Showing papers on "Self-healing hydrogels published in 2007"

A Novel Hydrogel with High Mechanical Strength: A Macromolecular Microsphere Composite Hydrogel

Abstract: The industrial and biomedical applications of hydrogels made from either natural or synthetic sources are strongly limited by their poor mechanical properties. A normal structure (NS) hydrogel breaks under low stress because there are very few energy dissipation mechanisms to slow crack propagation. In addition, as their crosslinking points are distributed irregularly and the polymer chains between the crosslinking points have different lengths, the stress cannot be evenly distributed between the polymer chains, and crack initiation is facile. Many efforts have been focused on increasing the mechanical strength of hydrogels, but the robustness still remains unsatisfactory. In recent years, three kinds of novel hydrogels with unique structures and high mechanical strength have been developed. Topological (TP) gels have figure-ofeight crosslinkers that can slide along polymer chains. The gel swells to about 500 times its original weight and can be stretched to nearly 20 times its original length. The nanocomposite (NC) hydrogel is made from specific polymers with a water-swellable inorganic clay. Most of the macromolecules are grafted onto nanoparticles, indicating that the nanoparticle clay acts as a highly multifunctional crosslinking agent. We believe that the high mechanical strength of this material has its origin in the very high functionality of the rigid crosslinked points and the lack of short chains between crosslinked components, as every active chain has to stretch between nanoparticles. The extension degree of a chain before breakage is controlled by the relationship between its relaxed end-to-end distance and its contour length, which is low for short chains. When a short chain in an NS hydrogel breaks, its load is thrown onto just one or two other adjacent chains, which dramatically increases their load. Hence, multiple chain fractures occur, causing voids and microcracks. However, in an NC hydrogel with large, rigid crosslinking points, the load from a single broken chain will be spread over many other chains, and the material is less likely to form the microcracks and voids responsible for initiating bulk failure. Gong et al. have reported a new method of obtaining strong and tough hydrogels by making double-network (DN) materials with a high molar ratio of the second network to the first network. In this case, the first network is highly crosslinked and the second network is loosely crosslinked. These DN hydrogels demonstrate extremely high mechanical strength. By adding a third component to a DN gel, either a weakly crosslinked network or noncrosslinked linear chains, gels with high-strength and low-frictional coefficients were obtained. Macromolecular microspheres (MMSs) have become an important structure in polymeric materials. The hydrogel microspheres on the microor nanoscale are known as microgels or nanogels, respectively. They are usually environmentally sensitive and are mainly used in drug delivery and other biomedical applications. However, it is difficult to form bulk hydrogels (macrogels) with these microgels, and when formed, the macrogels do not exhibit high mechanical strength. Very little work has been done on incorporating other kinds of microspheres into bulk hydrogel structures, and the improvement in mechanical strength is far less than for the three hydrogels mentioned above. Here, we report a new way of synthesizing hydrogels with a novel, well-defined network structure and high mechanical strength. In this method, a peroxidized MMS acts as both an initiator and a crosslinker. The mechanism for the formation of the peroxide and the initiation of polymerization, as well as for the formation of a hydrogel, are proposed in Scheme 1. The new hydrogel is a macromolecular microsphere composite (MMC) hydrogel. When the MMS emulsion is irradiated with Co c-rays in oxygen, peroxides (POOR and POOH; here P is the macromolecule that comprises the MMS, and R is a short alkyl group) are formed on the surface and possibly, to a certain extent, in the inner part of the MMS. The formation of peroxides on the MMS was proven with iodometry, which is the common method used to verify their formation and determine the amount formed in the polymers. Potassium iodide and isopropyl alcohol were added to the irradiated MMS emulsion, and as the solution was heated and refluxed for 30 min, it gradually became yellow, which indicates the formation of I2 and further establishes the presence of peroxides on the MMS. The peroxides decomposed under heat to form the free radicals PO , OR , and OH . PO initiated the grafting of C O M M U N IC A TI O N

Hyaluronic acid hydrogel for controlled self-renewal and differentiation of human embryonic stem cells

Abstract: Control of self-renewal and differentiation of human ES cells (hESCs) remains a challenge. This is largely due to the use of culture systems that involve poorly defined animal products and do not mimic the normal developmental milieu. Routine protocols involve the propagation of hESCs on mouse fibroblast or human feeder layers, enzymatic cell removal, and spontaneous differentiation in cultures of embryoid bodies, and each of these steps involves significant variability of culture conditions. We report that a completely synthetic hydrogel matrix can support (i) long-term self-renewal of hESCs in the presence of conditioned medium from mouse embryonic fibroblast feeder layers, and (ii) direct cell differentiation. Hyaluronic acid (HA) hydrogels were selected because of the role of HA in early development and feeder layer cultures of hESCs and the controllability of hydrogel architecture, mechanics, and degradation. When encapsulated in 3D HA hydrogels (but not within other hydrogels or in monolayer cultures on HA), hESCs maintained their undifferentiated state, preserved their normal karyotype, and maintained their full differentiation capacity as indicated by embryoid body formation. Differentiation could be induced within the same hydrogel by simply altering soluble factors. We therefore propose that HA hydrogels, with their developmentally relevant composition and tunable physical properties, provide a unique microenvironment for the self-renewal and differentiation of hESCs.

Multifunctional chondroitin sulphate for cartilage tissue-biomaterial integration.

Abstract: A biologically active, high-strength tissue adhesive is needed for numerous medical applications in tissue engineering and regenerative medicine. Integration of biomaterials or implants with surrounding native tissue is crucial for both immediate functionality and long-term performance of the tissue. Here, we use the biopolymer chondroitin sulphate (CS), one of the major components of cartilage extracellular matrix, to develop a novel bioadhesive that is readily applied and acts quickly. CS was chemically functionalized with methacrylate and aldehyde groups on the polysaccharide backbone to chemically bridge biomaterials and tissue proteins via a twofold covalent link. Three-dimensional hydrogels (with and without cells) bonded to articular cartilage defects. In in vitro and in vivo functional studies this approach led to mechanical stability of the hydrogel and tissue repair in cartilage defects.

Controlling hydrogelation kinetics by peptide design for three-dimensional encapsulation and injectable delivery of cells

Abstract: A peptide-based hydrogelation strategy has been developed that allows homogenous encapsulation and subsequent delivery of C3H10t1/2 mesenchymal stem cells. Structure-based peptide design afforded MAX8, a 20-residue peptide that folds and self-assembles in response to DMEM resulting in mechanically rigid hydrogels. The folding and self-assembly kinetics of MAX8 have been tuned so that when hydrogelation is triggered in the presence of cells, the cells become homogeneously impregnated within the gel. A unique characteristic of these gel-cell constructs is that when an appropriate shear stress is applied, the hydrogel will shear-thin resulting in a low-viscosity gel. However, after the application of shear has stopped, the gel quickly resets and recovers its initial mechanical rigidity in a near quantitative fashion. This property allows gel/cell constructs to be delivered via syringe with precision to target sites. Homogenous cellular distribution and cell viability are unaffected by the shear thinning process and gel/cell constructs stay fixed at the point of introduction, suggesting that these gels may be useful for the delivery of cells to target biological sites in tissue regeneration efforts.

Fabrication of 3D hepatic tissues by additive photopatterning of cellular hydrogels

Abstract: We have fabricated a hepatic tissue construct using a multilayer photopatterning platform for embedding cells in hydrogels of complex architecture. We first explored the potential of established hepatocyte culture models to stabilize isolated hepatocytes for photoencapsulation (e.g., double gel, Matrigel, cocultivation with nonparenchymal cells). Using photopolymerizable PEG hydrogels, we then tailored both the chemistry and architecture of the hydrogels to further support hepatocyte survival and liver-specific function. Specifically, we incorporated adhesive peptides to ligate key integrins on these adhesion-dependent cells. To identify the appropriate peptides for incorporation, the integrin expression of cultured hepatocytes was monitored by flow cytometry and their functional role in cell adhesion was assessed on full-length extracellular matrix (ECM) molecules and their adhesive peptide domains. In addition, we modified the hydrogel architecture to minimize barriers to nutrient transport for these highly metabolic cells. Viability of encapsulated cells was improved in photopatterned hydrogels with structural features of 500 microm in width over unpatterned, bulk hydrogels. Based on these findings, we fabricated a multilayer photopatterned PEG hydrogel structure containing the adhesive RGD peptide sequence to ligate the alpha5beta1 integrin of cocultured hepatocytes. Three-dimensional photopatterned constructs were visualized by digital volumetric imaging and cultured in a continuous flow bioreactor for 12 d where they performed favorably in comparison to unpatterned, unperfused constructs. These studies will have impact in the field of liver biology as well as provide enabling tools for tissue engineering of other organs.

Fabrication of microfluidic hydrogels using molded gelatin as a sacrificial element

Abstract: This paper describes a general procedure for the formation of hydrogels that contain microfluidic networks. In this procedure, micromolded meshes of gelatin served as sacrificial materials. Encapsulation of gelatin meshes in a hydrogel and subsequent melting and flushing of the gelatin left behind interconnected channels in the hydrogel. The channels were as narrow as ∼6 µm, and faithfully replicated the features in the original gelatin mesh. Fifty micrometre wide microfluidic networks in collagen and fibrin readily enabled delivery of macromolecules and particles into the channels and transport of macromolecules from channels into the bulk of the gels. Microfluidic gels were also suitable as scaffolds for cell culture, and could be seeded by human microvascular endothelial cells to form rudimentary endothelial networks for potential use in tissue engineering.

Hydrogels as extracellular matrices for skeletal tissue engineering: state-of-the-art and novel application in organ printing.

Abstract: Organ printing, a novel approach in tissue engineering, applies layered computer-driven deposition of cells and gels to create complex 3-dimensional cell-laden structures. It shows great promise in regenerative medicine, because it may help to solve the problem of limited donor grafts for tissue and organ repair. The technique enables anatomical cell arrangement using incorporation of cells and growth factors at predefined locations in the printed hydrogel scaffolds. This way, 3-dimensional biological structures, such as blood vessels, are already constructed. Organ printing is developing fast, and there are exciting new possibilities in this area. Hydrogels are highly hydrated polymer networks used as scaffolding materials in organ printing. These hydrogel matrices are natural or synthetic polymers that provide a supportive environment for cells to attach to and proliferate and differentiate in. Successful cell embedding requires hydrogels that are complemented with biomimetic and extracellular matrix components, to provide biological cues to elicit specific cellular responses and direct new tissue formation. This review surveys the use of hydrogels in organ printing and provides an evaluation of the recent advances in the development of hydrogels that are promising for use in skeletal regenerative medicine. Special emphasis is put on survival, proliferation and differentiation of skeletal connective tissue cells inside various hydrogel matrices.

Hydrogels as smart biomaterials

Abstract: Hydrogels were the first biomaterials rationally designed for human use. Beginning with the pioneering work of Wichterle and Lim on three-dimensional polymers that swell in water, we review the design, synthesis, properties, and applications of hydrogels. The field of hydrogels has moved forward at a dramatic pace. The development of suitable synthetic methods encompassing traditional chemistry to molecular biology has been used in the design of hydrogels mimicking basic processes of living systems. Stimuli-sensitive hydrogels, hydrogels with controlled degradability, genetically engineered poly(amino acid) polymers reversibly self-assembling in precisely defined three-dimensional structures, and hybrid polymers composed of two distinct classes of molecules are just some examples of these exciting novel biomaterials. The biocompatibility of hydrogels and their applications from implants to nanomaterials are also reviewed. Copyright © 2007 Society of Chemical Industry

A cell-laden microfluidic hydrogel

Abstract: The encapsulation of mammalian cells within the bulk material of microfluidic channels may be beneficial for applications ranging from tissue engineering to cell-based diagnostic assays. In this work, we present a technique for fabricating microfluidic channels from cell-laden agarose hydrogels. Using standard soft lithographic techniques, molten agarose was molded against a SU-8 patterned silicon wafer. To generate sealed and water-tight microfluidic channels, the surface of the molded agarose was heated at 71 °C for 3 s and sealed to another surface-heated slab of agarose. Channels of different dimensions were generated and it was shown that agarose, though highly porous, is a suitable material for performing microfluidics. Cells embedded within the microfluidic molds were well distributed and media pumped through the channels allowed the exchange of nutrients and waste products. While most cells were found to be viable upon initial device fabrication, only those cells near the microfluidic channels remained viable after 3 days, demonstrating the importance of a perfused network of microchannels for delivering nutrients and oxygen to maintain cell viability in large hydrogels. Further development of this technique may lead to the generation of biomimetic synthetic vasculature for tissue engineering, diagnostics, and drug screening applications.

A hydrogel-based microfluidic device for the studies of directed cell migration

Abstract: We have developed a hydrogel-based microfluidic device that is capable of generating a steady and long term linear chemical concentration gradient with no through flow in a microfluidic channel. Using this device, we successfully monitored the chemotactic responses of wildtype Escherichia coli (suspension cells) to α-methyl-DL-aspartate (attractant) and differentiated HL-60 cells (a human neutrophil-like cell line that is adherent) to formyl-Met-Leu-Phe (f-MLP, attractant). This device advances the current state of the art in microchemotaxis devices in that (1) it demonstrates the validity of using hydrogels as the building material for a microchemotaxis device; (2) it demonstrates the potential of the hydrogel based microfluidic device in biological experiments since most of the proteins and nutrients essential for cell survival are readily diffusible in hydrogel; (3) it is capable of applying chemical stimuli independently of mechanical stimuli; (4) it is straightforward to make, and requires very basic tools that are commonly available in biological labs. This device will also be useful in controlling the chemical and mechanical environment during the formation of tissue engineered constructs.

A Supramolecular-Hydrogel-Encapsulated Hemin as an Artificial Enzyme to Mimic Peroxidase**

Abstract: A challenge in chemistry is an artificial enzyme that mimics the functions of the natural system but is simpler than proteins. The intensive development of artificial enzymes that use a variety of matrices, the rapid progress in supramolecular gels, and the apparent “superactivity” exhibited by supramolecular hydrogel-immobilized enzymes, prompted us to evaluate whether supramolecular hydrogels will improve the activity of artificial enzymes for catalyzing reactions in water or in organic media. To demonstrate the concept, we used hemin as the prosthetic group to mimic peroxidase, a ubiquitous enzyme that catalyzes the oxidation of a broad range of organic and inorganic substrates by hydrogen peroxide or organic peroxides. The structures of the active site as well as the reaction mechanism of peroxidases are well studied. Much effort has been focused on incorporating metalloporphyrins into protein-like scaffolds in the quest towards peroxidase mimetics, which do not show satisfactory activity and selectivity mainly owing to the lack of the peptidic microenvironment that exists in the native peroxidase. The shape of the protein pocket and the amino acid residues or functional groups that surround the active site bring about the special inclusion behavior between the enzyme and the substrate. As a result, b-cyclodextrins (bCDs), which are a frequently used model system, act as an excellent enzyme model owing to their appropriate size and their fairly rigid and hydrophobic cavities that provide favorable binding of the prosthetic group as well as substrates. Experimentally, b-CD-modified hemins have showed higher activity relative to free hemin, suggesting that supramolecular hydrogels may act as an alternative matrix to encapsulate hemin for the mimetic of peroxidase. Supramolecular hydrogels, formed by the self-assembly of nanofibers of amphiphilic oligopeptides or small molecules, have served as scaffolds for tissue engineering, a medium for screening inhibitors of enzymes, 14] a matrix for biomineralization, and as biomaterials for wound healing. The application of supramolecular hydrogels as the skeletons of artificial enzymes has yet to be explored. Similar to peptide chains that form active sites in enzymes, the selfassembled nanofibers of amino acids in the supramolecular hydrogels could act as the matrices of artificial enzymes. Thus, the supramolecular-hydrogel systems serve two functions: 1) as the skeletons of the artificial enzyme to aid the function of the active site (e.g., hemin) and, 2) as the immobilization carriers to facilitate the recovery of the catalysts in practical applications. Herein, we mixed hemin chloride (3) into the hydrogel formed by the self-assembly of two simple derivatives of amino acids (1 and 2). The activity of this new type of artificial enzyme is higher than the activity of free hemin, hemin in bCD, or hemin in polymeric hydrogels. This artificial enzyme shows the highest activity in toluene for an oxidation reaction, reaching about 60% of the nascent activity of horseradish peroxidase (HRP). This result is particularly interesting because it implies that the control of the structure of hydrogelators could tailor the nanofibers as an adjustable microenvironment around active centers and thereby affect the performance of artificial enzymes. Moreover, the supramolecular hydrogel acts as an effective carrier to minimize the dimerization and oxidative degradation of free hemin in the peroxidization reaction. Overall, the supramolecular-hydrogel-based artificial enzyme offers a new opportunity to achieve catalysis with high operational stability and reusability, which ultimately would benefit industrial biotransformation. Scheme 1 illustrates the simple procedure of using supramolecular hydrogels to encapsulate hemin. Equal molar equivalents of 1 and 2 and two equivalents of Na2CO3 in water formed a suspension, which turned into a clear solution at about 60 8C. Then, 3 was added and dissolved immediately in the solution. The subsequent cooling of the solution to room temperature afforded a supramolecular hydrogel containing hemin molecules (Gel II). Without the addition of 3, the same procedure gave the control (Gel I). As a point of reference, we made the artificial peroxidases by using b-CD or a polyacrylamide hydrogel to encapsulate hemin according to the literatures. As shown in the TEM and AFM images in Figure 1, Gel I and Gel II have different morphologies. The networks of Gel I have 50–500-nm pores formed by the nanofibers (roughly 20 nm in diameter) of the self-assembled 1 and 2. Besides the relatively large pores, the TEM image of the nanofibers in Gel II, however, shows two distinct regions: the dark part (fibers of approximately 20 nm in diameter) and the gray part (surface layer of approximately 6 nm thickness). [*] Dr. Q. Wang, Dr. Z. Yang, Prof. C. K. Chang, Prof. B. Xu Department of Chemistry The Hong Kong University of Science and Technology Clear Water Bay, Hong Kong (P.R. China) Fax: (+852)2358-1594 E-mail: chang@ust.hk chbingxu@ust.hk

Preparation and characterization of polyvinyl alcohol-gelatin hydrogel membranes for biomedical applications.

Abstract: The purpose of this research was to design and develop hydrogels by esterification of polyvinyl alcohol (PVA) with gelatin. The membranes were characterized by Fourier Transform Infrared (FTIR) spectroscopy, x-ray diffraction (XRD), and differential scanning calorimetry. The viscosity of the esterified product (as solution) was compared with the mixture of PVA and gelatin of the same composition. The mechanical properties of the hydrogels were characterized by tensile tests. Swelling behavior and hemocompatibility of the membrane were also evaluated. The diffusion coefficient of salicylic acid (SA), when the receptor compartment contained Ringer's solution, through the membrane was determined. SA was used as a model drug. FTIR spectra of the membranes indicated complete esterification of the free carboxylic groups of gelatin. XRD studies indicated that the crystallinity of the membranes was mainly due to gelatin. The comparison of viscosity indicated an increase in segment density within the molecular coil. The membrane had sufficient strength and water-holding capacity. Hemocompatibility suggested that the hydrogel could be tried as wound dressing and as an implantable drug delivery system. The diffusion coefficient of SA through the membrane was found to be 1.32×10−5 cm2/s. The experimental results indicated that the hydrogel could be tried for various biomedical applications.

Facile RAFT Precipitation Polymerization for the Microwave-Assisted Synthesis of Well-Defined, Double Hydrophilic Block Copolymers and Nanostructured Hydrogels

Abstract: Water-soluble macromolecular chain transfer agents (Macro-CTAs) were developed for the microwave-assisted precipitation polymerization of N-isopropylacrylamide. Two types of Macro-CTAs, amphiphilic (Macro-CTA1) and hydrophilic (Macro-CTA2), were investigated regarding their activity for the facile formation of nanoparticles and double hydrophilic block copolymers by RAFT processes. While both Macro-CTAs functioned as steric stabilization agents, the variation in their surface activity afforded different levels of control over the resulting nanoparticles in the presence of cross-linkers. The cross-linked nanoparticles produced using the amphiphilic Macro-CTA1 were less uniform than those produced using the fully hydrophilic Macro-CTA2. The nanoparticles spontaneously formed core−shell structures with surface functionalities derived from those of the Macro-CTAs. In the absence of cross-linkers, both types of Macro-CTAs showed excellent control over the RAFT precipitation polymerization process with well-def...

A versatile strategy to fabricate hydrogel–silver nanocomposites and investigation of their antimicrobial activity

Abstract: In this study, hydrogel–silver nanocomposites have been synthesized by a unique methodology, which involves formation of silver nanoparticles within swollen poly (acrylamide-co-acrylic acid) hydrogels. The formation of silver nanoparticles was confirmed by transmission electron microscopy (TEM) and surface plasmon resonance (SPR) which was obtained at 406 nm. The TEM of hydrogel–silver nanocomposites showed almost uniform distribution of nanoparticles throughout the gel networks. Most of the particles, as revealed from the particle-size distribution curve, were 24–30 nm in size. The X-ray diffraction pattern also confirmed the face centered cubic (fcc) structure of silver nanoparticles. The nanocomposites demonstrated excellent antibacterial effects on Escherichia coli (E. coli). The antibacterial activity depended on size of the nanocomposites, amount of silver nanoparticles, and amount of monomer acid present within the hydrogel–silver nanocomposites. It was also found that immersion of plain hydrogel in 20 mg/30 ml AgNO3 solution yielded nanocomparticle–hydrogel composites with optimum bactericidal activity.

Inherent Antibacterial Activity of a Peptide-Based β-Hairpin Hydrogel

Abstract: Among several important considerations for implantation of a biomaterial, a main concern is the introduction of infection. We have designed a hydrogel scaffold from the self-assembling peptide, MAX1, for tissue regeneration applications whose surface exhibits inherent antibacterial activity. In experiments where MAX1 gels are challenged with bacterial solutions ranging in concentrations from 2 × 103 colony forming units (CFUs)/dm2 to 2 × 109 CFUs/dm2, gel surfaces exhibit broad-spectrum antibacterial activity. Results show that the hydrogel surface is active against Gram-positive (Staphylococcus epidermidis, Staphylococcus aureus, and Streptococcus pyogenes) and Gram-negative (Klebsiella pneumoniae and Escherichia coli) bacteria, all prevalent in hospital settings. Live−dead assays employing laser scanning confocal microscopy show that bacteria are killed when they engage the surface. In addition, the surface of MAX1 hydrogels was shown to cause inner and outer membrane disruption in experiments that moni...

Polyacrylamide-clay nanocomposite hydrogels : Rheological and light scattering characterization

Abstract: The free-radical polymerization of acrylamide in aqueous clay dispersions and the structure of the resulting polymer-clay nanocomposite hydrogels have been investigated by rheometry using oscillatory deformation tests. Laponite was used as clay particles in the hydrogel preparation. The reactions were carried out with and without the presence of the chemical cross-linker N,N'-methylenebis(acrylamide) (BAAm). In the absence of BAAm, increasing clay concentration from 0.2 to 7% results in 3 orders of magnitude increase of the elastic modulus Gof the hydrogels. At a clay concentration of 5% or above, all the reaction systems, with or without BAAm, exhibit similar elastic moduli, indicating that clay mainly determines the rubber elasticity of the hydrogels. The loss factor tan ‰ was found to be around 0.1, indicating that the nanocomposite hydrogels are much more viscous than the conventional hydrogels. Increasing the amount of clay also increases the viscous, energy dissipating properties of the nanocomposite hydrogels, which are responsible for their improved mechanical properties. Dynamics of the nanocomposite hydrogels was also investigated by dynamic light scattering. The ensemble- averaged scattered intensity of the hydrogels varies nonmonotonically with the clay concentration due to the action of clay both as a cross-linker and as an ionic component during the formation of the nanocomposite hydrogels. shown that the scattering intensity from polymer gels is always larger than that from the solution of the same polymer at the same concentration. The excess scattering over the scattering from polymer solution is related to the inhomogeneous distribu- tion of the polymer material along the gel sample, which is