Bioinspired Hydrogel Research Articles

Correction: In search of bioinspired hydrogels from amphiphilic peptides: a template for nanoparticle stabilization for the sustained release of anticancer drugs

Correction for ‘In search of bioinspired hydrogels from amphiphilic peptides: a template for nanoparticle stabilization for the sustained release of anticancer drugs’ by Radha Rani Mehra et al., New J. Chem., 2019, 43, 11666–11678.

Dynamic, Bioresponsive Hydrogels via Changes in DNA Aptamer Conformation.

DNA aptamers are integrated into synthetic hydrogel networks with the aim of creating hydrogels that undergo volume changes when exposed to target molecules. Specifically, single-stranded DNA aptamers in cDNA-bound, extended state are incorporated into hydrogel networks as cross-links, so that the nanoscale conformational change of DNA aptamers upon binding to target molecules will induce macroscopic volume decreases of hydrogels. Hydrogels incorporating adenosine triphosphate (ATP)-binding aptamers undergo controllable volume decreases of up to 40.3±4.6% when exposed to ATP, depending on the concentration of DNA aptamers incorporated in the hydrogel network, temperature, and target molecule concentration. Importantly, this approach can be generalized to aptamer sequences with distinct binding targets, as demonstrated here that hydrogels incorporating an insulin-binding aptamer undergo volume changes in response to soluble insulin. This work provides an example of bioinspired hydrogels that undergo macroscopic volume changes that stem from conformational shifts in resident DNA-based cross-links.

Calcium phosphate and calcium carbonate mineralization of bioinspired hydrogels based on β-chitin isolated from biomineral of the common cuttlefish (Sepia officinalis, L.)

Chitin, a bioactive, antibacterial and biodegradable polymer is commonly utilized by diverse marine organisms as the main scaffold material during biomineralization. Due to its properties, chitin is also of interest as a component of organo-inorganic composites for diverse biomedical applications. In this study, chitinous fibers isolated from the cuttlebone of the common cuttlefish (Sepia officinalis, L.) are characterized and evaluated for use as an integral part of mineralized hydrogels for biomedical applications. Since marine organisms use calcium carbonates (CaCO3), while vertebrates use calcium phosphates (CaP) as the main inorganic hard tissue components, and both minerals are used in hard tissue engineering, they were compared to determine which composite is potentially a better biomaterial. Hydrogel mineralization was conducted by subsequent dipping into cationic and anionic reactant solutions, resulting in the formation of a CaCO3 or CaP coating that penetrated into the hydrogel. Obtained composites were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), scanning electron microscopy (SEM), rheology, swelling tests and simple compression. The results indicate that β-chitin can be used for the preparation of moldable hydrogels that are easily mineralized. Mineralized hydrogels have higher elasticity than non-mineralized ones while swelling is better if the extent of mineralization is lower. Further optimization of the hydrogels composition could improve their stress response and Young’s modulus, where the current hydrogel with a higher extent of CaP mineralization excels in comparison to all other investigated composites.

Stimulation of wound healing using bioinspired hydrogels with basic fibroblast growth factor (bFGF).

IntroductionThe objective of this study is to stimulate wound healing using bioinspired hydrogels with basic fibroblast growth factor (bFGF).Materials and methodsInspired by the crosslinking mechanism in algae-based adhesives, hydrogels were fabricated with gum arabic, pectin, and Ca2+. The physical properties of the bioinspired hydrogels were characterized, and the in vitro release of bFGF was investigated. Then, the in vitro scratch assay for wound healing and in vivo wound healing experiment in a full-thickness excision wound model were performed for the bioinspired hydrogels with bFGF. Finally, histological examinations and organ toxicity tests were conducted to investigate the wound healing applications of the bioinspired hydrogels with bFGF.ResultsThe in vitro and in vivo results showed that the bioinspired hydrogels with bFGF could significantly enhance cell proliferation, wound re-epithelialization, collagen deposition, and contraction without any noticeable toxicity and inflammation compared with the hydrogels without bFGF and commercial wound healing products.ConclusionThese results suggest the potential application of bioinspired hydrogels with bFGF for wound healing.

Bioinspired Hydrogel Interferometer for Adaptive Coloration and Chemical Sensing.

Living organisms ubiquitously display colors that adapt to environmental changes, relying on the soft layer of cells or proteins. Adoption of soft materials into an artificial adaptive color system has promoted the development of material systems for environmental and health monitoring, anti-counterfeiting, and stealth technologies. Here, a hydrogel interferometer based on a single hydrogel thin film covalently bonded to a reflective substrate is reported as a simple and universal adaptive color platform. Similar to the cell or protein soft layer of color-changing animals, the soft hydrogel layer rapidly changes its thickness in response to external stimuli, resulting in instant color change. Such interference colors provide a visual and quantifiable means of revealing rich environmental metrics. Computational model is established and captures the key features of hydrogel stimuli-responsive swelling, which elucidates the mechanism and design principle for the broad-based platform. The single material-based platform has advantages of remarkable color uniformity, fast response, high robustness, and facile fabrication. Its versatility is demonstrated by diverse applications: a volatile-vapor sensor with highly accurate quantitative detection, a colorimetric sensor array for multianalyte recognition, breath-controlled information encryption, and a colorimetric humidity indicator. Portable and easy-to-use sensing systems are demonstrated with smartphone-based colorimetric analysis.

Bioinspired Supramolecular Lubricating Hydrogel Induced by Shear Force.

Bioinspired lubricating materials are great challenge toward artificial joints. In this contribution, we synthesize a bioinspired hydrogel by combining a thixotropic supramolecular network and polymer double network, exhibiting a unique shear-responsive lubricating property. The disassembly of the N-fluorenylmethoxycarbonyl-l-tryptophan supramolecular network triggered by shear force will endow lubricating function to the hydrogel; meanwhile PAAm and PVA double network acts as the supporting skeleton with high mechanical property. This work will bring new insight on the design of artificial lubricating joint.

Biogelx: Cell Culture on Self-Assembling Peptide Gels.

Aromatic peptide amphiphiles can form self-supporting nanostructured hydrogels with tunable mechanical properties and chemical compositions. These hydrogels are increasingly applied in two-dimensional (2D) and three-dimensional (3D) cell culture, where there is a rapidly growing need to store, grow, proliferate, and manipulate naturally derived cells within a hydrated, 3D matrix. Biogelx Limited is a biomaterials company, created to commercialize these bio-inspired hydrogels to cell biologists for a range of cell culture applications. This chapter describes methods of various characterization and cell culture techniques specifically optimized for compatibility with Biogelx products.

Ascidian‐Inspired Fast‐Forming Hydrogel System for Versatile Biomedical Applications: Pyrogallol Chemistry for Dual Modes of Crosslinking Mechanism

AbstractExploitation of unique biochemical and biophysical properties of marine organisms has led to the development of functional biomaterials for various biomedical applications. Recently, ascidians have received great attention, owing to their extraordinary properties such as strong underwater adhesion and rapid self‐regeneration. Specific polypeptides containing 3,4,5‐trihydroxyphenylalanine (TOPA) in the blood cells of ascidians are associated with such intrinsic properties generated through complex oxidative processes. In this study, a bioinspired hydrogel platform is developed, demonstrating versatile applicability for tissue engineering and drug delivery, by conjugating pyrogallol (PG) moiety resembling ascidian TOPA to hyaluronic acid (HA). The HA–PG conjugate can be rapidly crosslinked by dual modes of oxidative mechanisms using an oxidant or pH control, resulting in hydrogels with different mechanical and physical characteristics. The versatile utility of HA–PG hydrogels formed via different crosslinking mechanisms is tested for different biomedical platforms, including microparticles for sustained drug delivery and tissue adhesive for noninvasive cell transplantation. With extraordinarily fast and different routes of PG oxidation, ascidian‐inspired HA–PG hydrogel system may provide a promising biomaterial platform for a wide range of biomedical applications.

Bioinspired Adhesive Hydrogels Tackified by Nucleobases

AbstractBioinspired strategies for designing hydrogels with excellent adhesive performance have drawn much attention in biomedical applications. Here, bioinspired adhesive hydrogels tackified by independent nucleobase (adenine, thymine, guanine, cytosine, and uracil) from DNA and RNA are successfully explored. The nucleobase‐tackified hydrogels exhibit an excellent adhesive behavior for not only various solid substrates (polytetrafluoroethylene, plastics, rubbers, glasses, metals, and woods) but also biological tissues consisting of heart, liver, spleen, lung, kidney, bone, and muscle. The maximum adhesion strength of A‐, T‐, G‐, C‐, and U‐tackified hydrogels on the aluminum alloy surface is 780, 166, 250, 227, and 433 N m−1, respectively, superior to that of pure PAAm hydrogels (40 N m−1) after adhesive time of 10 min. It is anticipated that bioinspired hydrogels will play a significant role in the applications of wound dressing, medical electrodes, tissue adhesives, and portable equipment. Moreover, the bioinspired nucleobase‐tackified strategy would open a novel avenue for designing the next generation of soft and adhesive materials.

A Bioinspired Alginate-Gum Arabic Hydrogel with Micro-/Nanoscale Structures for Controlled Drug Release in Chronic Wound Healing.

Biopolymeric hydrogels have drawn increasing research interest in biomaterials due to their tunable physical and chemical properties for both creating bioactive cellular microenvironment and serving as sustainable therapeutic reagents. Inspired by a naturally occurring hydrogel secreted from the carnivorous Sundew plant for trapping insects, here we have developed a bioinspired hydrogel to deliver mitsugumin 53 (MG53), an important protein in cell membrane repair, for chronic wound healing. Both chemical compositions and micro-/nanomorphological properties inherent from the natural Sundew hydrogel were mimicked using sodium alginate and gum arabic with calcium ion-mediated cross-linking. On the basis of atomic force microscopy (AFM) force measurements, an optimal sticky hydrogel scaffold was obtained through orthogonal experimental design. Imaging and mechanical analysis showed the distinct correlation between structural morphology, adhesion characteristics, and mechanical properties of the Sundew-inspired hydrogel. Combined characterization and biochemistry techniques were utilized to uncover the underlying molecular composition involved in the interactions between hydrogel and protein. In vitro drug release experiments confirmed that the Sundew-inspired hydrogel had a biphasic-kinetics release, which can facilitate both fast delivery of MG53 for improving the reepithelization process of the wounds and sustained release of the protein for treating chronic wounds. In vivo experiments showed that the Sundew-inspired hydrogel encapsulating with rhMG53 could facilitate dermal wound healing in mouse model. Together, these studies confirmed that the Sundew-inspired hydrogel has both tunable micro-/nanostructures and physicochemical properties, which enable it as a delivery vehicle for chronic wounding healing. The research may provide a new way to develop biocompatible and tunable biomaterials for sustainable drug release to meet the needs of biological activities.

Bioinspired Hydrogels to Engineer Cancer Microenvironments.

Recent research has demonstrated that tumor microenvironments play pivotal roles in tumor development and metastasis through various physical, chemical, and biological factors, including extracellular matrix (ECM) composition, matrix remodeling, oxygen tension, pH, cytokines, and matrix stiffness. An emerging trend in cancer research involves the creation of engineered three-dimensional tumor models using bioinspired hydrogels that accurately recapitulate the native tumor microenvironment. With recent advances in materials engineering, many researchers are developing engineered tumor models, which are promising platforms for the study of cancer biology and for screening of therapeutic agents for better clinical outcomes. In this review, we discuss the development and use of polymeric hydrogel materials to engineer native tumor ECMs for cancer research, focusing on emerging technologies in cancer engineering that aim to accelerate clinical outcomes.

Biomimetic jellyfish-like PVA/graphene oxide nanocomposite hydrogels with anisotropic and pH-responsive mechanical properties

Jellyfish mesogloea with a well-developed anisotropic microstructure exhibits excellent and pH-responsive mechanical properties. It remains a great challenge to fabricate hydrogels mimicking the hierarchical structures and intriguing properties of biological hydrogels. Here we report the fabrication of a biomimetic jellyfish-like polyvinyl alcohol/graphene oxide (PVA/GO) nanocomposite hydrogel through a convenient and effective directional freezing–thawing technique. The resulting hydrogels show microstructures, water contents, and mechanical properties very similar to those of jellyfish mesogloea. Free-standing PVA/GO hydrogels with extremely high water contents (97–99 wt%) are obtained. The hydrogels show anisotropic porous structures consisted of microsized fibers and lamellae. The hydrogels exhibit high tensile and compressive strengths, up to 0.17 MPa and more than 2 MPa, respectively. In addition, anisotropic tensile mechanical properties are also observed. More interestingly, the PVA/GO nanocomposite hydrogels exhibit pH-responsive mechanical properties, which become weaker when swollen in acidic and basic solutions. Jellyfish-like structure that can mimic the swimming style of jellyfish is constructed with the PVA/GO nanocomposite hydrogel. This study might provide new idea for designing and fabricating novel biological or bio-inspired hydrogels for various applications in biomedical, industrial, and soft robotics fields.

Fabrication of a novel bio-inspired collagen–polydopamine hydrogel and insights into the formation mechanism for biomedical applications

A novel bio-inspired hydrogel with good biological property and initiative adhesive ability to cells has been fabricated via collagen self-assembly and the incorporation of PDA, which provides a significant potential in biomedical applications.

A high stiffness bio-inspired hydrogel from the combination of a poly(amido amine) dendrimer with DOPA.

A robust biodegradable hydrogel is constructed from two components containing G4.0 PAMAM and DOPA, which displays excellent interconnected porous 3D networks, higher mechanical strength, low and stable swelling and good biocompatibility. A mouse CSD model in vivo evidences that moderate bone-like tissue and extensive bony tissue are observed when the hydrogel is implanted.

Controlling mechanical properties of bio-inspired hydrogels by modulating nano-scale, inter-polymeric junctions.

Quinone tanning is a well-characterized biochemical process found in invertebrates, which produce diverse materials from extremely hard tissues to soft water-resistant adhesives. Herein, we report new types of catecholamine PEG derivatives, PEG-NH-catechols that can utilize an expanded spectrum of catecholamine chemistry. The PEGs enable simultaneous participation of amine and catechol in quinone tanning crosslinking. The intermolecular reaction between PEG-NH-catechols forms a dramatic nano-scale junction resulting in enhancement of gelation kinetics and mechanical properties of PEG hydrogels compared to results obtained by using PEGs in the absence of amine groups. Therefore, the study provides new insight into designing new crosslinking chemistry for controlling nano-scale chemical reactions that can broaden unique properties of bulk hydrogels.

Enzyme-catalysed assembly of DNA hydrogel

DNA is a remarkable polymer that can be manipulated by a large number of molecular tools including enzymes. A variety of geometric objects, periodic arrays and nanoscale devices have been constructed. Previously we synthesized dendrimer-like DNA and DNA nanobarcodes from branched DNA via ligases. Here we report the construction of a hydrogel entirely from branched DNA that are three-dimensional and can be crosslinked in nature. These DNA hydrogels were biocompatible, biodegradable, inexpensive to fabricate and easily moulded into desired shapes and sizes. The distinct difference of the DNA hydrogel to other bio-inspired hydrogels (including peptide-based, alginate-based and DNA (linear)-polyacrylamide hydrogels) is that the crosslinking is realized via efficient, ligase-mediated reactions. The advantage is that the gelling processes are achieved under physiological conditions and the encapsulations are accomplished in situ-drugs including proteins and even live mammalian cells can be encapsulated in the liquid phase eliminating the drug-loading step and also avoiding denaturing conditions. Fine tuning of these hydrogels is easily accomplished by adjusting the initial concentrations and types of branched DNA monomers, thus allowing the hydrogels to be tailored for specific applications such as controlled drug delivery, tissue engineering, 3D cell culture, cell transplant therapy and other biomedical applications.