Biomechanics and tissue engineering

Development of artificial scaffold for musculo-skeletal applications, especially in load-bearing situations, requires the consideration of biomechanical aspects for its integrity and its function. However, the biomechanical loading could also be used to favour tissue formation through mechano-transduction phenomena. Design of scaffold could take advantages of this intrinsic mechanical loadin

Efficient decellularization of equine tendon with preserved biomechanical properties and cytocompatibility for human tendon surgery indications.

Chronic and acute tendon injuries are frequent afflictions, for which treatment is often long and unsatisfactory. When facing extended injuries, matrices and scaffolds with sufficient biomechanical properties are required for surgical repair and could additionally serve as supports for cellular therapies to improve healing. In this study, protocols of either commonly used detergents only (SDS 1%, Triton 1%, TBP 1%, and Tween-20 1%) or a combination of freeze/thaw (F/T) cycles with decellularization agents (NaCl 1M, ddH <sub>2</sub> O) were evaluated for the decellularization of horse equine superficial digital flexor tendon (SDFT) for hand flexor or extensor tendon reconstruction. Decellularization efficiency was assessed microscopically by histological staining (HE, DAPI) and DNA quantification. Macroscopical structure and biomechanical integrity of the tendon matrices were further assessed by gross observation, histological staining (SR), and mechanical testing (ultimate strain and stress, Young's modulus, energy to failure) for select protocols. Decellularization with hypertonic NaCl 1M in association with F/T cycles produced the most robust tendon matrices, which were nontoxic after 10 days for subsequent recellularization with human fetal progenitor tendon cells (hFPTs). This standardized protocol uses a less aggressive decellularization agent than current practice, which allows subsequent reseeding with allogenic cells, therefore making them very suitable and bioengineered tendon matrices for human tendon reconstruction in the clinic

METRO - The role and future perspectives of Cohesion Policy in the planning of Metropolitan Areas and Cities. Annex II: The role of Metropolitan areas within the EU cohesion policy

This Annex to the final Report presents and discusses in a comparative manner the evidence collected in the nine case studies that have been explored in the framework of the ESPON Targeted Analysis METRO – The role and future perspectives of cohesion policy in the planning of Metropolitan Areas and Cities (Annexes III to XI). More in detail, the document synthesizes and compares the information collected by the various research teams through the application of the project’s analytical protocol and as a consequence of their continuous interaction with the respective stakeholders. The report is organised following the three main policy questions that have been driving the analysis: PQ1 | What role do metropolitan areas and cities play in the development, management and implementation of the European Union (EU) cohesion policy? PQ2 | What is the added value of the EU cohesion policy in the planning and implementation of metropolitan policies? PQ3 | What role does the EU cohesion policy play in consolidating metropolitan governance and cooperation? These questions are answered through the comparative analysis and assessment of the territorial and institutional contexts in which the nine stakeholders involved in the projects are active: Metropolitan City of Turin (CMTo), Barcelona Metropolitan Area (AMB), Lisbon Metropolitan Area (LMA), Brno Metropolitan Area (BMA), Metropolitan Area of Gdańsk-Gdynia-Sopot (MAG), Metropolitan City of Florence (CMFi), Métropole de Lyon (MdL), Brussels-Capital Region (BCR), Riga Metropolitan Area (RMA)

Modeling of failure mode in knee ligaments depending on the strain rate

BACKGROUND: The failure mechanism of the knee ligament (bone-ligament-bone complex) at different strain rates is an important subject in the biomechanics of the knee. This study reviews and summarizes the literature describing ligament injury as a function of stain rate, which has been published during the last 30 years. METHODS: Three modes of injury are presented as a function of strain rate, and they are used to analyze the published cases. The number of avulsions is larger than that of ligament tearing in mode I. There is no significant difference between the number of avulsions and ligament tearing in mode II. Ligament tearing happens more frequently than avulsion in mode III. RESULTS: When the strain rate increases, the order of mode is mode I, II, III, I, and II. Analytical models of ligament behavior as a function of strain rate are also presented and used to provide an integrated framework for describing all of the failure regimes. In addition, this study showed the failure mechanisms with different specimens, ages, and strain rates. CONCLUSION: There have been several a numbers of studies of ligament failure under various conditions including widely varying strain rates. One issue in these studies is whether ligament failure occurs mid-ligament or at the bone attachment point, with assertions that this is a function of the strain rate. However, over the range of strain rates and other conditions reported, there has appeared to be discrepancies in the conclusions on the effect of strain rate. The analysis and model presented here provides a unifying assessment of the previous disparities, emphasizing the differential effect of strain rate on the relative strengths of the ligament and the attachment

Tailoring swelling to control softening mechanisms during cyclic loading of PEG/cellulose hydrogel composites

One of the novel approaches for discogenic lower back pain treatment is to permanently replace the core of the intervertebral disc, so-called Nucleus Pulposus, through minimally invasive surgery. Recently, we have proposed Poly(Ethylene Glycol) Dimethacrylate (PEGDM) hydrogel reinforced with Nano-Fibrillated Cellulose (NFC) fibers as an appropriate replacement material. In addition to the tuneable properties, that mimic those of the native tissue, the surgeon can directly inject it into the degenerated disc and cure it in situ via UV-light irradiation. However, in view of clinical applications, the reliability of the proposed material has to be tested under long-term fatigue loading. To that end, the present study focused on the characterization of the fatigue behavior of the composite hydrogel and investigated the governing physical phenomena behind it. The results show that composite PEGDM-NFC hydrogel withstands the 10 million compression cycles at physiological condition. However, its modulus decreases by almost 10% in the first cycle and then remains constant, while cyclic loading does not affect the neat PEGDM hydrogel. The observed softening behavior has similar characteristics of the Mullins effect. It is shown that the reduction of modulus is due to the gradual change of NFC network, which is highly stretched in the swollen state. Moreover, the swelling degree of the matrix is correlated to the extent of softening during cyclic loading. Consequently, softening can be minimized by lowering the swelling of the composite hydrogel

Mechanical interaction between cells and fluid for bone tissue engineering scaffold: modulation of the interfacial shear stress

An analytical model of the fluid/cell mechanical interaction was developed. The interfacial shear stress, due to the coupling between the fluid and the cell deformation, was characterized by a new dimensionless number . For above a critical value, the fluid/cell interaction had a damping effect on the interfacial shear stress. Conversely, for below this critical value, interfacial shear stress was amplified. As illustration, the role of the dynamic fluid/cell mechanical coupling was studied in a specific biological situation involving cells seeded in a bone scaffold. For the particular bone scaffold chosen, the dimensionless number Nfs was higher than the critical value. In this case, the dynamic shear stress at the fluid/cell interface is damped for increasing excitation frequency. Interestingly, this damping effect is correlated to the pore diameter of the scaffold, furnishing thus target values in the design of the scaffold. Correspondingly, an efficient cell stimulation might be achieved with a scaffold of pore size larger than 300 μm as no dynamic damping effect is likely to take place. The analytical model proposed in this study, while being a simplification of a fluid/cell mechanical interaction, brings complementary insights to numerical studies by analyzing the effect of different physical parameters

Curing Kinetics and Mechanical Properties of a Composite Hydrogel for the Replacement of the Nucleus Pulposus

A polymer material system has been developed to propose an injectable, UV and in situ curable hydrogel with properties similar to the native nucleus pulposus of intervertebral disc. Neat hydrogels based on Tween® 20 trimethacrylates (T3) and N-vinyl-2-pyrrolidone (NVP) and composite hydrogels of same composition reinforced by nano-fibrillated cellulose were synthesized with different T3 concentrations and their curing kinetics was investigated by photorheology using UV light. The T3 concentration has an influence on the time of curing and final shear stiffness of the material. NFC does not alter the time of curing but increases the final mechanical performance of the hydrogels for a same chemical composition. Hydrogel samples, neat and composite, were then tested in unconfined compression at different hydration stages and in confined compression and their elastic modulus was determined. The amount of fluid present in the network is mostly responsible for the mechanical properties and NFC fibres proved to be an efficient reinforcement. The elastic modulus ranged from 0.02 to 8 MPa. Biocompatibility studies showed that cells are confluent at 90% and do not show any morphology change when in contact with the hydrogel. The present hydrogel can therefore be considered for NP replacement