Leon E. Govaert

Biodegradable Polymers in Bone Tissue Engineering

The use of degradable polymers in medicine largely started around the mid 20th century with their initial use as in vivo resorbing sutures. Thorough knowledge on this topic as been gained since then and the potential applications for these polymers were, and still are, rapidly expanding. After improving the properties of lactic acid-based polymers, these were no longer studied only from a scientific point of view, but also for their use in bone surgery in the 1990s. Unfortunately, after implanting these polymers, different foreign body reactions ranging from the presence of white blood cells to sterile sinuses with resorption of the original tissue were observed. This led to the misconception that degradable polymers would, in all cases, lead to inflammation and/or osteolysis at the implantation site. Nowadays, we have accumulated substantial knowledge on the issue of biocompatibility of biodegradable polymers and are able to tailor these polymers for specific applications and thereby strongly reduce the occurrence of adverse tissue reactions. However, the major issue of biofunctionality, when mechanical adaptation is taken into account, has hitherto been largely unrecognized. A thorough understanding of how to improve the biofunctionality, comprising biomechanical stability, but also visualization and sterilization of the material, together with the avoidance of fibrotic tissue formation and foreign body reactions, may greatly enhance the applicability and safety of degradable polymers in a wide area of tissue engineering applications. This review will address our current understanding of these biofunctionality factors, and will subsequently discuss the pitfalls remaining and potential solutions to solve these problems.

Time-dependent mechanical strength of 70/30 poly(L,DL-lactide): shedding light on the premature failure of degradable spinal cages

Study Design. In vitro studies on the mechanical strength of 70/30 poly(l,dl-lactic acid) (70/30 PLDLLA) cages. Objective. To evaluate the effect of loading rate, humidity, temperature, and continuous static loading on the strength of 70/30 PLDLLA, to elucidate the mechanism of premature failure of degradable spinal cages observed in earlier studies. Summary of Background Data. Degradable 70/30 PLDLLA cages have been designed to withstand mechanical loads in a goat lumbar spine for at least 6 months. Yet mechanical failure was observed after only 3 months in vivo. We hypothesize that this observation can be related to the time-dependent nature of the polymer. Methods. Degradable 70/30 PLDLLA cages were loaded to failure at loading rates between 10−3 and 10−1 mm/s under standard loading conditions (in air at room temperature: ±23°C). The experiments were also done at body temperature (37°C) and under wet conditions. Furthermore, we determined the time-to-failure for 70/30 PLDLLA cages subjected to loads well below their instantaneous mechanical strength. Results. The mechanical strength of 70/30 PLDLLA cages was lower for lower loading rates, higher temperature, and higher humidity. The cages already failed within less than 5 minutes when statically loaded at 75% of their strength, and within 1 day when loaded at about 50% of their strength. Extrapolation predicts cage failure at 3 months when loaded at 25% of their strength. Conclusion. Premature failure of 70/30 PLDLLA cages, as observed in vivo in earlier studies, is owing to mechanical loading and the time-dependent mechanical properties of the material. The standards for mechanical testing of implants made of strongly time-dependent materials like polylactide should be reconsidered.

Nonlinear Viscoelastic Behaviour of Thermorheologically Complex Materials

In previous work, a phenomenologically constitutive model was presented describing the finite, nonlinear, viscoelastic behaviour of polymer glasses up to yield. This model was, however, restricted to thermorheologically simple materials. In this paper this restriction is removed, thus extending the model to materials behaving thermorheologically complex. Based on linear viscoelasticity, this extension can be achieved by either adding a process in parallel, or in series. Experiments in the plastic range suggested an approach based on stress additivity, i.e. two processes in parallel. The resulting model consists of two linear relaxation time spectra in parallel, each having its own characteristic stress and temperature dependence. Whereas in the case of a single process the influence of stress and temperature is comparable, this is no longer valid for two processes since the molecular processes depend on a part of the applied stress rather than on the total applied stress itself. Numerical predictions using the extended representation showed that the model correctly describes the yield behaviour observed in practice. Simulations of creep experiments at various stress levels and temperatures showed a good qualitative agreement with experimental observations in literature.

Time-dependent failure of amorphous polylactides in static loading conditions

Polylactides are commonly praised for their excellent mechanical properties (e.g. a high modulus and yield strength). In combination with their bioresorbability and biocompatibility, they are considered prime candidates for application in load-bearing biomedical implants. Unfortunately, however, their long-term performance under static load is far from impressive. In a previous in vivo study on degradable polylactide spinal cages in a goat model it was observed that, although short-term mechanical and real-time degradation experiments predicted otherwise, the implants failed prematurely under the specified loads. In this study we demonstrate that this premature failure is attributed to the time-dependent character of the material used. The phenomenon is common to all polymers, and finds its origin in stress-activated segmental molecular mobility leading to a steady rate of plastic flow. The stress-dependence of this flow-rate is well captured by Eyring’s theory of absolute rates, as demonstrated on three amorphous polylactides of different stereoregularity. We show that the kinetics of the three materials are comparable and can be well described using the proposed modeling framework. The main conclusion is that knowledge of the instantaneous strength of a polymeric material is insufficient to predict its long-term performance.

Strain rate and temperature effects on energy absorption of polyethylene fibres and composites

The influence of strain rate and temperature on modulus, strength and work of fracture of high-performance polyethylene (HP-PE) fibres and composites is investigated. Results showed that an increase in strain rate and/or decrease in temperature leads to a reduction in work of fracture. At high strain rates or low temperatures a constant minimum level for the fracture energy is reached. The energy absorption capacity of HP-PE/epoxy laminates is investigated using full penetrating dart-impact tests and showed similar trends than observed for HP-PE fibres. The impact energy of these laminates could be described quantitatively in terms of fibre, matrix and delamination effects by combining the tensile test results on fibres and unidirectional composites with fracture toughness experiments on laminates.

Tensile strength and work of fracture of oriented polyethylene fibre

In the present investigation the influence of strain rate and temperature on modulus, strength and work of fracture of high-performance polyethylene (HPPE) fibre is studied. At low temperature and/or high strain rates the fibre shows brittle failure, displaying a pronounced strain rate and temperature dependence of the tensile strength. At high temperatures and/or low strain rates a transition from a brittle to a ductile failure mode could be observed. This brittle-to-ductile transition is analysed in terms of competitive failure modes, which leads to a simple model that can be used to predict the strain-rate dependence of the transition temperature. In the brittle failure mode it is observed that an increase in strain rate and/or decrease in temperature leads to a reduction in work of fracture. This reduction could successfully be predicted by combining a previously published mathematical model for the deformation of HPPE fibres with the observed strain-rate dependence of the tensile strength. From the numerical simulations it can be deduced that a constant minimum level for the fracture energy will be reached at high strain rates or low temperatures.

A micromechanical approach to time-dependent failure in off-axis loaded polymer composites

The time-dependent failure behaviour of off-axis loaded composites is investigated, assuming that fracture is matrix dominated. Since the stress and strain state of the matrix in composite structures is complex, the yield and fracture behaviour of a neat epoxy system is investigated under various multi-axial loading conditions. A good description of the multi-axial yielding behaviour of the matrix material is obtained with the three-dimensional (3D) pressure-modified Eyring equation. The parameters of this 3D yield expression are implemented into a constitutive model, which has been shown to describe the deformation behaviour of polymers under complex loading correctly. By means of a micromechanical approach, the matrix dominated off-axis strength of a unidirectional composite material was investigated. Numerical simulations show that a failure criterion based on maximum strain provides a good description for the rate dependent off-axis strength of unidirectional glass/epoxy composites. Furthermore, such a strain criterion is also able to describe the durability (creep) of off-axis loaded unidirectional composites.

Influence of applied stress and temperature on the deformation behaviour of high-strength poly(vinyl alcohol) fibres

The deformation behaviour of poly(vinyl alcohol) (PVA) fibres is studied using dynamic mechanical analysis, stress relaxation and uniaxial tensile experiments. Results indicate that the time and temperature dependences of these fibres decrease drastically under the influence of a statically applied stress or strain. These results are discussed in an attempt to relate the deformation behaviour of high-strength PVA fibres to events occurring on a molecular scale.

Time-dependent failure of amorphous poly-d,l-lactide: Influence of molecular weight

The specific time-dependent deformation response of amorphous poly(lactic acid) (PLA) is known to lead to rapid failure of these materials in load-bearing situations. We have investigated this phenomenon in uniaxial compression on P(L)DLLA samples with various molecular weights. The experiments revealed a strong dependence of the yield stress on the applied strain rate. Lower molecular weights showed identical deformation kinetics as higher molecular weights, albeit at lower stress values. This dependence on molecular weight was incorporated into an Eyring-equation by introducing mobility through a virtual temperature that is shifted by the deviation of the T(g) from T(g,∞). Stress-dependent lifetime of polymer constructs was described by the use of this modified Eyring-equation, combined with a critical plastic strain. This model proves useful in predicting the molecular weight dependence of the time to failure, although it slightly overestimates life time at low stress levels for a material with very low molecular weight. The versatility of the model is demonstrated on e-beam sterilized PLDLLA, where the resulting reduction in molecular weight induces a substantial decrease in lifetime. A single T(g) measurement provides sufficient information to predict the decrease in lifetime.

Radiopaque polymeric spinal cages: a prototype study

Back pain, originating from degeneration of intervertebral discs, is often alleviated by the insertion of one or more interbody fusion cages. The function of the cage is to restore the height between two adjacent vertebrae and to mediate osseous fusion. Most commercial cages consist of titanium or a titanium alloy, while polymeric cages, mostly consisting of polyether-etherketone (PEEK), are also in use. Titanium is known for its excellent biocompatibility. Titanium cages can be located easily with imaging techniques based on X-ray absorption (e.g. CT scans). However, they introduce artefacts in magnetic resonance (MR images). PEEK cages, on the other hand, do not show up in CT images. For this reason, small metallic markers are usually incorporated. The markers reveal the position of the cage, albeit indirectly. PEEK cages are clearly and integrally seen on MR images, as they are essential free of water. There are no artefacts or disturbances; this feature, as well as its strength, makes PEEK particularly attractive for the construction of cages. Here, we introduce new all-polymeric cages on the basis of an iodine-containing methacrylic copolymer (I-copolymer). This material has been prepared from methylmethacrylate and 2-[4-iodobenzoyl]-oxo-ethylmethacrylate. Copolymerisation of both monomers results in a high molecular weight material. Cytocompatibility experiments reveal that the material contains no toxic leachables and that cells can well adhere to and proliferate on the I-copolymer. Compression experiments at physiologically relevant strains disclose mechanical characteristics comparable to PEEK. The advantage of cages prepared from this I-copolymer over commercially available cages is that the present cage contains no metallic components, implying that it is compatible with MR imaging, and the presence of the iodine atoms ensures X-ray visibility.