Hydrogels For Biomedical Applications Research Articles

Tailoring of Physical Properties in Macroporous Poly(isocyanopeptide) Cryogels.

Over the years, synthetic hydrogels have proven remarkably useful as cell culture matrixes to elucidate the role of the extracellular matrix (ECM) on cell behavior. Yet, their lack of interconnected macropores undermines the widespread use of hydrogels in biomedical applications. To overcome this limitation, cryogels, a class of macroporous hydrogels, are rapidly emerging. Here, we introduce a new, highly elastic, and tunable synthetic cryogel, based on poly(isocyanopeptides) (PIC). Introduction of methacrylate groups on PIC facilitated cryopolymerization through free-radical polymerization and afforded cryogels with an interconnected macroporous structure. We investigated which cryogelation parameters can be used to tune the architectural and mechanical properties of the PIC cryogels by systematically altering cryopolymerization temperature, polymer concentration, and polymer molecular weight. We show that for decreasing cryopolymerization temperatures, there is a correlation between cryogel pore size and stiffness. More importantly, we demonstrate that by simply varying the polymer concentration, we can selectively tune the compressive strength of PIC cryogels without affecting their architecture. This unique feature is highly useful for biomedical applications, as it facilitates decoupling of stiffness from other variables such as pore size. As such, PIC cryogels provide an interesting new biomaterial for scientists to unravel the role of the ECM in cellular functions.

Novel Photothermal Graphene-Based Hydrogels in Biomedical Applications.

In the last decade, photothermal therapy (PTT) has attracted tremendous attention because it is non-invasive, shows high efficiency and antibacterial activity, and minimizes drug side effects. Previous studies demonstrated that PTT can effectively inhibit the growth of bacteria and promotes cell proliferation, accelerating wound healing and tissue regeneration. Among different NIR-responsive biomaterials, graphene-based hydrogels with photothermal properties are considered as the best candidates for biomedical applications, due to their excellent properties. This review summarizes the current advances in the development of innovative graphene-based hydrogels for PTT-based biomedical applications. Also, the information about photothermal properties and the potential applications of graphene-based hydrogels in biomedical therapies are provided. These findings provide a great potential for supporting their applications in photothermal biomedicine.

Variable swelling behavior of and drug encapsulation in a maleimide-modified hyaluronic acid nanogel-based hydrogel

Hyaluronic acid (HA) has garnered much attention in the development of novel hydrogels. Hydrogels, as drug delivery systems, are very important in tissue engineering applications. In this study, we developed a novel HA nanogel containing a cholesterol and maleimide derivative (HAMICH) and its corresponding crosslinked hydrogel (HAMICH gel) to encapsulate drugs for their subsequent release. HAMICH gels self-assemble into nanoparticles via hydrophobic interactions. Dynamic light scattering analysis of HAMICH revealed that the particle size tended to decrease with increasing degree of cholesterol moiety substitution. The HAMICH gel was prepared through a Michael addition reaction between HAMICH and pentaerythritol tetra(mercaptoethyl)polyoxyethylene. The concentration of HAMICH needed for gelation depends on the degree of cholesterol moiety substitution; the higher the substitution degree is, the greater the concentration of HAMICH needed. The HAMICH gel exhibited less swelling and a smaller volume change than the gel with an unmodified cholesterol moiety in phosphate-buffered saline (pH 7.4). The HAMICH gel displayed enhanced peptide and protein trapping abilities without hydrogel swelling, suggesting its potential as a HA hydrogel for biomedical applications.

Janus hydrogels: merging boundaries in tissue engineering for enhanced biomaterials and regenerative therapies.

In recent years, the design and synthesis of Janus hydrogels have witnessed a thriving development, overcoming the limitations of single-performance materials and expanding their potential applications in tissue engineering and regenerative medicine. Janus hydrogels, with their exceptional mechanical properties and excellent biocompatibility, have emerged as promising candidates for various biomedical applications, including tissue engineering and regenerative therapies. In this review, we present the latest progress in the synthesis of Janus hydrogels using commonly employed preparation methods. We elucidate the surface and interface interactions of these hydrogels and discuss the enhanced properties bestowed by the unique "Janus" structure in biomaterials. Additionally, we explore the applications of Janus hydrogels in facilitating regenerative therapies, such as drug delivery, wound healing, tissue engineering, and biosensing. Furthermore, we analyze the challenges and future trends associated with the utilization of Janus hydrogels in biomedical applications.

A novel injectable sericin hydrogel with strong fluorescence for tracing

Hydrogel systems with strong fluorescence, as convenient tracers or bio-probes, have attracted much attention in biomedical engineering. Currently, most hydrogels endowed fluorescent properties due to modifying additional fluorophores. However, these fluorophores owing to photobleaching and toxicity limit the practical applications of hydrogels. Herein, we prepared a novel self-luminescence hydrogel through double crosslinking glutaraldehyde and hydrogen peroxide/horseradish peroxidase (H2O2/HRP) with sericin protein. The double cross-linked sericin hydrogel exhibits strong green and red intrinsic fluorescence which can be excited over a wide range of wavelengths. Moreover, this hydrogel with strong intrinsic fluorescence could penetrate thick pigskin tissue, which has potential application in implantable bio-tracer areas. In addition to the above unique properties, this sericin hydrogel possesses two types of micropore structures with high porosity, swelling properties, pH-responsive degradability, super elasticity, injectability, viscosity, and excellent biocompatibility. The investigation could significantly expand the scope of protein hydrogels in biomedical applications.

Synthesis of novel antibacterial and biocompatible polymer nanocomposite based on polysaccharide gum hydrogels

According to recent studies on the benefits of natural polymer-based hydrogels in biomedical applications, gellan gum (GG)/acacia gum (AG) hydrogel was prepared in this study. In order to regulate the mechanical behavior of the hydrogel, graphite carbon nitride (g-C3N4) was included in the hydrogel matrix. In addition, metal oxide nanoparticles ZnCuFe2O4 were added to the composite for antibacterial activity. The prepared GG–AG hydrogel/g-C3N4/ZnCuFe2O4 nanobiocomposite was characterized by using FE-SEM, FTIR, EDX, XRD and TGA. The nanobiocomposite exhibited spherical morphology, which was related to the incorporation of the metal oxide nanoparticles. GG–AG hydrogel/g-C3N4/ZnCuFe2O4 nanobiocomposite showed 95.11%, 92.73% and 88.97% biocompatibility toward HEK293T cell lines within 24 h, 48 h and 72 h incubation, respectively, which indicates that this nanobiocomposite is completely biocompatible with healthy cells. Also, the nanobiocomposite was able to inhibit Pseudomonas aeruginosa biofilm growth on its surface up to 87%. Rheological studies showed that the nanobiocomposite has a viscoelastic structure and has a water uptake ratio of 93.2%. In comparison with other similar studies, this nanobiocomposite has exhibited superior antibacterial activity complete biocompatibility and proper mechanical properties, high swelling and water absorption capability. These results indicate that GG–AG hydrogel/g-C3N4/ZnCuFe2O4 nanocomposite can be considered as a potential candidate for biomedical applications such as tissue engineering and wound healing.

Antimicrobial Hydrogels: Potential Materials for Medical Application.

Microbial infections based on drug-resistant pathogenic organisms following surgery or trauma and uncontrolled bleeding are the main causes of increased mortality from trauma worldwide. The prevalence of drug-resistant pathogens has led to a significant increase in medical costs and poses a great threat to the normal life of people. This is an important issue in the field of biomedicine, and the emergence of new antimicrobial materials hydrogels holds great promise for solving this problem. Hydrogel is an important material with good biocompatibility, water absorption, oxygen permeability, adhesion, degradation, self-healing, corrosion resistance, and controlled release of drugs as well as structural diversity. Bacteria-disturbing hydrogels have important applications in the direction of surgical treatment, wound dressing, medical device coating, and tissue engineering. This paper reviews the classification of antimicrobial hydrogels, the current status of research, and the potential of antimicrobial hydrogels for one application in biomedicine, and analyzes the current research of hydrogels in biomedical applications from five aspects: metal-loaded hydrogels, drug-loaded hydrogels, carbon-material-loaded hydrogels, hydrogels with fixed antimicrobial activity and biological antimicrobial hydrogels, and provides an outlook on the high antimicrobial activity, biodegradability, biocompatibility, injectability, clinical applicability and future development prospects of hydrogels in this field.

Semi‐solid 3D printing of mesoporous silica nanoparticle‐incorporated xeno‐free nanomaterial hydrogels for protein delivery

AbstractMultifunctional biomaterial inks are in high demand for adapting hydrogels in biomedical applications through three‐dimensional (3D) printing. Our previously developed xeno‐free system consisting of anionic cellulose nanofibers (T‐CNF) and methacrylated galactoglucomannan (GGMMA) as a photo(bio)polymer provides high‐performance ink fidelity in extrusion‐based 3D printing. The fusion between nanoparticles and this biomaterial‐ink system is a promising yet challenging avenue worth exploring, due to the colloidal stability of T‐CNF being sensitive to electrostatic interactions. Mesoporous silica nanoparticles (MSNs), with their robust ceramic matrix and fine‐tunable surface chemistries, are well‐established nanocarriers for different biologicals. Here, we fabricated MSNs with different surface modifications resulting in a net surface charge ranging from highly negative to highly positive to develop printable MSNs‐laden nanocomposite biomaterial inks. We utilized rheology as a comprehensive tool to address the matrix interactions with differently surface‐charged MSNs. Fluorescently labeled bovine serum albumin (FITC‐BSA) was used as a model protein for MSN loading, whereby negatively or neutral‐charged MSNs were found suitable to formulate FITC‐BSA‐loaded biomaterial inks of T‐CNF/GGMMA. Depending on the particles’ surface charge, FITC‐BSA showed different release profiles and preserved its stability after release. Lastly, the proof‐of‐concept to deliver large‐sized biological cargo with MSN‐laden nanocomposite biomaterial inks was established via the 3D printing technique.

Energy‐Dissipative Hydrogels: A Promising Material for Tissue Regeneration†

Comprehensive SummaryHydrogels are promising candidates for mimicking native extracellular matrix (ECM) and are therefore widely adopted as scaffolds in tissue engineering. However, conventional hydrogels composed of static networks are prone to permanent structural damages and lack the ability to provide the time‐dependent mechanical cues, which are essential for cell development, ECM remodeling, and tissue regeneration. The recent substantial development in the structurally dynamic hydrogels with energy‐dissipative ability has demonstrated the unique capability of such viscoelastic hydrogels to withstand extreme biomechanical loads and regulate cellular behaviors not present in classical hydrogels. This review starts with the general design principles for energy‐dissipative hydrogels, followed by recent advancements in fabrication approaches for energy‐dissipative hydrogels. We then highlight some applications of energy‐dissipative hydrogels in tissue engineering, including bone and cartilage regeneration, vessel regeneration, nerve regeneration, and wound healing. Finally, we discuss about the key current challenges and future development of energy‐dissipative hydrogels for biomedical applications.

Plant-inspired adhesive and injectable natural hydrogels: invitroand invivo studies.

The development of alternative therapeutic treatments based on the use of medicinal and aromatic plants, such as Juniper communis L., has aroused interest in the medical field to find new alternatives to conventional therapeutic treatments, which have shown problems related to bacterial resistance, high costs, or sustainability in their production. The present work describes the use of hydrogels based on sodium alginate and carboxymethyl cellulose, with combinations of juniperus leaves and berry extracts, in order to characterize their chemical characteristics, antibacterial activity, tissue adhesion test, cytotoxicity in the L929 cell line, and their effects on an in vivo model in mice to maximize the use of these materials in the healthcare field. Overall, an adequate antibacterial potential against S. aureus, E. coli and P. vulgaris was obtained with doses above 100mg.mL-1 of hydrogels. Likewise, low cytotoxicity in hydrogels combined with extracts has been identified according to the IC50 value at 17.32µg.mL-1, compared to the higher cytotoxic activity expressed by the use of control hydrogels with a value at 11.05µg.mL-1. Moreover, in general, the observed adhesion was high to different tissues, showing its adequate capacity to be used in different tissue typologies. Furthermore, the invivo results have not shown erythema, edema, or other complications related to the use of the proposed hydrogels. These results suggest the feasibility of using these hydrogels in biomedical applications given the observed safety.

Hydrophobized Hydrogels: Construction Strategies, Properties, and Biomedical Applications

AbstractHydrogels, as 3D networks containing huge amount of water, display similarity to soft tissues, and thus they are of wide interest in tissue engineering. Hydrogels, due to biocompatibility and porous structure, are valuable therapeutic platforms for hydrophilic drugs. Over the last decade, there has been a strong emphasis on the development of hydrogel platforms with the ability to increase the solubility of hydrophobic drugs. However, the pronounced discrepancy between the hydrophilic character of hydrogels and the hydrophobic nature of numerous pharmacologically active compounds is problematic. In recent years, different strategies are applied using special polymer constructs or composite materials exploiting the advanced scientific knowledge in the area of polymer and lipid‐based nano‐ and microcarriers hydrophobization of the hydrogel turns out to be not only valuable in terms of achieving the ability to dissolve poorly soluble drugs in water, but also proves to be crucial in obtaining bioadhesion in wet conditions, but also, unexpected abnormal water swelling behavior, as well as in mechanical properties such as the dissipation mechanism and self‐healable hydrogel properties. This review is mainly focused on recent advances in the usage of hydrophobized hydrogels in biomedical applications.

Emerging Role of Injectable Dipeptide Hydrogels in Biomedical Applications.

Owing to their properties such as biocompatibility, tunable mechanical properties, permeability toward oxygen, nutrients, and the ability to hold a significant amount of water, hydrogels have wide applications in biomedical research. They have been engaged in drug delivery systems, 3D cell culture, imaging, and extracellular matrix (ECM) mimetics. Injectable hydrogels represent a major subset of hydrogels possessing advantages of site-specific conformation with minimal invasive techniques. It preserves the inherent properties of drug/biomolecules and is devoid of any side effects associated with surgery. Various polymeric materials utilized in developing injectable hydrogels are associated with the limitations of toxicity, immunogenicity, tedious manufacturing processes, and lack of easy synthetic tunability. Peptides are an important class of biomaterials that have interesting properties such as biocompatibility, stimuli responsiveness, shear thinning, self-healing, and biosignaling. They lack immunogenicity and toxicity. Therefore, numerous peptide-based injectable hydrogels have been explored in the past, and a few of them have reached the market. In recent years, minimalistic dipeptides have shown their ability to form stable hydrogels through cooperative noncovalent interactions. In addition to inherent properties of lengthy peptide-based injectable hydrogels, dipeptides have the unique advantages of low production cost, high synthetic accessibility, and higher stability. Given the instances of expanding significance of injectable peptide hydrogels in biomedical research and an emerging recent trend of dipeptide-based injectable hydrogels, a timely review on dipeptide-based injectable hydrogels shall highlight various aspects of this interesting class of biomaterials. This concise review that focuses on the dipeptide injectable hydrogel may stimulate the current trends of research on this class of biomaterial to translate its significance as interesting products for biomedical applications.

Silk fibroin hydrogels for biomedical applications

AbstractSilk fibroin hydrogels occupy an essential position in the biomedical field due to their remarkable biological properties, excellent mechanical properties, flexible processing properties, as well as abundant sources and low cost. Herein, we introduce the unique structures and physicochemical characteristics of silk fibroin, including mechanical properties, biocompatibility, and biodegradability. Then, various preparation strategies of silk fibroin hydrogels are summarized, which can be divided into physical cross‐linking and chemical cross‐linking. Emphatically, the applications of silk fibroin hydrogel biomaterials in various biomedical fields, including tissue engineering, drug delivery, and wearable sensors, are systematically summarized. At last, the challenges and future prospects of silk fibroin hydrogels in biomedical applications are discussed.

Marine‐Derived Hydrogels for Biomedical Applications

Marine organisms provide novel and broad sources for the preparations and applications of biomaterials. Since the urgent requirement of bio‐hydrogels to mimic tissue extracellular matrix (ECM), the natural biomacromolecule hydrogels derived from marine sources have received increasing attention. Benefiting from their outstanding bioactivity and biocompatibility, many attempts have been made to reconstruct ECM components by applying marine‐derived natural hydrogels. Moreover, marine hydrogels have been successfully applied in biomedicine by means of microfluidics, electrospray, and bioprinting. In this review, the classification and characteristics of marine‐derived hydrogels are summarized. In particular, their role in the development of biomaterials is also introduced. Then, the recent advances in bio‐fabrication strategies for various hydrogel materials are focused upon. Besides, the influences of hydrogel types on their functions in biomedical applications are discussed in depth. Finally, critical reflections on the limitations and future development of marine‐derived hydrogels are presented.

Recent developments in stimuli‐responsive hydrogels for biomedical applications

Hydrogels exhibit a performance similar to that of the extracellular matrix and are compatible with human tissues and organs. Stimuli-responsive hydrogels that can respond smartly to a variety of stimuli have recently attracted extensive interest for biomedical applications. The response of these hydrogels to various single/multiple stimuli shows great potential for drug delivery, biosensors, wound dressing, cancer therapy, and tissue engineering. This review summarises the recent advances in the design of different stimuli-responsive hydrogels and their biomedical applications. We herein describe the mechanisms underlying the stimulus–response, and summarise the strategies for fabricating stimuli-responsive hydrogels that can respond to single or multiple stimuli from endogenous (i.e. pH, enzymes, glucose, and reactive oxygen species) or exogenous (i.e. magnetic and electric fields, temperature, and photo) sources. The current challenges faced by stimuli-responsive hydrogels are discussed and an outlook on future research directions is provided.

Fabrication Strategies Towards Hydrogels for Biomedical Application: Chemical and Mechanical Insights.

This review aims at giving selected chemical and mechanical insights on design criteria that should be taken into account in hydrogel production for biomedical applications. Particular emphasis will be given to the chemical aspects involved in hydrogel design: macromer chemical composition, cross-linking strategies and chemistry towards "conventional" and smart/stimuli responsive hydrogels. Mechanical properties of hydrogels in view of regenerative medicine applications will also be considered.

Design strategies for adhesive hydrogels with natural antibacterial agents as wound dressings: Status and trends.

The wound healing process is usually susceptible to different bacterial infections due to the complex physiological environment, which significantly impairs wound healing. The topical application of antibiotics is not desirable for wound healing because the excessive use of antibiotics might cause bacteria to develop resistance and even the production of super bacteria, posing significant harm to human well-being. Wound dressings based on adhesive, biocompatible, and multi-functional hydrogels with natural antibacterial agents have been widely recognized as effective wound treatments. Hydrogels, which are three-dimensional (3D) polymer networks cross-linked through physical interactions or covalent bonds, are promising for topical antibacterial applications because of their excellent adhesion, antibacterial properties, and biocompatibility. To further improve the healing performance of hydrogels, various modification methods have been developed with superior biocompatibility, antibacterial activity, mechanical properties, and wound repair capabilities. This review summarizes hundreds of typical studies on various ingredients, preparation methods, antibacterial mechanisms, and internal antibacterial factors to understand adhesive hydrogels with natural antibacterial agents for wound dressings. Additionally, we provide prospects for adhesive and antibacterial hydrogels in biomedical applications and clinical research.

Preparation of injectable free‐HRP‐mediated and self‐catalyzed gelatin‐tyramine hydrogel for biomedical applications

AbstractApproaches of synthesizing injectable hydrogels have drawn significant attention in several fields including drug delivery, tissue adhesion, and wound healing. Among them, injectable horseradish peroxidase‐mediated hydrogels have emerged as a prospective candidate in the development of biomedical materials. In the study, we prepared a hematin‐gelatin‐tyramine (HGT) polymer which could be exploited to prepare an injectable hydrogel in absence of Horseradish peroxidase (HRP). The chemical structure of HGT was characterized by UV‐Vis, 1H‐NMR spectroscopies. The HGT hydrogel could be formed in situ rapidly in presence of a small amount of H2O2 (3‐15 mM). Besides, HGT can catalyze pyrogallol and guaiacol like the enzyme HRP, and HGT has good biodegradability. Further studies on the biocompatibility of hydrogels will be investigated towards tissue regeneration.

Biomolecule‐based hydrogels containing electrospun fiber mats with enhanced mechanical properties and biological activity

AbstractPhotopolymerizable hydrogels based on methacryloyl gelatin (GeIMA) have potential for biomedical applications, due to their high processability, biological activity, and possibility of cell encapsulation. However, biomolecule‐based hydrogels have often poor mechanical properties that limit their application. In this work, we prepared hydrogels with enhanced mechanical properties and biological activity by incorporating mats of electrospun polycaprolactone fibers containing GeIMA in GelMA hydrogels. These GelMA hydrogels with electrospun fiber mats were prepared by photopolymerizing either a blend of chopped fiber mats and GelMA or stacking electrospun fiber mats impregnated with GelMA. Cell encapsulation, viability and proliferation were also investigated. Scanning electron microscopy images showed pore walls of lyophilized hydrogels decorated with chopped fiber mats. Mechanical properties of hydrogels containing stacks of electrospun fiber mats were much higher than pure hydrogels. Encapsulated cells within hydrogels were observed to grow faster than in hydrogels with no fiber mats, as an indication that the extracellular matrix‐like texture of the fiber mats within the hydrogels can enhance the biological activity of the materials. The overall results revealed that the tested approaches to prepare hydrogels with electrospun fiber mats can expand the usage of biomolecule‐based hydrogels in biomedical applications.

“Smart” alginate hydrogels in biosensing, bioactuation and biocomputing: State-of-the-art and perspectives

In addressing the demand for biocompatible wearable, implantable and injectable biomedical devices, alginate hydrogels stand out as promising candidates. Alginate hydrogels have been used as matrix for immobilization of proteins, responsive polymers and nanomaterials that lead to a wide range of stimuli-responsive “smart” (bio)(nano)composite hydrogels. In this perspective, we analyzed the most recent applications of “smart” alginate composite hydrogels in biomedical applications, such as biosensing, drug delivery, wound healing and biocomputing. The design and key-responsive element of the composites were discussed as well as their practical application in biologically relevant conditions and in vivo. Finally, we provide our insights into the limitations, challenges and future directions of this exciting research field.