Hydrogels For Engineering Research Articles

Injectable, Pore-Forming, Perfusable Double-Network Hydrogels Resilient to Extreme Biomechanical Stimulations.

Biological tissues hinge on blood perfusion and mechanical toughness to function. Injectable hydrogels that possess both high permeability and toughness have profound impacts on regenerative medicine but remain a long‐standing challenge. To address this issue, injectable, pore‐forming double‐network hydrogels are fabricated by orchestrating stepwise gelation and phase separation processes. The interconnected pores of the resulting hydrogels enable direct medium perfusion through organ‐sized matrices. The hydrogels are amenable to cell encapsulation and delivery while promoting cell proliferation and spreading. They are also pore insensitive, tough, and fatigue resistant. When tested in biomimetic perfusion bioreactors, the hydrogels maintain physical integrity under prolonged, high‐frequency biomechanical stimulations (>6000 000 cycles at 120 Hz). The excellent biomechanical performance suggests the great potential of the new injectable hydrogel technology for repairing mechanically dynamic tissues, such as vocal folds, and other applications, such as tissue engineering, biofabrication, organs‐on‐chips, drug delivery, and disease modeling.

Overview of methods in Oil spill technology

Over the decades oil spills have been the biggest threat to the aquatic life and to a nation’s economy. Many methods were suggested in the literature to remove the oil that is present on the surface of sea water after the spill. Hydrogel formation is one of the best technique that could be adopted to handle oil spills. Since the oil spill is a oil and water emulsion, formation of hydrogels with these emulsions could lead to the recovery of oil. The formation of hydrogels can be either physically crosslinking the polymer molecules or covalent bonding among the entangled polymer molecules. The methods of making the hydrogels conceivable to acquire surface hydrophobicity and oleophilicity. Hydrogel technology could be more cost effective and efficient in recovering the oil from the spill, eco-friendly and easy to use. It is proposed that the hydrogels could be potential candidates for handling the oil spills. The methods described in this review explains the various hydrogels that could be utilized for oil spill recovery.

3D Bioprinting of Cell-Laden Hydrogels for Improved Biological Functionality.

The encapsulation of cells within gel-phase materials to form bioinks offers distinct advantages for next-generation 3D bioprinting. 3D bioprinting has emerged as a promising tool for patterning cells, but the technology remains limited in its ability to produce biofunctional, tissue-like constructs due to a dearth of materials suitable for bioinks. While early demonstrations commonly used viscous polymers optimized for printability, these materials often lacked cell compatibility and biological functionality. In response, advanced materials that exist in the gel phase during the entire printing process are being developed, since hydrogels are uniquely positioned to both protect cells during extrusion and provide biological signals to embedded cells as the construct matures during culture. Here, an overview of the design considerations for gel-phase materials as bioinks is presented, with a focus on their mechanical, biochemical, and dynamic gel properties. Current challenges and opportunities that arise due to the fact that bioprinted constructs are active, living hydrogels composed of both acellular and cellular components are also evaluated. Engineering hydrogels with consideration of cells as an intrinsic component of the printed bioink will enable control over the evolution of the living construct after printing to achieve greater biofunctionality.

A Modeling-Based Design to Engineering Protein Hydrogels with Random Copolymers.

Protein enzymes have shown great potential in numerous technological applications. However, the design of supporting materials is needed to preserve protein functionality outside their native environment. Direct enzyme-polymer self-assembly offers a promising alternative to immobilize proteins in an aqueous solution, achieving higher control of their stability and enzymatic activity in industrial applications. Herein, we propose a modeling-based design to engineering hydrogels of cytochrome P450 and of PETase with styrene/2-vinylpyridine (2VP) random copolymers. By tuning the copolymer fraction of polar groups and of charged groups via quaternization of 2VP for coassembly with cytochrome P450 and via sulfonation of styrene for coassembly with PETase, we provide quantitative guidelines to select either a protein-polymer hydrogel structure or a single-protein encapsulation. The results highlight that, regardless of the protein surface domains, the presence of polar interactions and hydration effects promote the formation of a more elongated enzyme-polymer complex, suggesting a membrane-like coassembly. On the other hand, the effectiveness of a single-protein encapsulation is reached by decreasing the fraction of polar groups and by increasing the charge fraction up to 15%. Our computational analysis demonstrates that the enzyme-polymer assemblies are first promoted by the hydrophobic interactions which lead the protein nonpolar residues to achieve the maximum coverage and to play the role of the most robust contact points. The mechanisms of coassembly are unveiled in the light of both protein and polymer physical-chemistry, providing bioconjugate phase diagrams for the optimal material design.

Injectable Mussel‐Inspired highly adhesive hydrogel with exosomes for endogenous cell recruitment and cartilage defect regeneration

In the early stage of osteoarthritis (OA), cartilage degradation in the surface region leads to superficial cartilage defect. However, enhancing the regeneration of cartilage defect remains a great challenge for existing hydrogel technology because of the weak adhesion to wet tissue. In the present study, an injectable mussel-inspired highly adhesive hydrogel with exosomes was investigated for endogenous cell recruitment and cartilage defect regeneration. The hydrogel with high bonding strength to the wet surface was prepared using a crosslinked network of alginate-dopamine, chondroitin sulfate, and regenerated silk fibroin (AD/CS/RSF). Compared with commercial enbucrilate tissue adhesive, the AD/CS/RSF hydrogel provided a comparative lap shear strength of 120 kPa, with a similar gelation time and a higher capacity for maintaining adhesive strength. The AD/CS/RSF/EXO hydrogel with encapsulated exosomes recruited BMSCs migration and inflation, promoted BMSCs proliferation and differentiation. Most importantly, the AD/CS/RSF/EXO hydrogel accelerated cartilage defect regeneration in situ, and extracellular matrix remodeling after injection in rat patellar grooves. The exosomes released by the hydrogels could recruit BMSCs into the hydrogel and neo-cartilage via the chemokine signaling pathway. Our findings reveal an injectable and adhesive hydrogel for superficial cartilage regeneration, which is a promising approach for minimally treating cartilage defect with arthroscopic assistance.

Recent Advances in Hydrogels: Ophthalmic Applications in Cell Delivery, Vitreous Substitutes, and Ocular Adhesives.

With the prevalence of eye diseases, such as cataracts, retinal degenerative diseases, and glaucoma, different treatments including lens replacement, vitrectomy, and stem cell transplantation have been developed; however, they are not without their respective shortcomings. For example, current methods to seal corneal incisions induced by cataract surgery, such as suturing and stromal hydration, are less than ideal due to the potential for surgically induced astigmatism or wound leakage. Vitrectomy performed on patients with diabetic retinopathy requires an artificial vitreous substitute, with current offerings having many shortcomings such as retinal toxicity. The use of stem cells has also been investigated in retinal degenerative diseases; however, an optimal delivery system is required for successful transplantation. The incorporation of hydrogels into ocular therapy has been a critical focus in overcoming the limitations of current treatments. Previous reviews have extensively documented the use of hydrogels in drug delivery; thus, the goal of this review is to discuss recent advances in hydrogel technology in surgical applications, including dendrimer and gelatin-based hydrogels for ocular adhesives and a variety of different polymers for vitreous substitutes, as well as recent advances in hydrogel-based retinal pigment epithelium (RPE) and retinal progenitor cell (RPC) delivery to the retina.

Engineering hydrogels with homogeneous mechanical properties for controlling stem cell lineage specification

The extracellular matrix (ECM) is mechanically inhomogeneous due to the presence of a wide spectrum of biomacromolecules and hierarchically assembled structures at the nanoscale. Mechanical inhomogeneity can be even more pronounced under pathological conditions due to injury, fibrogenesis, or tumorigenesis. Although considerable progress has been devoted to engineering synthetic hydrogels to mimic the ECM, the effect of the mechanical inhomogeneity of hydrogels has been widely overlooked. Here, we develop a method based on host-guest chemistry to control the homogeneity of maleimide-thiol cross-linked poly(ethylene glycol) hydrogels. We show that mechanical homogeneity plays an important role in controlling the differentiation or stemness maintenance of human embryonic stem cells. Inhomogeneous hydrogels disrupt actin assembly and lead to reduced YAP activation levels, while homogeneous hydrogels promote mechanotransduction. Thus, the method we developed to minimize the mechanical inhomogeneity of hydrogels may have broad applications in cell culture and tissue engineering.

The Translational Application of Hydrogel for Organoid Technology: Challenges and Future Perspectives.

Human organoids mimic the physiology and tissue architecture of organs and are of great significance for promoting the study of human diseases. Traditionally, organoid cultures rely predominantly on animal or tumor-derived extracellular matrix (ECM), resulting in poor reproducibility. This limits their utility in for large-scale drug screening and application for regenerative medicine. Recently, synthetic polymeric hydrogels, with high biocompatibility and biodegradability, stability, uniformity of compositions, and high throughput properties, have emerged as potential materials for achieving 3D architectures for organoid cultures. Compared to conventional animal or tumor-derived organoids, these newly engineered hydrogel-based organoids more closely resemble human organs, as they are able to mimic native structural and functional properties observed in-situ. In this review, recent developments in hydrogel-based organoid culture will be summarized, emergent hydrogel technology will be highlighted, and future challenges in applying them to organoid culture will be discussed.

Development of Nanosilicate-Hydrogel Composites for Sustained Delivery of Charged Biopharmaceutics.

Nanocomposite hydrogels containing two-dimensional nanosilicates (NS) have emerged as a new technology for the prolonged delivery of biopharmaceuticals. However, little is known about the physical-chemical properties governing the interaction between NS and proteins and the release profiles of NS-protein complexes in comparison to traditional poly(ethylene glycol) (PEG) hydrogel technologies. To fill this gap in knowledge, we fabricated a nanocomposite hydrogel composed of PEG and laponite and identified simple but effective experimental conditions to obtain sustained protein release, up to 23 times slower as compared to traditional PEG hydrogels, as determined by bulk release experiments and fluorescence correlation spectroscopy. Slowed protein release was attributed to the formation of NS-protein complexes, as NS-protein complex size was inversely correlated with protein diffusivity and release rates. While protein electrostatics, protein concentration, and incubation time were important variables to control protein-NS complex formation, we found that one of the most significant and less appreciated variable to obtain a sustained release of bioactive proteins was the buffer chosen for preparing the initial suspension of NS particles. The buffer was found to control the size of nanoparticles, the absorption potential, morphology, and stiffness of hydrogels. From these studies, we conclude that the PEG-laponite composite fabricated is a promising new platform for sustained delivery of positively charged protein therapeutics.

Research progress in decellularized extracellular matrix-derived hydrogels.

Decellularized extracellular matrix (dECM) is widely used in regenerative medicine as a scaffold material due to its unique biological activity and good biocompatibility. Hydrogel is a three-dimensional network structure polymer with high water content and high swelling that can simulate the water environment of human tissues, has good biocompatibility, and can exchange nutrients, oxygen, and waste with cells. At present, hydrogel is the ideal biological material for tissue engineering. In recent years, rapid development of the hydrogel theory and technology and progress in the use of dECM to form hydrogels have attracted considerable attention to dECM hydrogels as an innovative method for tissue engineering and regenerative medicine. This article introduces the classification of hydrogels, and focuses on the history and formation of dECM hydrogels, the source of dECM, the application of dECM hydrogels in tissue engineering and the commercial application of dECM materials.

Translational Applications of Hydrogels.

Advances in hydrogel technology have unlocked unique and valuable capabilities that are being applied to a diverse set of translational applications. Hydrogels perform functions relevant to a range of biomedical purposes—they can deliver drugs or cells, regenerate hard and soft tissues, adhere to wet tissues, prevent bleeding, provide contrast during imaging, protect tissues or organs during radiotherapy, and improve the biocompatibility of medical implants. These capabilities make hydrogels useful for many distinct and pressing diseases and medical conditions and even for less conventional areas such as environmental engineering. In this review, we cover the major capabilities of hydrogels, with a focus on the novel benefits of injectable hydrogels, and how they relate to translational applications in medicine and the environment. We pay close attention to how the development of contemporary hydrogels requires extensive interdisciplinary collaboration to accomplish highly specific and complex biological tasks that range from cancer immunotherapy to tissue engineering to vaccination. We complement our discussion of preclinical and clinical development of hydrogels with mechanical design considerations needed for scaling injectable hydrogel technologies for clinical application. We anticipate that readers will gain a more complete picture of the expansive possibilities for hydrogels to make practical and impactful differences across numerous fields and biomedical applications.

Engineering Hydrogels for Efficient Solar Desalination and Water Purification

ConspectusSafe and adequate water is a global challenge due to the growing population and pollution in the wake of natural disasters. Access to clean water is a cornerstone for the further development of our modern society. Solar-powered desalination and water purification have attracted much research attention due to the high solar-to-thermal conversion efficiency and ease of implementation in multiple scales, from compact, stand-alone devices for individual households to large, centralized dimensions for communities. Nevertheless, the generation of water vapor at low temperatures below the boiling point is usually a slow process under natural sunlight. The production rate of clean water relies on the efficiencies of solar energy conversion and utilization, which can be enhanced in two directions: systems optimization and materials innovation. Starting from bottom heating and volumetric heating, interfacial evaporation has been adopted recently to systematically reduce energy loss by localizing heat near the evaporation surface using photothermal materials. Meanwhile, carbonaceous materials, narrow bandgap semiconductors, and polymers with different structures were designed to achieve thermal management and water transport.In this Account, we highlight the recent progress of hydrogels as a highly tunable material platform for solar-powered desalination and water purification. We begin by introducing how gelation chemistry endows hydrogels with desirable properties and multiscale tunability from molecular to macroscopic levels. Then, we review three major strategies to promote efficient solar-to-vapor conversion in terms of reducing water evaporation enthalpy, optimizing heat distribution, and tailoring the evaporation surface. First, by selecting polymeric backbones with hydratable functional groups, the water state in hydrogels can be regulated to facilitate intermediate water, which has a lower evaporation enthalpy compared to that of the bulk water. This polymer–water interaction can be further tuned during synthesis and post-treatment. Second, light-absorbing additives within hydrogels should not only convert solar energy to heat effectively but also confine the heat near the evaporative surfaces. Third, since water molecules are encapsulated in the polymer network of hydrogels, the surface of the hydrogel becomes the evaporation front of liquid water. Hence, tailoring the surface topography and wettability of hydrogels has important effects on the evaporation rate. Next, we discuss key functions that endow hydrogel evaporators with excellent desalination and purification performances, including anti-salt-fouling property for stable and long-term desalination, as well as easy integration of functional materials to remove other contaminants, such as heavy metal ions and organic dyes, for greater distillate quality. Last, existing challenges and future opportunities in both fundamental studies and practical implementation of the hydrogel-based solar water purification systems are discussed.

3D biomaterial models of human brain disease

Inherent limitations of the traditional approaches to study brain function and disease, such as rodent models and 2D cell culture platforms, have led to the development of 3D in vitro cell culture systems. These systems, products of multidisciplinary efforts encompassing stem cell biology, materials engineering, and biofabrication, have quickly shown great potential to mimic biochemical composition, structural properties, and cellular morphology and diversity found in the native brain tissue. Crucial to these developments have been the advancements in stem cell technology and cell reprogramming protocols that allow reproducible generation of human subtype-specific neurons and glia in laboratory conditions. At the same time, biomaterials have been designed to provide cells in 3D with a microenvironment that mimics functional and structural aspects of the native extracellular matrix with increasing fidelity. In this article, we review the use of biomaterials in 3D in vitro models of neurological disorders with focus on hydrogel technology and with biochemical composition and physical properties of the in vivo environment as reference.

Mussel-inspired poly(γ-glutamic acid)/nanosilicate composite hydrogels with enhanced mechanical properties, tissue adhesive properties, and skin tissue regeneration

It was demonstrated herein that the adhesive property of catechol-functionalized nanocomposite hydrogel can be enhanced by tuning the cohesive strength due to the secondary crosslinking between catechol and synthetic bioactive nanosilicate, viz. Laponite (LP). The nanocomposite hydrogel consists of the natural anionic poly(γ-glutamic acid) (γ-PGA), which was functionalized with catechol moiety, and incorporated with disk-structured LP. The dual-crosslinked hydrogel was fabricated by enzymatic chemical crosslinking of catechol in the presence of horseradish peroxidase (HRP) and H2O2, and physical crosslinking between γ-PGA-catechol conjugate and LP. The PGADA/LP nanocomposite hydrogels with catechol moieties showed strong adhesiveness to various tissue layers and demonstrated an excellent hemostatic properties. These PGADA/LP nanocomposite hydrogels are potentially applied for injectable tissue engineering hydrogels, tissue adhesives, and hemostatic materials. Statement of significanceRecently, many attempts have been performed to manufacture high-performance tissue adhesives using synthetic and natural polymer-based materials. In order to apply in various biological substrates, commercially available tissue adhesives should have an improved adhesive property in wet conditions. Here, we designed a mussel-inspired dual crosslinked tissue adhesive that meets most of conditions as an ideal tissue adhesive. The designed tissue adhesive is composed of poly(γ-glutamic acid)-dopamine conjugate (PGADA)-gluing macromer, horseradish peroxidase (HRP)/hydrogen peroxide (H2O2)-enzymatic crosslinker, and Laponite (LP)-additional physical crosslinking nanomaterial. The PGADA hydrogel has tunable physicochemical properties by controlling the LP concentration. Furthermore, this dual crosslinked hydrogel shows strong tissue adhesive property, regardless of the tissue types. Specially the PGADA hydrogel has tissue adhesive strength four times higher than commercial bioadhesive. This dual crosslinked PGADA hydrogel with improved tissue adhesion property is a promising biological tissue adhesive for various tissue type in surgical operation.

Clinician's perspective on neuropathic pain and use of Lidocaine 5% patch with hydrogel technology in postherpetic neuralgia

Background: Neuropathic pain (NP) is a condition that affects the quality of life (QoL) of many patients. It is often difficult to treat effectively due to the complexity of this disorder. This study was aimed to assess clinician's perspectives on NP, particularly for postherpetic neuralgia (PHN), posttraumatic neuralgia (PTN), and painful diabetic neuropathy (PDN). Further, the study aimed to evaluate the safety and efficacy of lidocaine 5% patch with hydrogel technology in PHN. Materials and Methods: These two aspects were assessed through two prospective survey-based questionnaire studies that were conducted from January 2018 to December 2018 with clinicians from relevant specialties across India. Data were collected from clinicians' inputs based on their clinical practice and statistically analyzed. Results: More than half of the clinicians reported prolonged duration of NP in PHN, PTN, and PDN conditions. After applying lidocaine 5% patch with hydrogel technology, around 83.58% of clinicians opined that patients experienced a cooling and soothing effect due to the presence of a hydrogel layer in the patch. A significant reduction in pain score was reported by 76.11% of clinicians and 79.1% of them agreed that there was pain relief during the intermittent patch-free period also. The majority of the doctors (74.6%) reported an absence of any side effects. Conclusion: Study findings revealed that topical application of lidocaine 5% patch with hydrogel technology is safe and effective in PHN.

Технология получения нанокомпозитов для сорбционной очистки водных сред

The paper presents a technique for obtaining a universal composite nanomaterial for effective sorption water purification from pollutants of various chemical nature. The proposed material is a nanocomposite based on reduced graphene oxide modified with a functional organic component — polyaniline, which also includes oxidized carbon nanotubes as a structure former. The use of polyaniline makes it possible to significantly increase the activity and sorption capacity of the developed graphene material. The authors were developed a number of nanocomposites, which differ in the final stage of the pre-prepared hydrogel technology: drying in air (drying oven), freeze drying, drying under supercritical conditions (supercritical fluid — isopropyl alcohol). In addition, the effect of carbonization as an additional stage (T = 800 °C, argon) was studied in the article. The materials surface morphology was evaluated using scanning electron microscopy. The specific surface area and the parameters of the porous space were determined by nitrogen adsorption. The materials specific surface area increases depending on the choice of drying technology for the initial hydrogel (drying oven — 80 m2/g → freeze drying — 180 m2/g → supercritical drying — 290 m2/g), and also increases after the carbonization stage and reaches a value of ~ 350 m2/g. The nanocomposites sorption capacity to the organic dyes (methylene blue (MB) and solar yellow (SY)), as well as to heavy metals (for example, zinc ions) was determined. It was found that the value of MB sorption is up 1380 to 1800 mg/g, for SY — up 159 to 300 mg/g, for zinc — up 31 to 230 mg/g. At the same time, the sample processed under supercritical conditions, followed by carbonization, were shown the best characteristics.

Short self‐assembling peptides with a urea bond: A new type of supramolecular peptide hydrogel materials

AbstractThere is an increasing need to develop short self‐assembling peptides (SAPs) that can form hydrogels for cell engineering and biomedical applications. In this study, we proposed new short self‐assembling peptides with a symmetric structure via a urea bond. (FFiO)2 and (FFiK)2 were designed as amphiphilic peptides with a hydrophobic domain inside of zwitterionic hydrophilic ends and a urea bond embedded in the hydrophobic domain. The two peptides were synthesized by a liquid‐phase method. The simple structural design of these peptides makes their synthesis on a large scale possible. Both (FFiO)2 and (FFiK)2 assembled into β‐sheet structure and formed stable hydrogels under physiological pH conditions in a pH‐responsive manner. The urea bond was important for the formation of transparent hydrogels. Since (FFiK)2 exhibited self‐assembling properties superior to those of (FFiO)2, (FFiK)2 hydrogels were used as scaffolds for cell culture. (FFiK)2 hydrogels supported cell proliferation without significant cytotoxicity. Therefore, (FFiK)2 is a beneficial supramolecular peptide hydrogelator for cell engineering.

Hydrogel-Based Technologies for the Diagnosis of Skin Pathology

Hydrogels, swellable hydrophilic polymer networks fabricated through chemical cross-linking or physical entanglement are increasingly utilized in various biomedical applications over the past few decades. Hydrogel-based microparticles, dressings and microneedle patches have been explored to achieve safe, sustained and on-demand therapeutic purposes toward numerous skin pathologies, through incorporation of stimuli-responsive moieties and therapeutic agents. More recently, these platforms are expanded to fulfill the diagnostic and monitoring role. Herein, the development of hydrogel technology to achieve diagnosis and monitoring of pathological skin conditions are highlighted, with proteins, nucleic acids, metabolites, and reactive species employed as target biomarkers, among others. The scope of this review includes the characteristics of hydrogel materials, its fabrication procedures, examples of diagnostic studies, as well as discussion pertaining clinical translation of hydrogel systems.

Bioinspired Hydrogels with Muscle-Like Structure for AIEgen-Guided Selective Self-Healing

Living systems, including human beings, animals, and plants, display the power to self-heal spontaneously after being damaged. The self-healing is usually selective, which means that the healing ef...

Enzymatic Extraction of Bioactive and Self-Assembling Wool Keratin for Biomedical Applications.

Keratin is widely recognized as a high-quality renewable protein resource for biomedical applications. Despite their extensive existence, keratin resources such as feathers, wool, and hair exhibit high stability and mechanical properties because of their high disulfide bond content. Consequently, keratin extraction is challenging and its application is greatly hindered. In this work, a biological extraction strategy is proposed for the preparation of bioactive keratin and the fabrication of self-assembled keratin hydrogels (KHs). Based on moderate and controlled hydrolysis by keratinase, keratin with a high molecular weight of approximately 45and 28kDa that retain its intrinsic bioactivities is obtained. The keratin products show excellent ability to promote cell growth and migration and are conferred with significant antioxidant ability because of their intrinsically high cysteine content. In addition, without the presence of any cross-linking agent, the extracted keratin can self-assemble into injectable hydrogels. The KHs exhibit a porous network structure and 3D culture ability, showing potential in promoting wound healing. This enzyme-driven keratin extraction strategy opens up a new approach for the preparation of keratin that can self-assemble into injectable hydrogels for biomedical engineering.