Three-dimensional (3D) bioprinting is on the cusp of permitting the direct fabrication of artificial living tissue. Multicellular building blocks (bioinks) are dispensed layer by layer and scaled for ...the target construct. However, only a few materials are able to fulfill the considerable requirements for suitable bioink formulation, a critical component of efficient 3D bioprinting. Alginate, a naturally occurring polysaccharide, is clearly the most commonly employed material in current bioinks. Here, we discuss the benefits and disadvantages of the use of alginate in 3D bioprinting by summarizing the most recent studies that used alginate for printing vascular tissue, bone and cartilage. In addition, other breakthroughs in the use of alginate in bioprinting are discussed, including strategies to improve its structural and degradation characteristics. In this review, we organize the available literature in order to inspire and accelerate novel alginate-based bioink formulations with enhanced properties for future applications in basic research, drug screening and regenerative medicine.
•Nanoindentation of hydrated materials and tissues is a growing field.•Test techniques and data analysis both differ from traditional nanoindentation.•Numerous hydrated materials have been tested and ...their properties reported.
Nanoindentation techniques have recently been adapted for the study of hydrated materials, including biological materials and hydrogels. There are unique challenges associated with handling and testing hydrated samples. For hydrated materials, a poroelastic or poroviscoelastic analysis, which explicitly treats the fluid flow through the porous material, is used to extract material properties from experimental data. Some key results from recent works using nanoindentation to evaluate hydrated materials are reviewed in the context of these challenges. Finally, as these studies represent relatively recent developments in the nanoindentation field, an outlook for the future is presented, in which it is clear that a consensus is emerging for quantitative evaluation of hydrated materials via a modified nanoindentation approach.
A severe shortage of good quality donor cornea is now an international crisis in public health. Alternatives for donor tissue need to be urgently developed to meet the increasing demand for corneal ...transplantation. Hydrogels have been widely used as scaffolds for corneal tissue regeneration due to their large water content, similar to that of native tissue. However, these hydrogel scaffolds lack the fibrous structure that functions as a load-bearing component in the native tissue, resulting in poor mechanical performance. This work shows that mechanical properties of compliant hydrogels can be substantially enhanced with electrospun nanofiber reinforcement. Electrospun gelatin nanofibers were infiltrated with alginate hydrogels, yielding transparent fiber-reinforced hydrogels. Without prior crosslinking, electrospun gelatin nanofibers improved the tensile elastic modulus of the hydrogels from 78±19kPa to 450±100kPa. Stiffer hydrogels, with elastic modulus of 820±210kPa, were obtained by crosslinking the gelatin fibers with carbodiimide hydrochloride in ethanol before the infiltration process, but at the expense of transparency. The developed fiber-reinforced hydrogels show great promise as mechanically robust scaffolds for corneal tissue engineering applications.
Medical conditions that primarily or disproportionately affect women have historically been poorly studied. In contrast to the musculoskeletal and cardiovascular systems, there is no lengthy record ...of biomaterials research addressing women’s health needs. In this article, the historical reasons for this discrepancy are examined. The anatomy of both the nonpregnant and pregnant reproductive tissues is reviewed, including the ovaries, uterus, and (fetal) placenta. Examples of biomaterials-related women’s health research are described, including tissue engineering, organoids, and microphysiological systems. The future of the field is considered with dual focuses. First, there is a significant need for novel approaches to advance women’s health through materials and biomaterials, particularly in complex biomimetic hydrogels. Second, there is an exciting opportunity to enlarge the community of biomaterials scientists and engineers working in women’s health to encourage more contributions to its rapidly emerging product development pipeline.
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The remarkable mechanical performance of biological materials is based on intricate structure–function relationships. Nanoindentation has become the primary tool for characterising ...biological materials, as it allows to relate structural changes to variations in mechanical properties on small scales. However, the respective theoretical background and associated interpretation of the parameters measured via indentation derives largely from research on ‘traditional’ engineering materials such as metals or ceramics. Here, we discuss the functional relevance of indentation hardness in biological materials by presenting a meta-analysis of its relationship with indentation modulus. Across seven orders of magnitude, indentation hardness was directly proportional to indentation modulus. Using a lumped parameter model to deconvolute indentation hardness into components arising from reversible and irreversible deformation, we establish criteria which allow to interpret differences in indentation hardness across or within biological materials. The ratio between hardness and modulus arises as a key parameter, which is related to the ratio between irreversible and reversible deformation during indentation, the material’s yield strength, and the resistance to irreversible deformation, a material property which represents the energy required to create a unit volume of purely irreversible deformation. Indentation hardness generally increases upon material dehydration, however to a larger extent than expected from accompanying changes in indentation modulus, indicating that water acts as a ‘plasticiser’. A detailed discussion of the role of indentation hardness, modulus and toughness in damage control during sharp or blunt indentation yields comprehensive guidelines for a performance-based ranking of biological materials, and suggests that quasi-plastic deformation is a frequent yet poorly understood damage mode, highlighting an important area of future research.
Instrumented indentation is a widespread tool for characterising the mechanical properties of biological materials. Here, we show that the ratio between indentation hardness and modulus is approximately constant in biological materials. A simple elastic-plastic series deformation model is employed to rationalise part of this correlation, and criteria for a meaningful comparison of indentation hardness across biological materials are proposed. The ratio between indentation hardness and modulus emerges as the key parameter characterising the relative amount of irreversible deformation during indentation. Despite their comparatively high hardness to modulus ratio, biological materials are susceptible to quasiplastic deformation, due to their high toughness: quasi-plastic deformation is hence hypothesised to be a frequent yet poorly understood phenomenon, highlighting an important area of future research.
Eggshell is a target material for biomimicry: a biogenic material that is synthesized quickly under near-ambient conditions, and which has intriguing mechanical properties. Biomineralization in such ...natural systems utilizes organic molecules, both providing a surface to facilitate heterogeneous mineral nucleation and captured within the deposited mineral. Here, we examined the relationship between calcitic mineralized shell and the organic eggshell membrane. Elastic modulus and hardness of shell, as measured by nanoindentation in cross-section, exhibited approximately constant property values across three egg-laying species. Macro-scale fracture experiments demonstrated the structural importance of the fibrous eggshell membrane, with weak influence on egg fracture force but substantial effect on work of fracture. This effect was different for complete removal of the membrane versus chemical drying. The membrane thus represents a distinct target for improving egg mechanical properties independent of mineral quality.
Soft biological tissues demonstrate strong time-dependent mechanical behavior, arising from their intrinsic viscoelasticity and fluid flow-induced poroelasticity. It is increasingly recognized that ...time-dependent mechanical properties of soft tissues influence their physiological functions and are linked to several pathological processes. Nevertheless, soft tissue time-dependent characteristics, especially their micromechanical variation with tissue composition and location, remain poorly understood. Nanoindentation is a well-established technique to measure local elastic properties but has not been fully explored to determine micro-scale time-dependent properties of soft tissues. Here, a nanoindentation-based experimental strategy is implemented to characterize the micro-scale poroelastic and viscoelastic behavior of mouse heart, kidney, and liver tissues. It is demonstrated that heart tissue exhibits substantial mechanical heterogeneity where the elastic modulus varies spatially from 1 to 30 kPa. In contrast, both kidney and liver tissues show relatively homogeneous response with elastic modulus 0.5–3 kPa. All three tissues demonstrate marked load relaxation under constant indentation, where the relaxation behavior is observed to be largely dominated by tissue viscoelasticity. Intrinsic permeability varies among different tissues, where heart tissue is found to be less permeable compared to kidney and liver tissues. Overall, the results presented herein provide key insights into the time-dependent micromechanical behavior of different tissues and can therefore contribute to studies of tissue pathology and tissue engineering applications.
Highlights • Nanofibers improve both mechanical properties and biofunctionality of hydrogels. • An amplification metric can be defined to quantify the fiber enhancement effect.
Research into the human placenta’s complex functioning is complicated by a lack of suitable physiological
in vivo
models. Two complementary approaches have emerged recently to address these gaps in ...understanding, computational
in silico
techniques, including multi-scale modeling of placental blood flow and oxygen transport, and cellular
in vitro
approaches, including organoids, tissue engineering, and organ-on-a-chip models. Following a brief introduction to the placenta’s structure and function and its influence on the substantial clinical problem of preterm birth, these different bioengineering approaches are reviewed. The cellular techniques allow for investigation of early first-trimester implantation and placental development, including critical biological processes such as trophoblast invasion and trophoblast fusion, that are otherwise very difficult to study. Similarly, computational models of the placenta and the pregnant pelvis at later-term gestation allow for investigations relevant to complications that occur when the placenta has fully developed. To fully understand clinical conditions associated with the placenta, including those with roots in early processes but that only manifest clinically at full-term, a holistic approach to the study of this fascinating, temporary but critical organ is required.
The fetal membrane surrounds the fetus during pregnancy and is a thin tissue composed of two layers, the chorion and the amnion. While rupture of this membrane normally occurs at term, preterm ...rupture can result in increased risk of fetal mortality and morbidity, as well as danger of infection in the mother. Although structural changes have been observed in the membrane in such cases, the mechanical behaviour of the human fetal membrane in vivo remains poorly understood and is challenging to investigate experimentally. Therefore, the objective of this study was to develop simplified finite element models to investigate the mechanical behaviour and rupture of the fetal membrane, particularly its constituent layers, under various physiological conditions. It was found that modelling the chorion and amnion as a single layer predicts remarkably different behaviour compared with a more anatomically-accurate bilayer, significantly underestimating stress in the amnion and under-predicting the risk of membrane rupture. Additionally, reductions in chorion-amnion interface lubrication and chorion thickness (reported in cases of preterm rupture) both resulted in increased membrane stress. Interestingly, the inclusion of a weak zone in the fetal membrane that has been observed to develop overlying the cervix would likely cause it to fail at term, during labour. Finally, these findings support the theory that the amnion is the dominant structural component of the fetal membrane and is required to maintain its integrity. The results provide a novel insight into the mechanical effect of structural changes in the chorion and amnion, in cases of both normal and preterm rupture.
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