Showing papers on "Self-healing hydrogels published in 2015"
TL;DR: A review of the literature concerning classification of hydrogels on different bases, physical and chemical characteristics of these products, and technical feasibility of their utilization is presented in this paper, together with technologies adopted for hydrogel production together with process design implications, block diagrams, and optimized conditions of the preparation process.
3,529 citations
TL;DR: From Wichterle’s pioneering work to the most recent hydrogel-based inventions and products on the market, it provides the reader with a detailed introduction to the topic and perspective on further potential developments.
1,788 citations
TL;DR: Gelatin methacryloyl (GelMA) hydrogels have been widely used for various biomedical applications due to their suitable biological properties and tunable physical characteristics and are demonstrated in a wide range of tissue engineering applications including engineering of bone, cartilage, cardiac, and vascular tissues, among others.
1,646 citations
TL;DR: Three-dimensional structures based on femurs, branched coronary arteries, trabeculated embryonic hearts, and human brains were mechanically robust and recreated complex 3D internal and external anatomical architectures.
Abstract: We demonstrate the additive manufacturing of complex three-dimensional (3D) biological structures using soft protein and polysaccharide hydrogels that are challenging or impossible to create using traditional fabrication approaches. These structures are built by embedding the printed hydrogel within a secondary hydrogel that serves as a temporary, thermoreversible, and biocompatible support. This process, termed freeform reversible embedding of suspended hydrogels, enables 3D printing of hydrated materials with an elastic modulus <500 kPa including alginate, collagen, and fibrin. Computer-aided design models of 3D optical, computed tomography, and magnetic resonance imaging data were 3D printed at a resolution of ~200 μm and at low cost by leveraging open-source hardware and software tools. Proof-of-concept structures based on femurs, branched coronary arteries, trabeculated embryonic hearts, and human brains were mechanically robust and recreated complex 3D internal and external anatomical architectures.
1,224 citations
TL;DR: This article aims to review the literature concerning the choice of selectivity for hydrogels based on classification, application and processing to assess their potential in hi-tech applications in the biomedical, pharmaceutical, biotechnology, bioseparation, biosensor, agriculture, oil recovery and cosmetics fields.
905 citations
TL;DR: A 3D printable and highly stretchable tough hydrogel is developed by combining poly(ethylene glycol) and sodium alginate, which synergize to form a hydrogels tougher than natural cartilage.
Abstract: A 3D printable and highly stretchable tough hydrogel is developed by combining poly(ethylene glycol) and sodium alginate, which synergize to form a hydrogel tougher than natural cartilage. Encapsulated cells maintain high viability over a 7 d culture period and are highly deformed together with the hydrogel. By adding biocompatible nanoclay, the tough hydrogel is 3D printed in various shapes without requiring support material.
813 citations
TL;DR: Supramolecular hydrogels are used in the 3D printing of high-resolution, multi-material structures and support the patterning of multiple inks, cells, and void spaces.
Abstract: Supramolecular hydrogels are used in the 3D printing of high-resolution, multi-material structures. The non-covalent bonds allow the extrusion of the inks into support gels to directly write structures continuously in 3D space. This material system supports the patterning of multiple inks, cells, and void spaces.
777 citations
TL;DR: This extensive review identifies and discusses the multitude of response modalities that have been developed, including temperature, pH, chemical, light, electro, and shear-sensitive hydrogels.
Abstract: Over the past century, hydrogels have emerged as effective materials for an immense variety of applications. The unique network structure of hydrogels enables very high levels of hydrophilicity and biocompatibility, while at the same time exhibiting the soft physical properties associated with living tissue, making them ideal biomaterials. Stimulus-responsive hydrogels have been especially impactful, allowing for unprecedented levels of control over material properties in response to external cues. This enhanced control has enabled groundbreaking advances in healthcare, allowing for more effective treatment of a vast array of diseases and improved approaches for tissue engineering and wound healing. In this extensive review, we identify and discuss the multitude of response modalities that have been developed, including temperature, pH, chemical, light, electro, and shear-sensitive hydrogels. We discuss the theoretical analysis of hydrogel properties and the mechanisms used to create these responses, highlighting both the pioneering and most recent work in all of these fields. Finally, we review the many current and proposed applications of these hydrogels in medicine and industry.
750 citations
TL;DR: This SP hydrogel exhibits thermoplastic processability, injectability, and self-reparability because of the dynamic destruction and reconstruction of hydrogen bonds in response to temperature change.
Abstract: Polymerization of glycinamide-conjugated monomer alone in concentrated aqueous solution enables facile formation of a mechanically strong and a highly stable supramolecular polymer (SP) hydrogel because of the cooperatively hydrogen-bonded crosslinking and strengthening effect from dual amide motifs. This SP hydrogel exhibits thermoplastic processability, injectability, and self-reparability because of the dynamic destruction and reconstruction of hydrogen bonds in response to temperature change.
646 citations
TL;DR: This review highlights the latest advances in nanocomposite hydrogels as drug delivery vehicles and the inclusion/incorporation of nanoparticles in three-dimensional polymeric structures is an innovative means for obtaining multicomponent systems with diverse functionality within a hybrid hydrogel network.
Abstract: Considerable progress in the synthesis and technology of hydrogels makes these materials attractive structures for designing controlled-release drug delivery systems. In particular, this review highlights the latest advances in nanocomposite hydrogels as drug delivery vehicles. The inclusion/incorporation of nanoparticles in three-dimensional polymeric structures is an innovative means for obtaining multicomponent systems with diverse functionality within a hybrid hydrogel network. Nanoparticle-hydrogel combinations add synergistic benefits to the new 3D structures. Nanogels as carriers for cancer therapy and injectable gels with improved self-healing properties have also been described as new nanocomposite systems.
582 citations
TL;DR: This work reinforces soft hydrogels with highly organized, high-porosity microfibre networks that are 3D-printed with a technique termed as melt electrospinning writing, showing that the stiffness of the gel/scaffold composites increases synergistically (up to 54-fold), compared with hydrogel or microf fibre scaffolds alone.
Abstract: Despite intensive research, hydrogels currently available for tissue repair in the musculoskeletal system are unable to meet the mechanical, as well as the biological, requirements for successful outcomes. Here we reinforce soft hydrogels with highly organized, high-porosity microfibre networks that are 3D-printed with a technique termed as melt electrospinning writing. We show that the stiffness of the gel/scaffold composites increases synergistically (up to 54-fold), compared with hydrogels or microfibre scaffolds alone. Modelling affirms that reinforcement with defined microscale structures is applicable to numerous hydrogels. The stiffness and elasticity of the composites approach that of articular cartilage tissue. Human chondrocytes embedded in the composites are viable, retain their round morphology and are responsive to an in vitro physiological loading regime in terms of gene expression and matrix production. The current approach of reinforcing hydrogels with 3D-printed microfibres offers a fundament for producing tissue constructs with biological and mechanical compatibility.
TL;DR: These results demonstrate the multiple functions of nanosilicates conducive to the regeneration of bone in nonunion defects, including increased network stiffness and porosity, injectability, and enhanced mineralized matrix formation in a growth-factor-free microenvironment.
Abstract: Despite bone's impressive ability to heal after traumatic injuries and fractures, a significant need still exists for developing strategies to promote healing of nonunion defects. To address this issue, we developed collagen-based hydrogels containing two-dimensional nanosilicates. Nanosilicates are ultrathin nanomaterials with a high degree of anisotropy and functionality that results in enhanced surface interactions with biological entities compared to their respective three-dimensional counterparts. The addition of nanosilicates resulted in a 4-fold increase in compressive modulus along with an increase in pore size compared to collagen-based hydrogels. In vitro evaluation indicated that the nanocomposite hydrogels are capable of promoting osteogenesis in the absence of any osteoinductive factors. A 3-fold increase in alkaline phosphatase activity and a 4-fold increase in the formation of a mineralized matrix were observed with the addition of the nanosilicates to the collagen-based hydrogels. Overall, these results demonstrate the multiple functions of nanosilicates conducive to the regeneration of bone in nonunion defects, including increased network stiffness and porosity, injectability, and enhanced mineralized matrix formation in a growth-factor-free microenvironment.
TL;DR: An overview of adaptable‐hydrogel design considerations and linkage selections is presented, with a focus on various cell‐compatible crosslinking mechanisms that can be exploited to form adaptable hydrogels for tissue engineering.
Abstract: Adaptable hydrogels have recently emerged as a promising platform for three-dimensional (3D) cell encapsulation and culture. In conventional, covalently crosslinked hydrogels, degradation is typically required to allow complex cellular functions to occur, leading to bulk material degradation. In contrast, adaptable hydrogels are formed by reversible crosslinks. Through breaking and re-formation of the reversible linkages, adaptable hydrogels can be locally modified to permit complex cellular functions while maintaining their long-term integrity. In addition, these adaptable materials can have biomimetic viscoelastic properties that make them well suited for several biotechnology and medical applications. In this review, an overview of adaptable-hydrogel design considerations and linkage selections is presented, with a focus on various cell-compatible crosslinking mechanisms that can be exploited to form adaptable hydrogels for tissue engineering.
TL;DR: A series of tough polyion complex hydrogels is synthesized by sequential homopolymerization of cationic and anionic monomers, which are self-healable under ambient conditions with the aid of saline solution and can be built from their microgels, which is promising for 3D/4D printing and the additive manufacturing of hydrogel.
Abstract: A series of tough polyion complex hydrogels is synthesized by sequential homopolymerization of cationic and anionic monomers. Owing to the reversible interpolymer ionic bonding, the materials are self-healable under ambient conditions with the aid of saline solution. Furthermore, self-glued bulk hydrogels can be built from their microgels, which is promising for 3D/4D printing and the additive manufacturing of hydrogels.
TL;DR: In this paper, a new design strategy is proposed and demonstrated to improve both fatigue resistance and self-healing property of double network (DN) gels by introducing a ductile, nonsoft gel with strong hydrophobic interactions as the second network.
Abstract: Double network (DN) hydrogels with two strong asymmetric networks being chemically linked have demonstrated their excellent mechanical properties as the toughest hydrogels, but chemically linked DN gels often exhibit negligible fatigue resistance and poor self-healing property due to the irreversible chain breaks in covalent-linked networks. Here, a new design strategy is proposed and demonstrated to improve both fatigue resistance and self-healing property of DN gels by introducing a ductile, nonsoft gel with strong hydrophobic interactions as the second network. Based on this design strategy, a new type of fully physically cross-linked Agar/hydrophobically associated polyacrylamide (HPAAm) DN gels are synthesized by a simple one-pot method. Agar/HPAAm DN gels exhibit excellent mechanical strength and high toughness, comparable to the reported DN gels. More importantly, because the ductile and tough second network of HPAAm can bear stress and reconstruct network structure, Agar/HPAAm DN gels also demonstrate rapid self-recovery, remarkable fatigue resistance, and notable self-healing property without any external stimuli at room temperature. In contrast to the former DN gels in both network structures and underlying association forces, this new design strategy to prepare highly mechanical DN gels provides a new avenue to better understand the fundamental structure-property relationship of DN hydrogels, thus broadening current hydrogel research and applications.
TL;DR: This work designs, fabricate, and characterize photopatterned, self-folding functional microgrippers that combine a swellable, photo-cross-linked pNIPAM-AAc soft-hydrogel with a nonswellable and stiff segmented polymer (polypropylene fumarate, PPF).
Abstract: Hydrogels such as poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAM-AAc) can be photopatterned to create a wide range of actuatable and self-folding microstructures. Mechanical motion is derived from the large and reversible swelling response of this cross-linked hydrogel in varying thermal or pH environments. This action is facilitated by their network structure and capacity for large strain. However, due to the low modulus of such hydrogels, they have limited gripping ability of relevance to surgical excision or robotic tasks such as pick-and-place. Using experiments and modeling, we design, fabricate, and characterize photopatterned, self-folding functional microgrippers that combine a swellable, photo-cross-linked pNIPAM-AAc soft-hydrogel with a nonswellable and stiff segmented polymer (polypropylene fumarate, PPF). We also show that we can embed iron oxide (Fe2O3) nanoparticles into the porous hydrogel layer, allowing the microgrippers to be responsive and remotely guided using magnetic fields. Usi...
TL;DR: The widely used photoresists, the development of TPP photoinitiators, the strategies for improving the resolution and the microfabrication of 3D hydrogels are reviewed.
Abstract: 3D printing technology has attracted much attention due to its high potential in scientific and industrial applications. As an outstanding 3D printing technology, two-photon polymerization (TPP) microfabrication has been applied in the fields of micro/nanophotonics, micro-electromechanical systems, microfluidics, biomedical implants and microdevices. In particular, TPP microfabrication is very useful in tissue engineering and drug delivery due to its powerful fabrication capability for precise microstructures with high spatial resolution on both the microscopic and the nanometric scale. The design and fabrication of 3D hydrogels widely used in tissue engineering and drug delivery has been an important research area of TPP microfabrication. The resolution is a key parameter for 3D hydrogels to simulate the native 3D environment in which the cells reside and the drug is controlled to release with optimal temporal and spatial distribution in vitro and in vivo. The resolution of 3D hydrogels largely depends on the efficiency of TPP initiators. In this paper, we will review the widely used photoresists, the development of TPP photoinitiators, the strategies for improving the resolution and the microfabrication of 3D hydrogels.
TL;DR: This review strives to highlight the development and fundamentals of DN gels covering from preparation methods, network structures, to toughening mechanisms over the last decade to derive new design principles for the next-generation tough hydrogels.
Abstract: Double network (DN) hydrogels as promising soft-and-tough materials intrinsically possess extraordinary mechanical strength and toughness due to their unique contrasting network structures, strong interpenetrating network entanglement, and efficient energy dissipation. It has been ∼11 years since the first PAMPS–PAAm DN hydrogel was developed, but the research and development of new DN hydrogels are still at a very early stage. A vast number of network monomers available in the current chemical inventory provide the possibility to design new DN gels and to explore the fundamental relationship of DN gels among network structures, mechanical properties, and toughening mechanisms, which help to derive new design principles for the next-generation tough hydrogels. In this review, we strive to highlight the development and fundamentals of DN gels covering from preparation methods, network structures, to toughening mechanisms over the last decade.
TL;DR: A new series of in situ forming antibacterial conductive degradable hydrogels using quaternized chitosan (QCS) grafted polyaniline with oxidized dextran as crosslinker is developed as a new class of bioactive scaffolds for tissue regeneration applications.
TL;DR: This work develops a physical description of polymer-nanoparticle gel formation that is utilised to design biocompatible gels for minimally-invasive drug delivery and introduces a facile and generalizable class of mouldable hydrogels amenable to a range of biomedical and industrial applications.
Abstract: Mouldable hydrogels find a variety of applications in the biomedical industry. Here, Appel et al. show a method to fabricate hydrogels through a self-assembly process based on the interaction between biopolymers and functional nanoparticles for multistage drug delivery in vivo.
TL;DR: A smart valve is created by 4D printing of hydrogels that are both mechanically robust and thermally actuating, and created by printing the "dynamic" hydrogel ink alongside other static materials.
Abstract: A smart valve is created by 4D printing of hydrogels that are both mechanically robust and thermally actuating. The printed hydrogels are made up of an interpenetrating network of alginate and poly(N-isopropylacrylamide). 4D structures are created by printing the "dynamic" hydrogel ink alongside other static materials.
TL;DR: A new type of "rigid and tough" hydrogel with excellent elasticity is designed by dense clustering of hydrogen bonds within a loose chemical network that displays good fatigue-resistance and complete and extremely fast recovery of shape and mechanical properties.
Abstract: A new type of "rigid and tough" hydrogel with excellent elasticity is designed by dense clustering of hydrogen bonds within a loose chemical network. The resultant hydrogel exhibits a good combination of high modulus (28 MPa), toughness (9300 J m(-3) ), extensibility (800%), and tensile stress (2 MPa). Furthermore, the gel displays good fatigue-resistance and complete and extremely fast recovery of shape and mechanical properties (3 min at 37°C).
TL;DR: The scope of this article is to review the literature on thermosensitive hydrogels published over the past seven years and concentrates on natural polymers as well as synthetic polymers, including systems based on N-isopropylacrylamide (NIPAAm), poly(ethylene oxide)-b- poly(propylene oxide)- b-poly(methylene oxide) (PEO-PPO-PEO) and poly(organophosphazenes)
TL;DR: In this paper, a void-forming hydrogel was used to control mesenchymal stem cell osteogenesis and cell deployment in vitro and in vivo, respectively, by modifying the hydrogels' elastic modulus or its chemistry.
Abstract: The effectiveness of stem cell therapies has been hampered by cell death and limited control over fate. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype. Stem cell behaviour can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel's elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel's elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem cell behaviours in situ.
TL;DR: It is demonstrated that non-invasive, transdermal time-regulated activation of cell-adhesive RGD peptide on implanted biomaterials regulates in vivo cell adhesion, inflammation, fibrous encapsulation, and vascularization of the material.
Abstract: Transdermal light-triggered activation of cell-adhesive peptides on the surface of implanted hydrogels alters cell–material interactions, such as cell adhesion and spatial patterning, and fibrous encapsulation and vascularization of the material.
TL;DR: Results showed that the removal of divalent metal ions significantly impacted the formation of the gelatin network and the purified gelatin hydrogels had less interactions between gelatin molecules and form larger-pore network which enabled EDC to penetrate and crosslink the gel more efficiently.
Abstract: The usage of gelatin hydrogel is limited due to its instability and poor mechanical properties, especially under physiological conditions Divalent metal ions present in gelatin such as Ca2+ and Fe2+ play important roles in the gelatin molecule interactions The objective of this study was to determine the impact of divalent ion removal on the stability and mechanical properties of gelatin gels with and without chemical crosslinking The gelatin solution was purified by Chelex resin to replace divalent metal ions with sodium ions The gel was then chemically crosslinked by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) Results showed that the removal of divalent metal ions significantly impacted the formation of the gelatin network The purified gelatin hydrogels had less interactions between gelatin molecules and form larger-pore network which enabled EDC to penetrate and crosslink the gel more efficiently The crosslinked purified gels showed small swelling ratio, higher crosslinking density and dramatically increased storage and loss moduli The removal of divalent ions is a simple yet effective method that can significantly improve the stability and strength of gelatin hydrogels The in vitro cell culture demonstrated that the purified gelatin maintained its ability to support cell attachment and spreading
TL;DR: A modular hydrogel system that facilitates extrusion bioprinting of cell-laden hydrogels, incorporates tissue-specific factors derived from decellularized tissue extracellular matrix, thus mimicking biochemical tissue profile, and allows control over mechanical properties to mimic the tissue stiffness is described.
TL;DR: Control over the material’s mechanical hierarchy of energy-dissipating modes under dynamic mechanical loading is demonstrated, and therefore the ability to engineer a priori the viscoelastic properties of these materials by controlling the types of crosslinks rather than by modifying the polymer itself is demonstrated.
Abstract: In conventional polymer materials, mechanical performance is traditionally engineered via material structure, using motifs such as polymer molecular weight, polymer branching, or block copolymer design. Here, by means of a model system of 4-arm poly(ethylene glycol) hydrogels crosslinked with multiple, kinetically distinct dynamic metal-ligand coordinate complexes, we show that polymer materials with decoupled spatial structure and mechanical performance can be designed. By tuning the relative concentration of two types of metal-ligand crosslinks, we demonstrate control over the material's mechanical hierarchy of energy-dissipating modes under dynamic mechanical loading, and therefore the ability to engineer a priori the viscoelastic properties of these materials by controlling the types of crosslinks rather than by modifying the polymer itself. This strategy to decouple material mechanics from structure is general and may inform the design of soft materials for use in complex mechanical environments. Three examples that demonstrate this are provided.
TL;DR: In this article, thermally responsive and conductive hybrid hydrogels are synthesized by in situ formation of continuous network of conductive polymer hydrogel crosslinked by phytic acid in poly(N-isopropylacrylamide) matrix.
Abstract: Stimuli-responsive hydrogels with decent electrical properties are a promising class of polymeric materials for a range of technological applications, such as electrical, electrochemical, and biomedical devices. In this paper, thermally responsive and conductive hybrid hydrogels are synthesized by in situ formation of continuous network of conductive polymer hydrogels crosslinked by phytic acid in poly(N-isopropylacrylamide) matrix. The interpenetrating binary network structure provides the hybrid hydrogels with continuous transporting path for electrons, highly porous microstructure, strong interactions between two hydrogel networks, thus endowing the hybrid hydrogels with a unique combination of high electrical conductivity (up to 0.8 S m−1), high thermoresponsive sensitivity (significant volume change within several seconds), and greatly enhanced mechanical properties. This work demonstrates that the architecture of the filling phase in the hydrogel matrix and design of hybrid hydrogel structure play an important role in determining the performance of the resulting hybrid material. The attractive performance of these hybrid hydrogels is further demonstrated by the developed switcher device which suggests potential applications in stimuli-responsive electronic devices.
TL;DR: The synthesis and characterization of boronate ester-cross-linked hydrogels capable of self-healing behavior at neutral and acidic pH is described, which demonstrates a new strategy to produce boronic acid materials capable ofSelf- healing at physiological pH.
Abstract: This report describes the synthesis and characterization of boronate ester-cross-linked hydrogels capable of self-healing behavior at neutral and acidic pH. This atypically wide pH range over which healing behavior is observed was achieved through the use of an intramolecular coordinating boronic acid monomer, 2-acrylamidophenylboronic acid (2APBA), where the internal coordination helped to stabilize cross-links formed at acidic and neutral pH. Two different hydrogels were formed from a 2APBA copolymer cross-linked with either poly(vinyl alcohol) or a catechol-functionalized copolymer. The self-healing ability of these hydrogels was characterized through physical testing and rheological studies. Furthermore, the catechol cross-linked hydrogel was shown to be oxygen sensitive, demonstrating reduced self-healing and stress relaxation after partial oxidation. The synthesis of these hydrogels demonstrates a new strategy to produce boronic acid materials capable of self-healing at physiological pH.