In vivo biofunctional evaluation of hydrogels for disc regeneration

Purpose Regenerative strategies aim to restore the original biofunctionality of the intervertebral disc. Different biomaterials are available, which might support disc regeneration. In the present study, the prospects of success of two hydrogels functionalized with anti-angiogenic peptides and seeded with bone marrow derived mononuclear cells (BMC), respectively, were investigated in an ovine nucleotomy model. Methods In a one-step procedure iliac crest aspirates were harvested and, subsequently, separated BMC were seeded on hydrogels and implanted into the ovine disc. For the cell-seeded approach a hyaluronic acid-based hydrogel was used. The anti-angiogenic potential of newly developed VEGF-blockers was investigated on ionically crosslinked metacrylated gellan gum hydrogels. Untreated discs served as nucleotomy controls. 24 adult merino sheep were used. After 6 weeks histological, after 12 weeks histological and biomechanical analyses were conducted. Results Biomechanical tests revealed no differences between any of the implanted and nucleotomized discs. All implanted discs significantly degenerated compared to intact discs. In contrast, there was no marked difference between implanted and nucleotomized discs. In tendency, albeit not significant, degeneration score and disc height index deteriorated for all but not for the cell-seeded hydrogels from 6 to 12 weeks. Cell-seeded hydrogels slightly decelerated degeneration. Conclusions None of the hydrogel configurations was able to regenerate biofunctionality of the intervertebral disc. This might presumably be caused by hydrogel extrusion. Great importance should be given to the development of annulus sealants, which effectively exploit the potential of (cell-seeded) hydrogels for biological disc regeneration and restoration of intervertebral disc functioningThis work was supported by the EU-project Disc Regeneration (NMP3-LA-2008-213904). Technical assistance of Iris Baum and the whole animal surgery team of the Institute of Orthopaedic Research and Biomechanics, Ulm, are gratefully acknowledged. DDAHA hydrogels were kindly provided by Cristina Longinotti (DDAHA, Anika Therapeutics, Abano Therme, Italy)

CHARACTERIZATION AND MODELING OF LOW FREQUENCY DISPERSIVE EFFECTS IN III-V ELECTRON DEVICES

In this thesis, three years are enclosed of research activity in the topic of non linear characterization and modelling of microwave devices. I investigated various issues related to those topics which are closely related. In fact, to obtain good predictions, empirical models require accurate measurements. This aspect is particularly important when we want to predict the behavior of devices in nonlinear regime. More and more applications take advantage of devices operation in non-linear regime. For such a reason, non linear characterization is an hot topic and research activities have focused particular attention on the need of characterize the nonlinear behaviour of electron devices to obtain more accurate model prediction under actual operating conditions. The importance of this theme can be clearly understood by considering how, in recent years, microwave technologies have become attractive for communication applications and a number of commercial devices which are largely used in everyday life (e.g., cell phone, GPS, wireless communication and so on). In the first chapter the most important properties of devices and technologies used in microwave electronics circuits will be dealt with. Particular attention is devoted to the comparison between two III-V semiconductors for the fabrication of these devices: GaAs, proven technology and used for years, and GaN, a youngest technology still being tested. After this some of the most interesting issues related to III-V electron devices, are discussed, such as low frequency dispersion. Finally a brief look will be given at the non linear models for these devices. In the second Chapter the most important microwave measurement systems exploited to characterize the non linear dynamic behaviour of electron devices will be discussed: pulsed setups, load / source-pull measurement systems, and Large Signal time domain characterization systems. In particular, for each measurement technique, it has been described the principle of operation and the application they are used for. In chapter III an alternative, technology-independent large-signal measurement setup, developed during the PhD studies, is proposed for the experimental investigation on the low frequency dispersion of current/voltage characteristics in micro- and millimetre-wave electron devices and for their modeling. The proposed measurement technique will be presented describing its hardware and software implementations and showing different experimental examples. In Chapter IV a new modeling approach will be presented accounting for the nonlinear description of low-frequency dispersive effects (due to thermal phenomena and traps) affecting electron devices. The model will be identified by exploiting measurements carried out with the measurement system described in chapter III. In the last Chapter a new, low-cost technique will be described for drawing “load-pull contours” which are a powerful tool for power amplifier design. By exploiting the lowfrequency measurement system described in chapter III and conventional descriptions of device parasitic elements and nonlinear reactive effects, the proposed approach allows to obtain the same information gathered by expensive highfrequency load pull measurement systems

Nonlinear-embedding design methodology oriented to LDMOS power amplifiers

In this paper, we apply for the first time the nonlinear embedding technique to the design of power amplifiers (PAs) based on laterally-diffused metal-oxide-semiconductor (LDMOS) field effect transistors. Such a design technique is based on setting the transistor load line at the intrinsic current-generator plane, according to well-known theoretical guidelines. Then, the selected operating condition can be transposed at any design frequency at the extrinsic transistor terminals, by means of a model of the device nonidealities, such as the nonlinear intrinsic capacitances and the linear parasitic effects. A harmonically-tuned high-efficiency class-F and a wideband class-AB PAs operating within the FM broadcasting band 88 ÷ 108 MHz based on a 10-W LDMOS are then designed and realized. To definitely assess the validity of the proposed approach for the LDMOS technology, we compare the measured performance on the fabricated PAs with the expected predictions

Assessing GaN FET Performance Degradation in Power Amplifiers for Pulsed Radar Systems

GaN FETs have achieved superior performance in the design of microwave power circuits. Nevertheless, the amount of dispersion related to this technology poses severe issues for the correct modeling and characterization of these devices. In this letter, the effects of GaN FET dispersion on the design of power amplifiers (PAs) with dynamic power supply, largely adopted in state-of-the-art high-efficiency pulsed radar transmitters, are discussed. In particular, we propose a technique for evaluating GaN device performance degradation in new-generation PAs that represents an effective alternative to pulsed-RF multiharmonic source/load-pull microwave setups

A Non-Quasi-Static FET Model Extraction Procedure Using the Dynamic-Bias Technique

We extend the recently proposed dynamic-bias measurement technique to the identification of non-quasi-static FET models. In particular, we propose to exploit two high-frequency tickles superimposed on the low-frequency large-signal excitation. The tickle frequencies are chosen in order to separately extract the quasi-static and non-quasi-static model parameters. As case study, we extracted and validated the model of an GaAs pHEMT

Dynamic-Bias S-Parameters: A New Measurement Technique for Microwave Transistors

We present the first application of the recently introduced dynamic-bias measurement to the acquisition of the scattering (S-) parameters of microwave transistors under large-signal operating conditions. We demonstrate that by properly acquiring and processing dynamic-bias measurements, one can derive the S-parameters of a nonlinear device-under test across a time-varying large-signal operating point (LSOP). Interestingly, these time-varying S-parameters can be used similar to the conventional S-parameters for characterization and modeling purposes. As compared with similar existing approaches, like those based on the pulsed S-parameter measurements, with the proposed technique, one can obtain, as a result of one measurement, the frequency-dependent S-parameters at each instantaneous point touched by the LSOP. We report experimental dynamic-bias S-parameters of a 0.15-μm GaAs pHEMT and a 0.25-μm GaN HEMT

Nonlinear Modelling of GaN Transistors: Behavioural and Analytical Approaches

Gallium Nitride (GaN) transistors are increasingly attracting the attention of the microwave research community due to their performance in terms of power density and frequency capabilities. As a matter of fact, GaN is considered as the leading technology for future telecom and space applications. Nevertheless, nonlinear modelling of GaN transistors is still an open issue that continuously poses new challenges. In this paper, the comparison between two models, based on behavioural and analytical approaches, will be deeply discussed with the aim of pointing out advantages and disadvantages of each modelling technique

A new description of fast charge-trapping effects in GaN FETs

A nonlinear multi-bias model oriented to accurately predict the effects of charge-trapping in Gallium Nitride (GaN) HEMTs is proposed. As a case study, we considered a 0.25-μm 8×75-μm GaN HEMT. The model is identified by using CW low-frequency time-domain data and validated through high-frequency vector nonlinear measurements

A New Dynamic-Bias Measurement Setup for Nonlinear Transistor Model Identification

In this paper, we present a new dynamic-bias measurement setup and its application to the extraction of a nonlinear model for microwave field-effect transistors. The dynamic-bias technique has been recently proposed and relies on the use of low-frequency (LF) and high-frequency (HF) vector-calibrated measurements acquired, for instance, by means of a large-signal network analyzer. In this paper, we propose a new and alternative technique to perform the dynamic-bias measurements, based on relatively low-cost instrumentation commonly available in microwave laboratories. The new acquisition system is composed of a four-channel vector LF receiver (e.g., an oscilloscope) and a one-channel HF scalar receiver (e.g., a spectrum analyzer), which replace the eight-channel vector receiver. Moreover, the proposed architecture greatly simplifies the measurement setup and the calibration procedure. As a case study, a 0.25-μm GaN HEMT is considered. Dynamic-bias measurements, carried out by means of the proposed measurement setup, are used for the identification of a nonlinear model of this device. Finally, the model is fully validated through comparison with time-domain harmonic load–pull measurements carried out at 5 GHz