Natural Polymer Hydrogels Research Articles

Gelatin methacryloyl hydrogels functionalized with endothelin-1 for angiogenesis and full-thickness wound healing.

Natural polymer hydrogels are widely used as wound dressings, but they do not have enough bioactivity to accelerate angiogenesis and re-epithelialization. Herein, a therapeutic system was firstly constructed in which endothelin-1 (ET-1), as an endogenous vasoconstrictor peptide, was embedded in a photo-crosslinking gelatin methacryloyl (GelMA) hydrogel for full-thickness wound healing. The multifunctional GelMA-ET-1 hydrogels contained the arginine-glycine-aspartate (RGD) motifs of gelatin that provided adhesive sites for cell proliferation and migration. The ET-1 was wrapped within the network of crosslinked GelMA hydrogels via intermolecular hydrogen bonding interactions, effectively avoiding oxidization by atmospheric oxygen and in vivo enzymatic biodegradation. Notably, the ET-1 in the functional hydrogels significantly promoted the proliferation, migration and angiogenesis-related gene expression of human umbilical vein endothelial cells (HUVECs) and fibroblasts. The full-thickness skin defect model of rats further revealed that the GelMA-ET-1 hydrogels significantly accelerated new blood vessel formation, collagen deposition and re-epithelialization. After 14 days, the full-thickness skin defects almost closed and were filled with the newly formed tissue. Hence, the photo-crosslinking GelMA-ET-1 hydrogels functionalized with ET-1 can be employed as a promising therapeutic system for wound healing.

Bio-based poly (γ-glutamic acid) hydrogels reinforced with bacterial cellulose nanofibers exhibiting superior mechanical properties and cytocompatibility

Natural polymer hydrogels are expected to be promising biomaterial because of its excellent biocompatibility and biodegradability, but they are soft and easily broken. Herein, the poly (γ-glutamic acid) (γ-PGA)/bacterial cellulose (BC) composite hydrogels with excellent mechanical properties were constructed by introducing bacterial cellulose. The γ-PGA/BC composite hydrogels were obtained by the covalent cross-linking of γ-PGA in the BC nanofibers suspensions. The γ-PGA/BC composite hydrogels exhibited excellent strength and toughness due to the more effective energy dissipation of hydrogen bonds network among BC nanofibers and γ-PGA hydrogel matrix and BC also acts as an enhancer. The compressive fracture strength and toughness of the γ-PGA/BC composite hydrogels could reach up to 5.72 MPa and 0.42 MJ/m3 respectively. Additionally, the tensile strength of γ-PGA/BC composite hydrogels were improved 8.16 times compared with γ-PGA single network hydrogels. More significantly, BC could disperse evenly in the γ-PGA hydrogels because of the hydrophilic nature of γ-PGA and BC nanofillers, which led to good interface compatibility. The result of cytotoxicity tests indicated that γ-PGA/BC composite hydrogels present excellent cytocompatibility, which suggested that the γ-PGA/BC composite hydrogels could serve as promising materials for many biomaterial related applications.

High strength and bioactivity polyvinyl alcohol/collagen composite hydrogel with tannic acid as cross‐linker

AbstractHydrogels have great potential applications in biomedical materials, but their applications in complex physiological environments are severely limited by their weak strength and biotoxicity. Generally, synthetic polymer hydrogels and natural polymer hydrogels have complementary advantages in terms of mechanical strength and biological activity. Herein, tannic acid (TA), a natural material, was introduced into the polyvinyl alcohol/collagen (PVA‐COL) double network to prepare a hydrogel (PVA‐COL‐TA) with good bioactivity and mechanical properties. The tensile strength of the composite hydrogel can reach up to 20 times that of the pure PVA hydrogel. And the hydrogel after swelling under physiological conditions also exhibits stable mechanical properties. The introduction of TA can reduce the degradation rate of COL, enabling it to continue to exert biological activity. in vitro cytocompatibility experiments showed that PVA‐COL‐TA hydrogel has good sustained biological activity and the potential for biomedical materials.

Review on Magnetic Natural Polymer Constructed Hydrogels as Vehicles for Drug Delivery.

Hydrogels prepared from natural polymers have captured extensive attention over the past decades because of their exceptional biocompatibility and nontoxicity, ease of gelation, and functionalization. Thus, natural polymer hydrogels are considered as promising biomaterials that show great potential in the biomedical field. In drug-delivery systems, the extent and the rate with which the drugs reach their targets are highly carrier-dependent, so the demand for intelligent drug-delivery systems is gradually increasing. Recently, natural polymer hydrogels functionalized with magnetic materials have been used as a novel smart response device for drug delivery because of the quick response and remote controllability. This review aims to give the latest advances of magnetic hydrogels based on natural polymers such as polysaccharide, protein, and DNA in drug-delivery systems. Specifically, the first part compares several general synthesis strategies of magnetic natural polymer hydrogels. The applications of magnetic natural polymer hydrogels are described in the second part. For the last part, an overview of the application in drug delivery for the magnetic hydrogels constructed from several representative natural polymers is presented.

A flexible, high-voltage and safe zwitterionic natural polymer hydrogel electrolyte for high-energy-density zinc-ion hybrid supercapacitor

Abstract With the development of flexible wearable electronic devices, energy storage equipment like supercapacitor with high energy density, good mechanical properties and safety has attracted more and more attention. However, the currently existing energy storage materials normally suffer from several drawbacks, such as poor flexibility, hidden danger, toxicity and especially low energy density, limiting their practical applications. Expanding the voltage window by employing the hydrogel electrolyte is regarded as an effective method to improve the energy density of supercapacitor. Herein, we employ a zwitterionic natural polymer hydrogel with excellent mechanical strength and flexibility as electrolyte to assemble a solid-state zinc-ion hybrid supercapacitor (H-ZHS) with Zn foil and activated carbon electrode. The H-ZHS exhibits an amazingly wide and stable voltage window of 2.4 V, high maximum energy density of 286.6 Wh kg−1 at the power density of 220 W kg−1 and superior capacity retention of 95.4% after 2000 cycles at 2 A g−1 calculated based on mass of activated carbon electrode. The strategy in this work should provide a new insight in exploring zinc-ion hybrid supercapacitor with high energy density for flexible wearable electronic devices.

Preparation of Cu2O-Fe3O4@carbon nanocomposites derived from natural polymer hydrogel template for organic pollutants degradation

In this paper, a novel preparation method was applied to fabricate 3D porous Cu2O-Fe3O4@carbon nanocomposites (Cu2O-Fe3O4@CN) using natural polymer hydrogel. The polymer hydrogel was used as template to immobilize cupric ions and ferrous ions first, it was then followed by a series of preparing processes including sedimentation, desiccation and calcination. Characterization analysis including TEM, EDS, XPS, XRD and VSM were employed to characterize the morphologies and structures of Cu2O-Fe3O4@CN. The photocatalytic performance of Cu2O-Fe3O4@CN for organic contaminant degradation under visible light irradiation was also evaluated. The effect of different preparation conditions on the morphology structure and photocatalytic performance of Cu2O-Fe3O4@CN was investigated and the optimal parameters were determined. After four repetitive use, the degradation efficiency only decreased from 95.1% to 90.1%, which suggested the great potential of Cu2O-Fe3O4@CN in industrialization and commercialization. Cu2O; Fe3O4; Nano materials; Sodium alginate; Photocatalysis; Synergistic effect

Applications of Fibrin-based products in Endodontics: A Literature Review

Introduction: Endodontic treatment of necrotic immature teeth is quite challenging. Current concepts for revitalization of these teeth known as regenerative endodontic treatment (RET) is based on key elements necessary for tissue engineering including stem cells, three-dimensional (3D) scaffolds, and growth factors. Utilizing an applicable scaffold for narrow root canal space with adequate properties is essential for successful outcome. Fibrin-based products are materials with various advantages as a scaffold. This review article aims to discuss the properties of different types of fibrin-based products and debates whether they are appropriate scaffolds for RET or not? Methods: An electronic search was performed using databases such as Google Scholar, PubMed, PubMed Central, Science Direct, and Scopus. Keywords such as (“scaffold”)AND (“fibrin gel” OR “fibrin sealant” OR “fibrin glue” OR “fibrin tissue adhesive” OR “fibrin hydrogel” OR “platelet concentrate”) AND (“tooth” OR “teeth”) AND/OR (“regenerative endodontics” OR “dentistry”) were used. Exclusion criteria included studies published in a language other than English and abstracts from congress. Results: Fibrin gel is a protein-based natural polymer hydrogel scaffold which can be easily used in the root canal. Platelet concentrates are autologous fibrin-based products used as scaffolds for RET with various favorable properties especially due to containing various growth factors. Conclusion: It seems that fibrin gel and platelet concentrates have adequate properties for use in RET; however, more evidence is required regarding the clinical outcome of applying these products as scaffolds for RET.

Optimizing Blended Collagen-Fibrin Hydrogels for Cardiac Tissue Engineering with Human iPSC-derived Cardiomyocytes.

Natural polymer hydrogels are used ubiquitously as scaffold materials for cardiac tissue engineering as well as for soft tissue engineering more broadly because of FDA approval, minimal immunogenicity, and well-defined physiological clearance pathways. However, the relationships between natural polymer hydrogels and resident cell populations in directing the development of engineered tissues are poorly defined. This interaction is of particular concern for tissues prepared with iPSC-derived cell populations, in which population purity and batch-to-batch variability become additional critical factors to consider. Herein, the design space for a blended fibrin and collagen scaffold is characterized for applications in creating engineered myocardium with human iPSC-derived cardiomyocytes. Stiffness values of the acellular hydrogel formulations approach those of native myocardium in compression, but deviate significantly in tension when compared to rat myocardium in both transverse and longitudinal fiber orientations. A response surface methodology approach to understanding the relationship between collagen concentration, fibrin concentration, seeding density, and cardiac purity found a statistically significant predictive model across three repeated studies that confirms that all of these factors contribute to tissue compaction. In these constructs, increased fibrin concentration and seeding density were each associated with increased compaction, while increased collagen concentration was associated with decreased compaction. Both the lowest (24.4% cTnT+) and highest (60.2% cTnT+) cardiomyocyte purities evaluated were associated with decreased compaction, whereas the greatest compaction was predicted to occur in constructs prepared with a 40–50% cTnT+ population. Constructs prepared with purified cardiomyocytes (≥75.5% cTnT+) compacted and formed syncytia well, although increased fibrin concentration in these groups was associated with decreased compaction, a reversal of the trend observed in unpurified cardiomyocytes. This study demonstrates an analytical approach to understanding cell–scaffold interactions in engineered tissues and provides a foundation for the development of more sophisticated and customized scaffold platforms for human cardiac tissue engineering.

Optimization Of Swelling, Drug Loading And Release From Natural Polymer Hydrogels

The current work deals with synthesis of natural polymer hydrogels (Sodium alginate-Chitosan- Arabic Gum) as beads. The beads are formulated with different polymer proportions depending on the experimental central composite (design) Response Surface Methodology (RSM) has been used. The degree of swelling in acidic and neutral mediums was investigated, analyzed, modeled and optimized statistically. A typical drug (Allopurinol) was loaded by using optimized polymer formulations. The loading capacity and the in vitro release profiles were estimated. The shape and morphological analysis for the beads before and after drug releasing have been investigated also by using Scanning Electron Microscope. The results obtained confirmed that Arabic Gum content was a significant parameter in the swelling processes regardless the pH of the swelling media. Thus, swelling indices of the beads were higher in acidic medium (pH 3.9) compared to that once in (pH 7.1), to indicate a pH-sensitive swelling behavior. An optimum RSM results for swelling indices of 504.98 % and 207.97 % were obtained in acidic and neutral medium respectively. The in vitro drug release showed equilibrium after 12 hours where as (66.1- 85.7 %) and (44-54 %) was released at pH 3.9 and 7.1 respectively. The SEM analysis of the polymer beads confirmed that the beads had lost their shape due to erosion and swelling activities after releasing of the drug.

Hydrogel Cryopreservation System: An Effective Method for Cell Storage.

At present, living cells are widely used in cell transplantation and tissue engineering. Many efforts have been made aiming towards the use of a large number of living cells with high activity and integrated functionality. Currently, cryopreservation has become well-established and is effective for the long-term storage of cells. However, it is still a major challenge to inhibit cell damage, such as from solution injury, ice injury, recrystallization and osmotic injury during the thawing process, and the cytotoxicity of cryoprotectants. Hence, this review focused on different novel gel cryopreservation systems. Natural polymer hydrogel cryopreservation, the synthetic polymer hydrogel cryopreservation system and the supramolecular hydrogel cryopreservation system were presented, respectively. Due to the unique three-dimensional network structure of the hydrogel, these hydrogel cryopreservation systems have the advantages of excellent biocompatibility for natural polymer hydrogel cryopreservation systems, designability for synthetic polymer hydrogel cryopreservation systems, and versatility for supramolecular hydrogel cryopreservation systems. To some extent, the different hydrogel cryopreservation methods can confine ice crystal growth and decrease the change rates of osmotic shock in cell encapsulation systems. It is notable that the cryopreservation of complex cells and tissues is demanded in future clinical research and therapy, and depends on the linkage of different methods.

Enhancing Mechanical Properties of Silk Fibroin Hydrogel through Restricting the Growth of β-Sheet Domains.

Usually, regenerated silk fibroin (RSF) hydrogels cross-linked by chemical agents such as horseradish peroxide (HRP)/H2O2 perform elastic properties, while display unsatisfactory strength for practical applications especially as load-bearing materials, and inadequate stability when incubated in a simulated in vivo environment. Here, the RSF hydrogel with both excellent strength and elasticity was prepared by inducing the conformation transition from random coil to β-sheet in a restricted RSF network precross-linked by HRP/H2O2. Such "dual-networked" hydrogels, regarding the one with 10 wt % RSF (Mw: 220 kDa) as a representative, show around 100% elongation, as well as the compressive modulus and tensile modulus up to 3.0 and 2.5 MPa respectively, which are much higher than those of physically cross-linked natural polymer hydrogels (commonly within 0.01-0.1 MPa at the similar solid content). It has been shown that the enhanced comprehensive mechanical properties of RSF hydrogels derive from the formation of small-sized and uniformly distributed β-sheet domains in the hydrogel during the conformation transition of RSF whose size is limited by the first network formed by cross-linkers with HRP/H2O2. Importantly, the tough RSF hydrogel changes the normally weak recognition of various RSF hydrogels and holds a great potential to be the material in biomedical field because it seems to be very promising regarding its biocompatibility, biodegradability, etc.

Tough biohydrogels with interpenetrating network structure by bienzymatic crosslinking approach

Enzymatically crosslinked biohydrogels have increasingly attracted attention mainly due to the mildness of this type of reaction. However, their mechanical strength is usually so weak that their applications are limited in the field of medicine. In order to improve their mechanical properties and degradation resistance, bienzymatic crosslinking approach was utilized to prepare biohydrogels of gelatin and chitosan with an interpenetrating polymer network (IPN) structure in this report. First of all, chitosan was grafted with phloretic acid (chitosan-PA) used as a substrate of horseradish peroxidase (HRP). After that, the gelation process of gelatin/chitosan-PA IPN hydrogels was monitored by a rheometer. The results indicated the formation of dual networks: one gelatin network crosslinked by transglutaminase (TG) and another chitosan-PA network crosslinked by HRP in the presence of a low concentration of H2O2. In addition, the mechanical performances of the hydrogels were measured by a universal testing machine. It was found that the mechanical properties of the IPN gels were significantly improved compared with gelatin hydrogel crosslinked by TG. Moreover, the swelling ratio, degradation behavior, and cytocompatibility of the IPN hydrogels were investigated in detail. The preliminary biological evaluation indicated that the IPN hydrogels can support L929 cell adhesion and proliferation. Overall, the gelatin/chitosan IPN hydrogels prepared by bienzymatic crosslinking approach have excellent biocompatibility and mechanical properties. Therefore, dual enzyme-mediated crosslinking of natural polymer hydrogels is promising for the development of tissue engineering scaffolds and wound dressing.

Kinetic release studies of nitrogen-containing bisphosphonate from gum acacia crosslinked hydrogels

Natural polymer hydrogels are useful for controlling release of drugs. In this study, hydrogels containing gum acacia were synthesized by free-radical polymerization of acrylamide with gum acacia. The effect of gum acacia in the hydrogels on the release mechanism of nitrogen-containing bisphosphonate (BP) was studied at pH 1.2 and 7.4. The hydrogels exhibited high swelling ratios at pH 7.4 and low swelling ratios at pH 1.2. The release study was performed using UV–Visible spectroscopy via complex formation with Fe(III) ions. At pH 1.2, the release profile was found to be anomalous while at pH 7.4, the release kinetic of BP was a perfect zero-order release mechanism. The hydrogels were found to be pH-sensitive and the release profiles of the BP were found to be influenced by the degree of crosslinking of the hydrogel network with gum acacia. The preliminary results suggest that these hydrogels are promising devices for controlled delivery of bisphosphonate to the gastrointestinal region.

Degradable natural polymer hydrogels for articular cartilage tissue engineering

AbstractArticular cartilage has poor ability to heal once damaged. Tissue engineering with scaffolds of polymer hydrogels is promising for cartilage regeneration and repair. Polymer hydrogels composed of highly hydrated crosslinked networks mimic the collagen networks of the cartilage extracellular matrix and thus are employed as inserts at cartilage defects not only to temporarily relieve the pain but also to support chondrocyte proliferation and neocartilage regeneration. The biocompatibility, biofunctionality, mechanical properties, and degradation of the polymer hydrogels are the most important parameters for hydrogel‐based cartilage tissue engineering. Degradable biopolymers with natural origin have been widely used as biomaterials for tissue engineering because of their outstanding biocompatibility, low immunological response, low cytotoxicity, and excellent capability to promote cell adhesion, proliferation, and regeneration of new tissues. This review covers several important natural proteins (collagen, gelatin, fibroin, and fibrin) and polysaccharides (chitosan, hyaluronan, alginate and agarose) widely used as hydrogels for articular cartilage tissue engineering. The mechanical properties, structures, modification, and structure–performance relationship of these hydrogels are discussed since the chemical structures and physical properties dictate the in vivo performance and applications of polymer hydrogels for articular cartilage regeneration and repair. © 2012 Society of Chemical Industry

Engineering cartilage tissue interfaces using a natural glycosaminoglycan hydrogel matrix — An in vitro study

Hydrogels are suitable matrices for cartilage tissue engineering on account of their resemblance to native extracellular matrix of articular cartilage and also considering its ease of application, they can be delivered to the defect site in a minimally invasive manner. In this study, we evaluate the suitability of a fast gelling natural biopolymer hydrogel matrix for articular cartilage tissue engineering. A hydrogel based on two natural polymers, chitosan and hyaluronic acid derivative was prepared and physicochemically characterized. Chondrocytes were then encapsulated within the hydrogel and cultured over a period of one month. Cartilage regeneration was assessed by histological, biochemical and gene expression studies. Chondrocytes maintained typical round morphology throughout the course of this investigation, indicating preservation of their phenotype with sufficient production of extracellular matrix and expression of typical chondrogenic markers Collagen type 2 and aggrecan. The results suggest that the natural polymer hydrogel matrix can be used as an efficient matrix for articular cartilage tissue engineering.

Hydrogels for Cardiac Tissue Engineering

Cardiac tissue regeneration is an integrated process involving both cells and supporting matrix. Cardiomyocytes and stem cells are utilized to regenerate cardiac tissue. Hydrogels, because of their tissue-like properties, have been used as supporting matrices to deliver cells into infarcted cardiac muscle. Bioactive and biocompatible hydrogels mimicking biochemical and biomechanical microenvironments in native tissue are needed for successful cardiac tissue regeneration. These hydrogels not only retain cells in the infarcted area, but also provide support for restoring myocardial wall stress and cell survival and functioning. Many hydrogels, including natural polymer hydrogels, synthetic polymer hydrogels, and natural/synthetic hybrid hydrogels are employed for cardiac tissue engineering. In this review, types of hydrogels used for cardiac tissue engineering are briefly introduced. Their advantages and disadvantages are discussed. Furthermore, strategies for cardiac regeneration using hydrogels are reviewed.