Time-dependent hyper-viscoelastic parameter identification of human articular cartilage and substitute materials.

Numerical simulations are a valuable tool to understand which processes during mechanical stimulations of hydrogels for cartilage replacement influence the behavior of chondrocytes and contribute to the success or failure of these materials as implants. Such simulations critically rely on the correct prediction of the material response through appropriate material models and corresponding parameters. In this study, we identify hyper-viscoelastic material parameters for numerical simulations in COMSOL Multiphysics® v. 5.6 for human articular cartilage and two replacement materials, the commercially available ChondroFillerliquid and oxidized alginate gelatin (ADA-GEL) hydrogels. We incorporate the realistic experimental boundary conditions into an inverse parameter identification scheme based on data from multiple loading modes simultaneously, including cyclic compression-tension and stress relaxation experiments. We provide individual parameter sets for the unconditioned and conditioned responses and discuss how viscoelastic effects are related to the materials' microstructure. ADA-GEL and ChondroFillerliquid exhibit faster stress relaxation than cartilage with lower relaxation time constants, while cartilage has the largest viscoelastic stress contribution. The elastic response predominates in ADA-GEL and ChondroFillerliquid, while the viscoelastic response predominates in cartilage. These results will help to simulate mechanical stimulations, support the development of suitable materials with distinct mechanical properties in the future and provide parameters and insight into the time-dependent material behavior of human articular cartilage.

Hyperelastic parameter identification of human articular cartilage and substitute materials.

Numerical simulations are a valuable tool in the field of tissue engineering for cartilage repair and can help to understand which mechanical properties affect the behavior of chondrocytes and contribute to the success or failure of surrogate materials as implants. However, special attention needs to be paid when identifying corresponding material parameters in order to provide reliable numerical predictions of the material's response. In this study, we identify hyperelastic material parameters for numerical simulations in COMSOL Multiphysics® v. 5.6 for human articular cartilage and two surrogate materials, commercially available ChondroFillerliquid, and oxidized alginate-gelatin (ADA-GEL) hydrogels. We consider several hyperelastic isotropic material models and provide separate parameter sets for the unconditioned and the conditioned material response, respectively, based on previously generated experimental data including both compression and tension experiments. We compare a direct parameter identification approach assuming homogeneous deformation throughout the specimen and an inverse approach, where the experiments are simulated using a finite element model with realistic boundary conditions in COMSOL Multiphysics® v. 5.6. We demonstrate that it is important to consider both compression and tension data simultaneously and to use the inverse approach to obtain reliable parameters. The one-term Ogden model best represents the unconditioned response of cartilage, while the conditioned response of cartilage and ADA-GEL is equally well represented by the two-term Ogden and five-term Mooney-Rivlin models. The five-term Mooney-Rivlin model is also most suitable to model the unconditioned response of ADA-GEL. For ChondroFillerliquid, we suggest using the five-term Mooney-Rivlin or two-term Ogden model for the unconditioned and the two-term Ogden model for the conditioned material response. These results will help to choose appropriate material models and parameters for simulations of whole joints or to advance mechanical-stimulation assisted cartilage tissue engineering in the future.

Mechanical properties of cell- and microgel bead-laden oxidized alginate-gelatin hydrogels.

3D-printing technologies, such as biofabrication, capitalize on the homogeneous distribution and growth of cells inside biomaterial hydrogels, ultimately aiming to allow for cell differentiation, matrix remodeling, and functional tissue analogues. However, commonly, only the mechanical properties of the bioinks or matrix materials are assessed, while the detailed influence of cells on the resulting mechanical properties of hydrogels remains insufficiently understood. Here, we investigate the properties of hydrogels containing cells and spherical PAAm microgel beads through multi-modal complex mechanical analyses in the small- and large-strain regimes. We evaluate the individual contributions of different filler concentrations and a non-fibrous oxidized alginate-gelatin hydrogel matrix on the overall mechanical behavior in compression, tension, and shear. Through material modeling, we quantify parameters that describe the highly nonlinear mechanical response of soft composite materials. Our results show that the stiffness significantly drops for cell- and bead concentrations exceeding four million per milliliter hydrogel. In addition, hydrogels with high cell concentrations (≥6 mio ml-1) show more pronounced material nonlinearity for larger strains and faster stress relaxation. Our findings highlight cell concentration as a crucial parameter influencing the final hydrogel mechanics, with implications for microgel bead drug carrier-laden hydrogels, biofabrication, and tissue engineering.

Complex mechanical behavior of human articular cartilage and hydrogels for cartilage repair.

The mechanical behavior of cartilage tissue plays a crucial role in physiological mechanotransduction processes of chondrocytes and pathological changes like osteoarthritis. Therefore, intensive research activities focus on the identification of implant substitute materials that mechanically mimic the cartilage extracellular matrix. This, however, requires a thorough understanding of the complex mechanical behavior of both native cartilage and potential substitute materials to treat cartilage lesions. Here, we perform complex multi-modal mechanical analyses of human articular cartilage and two surrogate materials, commercially available ChondroFillerliquid, and oxidized alginate-gelatin (ADA-GEL) hydrogels. We show that all materials exhibit nonlinearity and compression-tension asymmetry. However, while hyaline cartilage yields higher stresses in tension than in compression, ChondroFillerliquid and ADA-GEL exhibit the opposite trend. These characteristics can be attributed to the materials' underlying microstructure: Both cartilage and ChondroFillerliquid contain fibrillar components, but the latter constitutes a bi-phasic structure, where the 60% nonfibrillar hydrogel proportion dominates the mechanical response. Of all materials, ChondroFillerliquid shows the most pronounced viscous effects. The present study provides important insights into the microstructure-property relationship of cartilage substitute materials, with vital implications for mechanically-driven material design in cartilage engineering. In addition, we provide a data set to create mechanical simulation models in the future.

Alginate-based hydrogels show the same complex mechanical behavior as brain tissue.

Mimicking the mechanical properties of native human tissues is one key route in tissue engineering. However, the successful creation of functional tissue equivalents requires the comprehensive understanding of the complex and nonlinear mechanical properties of both native tissues and biomaterials. Here, we demonstrate that it is possible to replicate the complex mechanical behavior of soft tissues, exemplary shown for porcine brain tissue, under multiple loading conditions, compression, tension, and torsional shear, through simple blends of alginate and gelatin hydrogels. Alginate exhibits a pronounced compression-tension asymmetry and a nonlinear behavior, while gelatin shows an almost linear response. Blended together, alginate-gelatin (ALG-GEL) hydrogels can resemble the characteristic nonlinear, conditioning, and compression-tension-asymmetric behavior of brain tissue. We demonstrate that hydrogel concentration and incubation effectively tune the stiffness and loading-mode-specific stress relaxation behavior. The stiffness increases with increasing hydrogel concentration and decreases with increasing incubation time. In addition, we observe slower stress relaxation after long incubation times. Our systematic approach highlights the importance of single component, multi-modal mechanical analysis of hydrogels to understand the distinct structure-mechanics relation of each hydrogel component to eventually mimic the response of native tissues. The presented dataset will allow for the structurally derived compositional design of hydrogels for a broad variety of tissue engineering applications.

Biofabrication of vessel-like structures with alginate di-aldehyde-gelatin (ADA-GEL) bioink.

One of the key challenges in the field of blood vessel engineering is the in vitro production of small and large diameter vessels. Considering that a combination of alginate di-aldehyde and gelatin (ADA-GEL) has been successfully applied for different biofabrication approaches, the aim of this study was to exploit ADA-GEL for the fabrication of vessel structures with diameters up to 4 mm. To explore plotting possibilities and to study the swelling behaviour, a library of vessel-like constructs with different diameters made from 2, 3 and 4% (w/v) alginate was created by using various hand-crafted double-needle extrusion systems. Vessel diameters were varied through changes of the double-needle core and outer diameters. A straightforward model for the production of vessel of different diameters from a variety of double-needle systems was established and vessel-constructs with diameters of up to 3.7 mm could be created. It was successfully demonstrated that an artificial vessel, consisting of an outer layer of 7.5% ADA50-GEL50 and an inner core of 3% gelatin, can support the proliferation and migration of an immobilized co-culture containing fibroblast (NHDF) and endothelial (HUVEC) cells. The openness and tightness of the hollow ADA-GEL structures were further confirmed by a dye injection test. Nanoindentation was performed to determine the Young's modulus of the used materials. Cell vitality was proved after 1, 2 and 3 weeks of incubation. The results showed a nearly twofold increase of viable cells per week. Fluorescent images confirmed cell migration during the whole incubation time.

Formation of carbon monoxide in air compressors.

Oil-lubricated compressors are said to contaminate the air they compress with carbon monixde from pyrolyzed and oxidized lubricants. Experiments were performed in an instrumented compressor to determine if synthetic oils as lubricants would results in less contamination. The results suggest that for all oils the contamination is actually not great. Published results from low-temperature oxidation of hydrocarbons support this estimate.