Molecular Encryption and Reconfiguration for Remodeling of Dynamic Hydrogels

Dynamic materials have been widely studied for regulation of cell adhesion that is important to a variety of biological and biomedical applications. These materials can undergo changes mainly through one of the two mechanisms: ligand release in response to chemical, physical, or biological stimuli, and ligand burial in response to mechanical stretching or the change of electrical potential. This study demonstrates an encrypted ligand and a new hydrogel that are capable of inducing and inhibiting cell adhesion, which is controlled by molecular reconfiguration. The ligand initially exhibits an inert state; it can be reconfigured into active and inert states by using unblocking and recovering molecules in physiological conditions. Since molecular reconfiguration does not require the release of the ligand from the hydrogels, inhibiting and inducing cell adhesion on the hydrogels can be repeated for multiple cycles.     

可注射水凝胶的制备与应用

可注射水凝胶在再生医学和药物控释等方面有着广泛的用途,是近年来生物医用材料领域新的研究方向.本文综述了近年来人们在可注射水凝胶制备和应用方面的研究进展,最后展望了其发展前景.     

Synthetic Hydrogels with Covalently Incorporated Saccharides Studied for Biomedical Applications – 15 Year Overview

Glycosylated materials have attracted special attention in biomedical field because of the unique properties of the individual carbohydrates in recognition mechanisms in many biological events. Sugar residues decorating a polymer surface can be regarded as multivalent ligands for interaction with various glycoproteins. This phenomenon provides the basis for several biomedical applications; of these, ligand-based targeted therapy is the most frequently cited. Materials functionalized with individual carbohydrates can be used for the selective binding of lectin proteins. Carbohydrate–lectin interactions underpin the development of diverse biosensor devices and bioassays aimed at pathogen detection. Because of the high content of hydroxyl groups and the consequent high hydrophilicity, saccharide-based monomers are perfect candidates for incorporation into hydrogels. Such functionalization allows synthetic materials to acquire unique properties and enhance their performance. This review covers developments over the past 15 years in the field of the synthesis of chemically crosslinked nano-, micro- and bulk hydrogels with covalently incorporated mono-, di- or trisaccharides. A brief view on the potential biomedical applications of these unique hydrogels is provided with particular emphasis on carriers for delivery of bioactive molecules, bioactivated materials for cell culture and tissue engineering as well as capture systems for pathogenic microorganisms.     

Thermo-Responsive Hydrogels Coupled with Photothermal Agents for Biomedical Applications

Intelligent hydrogels are materials with abilities to change their chemical nature or physical structure in response to external stimuli showing promising potential in multitudinous applications. Especially, photo-thermo coupled responsive hydrogels that are prepared by encapsulating photothermal agents into thermo-responsive hydrogel matrix exhibit more attractive advantages in biomedical applications owing to their spatiotemporal control and precise therapy. This work summarizes the latest progress of the photo-thermo coupled responsive hydrogel in biomedical applications. Three major elements of the photo-thermo coupled responsive hydrogel, i.e., thermo-responsive hydrogel matrix, photothermal agents, and construction methods are introduced. Furthermore, the recent developments of these hydrogels for biomedical applications are described with some selected examples. Finally, the challenges and future perspectives for photo-thermo coupled responsive hydrogels are outlined.     

Comprehensive Examination of Mechanical and Diffusional Effects on Cell Behavior Using a Decoupled 3D Hydrogel System

Hydrogels possess several physical and chemical properties suitable for engineering cellular environments for biomedical applications. Despite recent advances in hydrogel systems for cell culture, it is still a significant challenge to independently control the mechanical and diffusional properties of hydrogels, both of which are well known to influence various cell behaviors when using hydrogels as 3D cell culture systems. Controlling the crosslinking density of a hydrogel system to tune the mechanical properties inevitably affects their diffusional properties, as the crosslinking density and diffusion are often inversely correlated. In this study, a polymeric crosslinker is demonstrated that allows for the adjustment of the degree of substitution of reactive functional groups. By using this polymeric crosslinker, the rigidity of the resulting hydrogel is controlled in a wide range without changing the polymer concentration. Furthermore, their diffusional properties, as characterized by their swelling ratios, pore diameters, and drug release rates, are not significantly affected by the changes in the degree of substitution. 3D cell studies using this hydrogel system successfully demonstrate the varying effects of mechanical properties on different cell types, whereas those in a conventional hydrogel system are more significantly influenced by changes in diffusional properties.     

水凝胶及其在药物控释体系上的应用

智能水凝胶作为药物载体有着良好的应用前景。人体环境中存在一些变化的因素，如温度、pH。因此，温度敏感性水凝胶和pH敏感性水凝胶可用于药物在人体中的控释体系。本文主要介绍水凝胶材料的种类以及智能水凝胶在药物控释体系上的应用。     

Nanofibers for Biomedical and Healthcare Applications

Unique features of nanofibers provide enormous potential in the field of biomedical and healthcare applications. Many studies have proven the extreme potential of nanofibers in front of current challenges in the medical and healthcare field. This review highlights the nanofiber technologies, unique properties, fabrication techniques (i.e., physical, chemical, and biological methods), and emerging applications in biomedical and healthcare fields. It summarizes the recent researches on nanofibers for drug delivery systems and controlled drug release, tissue‐engineered scaffolds, dressings for wound healing, biosensors, biomedical devices, medical implants, skin care, as well as air, water, and blood purification systems. Attention is given to different types of fibers (e.g., mesoporous, hollow, core‐shell nanofibers) fabricated from various materials and their potential biomedical applications.     

Novel poly(amido-amine)-based hydrogels as scaffolds for tissue engineering

Biodegradable and biocompatible amphoteric poly(amido-amine) (PAA)-based hydrogels, containing carboxyl groups along with amino groups in their repeating unit, were considered as scaffolds for tissue engineering applications. These hydrogels were obtained by co-polymerising 2,2-bisacrylamidoacetic acid with 2-methylpiperazine with or without the addition of different mono-acrylamides as modifiers, and in the presence of primary bis-amines as crosslinking agents. Hybrid PAA/albumin hydrogels were also prepared. The polymerisation reaction was a Michael-type polyaddition carried out in aqueous media. The PAA hydrogels were soft and swellable materials. Cytotoxicity tests were carried out by the direct contact method with fibroblast cell lines on the hydrogels both in their native state (that is, as free bases) and as salts with acids of different strength, namely hydrochloric, sulfuric, acetic and lactic acid. This was done in order to ascertain whether counterion-specific differences in cytotoxicity existed. It was found that all the amphoteric PAA hydrogels considered were cytobiocompatible both as free bases and salts. Selected hydrogels samples underwent degradation tests under controlled conditions simulating biological environments, i.e. Dulbecco medium at pH 7.4 and 37 degrees C. All samples degraded completely and dissolved within 10 d, with the exception of hybrid PAA/albumin hydrogels that did not dissolve even after eight months. The degradation products of all samples turned to be non-cytotoxic. All these results led us to conclude that PAA-based hydrogels have a definite potential as degradable matrices for biomedical applications.     

Multifunctional bioerodible/biodegradable polymeric materials

As a part of our continuing interest in the preparation of multifunctional polymeric materials and evaluation of their potential in biomedical and environmental field, a survey on new polymeric systems susceptible to bioerosion and/or biodegradation attack is presented. In particular attention has been focused on the preparation and characterization of the following classes of polymeric materials: 1) hydroxyl-containing polyesters; 2) functionalized cyclodextrins; 3) hydrophilic polymers containing carboxylic groups; 4) hydrogels for the release of phytodrugs; 5) hybrid polymeric materials; 6) synthetic and semisynthetic polyfunctional polymeric materials for the removal of uremic toxins. A few examples of the use of these polymers in the controlled release of drugs and as coadjuvants in the chronic renal failure treatment will be also presented.     

Advances in nitric oxide-releasing hydrogels for biomedical applications

Hydrogels provide a plethora of advantages to biomedical treatments due to their highly hydrophilic nature and tissue-like mechanical properties. Additionally, the numerous and widespread endogenous roles of nitric oxide have led to an eruption in research developing biomimetic solutions to the many challenges the biomedical world faces. Though many design factors and fabrication details must be considered, utilizing hydrogels as nitric oxide delivery vehicles provides promising materials in several applications. Such applications include cardiovascular therapy, vasodilation and angiogenesis, antimicrobial treatments, wound dressings, and stem cell research. Herein, a recent update on the progress of NO-releasing hydrogels is presented in depth. In addition, considerations for the design and fabrication of hydrogels and specific biomedical applications of nitric oxide-releasing hydrogels are discussed.     

药物控制释放用天然多糖载体的制备技术研究进展

药物的控制释放体系是生物医用材料研究领域的重要课题,其支撑点是要有性能良好的高分子药物载体。由于天然多糖作为药物控制释放材料具有比合成聚合物更多的优势,因而一直是国内外学者研究的重点。文章从微球与胶囊、水凝胶、压缩膜三方面分别对天然多糖药物载体的制备技术进行了简述,并提出了多糖研究中存在的主要问题和今后的研究重点。     

The Power of Confocal Laser Scanning Microscopy in Supramolecular Chemistry: In situ Real-time Imaging of Stimuli-Responsive Multicomponent Supramolecular Hydrogels

Multicomponent supramolecular hydrogels are promising scaffolds for applications in biosensors and controlled drug release due to their designer stimulus responsiveness. To achieve rational construction of multicomponent supramolecular hydrogel systems, their in-depth structural analysis is essential but still challenging. Confocal laser scanning microscopy (CLSM) has emerged as a powerful tool for structural analysis of multicomponent supramolecular hydrogels. CLSM imaging enables real-time observation of the hydrogels without the need of drying and/or freezing to elucidate their static and dynamic properties. Through multiple, selective fluorescent staining of materials of interest, multiple domains formed in supramolecular hydrogels (e. g. inorganic materials and self-sorting nanofibers) can also be visualized. CLSM and the related microscopic techniques will be indispensable to investigate complex life-inspired supramolecular chemical systems.     

Recent advances on bioprinting of hydrogels containing carbon materials

The intrinsic properties and versatility of carbon materials (CMs) have recently raised a growing interest in their combination with hydrogels towards the development of advanced materials for biomedical applications. The increasing demand for biomimetic constructs that closely mimic the intricate composition and structure of native tissues has boosted the interest in using three-dimensional (3D) bioprinting technologies for the processing of CMs-containing hydrogels into specialized and more complex constructs capable of steering cell behavior. This review summarizes the progress on the bioprinting of 3D hydrogels containing CMs, focusing on the role of CMs on biomaterial ink design and their impact on both the printing process and the biological function of fabricated constructs. Recent findings demonstrate that CMs are versatile materials that have been mostly used to (1) tune the rheological properties of biomaterial inks, (2) improve the mechanical properties of hydrogels, and/or (3) confer new physical features to hydrogels, such as shape memory, roughness, and thermal and electrical conductivity, which have been shown to modulate the biological response of bioprinted constructs.     

Tunable biohybrid hydrogels from coacervation of hyaluronic acid and PEO-based block copolymers

Accurately tuning the macroscopic properties of biopolymer-based hydrogels remains challenging due to the ill-defined molecular architecture of the natural building blocks. Here, we report a biohybrid coacervate hydrogel, combining the biocompatibility and biodegradability of naturally occurring hyaluronic acid (HA) with the tunability of a synthetic polyethylene oxide (PEO) -based ABA-triblock copolymer. Coacervation of the cationic ammonium or guanidinium-functionalized copolymer A-blocks with the anionic HA leads to hydrogel formation. Both mechanical properties and water content of the self-healing hydrogels can be controlled independently by altering the copolymer structure. By controlling the strength of the interaction between the polymer network and small-molecule cargo, both release rate and maximum release are controlled. Finally, we show that coacervation of HA and the triblock copolymer leads to increased biostability upon exposure to hyaluronidase. We envision that noncovalent crosslinking of HA hydrogels through coacervation is an attractive strategy for the facile synthesis of tunable hydrogels for biomedical applications.     

Comparative evaluation of various structures in polymer controlled drug delivery systems and the effect of their morphology and characteristics on drug release

Oral controlled drug delivery systems have become an essential part of the development of new medicines. In this investigation, several controlled release drug delivery systems with various structures were designed and evaluated. The materials used in their preparation were mainly hydropolymers that play a dominant role as drug carriers. Polymer selection is determined by the intended use and the desired release profile. The design of the devices was based on a matrix tablet, which is used as a core tablet for the preparation of all other systems such as multilayer systems, core in cup systems and hybrid systems. The findings of the study indicate that all systems exhibit controlled release characteristics. Furthermore, the structure of the device appears to significantly affect its behavior, i.e., the drug release and its release rate. Increasing the covered area of the core tablet results in a decrease of drug release since the cover hindrances the contact of the liquid with the core surface and modifies its dissolution and consequently its release. The hybrid systems exhibited pulsatile release, a feature offering significant advantages for certain therapies. Furthermore, the materials used considerably influence the behavior and function of the system. These effects may be attributed to the nature and the properties of the materials employed. Release mechanisms are also affected considerably by these factors.     

Chitosan based hybrid hydrogels for drug delivery: Preparation,biodegradation, thermal,and mechanical properties

In the present paper, biodegradable hybrid hydrogels were prepared by using chitosan as a natural polymer and polyurethane containing azomethine as a synthetic polymer for the drug delivery application for 5-fluorouracil. The fabricated hydrogels were characterized via FT-IR and SEM analysis. Besides, the thermal, mechanical, and wettability properties, water uptake, biodegradation, protein absorption, drug loading, and release behaviors of the hybrid hydrogels were studied. The obtained results indicated that the fabricated hybrid hydrogels have exhibited good mechanical, hydrophilic, water uptake, and biodegradation behaviors. The hybrid hydrogels also showed 50% drug release amounts and they could be a good candidate for the controlled delivery of 5-FU due to these properties.     

Vanillin cross-linked hydrogel membranes interfacial reinforced by carbon nitride nanosheets for enhanced antibacterial activity and mechanical properties

Biopolymer based hydrogels are highly adaptable, compatible and have shown great potential in biological tissues in biomedical applications. However, the development of bio-based hydrogels with high strength and effective antibacterial activity remains challenging. Herein, a series of Vanillin-cross-linked chitosan nanocomposite hydrogel interfacially reinforced by g-C₃N₄ nanosheet carrying starch-caped Ag NPs were prepared for wound healing applications. The study aimed to enhance the strength, sustainability and control release ability of the fabricated membranes. Starch-caped silver nanoparticles were incorporated to enhance the anti-bacterial activities The fabricated membranes were assessed using various characterization techniques such as FT-IR, XRD, SEM, mechanical testing, Gel fraction and porosity alongside traditional biomedical tests i.e., swelling percentage, moisture retention ability, water vapor transmission rate, oxygen permeability, anti-bacterial activity and drug-release of the fabricated membranes. The mechanical strength reached as high as 25.9 ± 0.24 MPa for the best optimized sample. The moisture retention lied between 87–89%, gel fraction 80–85%, and water vapor transmission up to 104 ± 1.9 g/m²h showing great properties of the fabricated membrane. Swelling percentage surged to 225% for blood while porosity fluctuated between 44% ± 2.1% and 52.5% ± 2.3%. Oxygen permeability reached up to 8.02 mg/L showing the breathable nature of fabricated membranes. The nanocomposite membrane shown excellent antibacterial activity for both gram-positive and gram-negative bacteria with a maximum zone of inhibition 30 ± 0.25 mm and 36.23 ± 0.23 mm respectively. Furthermore, nanoparticles maintained sustainable release following non-fickian diffusion. The fabricated membrane demonstrated the application of inorganic filler to enhance the strength of biopolymer hydrogel with superior properties. These results envisage the potential of synthesized membrane to be used as wound dressing, artificial skin and load-bearing scaffolds.     

Stimuli-responsive hydrogels based on polysaccharides incorporated with thermo-responsive polymers as novel biomaterials

In recent years, intelligent hydrogels which can change their swelling behavior and other properties in response to environmental stimuli such as temperature, pH, solvent composition and electric fields, have attracted great interest. The hydrogels based on polysaccharides incorporated with thermo-responsive polymers have shown unique properties such as biocompatibility, biodegradability, and biological functions in addition to the stimuli-responsive characters. These "smart" hydrogels exhibit single or multiple stimuli-responsive characters which could be used in biomedical applications, including controlled drug delivery, bioengineering or tissue engineering. This review focuses on the recent developments and future trends dealing with stimuli-responsive hydrogels based on grafting/blending of polysaccharides such as chitosan, alginate, cellulose, dextran and their derivatives with thermo-sensitive polymers. This review also screens the current applications of these hydrogels in the fields of drug delivery, tissue engineering and wound healing.     

DNA-based supramolecular hydrogels: From construction strategies to biomedical applications

DNA-based supramolecular hydrogels are important and promising biomaterials for various applications due to their inherent biocompatibility and tunable physicochemical properties. The three-dimensional supramolecular matrix of DNA formed by non-covalently dynamic cross-linking provides exceptional adaptability, self-healing, injectable and responsive properties for hydrogels. In addition, DNA hydrogels are also ideal bio-scaffold materials owing to their tissue-like mechanics and intrinsic biological functions. Technically, DNA can assemble into supramolecular networks by pure complementary base pairing; it can also be combined with other building blocks to construct hybrid hydrogels. This review focuses on the development and construction strategies of DNA hydrogels. Assembly and synthesis methods, diverse responsiveness and biomedical applications are summarized. Finally, the challenges and prospects of DNA-based supramolecular hydrogels are discussed.     

Varying the Stiffness and Diffusivity of Rod-Shaped Microgels Independently through Their Molecular Building Blocks

Microgels are water-swollen, crosslinked polymers that are widely used as colloidal building blocks in scaffold materials for tissue engineering and regenerative medicine. Microgels can be controlled in their stiffness, degree of swelling, and mesh size depending on their polymer architecture, crosslink density, and fabrication method—all of which influence their function and interaction with the environment. Currently, there is a lack of understanding of how the polymer composition influences the internal structure of soft microgels and how this morphology affects specific biomedical applications. In this report, we systematically vary the architecture and molar mass of polyethylene glycol-acrylate (PEG-Ac) precursors, as well as their concentration and combination, to gain insight in the different parameters that affect the internal structure of rod-shaped microgels. We characterize the mechanical properties and diffusivity, as well as the conversion of acrylate groups during photopolymerization, in both bulk hydrogels and microgels produced from the PEG-Ac precursors. Furthermore, we investigate cell-microgel interaction, and we observe improved cell spreading on microgels with more accessible RGD peptide and with a stiffness in a range of 20 kPa to 50 kPa lead to better cell growth.