No abstract available.
Hydrogel* ; Hydrogels* ; Regenerative Medicine*

BACKGROUND: Biopolymeric in situ hydrogels play a crucial role in the regenerative repair and replacement of infected or injured tissue. They possess excellent biodegradability and biocompatibility in the biological system, however only a few biopolymeric in situ hydrogels have been approved clinically. Researchers have been investigating new advancements and designs to restore tissue functions and structure, and these studies involve a composite of biometrics, cells and a combination of factors that can repair or regenerate damaged tissue. METHODS: Injectable hydrogels, cross-linking mechanisms, bioactive materials for injectable hydrogels, clinically applied injectable biopolymeric hydrogels and the bioimaging applications of hydrogels were reviewed. RESULTS: This article reviews the different types of biopolymeric injectable hydrogels, their gelation mechanisms, tissue engineering, clinical applications and their various in situ imaging techniques. CONCLUSION: The applications of bioactive injectable hydrogels and their bioimaging are a promising area in tissue engineering and regenerative medicine. There is a high demand for injectable hydrogels for in situ imaging.
Biopolymers* ; Hydrogel* ; Hydrogels* ; Regenerative Medicine ; Tissue Engineering*

BACKGROUND: Several injectable hydrogels have been developed extensively for a broad range of biomedical applications. Injectable hydrogels forming in situ through the change in external stimuli have the distinct properties of easy management and minimal invasiveness, and thus provide the advantage of bypassing surgical procedures for administration resulting in better patient compliance. METHODS: The injectable in situ-forming hydrogels can be formed irreversibly or reversibly under physiological stimuli. Among several external stimuli that induce formation of hydrogels in situ, in this review, we focused on the electrostatic interactions as the most simple and interesting stimulus. RESULTS: Currently, numerous polyelectrolytes have been reported as potential electrostatically interactive in situ-forming hydrogels. In this review, a comprehensive overview of the rapidly developing electrostatically interactive in situ-forming hydrogels, which are produced by various anionic and cationic polyelectrolytes such as chitosan, celluloses, and alginates, has been outlined and summarized. Further, their biomedical applications have also been discussed. CONCLUSION: The review concludes with perspectives on the future of electrostatically interactive in situ-forming hydrogels.
Alginates ; Chitosan ; Hydrogel* ; Hydrogels* ; Patient Compliance ; Regenerative Medicine

We investigated the combined moisturizing effect of liposomal serine and a cosmeceutical base selected in this study. Serine is a major amino acid consisting of natural moisturizing factors and keratin, and the hydroxyl group of serine can actively interact with water molecules. Therefore, we hypothesized that serine efficiently delivered to the stratum corneum (SC) of the skin would enhance the moisturizing capability of the skin. We prepared four different cosmeceutical bases (hydrogel, oil-in-water (O/W) essence, O/W cream, and water-in-oil (W/O) cream); their moisturizing abilities were then assessed using a Corneometer(R). The hydrogel was selected as the optimum base for skin moisturization based on the area under the moisture content change-time curves (AUMCC) values used as a parameter for the water hold capacity of the skin. Liposomal serine prepared by a reverse-phase evaporation method was then incorporated in the hydrogel. The liposomal serine-incorporated hydrogel (serine level=1%) showed an approximately 1.62~1.77 times greater moisturizing effect on the skin than those of hydrogel, hydrogel with serine (1%), and hydrogel with blank liposome. However, the AUMCC values were not dependent on the level of serine in liposomal serine-loaded hydrogels. Together, the delivery of serine to the SC of the skin is a promising strategy for moisturizing the skin. This study is expected to be an important step in developing highly effective moisturizing cosmeceutical products.
Hyaluronic Acid* ; Hydrogel* ; Hydrogels* ; Liposomes ; Serine* ; Skin* ; Water

A paradigm shift is taking place in medicine and dentistry from using synthetic implants and tissue grafts to a tissue engineering approach that uses degradable porous three-dimensional (3D) material hydrogels integrated with cells and bioactive factors to regenerate tissues such as dental bone and other oral tissues. Hydrogels have been established as a biomaterial of choice for many years, as they offer diverse properties that make them ideal in regenerative medicine, including dental applications. Being highly biocompatible and similar to native extracellular matrix, hydrogels have emerged as ideal candidates in the design of 3D scaffolds for tissue regeneration and drug delivery applications. However, precise control over hydrogel properties, such as porosity, pore size, and pore interconnectivity, remains a challenge. Traditional techniques for creating conventional crosslinked polymers have demonstrated limited success in the formation of hydrogels with large pore size, thus limiting cellular infiltration, tissue ingrowth, vascularization, and matrix mineralization (in the case of bone) of tissue-engineered constructs. Emerging technologies have demonstrated the ability to control microarchitectural features in hydrogels such as the creation of large pore size, porosity, and pore interconnectivity, thus allowing the creation of engineered hydrogel scaffolds with a structure and function closely mimicking native tissues. In this review, we explore the various technologies available for the preparation of macroporous scaffolds and their potential applications.
Dentistry* ; Extracellular Matrix ; Hydrogel ; Hydrogels ; Polymers* ; Porosity ; Regeneration ; Regenerative Medicine ; Tissue Engineering ; Transplants

BACKGROUND: Management of postprandial hyperglycemia is a key aspect in diabetes treatment. We developed a novel system to measure glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET) for simple monitoring of postprandial glucose excursions. In this study, we evaluated the relationship between our system and continuous glucose monitoring (CGM) by comparing glucose AUC obtained using MIET with that obtained using CGM for a long duration. METHODS: Twenty diabetic inpatients wearing a CGM system were enrolled. For MIET measurement, a plastic microneedle array was applied to the skin as pretreatment, and hydrogels were placed on the pretreated area to collect interstitial fluid. Hydrogels were replaced every 2 or 4 hours and AUC was predicted on the basis of glucose and sodium ion levels. RESULTS: AUC predicted by MIET correlated well with that measured by CGM (r=0.93). Good performances of both consecutive 2- and 4-hour measurements were observed (measurement error: 11.7%±10.2% for 2 hours and 11.1%±7.9% for 4 hours), indicating the possibility of repetitive measurements up to 8 hours. The influence of neither glucose fluctuation nor average glucose level over the measurement accuracy was observed through 8 hours. CONCLUSION: Our system showed good relationship with AUC values from CGM up to 8 hours, indicating that single pretreatment can cover a large portion of glucose excursion in a day. These results indicated possibility of our system to contribute to convenient monitoring of glucose excursions for a long duration.
Area Under Curve* ; Extracellular Fluid ; Glucose* ; Humans ; Hydrogel ; Hydrogels ; Hyperglycemia ; Inpatients ; Plastics ; Skin ; Sodium

PURPOSE: In this study, we investigated the potential of injectable hydrogel scaffolds for the regeneration of nucleus pulposus. MATERIALS AND METHODS: We prepared injectable hydrogels [Chitosan-Pluronic (CP), CP/Osteogenic Protein-1 (CP/OP-1), CP/Gly-Arg-Gly-Asp-Ser (CP/GRGDS), CP/GRGDS/OP-1] for this study. One of the four potential materials was selected through the cell viability tests. For each material, primary cultured nucleus pulposus (NP) cells from New Zealand rabbits were seeded onto each material. For the investigation of the effects of mechanical stimulation, the commercially available bioreactor was used. 0.2 MPa of intermittent hydrostatic pressure was imposed for 3 days after 7th day of seeding with the pattern of 2 min and 15 min for stimulating and resting, respectively. The specimens were harvested at 1, 10, 14 day after seeding for analyses. RESULTS: The MTT assay for 5 days revealed that CP/OP-1 group showed significant increase. The other two groups (CP/GRGDS and CP/GRGDS/OP-1) showed that the proliferation rate increased until 3 days after culture, while it decreased on day 5. The mechanical stimuli induced higher amounts of DNA measured in CP/OP- 1 on day 5 after culture. However, no significant difference was observed between two groups. CONCLUSION: We came to the conclusions that the biochemical environment as well as mechanical stimulation may play an important role in regenerating nucleus pulposus matrix, especially in CP/OP-1 in this study. However, further study are recommended in relation to mechanical effects as well as biochemical conditions.
Bioreactors ; Cell Survival ; DNA ; Hydrogel ; Hydrogels ; Hydrostatic Pressure ; Intervertebral Disc ; Porphyrins ; Rabbits ; Regeneration ; Seeds

Tissue stroma is responsible for extracellular matrix (ECM) formation and secretion of factors that coordinate the behaviour of the surrounding cells through the microenvironment created. It's inability to spontaneously regenerate makes it a good candidate for research studies such as testing various tissue engineered products capable of replacing the stroma in order to assure normal tissue regeneration and function. In this study, a bioactive stroma was obtained considering two main components: 1) the artificial ECM formed using atelocollagen-oxidized polysaccharides hydrogels in which the polysaccharide compound (oxidised gellan or pullulan) has the role of crosslinker and 2) encapsulated stromal cells (dermal fibroblasts, ovarian theca-interstitial and granulosa cells). The cell-hosting ability of the hydrogels is demonstrated by a good diffusion of globular proteins (albumin) while the fibrillar morphology proves to be optimal for cell adhesion. These structural properties and cytocompatibility of the components maintain good cell viability and cell encapsulation for more than 12 days. Nevertheless, the results indicate some differences favouring the gellan crosslinked hydrogels. Ovarian stromal cells functionality was maintained as indicated by hormone secretion, confirming cell-cell signalling in encapsulated and co-culture conditions. In vivo implantation shows the regenerative potential of the cell-populated hydrogels as they are integrated into the natural tissue. The possibility of cryopreserving the hydrogel-cell system, while maintaining both cell viability and hydrogel structural integrity underlines the potential of these ready-to-use hydrogels as bioactive stroma for multipurpose tissue regeneration.
Cell Adhesion ; Cell Survival ; Coculture Techniques ; Diffusion ; Extracellular Matrix ; Fibroblasts ; Hydrogel* ; Hydrogels* ; Polysaccharides* ; Regeneration ; Stromal Cells

BACKGROUND: Polymeric hydrogels are extensively used as promising biomaterials in a broad range of biomedical applications, including tissue engineering, regenerative medicine, and drug delivery. These materials have advantages such as structural similarity to the native extracellular matrix (ECM), multi-tunable physicochemical and biological properties, and biocompatibility. METHODS: In situ forming hydrogels show a phase transition from a solution to a gel state through various physical and chemical cross-linking reactions. These advanced hydrogel materials have been widely used for tissue regenerative medicine because of the ease of encapsulating therapeutic agents, such as cells, drugs, proteins, and genes. RESULTS: With advances in biomaterials engineering, these hydrogel materials have been utilized as either artificial cellular microenvironments to create engineered tissue constructs or as bioactive acellular matrices to stimulate the native ECM for enhanced tissue regeneration and restoration. CONCLUSION: In this review, we discuss the use of in situ cross-linkable hydrogels in tissue engineering and regenerative medicine applications. In particular, we focus on emerging technologies as a powerful therapeutic tool for tissue regenerative medicine applications.
Biocompatible Materials ; Cellular Microenvironment ; Extracellular Matrix ; Hydrogel* ; Hydrogels* ; Phase Transition ; Polymers ; Regeneration ; Regenerative Medicine* ; Tissue Engineering

BACKGROUND: The tissue engineering and regenerative medicine approach require biomaterials which are biocompatible, easily reproducible in less time, biodegradable and should be able to generate complex three-dimensional (3D) structures to mimic the native tissue structures. Click chemistry offers the much-needed multifunctional hydrogel materials which are interesting biomaterials for the tissue engineering and bioprinting inks applications owing to their excellent ability to form hydrogels with printability instantly and to retain the live cells in their 3D network without losing the mechanical integrity even under swollen state. METHODS: In this review, we present the recent developments of in situ hydrogel in the field of click chemistry reported for the tissue engineering and 3D bioinks applications, by mainly covering the diverse types of click chemistry methods such as Diels–Alder reaction, strain-promoted azide-alkyne cycloaddition reactions, thiol-ene reactions, oxime reactions and other interrelated reactions, excluding enzyme-based reactions. RESULTS: The click chemistry-based hydrogels are formed spontaneously on mixing of reactive compounds and can encapsulate live cells with high viability for a long time. The recent works reported by combining the advantages of click chemistry and 3D bioprinting technology have shown to produce 3D tissue constructs with high resolution using biocompatible hydrogels as bioinks and in situ injectable forms. CONCLUSION: Interestingly, the emergence of click chemistry reactions in bioink synthesis for 3D bioprinting have shown the massive potential of these reaction methods in creating 3D tissue constructs. However, the limitations and challenges involved in the click chemistry reactions should be analyzed and bettered to be applied to tissue engineering and 3D bioinks. The future scope of these materials is promising, including their applications in in situ 3D bioprinting for tissue or organ regeneration.
Biocompatible Materials ; Bioprinting* ; Click Chemistry ; Cycloaddition Reaction ; Hydrogel* ; Hydrogels* ; Ink* ; Regeneration ; Regenerative Medicine ; Tissue Engineering*