Advances in engineering hydrogels
TL;DR: The advances in making hydrogels with improved mechanical strength and greater flexibility for use in a wide range of applications are reviewed, foreseeing opportunities in the further development of more sophisticated fabrication methods that allow better-controlled hydrogel architecture across multiple length scales.
Abstract: BACKGROUND Hydrogels are formed through the cross-linking of hydrophilic polymer chains within an aqueous microenvironment. The gelation can be achieved through a variety of mechanisms, spanning physical entanglement of polymer chains, electrostatic interactions, and covalent chemical cross-linking. The water-rich nature of hydrogels makes them broadly applicable to many areas, including tissue engineering, drug delivery, soft electronics, and actuators. Conventional hydrogels usually possess limited mechanical strength and are prone to permanent breakage. The lack of desired dynamic cues and structural complexity within the hydrogels has further limited their functions. Broadened applications of hydrogels, however, require advanced engineering of parameters such as mechanics and spatiotemporal presentation of active or bioactive moieties, as well as manipulation of multiscale shape, structure, and architecture. ADVANCES Hydrogels with substantially improved physicochemical properties have been enabled by rational design at the molecular level and control over multiscale architecture. For example, formulations that combine permanent polymer networks with reversibly bonding chains for energy dissipation show strong toughness and stretchability. Similar strategies may also substantially enhance the bonding affinity of hydrogels at interfaces with solids by covalently anchoring the polymer networks of tough hydrogels onto solid surfaces. Shear-thinning hydrogels that feature reversible bonds impart a fluidic nature upon application of shear forces and return back to their gel states once the forces are released. Self-healing hydrogels based on nanomaterial hybridization, electrostatic interactions, and slide-ring configurations exhibit excellent abilities in spontaneously healing themselves after damages. Additionally, harnessing techniques that can dynamically and precisely configure hydrogels have resulted in flexibility to regulate their architecture, activity, and functionality. Dynamic modulations of polymer chain physics and chemistry can lead to temporal alteration of hydrogel structures in a programmed manner. Three-dimensional printing enables architectural control of hydrogels at high precision, with a potential to further integrate elements that enable change of hydrogel configurations along prescribed paths. OUTLOOK We envision the continuation of innovation in new bioorthogonal chemistries for making hydrogels, enabling their fabrication in the presence of biological species without impairing cellular or biomolecule functions. We also foresee opportunities in the further development of more sophisticated fabrication methods that allow better-controlled hydrogel architecture across multiple length scales. In addition, technologies that precisely regulate the physicochemical properties of hydrogels in spatiotemporally controlled manners are crucial in controlling their dynamics, such as degradation and dynamic presentation of biomolecules. We believe that the fabrication of hydrogels should be coupled with end applications in a feedback loop in order to achieve optimal designs through iterations. In the end, it is the combination of multiscale constituents and complementary strategies that will enable new applications of this important class of materials.
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TL;DR: Common approaches to 3D culture are reviewed, the significance of 3D cultures in drug resistance and drug repositioning is discussed and some of the challenges of applying 3D cell cultures to high-throughput drug discovery are addressed.
Abstract: Drug development is a lengthy and costly process that proceeds through several stages from target identification to lead discovery and optimization, preclinical validation and clinical trials culminating in approval for clinical use. An important step in this process is high-throughput screening (HTS) of small compound libraries for lead identification. Currently, the majority of cell-based HTS is being carried out on cultured cells propagated in two-dimensions (2D) on plastic surfaces optimized for tissue culture. At the same time, compelling evidence suggests that cells cultured in these non-physiological conditions are not representative of cells residing in the complex microenvironment of a tissue. This discrepancy is thought to be a significant contributor to the high failure rate in drug discovery, where only a low percentage of drugs investigated ever make it through the gamut of testing and approval to the market. Thus, three-dimensional (3D) cell culture technologies that more closely resemble in vivo cell environments are now being pursued with intensity as they are expected to accommodate better precision in drug discovery. Here we will review common approaches to 3D culture, discuss the significance of 3D cultures in drug resistance and drug repositioning and address some of the challenges of applying 3D cell cultures to high-throughput drug discovery.
911 citations
Cites background from "Advances in engineering hydrogels"
...At the same time, they are chemically and physically well-defined and often have tunable mechanical properties to achieve a desired stiffness or porosity (Worthington et al., 2015; Zhang and Khademhosseini, 2017)....
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...Polyethylene glycol (PEG), polylactic acid (PA), polyglycolic acid (PGA) and other unnatural polymer hydrogels (Raeber et al., 2005; Zhang and Khademhosseini, 2017) have the advantage of being comparatively inexpensive, are relatively inert, have reproducible material properties that are usually…...
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...Polyethylene glycol (PEG), polylactic acid (PA), polyglycolic acid (PGA) and other unnatural polymer hydrogels (Raeber et al., 2005; Zhang and Khademhosseini, 2017) have the advantage of being comparatively inexpensive, are relatively inert, have reproducible material properties that are usually easy to tune through synthesis or crosslinking, and are reproducible, thereby supporting the acquisition of consistent results....
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TL;DR: In this article, the fundamental principles of materials design for efficient solar-to-thermal energy conversion and vapour generation are summarized for both fundamental research and practical water-purification applications.
Abstract: Solar-powered water evaporation — the extraction of vapour from liquid water using solar energy — provides the basis for the development of eco-friendly and cost-effective freshwater production. Liquid water consumes and carries energy, and, thus, plays an essential role in this process. As such, extensive experimental and theoretical studies have been focused on water management to achieve efficient solar vapour generation. Many innovative materials have been proposed to enable highly controllable and efficient solar-to-thermal energy conversion to address the challenges in the energy–water nexus from the microscale to the molecular level. In this Review, we summarize the fundamental principles of materials design for efficient solar-to-thermal energy conversion and vapour generation. We discuss how to integrate photothermal materials, nanostructures/microstructures and water–material interactions to improve the performance of the evaporation system via in situ utilization of solar energy. Focusing on materials science and engineering, we overview the key challenges and opportunities for nanostructured and microstructured materials in both fundamental research and practical water-purification applications. Materials engineering enables the control of water–material interactions in solar vapour generators, which aim to efficiently utilize solar energy for the cost-effective production of clean water. This Review discusses material-design principles for solar evaporators, spanning from macrostructures to molecular configurations.
615 citations
TL;DR: This review covers the smart designs of structural materials inspired by natural materials and their utility in the construction of flexible devices, and summarizes structural materials that accommodate mechanical deformations, which is the fundamental requirement for flexible devices to work properly in complex environments.
Abstract: Exciting advancements have been made in the field of flexible electronic devices in the last two decades and will certainly lead to a revolution in peoples’ lives in the future. However, because of the poor sustainability of the active materials in complex stress environments, new requirements have been adopted for the construction of flexible devices. Thus, hierarchical architectures in natural materials, which have developed various environment-adapted structures and materials through natural selection, can serve as guides to solve the limitations of materials and engineering techniques. This review covers the smart designs of structural materials inspired by natural materials and their utility in the construction of flexible devices. First, we summarize structural materials that accommodate mechanical deformations, which is the fundamental requirement for flexible devices to work properly in complex environments. Second, we discuss the functionalities of flexible devices induced by nature-inspired stru...
518 citations
TL;DR: Advances in biomaterials for drug delivery are enabling significant progress in biology and medicine, including major breakthroughs in materials for cancer immunotherapy, autoimmune diseases, and genome editing.
Abstract: Advances in biomaterials for drug delivery are enabling significant progress in biology and medicine. Multidisciplinary collaborations between physical scientists, engineers, biologists, and clinicians generate innovative strategies and materials to treat a range of diseases. Specifically, recent advances include major breakthroughs in materials for cancer immunotherapy, autoimmune diseases, and genome editing. Here, strategies for the design and implementation of biomaterials for drug delivery are reviewed. A brief history of the biomaterials field is first established, and then commentary on RNA delivery, responsive materials development, and immunomodulation are provided. Current challenges associated with these areas as well as opportunities to address long-standing problems in biology and medicine are discussed throughout.
517 citations
TL;DR: It is demonstrated that enhancing the hydrability of the h-LAH could change the water state and partially activate the water, hence facilitating water evaporation, and raises the solar vapor generation to a record rate of ~3.6 kg m−2 hour−1 under 1 sun.
Abstract: Water purification by solar distillation is a promising technology to produce fresh water. However, solar vapor generation, is energy intensive, leading to a low water yield under natural sunlight. Therefore, developing new materials that can reduce the energy requirement of water vaporization and speed up solar water purification is highly desirable. Here, we introduce a highly hydratable light-absorbing hydrogel (h-LAH) consisting of polyvinyl alcohol and chitosan as the hydratable skeleton and polypyrrole as the light absorber, which can use less energy ( −2 hour −1 under 1 sun. The h-LAH-based solar still also exhibits long-term durability and antifouling functionality toward complex ionic contaminants.
475 citations
References
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TL;DR: Naive mesenchymal stem cells are shown here to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity, consistent with the elasticity-insensitive commitment of differentiated cell types.
12,204 citations
TL;DR: The composition and synthesis of hydrogels, the character of their absorbed water, and permeation of solutes within their swollen matrices are reviewed to identify the most important properties relevant to their biomedical applications.
5,173 citations
TL;DR: 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation and developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.
Abstract: Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.
4,841 citations
"Advances in engineering hydrogels" refers methods in this paper
...Three-dimensional printing represents another facile technique for constructing volumetric objects (113, 114)....
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TL;DR: The synthesis of hydrogels from polymers forming ionically and covalently crosslinked networks is reported, finding that these gels’ toughness is attributed to the synergy of two mechanisms: crack bridging by the network of covalent crosslinks, and hysteresis by unzipping thenetwork of ionic crosslinks.
Abstract: Hydrogels with improved mechanical properties, made by combining polymer networks with ionic and covalent crosslinks, should expand the scope of applications, and may serve as model systems to explore mechanisms of deformation and energy dissipation. Hydrogels are used in flexible contact lenses, as scaffolds for tissue engineering and in drug delivery. Their poor mechanical properties have so far limited the scope of their applications, but new strong and stretchy materials reported here could take hydrogels into uncharted territories. The new system involves a double-network gel, with one network forming ionic crosslinks and the other forming covalent crosslinks. The fracture energy of these materials is very high: they can stretch to beyond 17 times their own length even when containing defects that usually initiate crack formation in hydrogels. The materials' toughness is attributed to crack bridging by the covalent network accompanied by energy dissipation through unzipping of the ionic crosslinks in the second network. Hydrogels are used as scaffolds for tissue engineering1, vehicles for drug delivery2, actuators for optics and fluidics3, and model extracellular matrices for biological studies4. The scope of hydrogel applications, however, is often severely limited by their mechanical behaviour5. Most hydrogels do not exhibit high stretchability; for example, an alginate hydrogel ruptures when stretched to about 1.2 times its original length. Some synthetic elastic hydrogels6,7 have achieved stretches in the range 10–20, but these values are markedly reduced in samples containing notches. Most hydrogels are brittle, with fracture energies of about 10 J m−2 (ref. 8), as compared with ∼1,000 J m−2 for cartilage9 and ∼10,000 J m−2 for natural rubbers10. Intense efforts are devoted to synthesizing hydrogels with improved mechanical properties11,12,13,14,15,16,17,18; certain synthetic gels have reached fracture energies of 100–1,000 J m−2 (refs 11, 14, 17). Here we report the synthesis of hydrogels from polymers forming ionically and covalently crosslinked networks. Although such gels contain ∼90% water, they can be stretched beyond 20 times their initial length, and have fracture energies of ∼9,000 J m−2. Even for samples containing notches, a stretch of 17 is demonstrated. We attribute the gels’ toughness to the synergy of two mechanisms: crack bridging by the network of covalent crosslinks, and hysteresis by unzipping the network of ionic crosslinks. Furthermore, the network of covalent crosslinks preserves the memory of the initial state, so that much of the large deformation is removed on unloading. The unzipped ionic crosslinks cause internal damage, which heals by re-zipping. These gels may serve as model systems to explore mechanisms of deformation and energy dissipation, and expand the scope of hydrogel applications.
3,856 citations
"Advances in engineering hydrogels" refers background or methods in this paper
...Alternatively, hydrogels formed throughhybridizationwith nanomaterials (39, 48), via crystallite cross-linking (49), or bymixingmultiple components (38, 41, 50), may possess substantially improved mechanical properties (51)....
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...[Adapted with permission from (41), copyright 2012 Nature...
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TL;DR: This work highlights recent developments in engineering uncrosslinked and crosslinked hydrophilic polymers for biomedical and biological applications and shows how such systems' intelligent behavior can be used in sensors, microarrays, and imaging.
Abstract: Hydrophilic polymers are the center of research emphasis in nanotechnology because of their perceived “intelligence”. They can be used as thin films, scaffolds, or nanoparticles in a wide range of biomedical and biological applications. Here we highlight recent developments in engineering uncrosslinked and crosslinked hydrophilic polymers for these applications. Natural, biohybrid, and synthetic hydrophilic polymers and hydrogels are analyzed and their thermodynamic responses are discussed. In addition, examples of the use of hydrogels for various therapeutic applications are given. We show how such systems’ intelligent behavior can be used in sensors, microarrays, and imaging. Finally, we outline challenges for the future in integrating hydrogels into biomedical applications.
3,524 citations