"Nonswellable" Hydrogel Without Mechanical Hysteresis Kamata, Hiroyuki; Akagi, Yuki; Kayasuga-Kariya, Yuko ...
Science (American Association for the Advancement of Science),
02/2014, Letnik:
343, Številka:
6173
Journal Article
Recenzirano
Hydrogels are three-dimensional polymer networks that contain a large amount of water inside. Certain hydrogels can be injected in solution and transformed into the gel state with the required shape. ...Despite their potential biomedical applications, the use of hydrogels has been severely limited because all the conventional hydrogels inevitably "swell" under physiological conditions, which drastically degrades their mechanical properties. We report the synthesis of injectable "nonswellable" hydrogels from hydrophilic and thermoresponsive polymers, in which two independently occurring effects (swelling and shrinking) oppose each other. The hydrogels can endure a compressive stress up to 60 megapascals and can be stretched more than sevenfold without hysteresis. Our results demonstrate that the suppression of swelling helps retain the mechanical properties of hydrogels under physiological conditions.
Exposure of articular cartilage to excessive mechanical loading is deeply involved in the pathogenesis of osteoarthritis. Here, we identify gremlin-1 as a mechanical loading-inducible factor in ...chondrocytes, detected at high levels in middle and deep layers of cartilage after cyclic strain or hydrostatic pressure loading. Gremlin-1 activates nuclear factor-κB signalling, leading to subsequent induction of catabolic enzymes. In mice intra-articular administration of gremlin-1 antibody or chondrocyte-specific deletion of Gremlin-1 decelerates osteoarthritis development, while intra-articular administration of recombinant gremlin-1 exacerbates this process. Furthermore, ras-related C3 botulinum toxin substrate 1 activation induced by mechanical loading enhances reactive oxygen species (ROS) production. Amongst ROS-activating transcription factors, RelA/p65 induces Gremlin-1 transcription, which antagonizes induction of anabolic genes such as Sox9, Col2a1, and Acan by bone morphogenetic proteins. Thus, gremlin-1 plays essential roles in cartilage degeneration by excessive mechanical loading.
Hydrogels are promising materials for biomedical applications, where timely degradation is often preferred. In the conventional design, however, the cleavage of polymer networks essentially causes ...considerable morphological changes (i.e., degradation‐induced swelling), triggering various medical complications. Herein, we report a rational strategy to suppress the degradation‐induced swelling based on the synthetic control of the polymer–solvent interaction parameter (χ) of constituent polymer networks. The resultant hydrogels with an optimal χ parameter (χ37 °C≈0.53; non‐osmostic hydrogels) displayed the capability to retain their original shape and degrade without generating significant swelling pressure under physiological conditions (Π37 °C<1 kPa). This concept of the safely degradable non‐osmotic hydrogel is theoretically universal, and can be exploited for other types of synthetic hydrogels in various settings.
Degradation without swelling: Hydrogels with an optimal polymer–solvent interaction parameter were synthesized to achieve non‐osmotic conditions. The resultant non‐osmotic hydrogels displayed the capability to retain their original shape (see picture) and degrade without accompanying significant morphological changes under physiological conditions.
Pluripotent stem cells (PSCs) are attractive regenerative therapy tools for skeletal tissues. However, a deep understanding of skeletal development is required in order to model this development with ...PSCs, and for the application of PSCs in clinical settings. Skeletal tissues originate from three types of cell populations: the paraxial mesoderm, lateral plate mesoderm, and neural crest. The paraxial mesoderm gives rise to the sclerotome mainly through somitogenesis. In this process, key developmental processes, including initiation of the segmentation clock, formation of the determination front, and the mesenchymal-epithelial transition, are sequentially coordinated. The sclerotome further forms vertebral columns and contributes to various other tissues, such as tendons, vessels (including the dorsal aorta), and even meninges. To understand the molecular mechanisms underlying these developmental processes, extensive studies have been conducted. These studies have demonstrated that a gradient of activities involving multiple signaling pathways specify the embryonic axis and induce cell-type-specific master transcription factors in a spatiotemporal manner. Moreover, applying the knowledge of mesoderm development, researchers have attempted to recapitulate the in vivo development processes in in vitro settings, using mouse and human PSCs. In this review, we summarize the state-of-the-art understanding of mesoderm development and in vitro modeling of mesoderm development using PSCs. We also discuss future perspectives on the use of PSCs to generate skeletal tissues for basic research and clinical applications.
Hydrogels are considered key tools for the design of biomaterials, such as wound dressings, drug reservoirs, and temporary scaffolds for cells. Despite their potential, conventional hydrogels have ...limited applicability under wet physiological conditions because they suffer from the uncontrollable temporal change in shape: swelling takes place immediately after the installation. Swollen hydrogels easily fail under mechanical stress. The morphological change may cause not only the slippage from the installation site but also local nerve compression. The design of hydrogels that can retain their original shape and mechanical properties in an aqueous environment is, therefore, of great importance. On the one hand, the controlled degradation of used hydrogels has to be realized in some biomedical applications. This Progress Report provides a brief overview of the recent progress in the development of hydrogels for biomedical applications. Practical approaches to control the swelling properties of hydrogels are discussed. The designs of hydrogels with controlled degradation properties as well as the theoretical models to predict the degradation behavior are also introduced. Moreover, current challenges and limitation toward biomedical applications are discussed, and future directions are offered.
Hydrogels are considered key components for the design of biomaterials. Conventional hydrogels, however, have limited applicability under wet physiological conditions where they inevitably swell over time. Control over swelling by the introduction of thermoresponsive segments as well as theoretical models to predict the degradation behavior may be powerful tools for the design of hydrogels for biomedical applications.
Dynamically crosslinked gels are appealing materials for applications that require time‐dependent mechanical responses. DNA duplexes are ideal crosslinkers for building such gels because of their ...excellent sequence addressability and flexible tunability in bond energy. However, the mechanical responses of most DNA gels are complicated and unpredictable. Here, a DNA gel with a highly homogeneous gel network and well predictable mechanical behaviors is demonstrated by using a pair of star‐polymer–DNA precursors with presimulated DNA sequences showing the two‐state transition. The melting curve analysis of the DNA gels reveals the good correspondence between the thermodynamic potentials of the DNA crosslinkers and the presimulated values by DNA calculators. Stress‐relaxation tests and dissociation kinetics measurements show that the macroscopic relaxation time of the DNA gels is approximately equal to the lifetime of the DNA crosslinkers over 4 orders of magnitude from 0.1–2000 s. Furthermore, a series of durability tests find the DNA gels are hysteresis‐less and self‐healable after the applications of repeated temperature and mechanical stimuli. These results demonstrate the great potential of star‐polymer–DNA precursors for building gels with predictable and tunable viscoelastic properties, suitable for applications such as stress‐response extracellular matrices, injectable solids, and soft robotics.
DNA gels with predictable mechanical responses are developed using a star‐polymer strategy and a pair of presimulated DNA sequences. The macroscopic stress‐relaxation time of the DNA gel is connected directly to the microscopic lifetime of the DNA crosslinkers over an extended time range from 0.1–2000 s. In addition, the DNA gels are spatially homogeneous, hysteresis‐less, and self‐healable.
In bone marrow, special microenvironments, known as niches, are essential for the maintenance of hematopoietic stem cells (HSCs). A population of mesenchymal stem cells, termed CXC chemokine ligand ...12 (CXCL12)-abundant reticular (CAR) cells or leptin receptor-expressing cells are the major cellular component of HSC niches. The molecular regulation of HSC niche properties is not fully understood. The role of Runx transcription factors, Runx1 and Runx2 in HSC cellular niches remains unclear. Here we show that Runx1 is predominantly expressed in CAR cells and that mice lacking both Runx1 and Runx2 in CAR cells display an increase in fibrosis and bone formation with markedly reduced hematopoietic stem and progenitor cells in bone marrow. In vitro, Runx1 is induced by the transcription factor Foxc1 and decreases fibrotic gene expression in CAR cells. Thus, HSC cellular niches require Runx1 or Runx2 to prevent their fibrotic conversion and maintain HSCs and hematopoiesis in adults.
Rubber elasticity is the archetype of the entropic force emerging from the second law of thermodynamics; numerous experimental and theoretical studies on natural and synthetic rubbers have shown that ...the elasticity originates mostly from entropy change with deformation. Similarly, in polymer gels containing a large amount of solvent, it has also been postulated that the shear modulus (the modulus of rigidity)G, which is a kind of modulus of elasticity, is approximately equivalent to the entropy contributionGS, but this has yet to be verified experimentally. In this study, we measure the temperature dependence of the shear modulusGin a rubberlike (hyperelastic) polymer gel whose polymer volume fraction is at most 0.1. As a result, we find that the energy contributionGE=G−GScan be a significant negative value, reaching up to double the shear modulusG(i.e.,|GE|≃2G), although the shear modulus of stable materials is generally bound to be positive. We further argue that the energy contributionGEis governed by a vanishing temperature that is a universal function of the normalized polymer concentration, andGEvanishes when the solvent is removed. Our findings highlight the essential difference between rubber elasticity and gel elasticity (which were previously thought to be the same) and push the established field of gel elasticity into a new direction.
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