Mobility” P2EZP2-178435). R.C. acknowledges TA Instruments for providing the DHR-3 rheometer under the Young Distinguished Rheologist Award instrument grant. S.S. and E.W.M acknowledge the European Research Council (H2020-EU.1.1., SYNMAT project, ID 788618).Netherlands Organisation for Scientific Research; 024.003.013Swiss National Science Foundation; P2EZP2-17843

Friction reducing ability of a poly-l-lysine and dopamine modified hyaluronan coating for polycaprolactone cartilage resurfacing implants

Frictional properties of cartilage resurfacing implants should be sufficiently low to limit damaging of the opposing cartilage during articulation. The present study determines if native lubricious molecule proteoglycan 4 (PRG4) can adsorb onto a layer-by-layer bioinspired coating composed of poly-l-lysine (PLL) and dopamine modified hyaluronic acid (HADN) and thereby can reduce the friction between implant and articular cartilage. An ELISA was developed to quantify the amount of immobilized human recombinant (rh)PRG4 after exposure to the PLL-HADN coating. The effect on lubrication was evaluated by comparing the coefficient of friction (CoF) of bare polycaprolactone (PCL) disks to that of PLL-HADN coated PCL disks while articulated against cartilage using a ring-on-disk geometry and a lubricant solution consisting of native synovial fluid components including rhPRG4. The PLL-HADN coating effectively immobilized rhPRG4. The surface roughness of PCL disks significantly increased while the water contact angle significantly decreased after application of the coating. The average CoF measured during the first minute of bare PCL against cartilage exceeded twice the CoF of the PLL-HADN coated PCL against cartilage. After 60 min, the CoF reached equilibrium values which were still significantly higher for bare PCL compared to coated PCL. The present study demonstrated that PCL can effectively be coated with PLL-HADN. Additionally, this coating reduces the friction between PCL and cartilage when a PRG4-rich lubricant is used, similar to the lubricating surface of native cartilage. This makes PLL-HADN coating a promising application to improve the clinical success of PCL-based cartilage resurfacing implants.</p

The impact of water content and mixing time on the linear and non-linear rheology of wheat flour dough

The viscoelastic properties of wheat flour dough are known to be very sensitive to small changes in water content and mixing time. In this study the simple scaling law originally proposed by Hibberd (1970) [Rheol. Acta 9, 497-500] to capture the water dependency of the dynamic moduli in small amplitude oscillatory shear, was also applied to creep-recovery shear tests and extensional tests. The scaling law turns out to be valid not only in the linear region, but to a certain extent also in the non-linear region. At sufficiently high water levels, a ‘free’ water phase exists in dough, which attenuates the starch-starch and gluten-starch interactions. Dough characterisation after different mixing times shows that overmixing may cause a disaggregation or even depolymerisation of the gluten network. The network breakdown, as well as the subsequent (partial) recovery, are clearly reflected in the value of the strain-hardening index, for which a maximum is reached at a mixing time close to the optimum as determined with the Mixograph. Finally, the gluten proteins turn out to be much less susceptible to overmixing in an oxygen-lean environment, which demonstrates the significant role of oxygen in the degradation process

The interplay between the main flour constituents in the rheological behaviour of wheat flour dough

There is still considerable debate in the literature about the respective roles of starch and gluten in both the linear and non-linear rheology of wheat flour dough. Hence, to elucidate the individual contributions of gluten and starch to the overall dough behaviour, the rheological properties of dough and mixtures of different gluten-starch ratios were studied systematically in shear and extension, by means of an adequate rheological toolbox consisting of linear small amplitude oscillatory shear tests and non-linear tests such as creep-recovery in shear and uniaxial extension. The starch component plays a pivotal role in linear dough rheology. With increasing starch content, the linearity limit observed in oscillatory shear tests decreases as a power-law function. Starch also clearly affects the extensional viscosity at small strains. Consequently, in the linear region differences between different gluten systems may become obscured by the presence of starch. As breadmaking qualities are known to be intrinsically linked to the gluten network, it is imperative to probe the non-linear behaviour of dough in order to expose differences in flour quality. The quality differences between a strong and a weak flour type were revealed most clearly in the value of the strain-hardening index in uniaxial extension and the total recovery compliance in non-linear creep-recovery tests. Notwithstanding its earlier successful application to pure gluten gels, the accuracy of the critical gel model in predicting the linear rheological properties of dough was found to be limited, due to dough having a small linearity limit and a finite longest relaxation time

Towards unraveling the sintering process of two polystyrene particles by numerical simulations

\u3cp\u3eIn this work, we study different rheological and thermal phenomena present during laser sintering of two polystyrene (PS) particles using fully resolved numerical simulations. In our analysis, we varied the laser power, the initial temperature and the thermal convection coefficient, used different rheological descriptions for the flow behavior and in addition studied the effect of the substrate (used in the experiments) on the temperature distribution of the system. Although we are not able to fully describe the results of the experiments with our simulations for the given parameter set, we obtained important insights in the significance of thermal initial and boundary conditions by systematically studying the sintering process.\u3c/p\u3

A novel experimental setup for in situ optical and X-ray imaging of laser sintering of polymer particles

We present a unique laser sintering setup that allows real time studies of the structural evolution during laser sintering of polymer particles. The device incorporates the main features of classical selective laser sintering machines for 3D printing of polymers and at the same time allows in situ visualization of the sintering dynamics with optical microscopy as well as X-ray scattering. A main feature of the setup is the fact that it provides local access to one particle-particle bridge during sintering. In addition, due to the small scale of the device and the specific laser arrangement process, parameters such as the temperature, laser energy, laser pulse duration, and spot size can be precisely controlled. The sample chamber provides heating up to 360 °C, which allows for sintering of commodity as well as high performance polymers. The latter parameters are controlled by the use of a visible light laser combined with an acousto-optic modulator for pulsing, which allows small and precise spot sizes and pulse times and pulse energies as low as 500 μs and 17 μJ. The macrostructural evolution of the particle bridge during sintering is followed via optical imaging at high speed and resolution. Placing the setup in high flux synchrotron radiation with a fast detector simultaneously allows in situ time-resolved X-ray characterizations. To demonstrate the capabilities of the device, we studied the laser sintering of two spherical PA12 particles. The setup provides crucial real-time information concerning the sintering dynamics as well as crystallization kinetics, which was not accessible up to now.status: publishe

AI18F-3p-C-NETA-TATE: Combining a versatile and highly effective chelator with an established somatostatin analogue

Aim/Introduction: Somatostatin-based radiopharmaceuticals (e.g. [68Ga]Ga-DOTATATE and [177Lu]Lu-DOTATATE) have been used to diagnose, monitor, and treat neuroendocrine tumour patients with great success. [18F]AlF-NOTA-octreotide, a promising 18F-labeled somatostatin analogue and potential alternative for 68GaDOTA-peptides, is under clinical evaluation. Ideally, the same precursor (combination of chelator-linker-vector) can be used for production of both diagnostic and therapeutic radiopharmaceuticals with very similar (e.g. Al18F/213Bi/177Lu) or identical (e.g. complementary Tb-radionuclides) pharmacokinetic properties, allowing accurate, personalised dosimetry estimation and radionuclide therapy of NET patients. In this study we evaluate the versatile and highly effective chelator 3p-C-NETA3 and present first results of radiosynthesis and stability of Al[18F]F-3p-C-NETA-TATE. Materials and Methods: 3p-C-NETA was radiolabelled with diagnostic (68Ga, Al18F) or therapeutic  (177Lu,161Tb,213Bi) radionuclides at different temperatures. The in vitro stability of the corresponding radiocomplexes was determined in PBS and human serum at 37 °C. 3p-C-NETA-TATE was synthesised using standard solid-phase peptide synthesis and purifed using HPLC. Al[18F]F-3p-C-NETA-TATE was synthesised in an automated AllInOne module and analysed using radio-HPLC. Finally, the in vitro stability of Al[18F]F-3p-C-NETA-TATE was evaluated in formulation buffer, PBS and human serum at 37 °C. Results: 3p-C-NETA was efficiently labelled with 177Luand 213Bi (RCY>95%) at room temperature and with 161Tb(>95%) and 68Ga (>90%) at 55 °C. Al18F-labeling required a higher temperature of 95 °C to achieve good yields (>85%).The 177Lu- and 161Tb-3p-C-NETA-complex showed excellent invitro stability in both PBS and human serum over a period of eight days (97% intact). We also observed high in vitro stability up to 2 h for Al[18F]F-3p-C-NETA-TATE (>93% intact in PBS and human serum). In contrast, [68Ga]Ga-3p-C-NETA was stable in PBS (>90% intact), but not in human serum (only 60% intact after 2h). Al[18F]F-3p-C-NETA-TATE was obtained in good RCY (56%) and radiochemical purity (98%). Al[18F]F-3pC-NETA-TATE displayed excellent in vitro stability with >95%intact tracer after 4 hours in all tested conditions. Conclusion:  3p-C-NETA is an excellent chelator that can be used for both targeted radionuclide therapy (177Lu, 213Bi and 161Tb) and diagnostic applications (Al18F) and has the potential to replace DOTA analogues in current clinical use. Al[18F]F-3p-CNETA-TATE will be further evaluated using µPET/MRI imaging in healthy rats and SSTR2 positive tumour mice, in a head-to-head comparison with Al18F-NOTA-octreotide.