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In recent years, injectable hydrogels and cardiac patches have provided a promising approach to improve cardiac regeneration and function after myocardial infarction, however, the crucial designing factors of these biomaterials have been less reviewed. Therefore, in this review, we speculate on the prominent design parameters. A profound understanding of the main properties of native heart tissue can guide the efforts to obtain biomaterials with desirable biomimicking properties that improve the effectiveness of future fabricated myocardial biomaterials. Moreover, the injectable hydrogels and cardiac patches with reactive oxygen species scavenging properties will be reviewed in detail owing to the promising results of in vitro and in vivo studies on cardiac regeneration after myocardial infarction. This review can pave the way for an optimized design for effective cardiac biomaterials by considering the optimum ranges for physical, chemical, and biological characteristics of biomaterials, as well as the study of undetected parameters that can be investigated in future studies. [ABSTRACT FROM AUTHOR]

AbstractGraphene oxide (GO) is widely used in bone tissue engineering due to its good biocompatibility and proliferation, and is often used in combination with other hydrogels, which not only reduces the cytotoxicity of GO but also improves the mechanical properties of the hydrogels. We developed injectable carboxymethyl chitosan (CMC)/hydroxyethyl cellulose (HEC)/β-tricalcium phosphate (β-TCP)/GO hydrogel via hydrogen bonding cross-linked between (CMC) and (HEC), also, calcium cross-linked by β-TCP was also involved to further improvement of mechanical properties of the hydrogel, and incorporate different concentration of GO in these hydrogel systems. The characterization of the novel hydrogel was tested by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). The swelling ratio and mechanical properties were investigated, the results showed that the addition of GO was able to reduce the swelling rate of hydrogels and improve their mechanical properties, with the best effect in the case of 1 mg/mL content. In vivo experimental studies showed that the hydrogel significantly promoted the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), with the best effect at a concentration of 2 mg/mL. The results of the cellular experiments were similar. Therefore, the novel environment-friendly and non-toxic injectable CMC/HEC/β-TCP/GO hydrogel system may have potential applications in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Nowadays, chemotherapy is a common clinical treatment for cancer, but it still faces many limitations and challenges. Therefore, the combination of chemotherapy and other treatments often enhances the effectiveness of treatments. Herein, an injectable hydrogel of PC10ARGD/Cu2+/DOX based on Cu2+, hydrophilic doxorubicin (DOX), and genetically engineered polypeptide PC10ARGD was prepared. First, Cu2+ was attached to the histidines in the PC10ARGD polypeptide by the coordination reaction to form PC10ARGD/Cu2+ hydrogel, then the PC10ARGD/Cu2+/DOX hydrogel was prepared by encapsulating the DOX into the PC10ARGD/Cu2+ hydrogel. The results of scanning electron microscopy showed that the PC10ARGD/Cu2+/DOX hydrogel displayed loose porous morphology. In vitro, reactive oxygen species production results showed that the PC10ARGD/Cu2+/DOX hydrogel could continuously produce ·OH in the presence of H2O2. In vitro MTT results showed that the PC10ARGD/Cu2+/DOX hydrogel had a good inhibitory effect on cell activity. Flow cytometry further confirmed the antitumor effect of the PC10ARGD/Cu2+/DOX hydrogel. In vivo experiment results showed that the tumor volume of mice treated with the PC10ARGD/Cu2+/DOX hydrogel was significantly inhibited compared with control groups, which was due to the combination of chemodynamic and chemotherapy. The results of body weight and blood analysis of mice showed that the PC10ARGD/Cu2+/DOX hydrogel possessed good biocompatibility. [ABSTRACT FROM AUTHOR]

Injectable hydrogel provides an excellent substrate for bone tissue engineering (BTE) applications due to its water base, and capacity to encapsulate, manipulate, and easily reach to the adjacent tissue with minimal invasiveness. The purpose of the present study, is to develop an injectable hydrogel with a combination of chitosan, hyaluronic acid, and hydroxyapatite for enhanced bone regeneration and remodeling. Blend hydrogels have enough surface roughness and porosity that helps to attach bone cells. Hydrogel synthesis was confirmed with XRD, FTIR, EDX and TGA characterization. These hydrogels demonstrated adequate swelling and mechanical properties for its use in BTE applications. These hydrogels have the acceptable range of mechanical strength required for injectable hydrogels for bone regeneration. The synthesized hydrogel showed enough range of percolation capacity needed for the permeability of medicine, growth factors, and nutritional molecules. All these findings suggest the use of synthesized hydrogels for bone regeneration in biomedical engineering applications. [ABSTRACT FROM AUTHOR]

Inspired by the commonly used creams in dermatology, the present study introduced a simple method to prepare a granular hydrogel that could be applied to the whole wound area via spread to promote wound healing. Gelatin microspheres were fabricated and densely stacked, followed by adsorbing dopamine and Zn2+ solution. Dopamine polymerised in-situ to form gelatin/polydopamine (PDA)/Zn2+ composite microspheres, which were self-assembled to form a granular hydrogel. Zn2+ accelerated dopamine polymerization. PDA formed Schiff base and hydrogen bond with gelatin, realizing the assembly among the composite microspheres. The granular hydrogel exhibited bulk feature, shear-thinning and self-healing properties, which was injectable and spreadable like creams. Zn2+ in hydrogel showed sustained and stable release within 7 d. The granular hydrogel was applied to wound and significantly promoted wound healing, shortening the healing time within 10 days. The present injectable granular hydrogel thus showed convenient and advanced features towards surgical wound treatment. [ABSTRACT FROM AUTHOR]

\nIMPACT STATEMENTA sealant has been developed that improves upon current catheter-based treatments in the following ways: 1) Efficient delivery system, 2) No in situ polymerization, 3) No harmful byproducts, and 4) Cost effective formulation. During the development process, particular attention was given to materials that were tunable, safe, and effective sealant agents. The thermo-responsive properties of poly(N-isopropylacrylamide) (PNIPAM) provides an ideal foundation to develop an optimized solution. Through a combination of model-based and material testing, a hydrogel was developed that balances conformational factors to achieve a customized transition temperature, radiopacity suitable for visualization, mechanical properties suitable for delivery via 3Fr catheter, sufficient cohesion once applied to resist migration under physiological pressures and an improved safety profile. Two applications, embolization of lymphatic leakage and exclusions of the left atrial appendage (LAA), to eliminate LAA dead space to reduce the risk of thromboembolic events, were considered. The material and benchtop results for this product demonstrate the suitability of this new material not only for these applications but for other potential healthcare applications.A sealant has been developed that improves upon current catheter-based treatments in the following ways: 1) Efficient delivery system, 2) No in situ polymerization, 3) No harmful byproducts, and 4) Cost effective formulation. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. This study aimed to compare the effect of sunitinib-loaded poly (glycerol sebacate) (PGS)/gelatin nanoparticles doped in an injectable hydrogel with bevacizumab as a standard treatment of DR. The shear-sensitive hydrogel was prepared based on tragacanthic acid (TA) cross-linked with sodium acetate. DR was induced in rats by streptozotocin (STZ), and the animals were injected intravitreally a single dose of 20 µL sunitinib solution in three different concentrations (12.5, 25, and 50 µg/mL), sunitinib-loaded nanoparticles in hydrogel (413 µg/mL) and bevacizumab solution (6.25 mg/mL). The efficacy of the treatments was studied by histological and immunohisitological tests, angiogenesis, and optical coherence tomography (OCT). Vascular endothelial growth factor (VEGF) concentration was measured in the retina. The results revealed that 20 µL of sunitinib with the concentration of 25 µg/mL was effective in DR without any disruption in the retina or any other side effects. This dose was considered the therapeutic dose for nanoparticles. Sunitinib loaded PGS/gelatin nanoparticles that were incorporated in the injectable hydrogel were as effective as bevacizumab in controlling DR. Although sunitinib solution reduced VEGF production and neovascularization in the retina compared to the negative control group, it was not as suitable as the nanoparticles. TA-based hydrogel showed no toxicity on the normal retina, and the angiography and histologic studies confirmed the VEGF results.' Sunitinib nanoparticles doped in TA hydrogel may be an appropriate substitution of bevacizumab in the treatment of DR. [ABSTRACT FROM AUTHOR]

The present study focused on the combination of biphasic calcium phosphate (BCP) nanoparticles into the modified hyaluronic acid based injectable hydrogels for bone tissue engineering. Self-cross-linked thiolated hyaluronic acid (HA-HS) injectable hydrogels loaded with biphasic calcium phosphate (BCP) nanoparticles were prepared by disulfide cross-linking to mimic the extracellular matrix as a potential material for bone treatment. Varying concentration of HA-HS ranging between 1 and 5w/v% was tested to optimize the optimum concentration and were further modified with varying BCP concentrations for final optimization. Physico-chemical characterizations of the prepared hydrogel such as SEM, EDS, FT-IR, and XRD confirmed that the BCP has effectively loaded and distributed homogeneously in the HA-HS hydrogel. The results showed that the 3% (w/v) HA-HS hydrogel exhibits the appropriate properties for injectable hydrogel system such as gelation times, swelling rate and in vitro degradation behavior among all tested concentrations. Cell viability and cell proliferation using osteoblast cells (MC3T3-E1) demonstrated that the BCP laden modified hydrogel are biocompatible in vitro. In light of the encouraging results obtained, BCP laden HA-HS hydrogels might offer the potential to be used as injectable hydrogel in bone tissue engineering. [ABSTRACT FROM AUTHOR]

In current clinical settings, frequent intravitreal (IVT) injections of anti-vascular endothelial growth factors are used due to their short in-vivo half-life and rapid clearance from the back of the eye. The IVT injections are associated with pain, risk of infection, retinal detachment, and financial burden. Biologics molecules can undergo physical, chemical, and enzymatic degradation during formulation development and in the biological environment. Moreover, the complex ocular structures also act as a rate-limiting barrier for these biologics. Thus, delivering stable and clinically relevant biologics concentration to the back of the eye is still a challenge. Compare to other drug delivery platforms, injectable in-situ gelling depot systems (IISGDs) have emerged as an effective system for biologics delivery. In this review, we have discussed various biologics used in ocular therapeutics and their associated challenges. Different routes of delivery and associated tissue barriers are also discussed. Different types of IISGDs developed to date for biologics delivery to the back of the eye were also covered. To conclude, various critical parameters related to the formulation development process and injectable depot systems that need careful consideration and further investigations were highlighted. [ABSTRACT FROM AUTHOR]

An injectable composite hydrogel composed of polyvinyl alcohol (PVA) and bioactive glass (BG) particles were synthesized by a physical crosslinking approach. The morphology, mechanical properties, and viscoelasticity of the PVA/BG composite hydrogel were characterized. Scanning electronic microscopy (SEM) showed uniform and homogeneous distribution of BG particles throughout the composite hydrogel. The incorporation of 2.5 wt% of BG particles in the composite hydrogel formulations, enhanced the static compressive strength and static elastic modulus by 325% and 150%, respectively. The storage molds (G′) was greater than the loss modules (G′′) at all the frequency range studied, which revealed a self-standing elastic composite hydrogel with a smooth injectability. The PVA/BG composite hydrogel was also implanted subcutaneously in the dorsal region of adult male rats. After 4 weeks of implantation, no inflammatory cells were seen within and around the implant, which indicated that the composite hydrogel was biocompatible. The properties of the synthesized injectable PVA/BG composite hydrogel demonstrate its capability toward bone regeneration. [ABSTRACT FROM AUTHOR]

A high number of sport injuries result in damage to articular cartilage, a tissue type with poor self-healing capacity. Articular cartilage tissue is a sophisticated hydrogel, which contains 80% water and possesses strong mechanical properties. For this reason, synthetic hydrogels are thought to be an optimal material for cartilage regeneration. In the last decade, more than 2,000 research papers pertaining to "hydrogel and cartilage" have been published. Due to its biomimetic properties and user-friendly nature, especially in the field of minimal invasive surgery, intelligent injectable hydrogel have gradually become a focal point in cartilage research in recent years. In this review, we systematically summarize current "state-of-the-art" manufacture technologies of injectable hydrogels including ion-induced, thermo-induced, non-induced chemical, and light-induced crosslinking. We also review current strategies for designing intelligent injectable hydrogels, such as component-based, mechanical property-based and structure-based intelligent design to simulate the natural articular cartilage. Lastly, the applications of intelligent injectable hydrogels for cartilage regeneration are presented, and their outlooks for future clinical translation is dicussed. [ABSTRACT FROM AUTHOR]

In recent years, injectable hydrogels that undergo sol-to-gel phase transition in response to the physiological pH- and temperature have attracted increasing attention in therapeutics delivery. In this study, we developed a biodegradable pH- and temperature-sensitive pentablock copolymers by chemical conjugation of L-cysteine oligomer to the backbone of poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) (PCLA-PEG-PCLA) copolymers. A series of pentablock copolymers with various chain lengths were prepared by tuning the reaction time and temperature. These copolymers were freely soluble in water at high pH and low temperature; whereas, they could form a stable gel at the physiological condition (pH 7.4, 37 °C). An in vivo injectable study in the back of Sprague-Dawley (SD) rats indicated that the copolymer could form an in situ gel. In addition, an in vivo biodegradation study of the hydrogels showed controlled degradation of the gel matrix without inflammation at the injection site. Overall, our results show that biodegradable pH- and temperature-responsive hydrogel prepared in this study found to be bioresorbable and could be used as a controlled therapeutics delivery vehicle. [ABSTRACT FROM AUTHOR]

A series of injectable in situ dual-crosslinking hydrogels (HA/ALG) based on oxidized sodium alginate (oxi-ALG) and hyaluronic acid modified with thiol and hydrazide (HA-SH/CDH) were prepared via hydrazone bonds and disulfide bonds. The chemical structures, morphologies, rheological properties, gelling time, swelling ratio, degradation rate and drug release behavior of hydrogels were investigated. HA/ALG hydrogels exhibited tunable gelling time, rheological properties, swelling ratio and degradation rate with varying precursor concentrations. The gelling time of HA/ALG hydrogels ranged from 157 s to 955 s, the values of yield stress of HA2/ALG2, HA3/ALG3 and HA4/ALG4 hydrogels were 1724, 4349 and 5306 Pa, and the degradation percentage of HA2/ALG2, HA3/ALG3 and HA4/ALG4 hydrogels were about 64%, 51% and 42% after incubating 35 days, respectively. Bovine serum albumin (BSA) was used as a model drug to investigate the drug controlled release properties, and the in vitro cumulative release percentage of BSA from HA2/ALG2, HA3/ALG3 and HA4/ALG4 drug-loaded hydrogels were about 79%, 72% and 69% after 20 days. The series of injectable in situ dual-crosslinking HA/ALG hydrogels could be an attractive candidate for drug delivery system, tissue engineering and regenerative medicine. Injectable in situ dual-crosslinking hydrogels (HA/ALG) were prepared from thiol- and hydrazide-bifunctionalized hyaluronic acid (HA-SH/CDH) and oxidized alginates (oxi-ALG). Hydrogels exhibited tunable gelling time, appropriate rheology properties, high swelling ratio, low degradation percentage and sustainable controlled release properties, signifying that they could be potentially used in the fields of drug controlled release, cell encapsulation, tissue engineering and regenerative medicine. [ABSTRACT FROM AUTHOR]

Proteins are ideal raw materials for preparing biomaterials with better biocompatibility and larger elastic range than synthetic polymers. Injectable hydrogels are highly desired for minimal invasive strategies. At present, preparation of injectable hydrogels with good comprehensive properties using natural materials receives more and more attention. In this article, BSA was treated with urea and glutathione to prepare bovine serum albumin hydrogel controlled by two dynamic equilibrium bonds (disulfide and hydrogen bonds). The hydrogen bond equilibrium between urea-protein and protein-protein as well as the exchange reaction equilibrium between thiol-disulfide bonds in the system not only facilitated to enhance the mechanical properties, but also to reduce the gelation time to 5 min. Moreover, this novel albumin hydrogel was proved to be of good biocompatibility. Therefore, the albumin hydrogels in this article were injectable within the physiological range and shown low cytotoxicity, good machanical property (storage modulus could be greater than 10 kPa and compressive stress could reach 0.2 MPa) and good injectability, which exhibited promising prospect. [ABSTRACT FROM AUTHOR]

Injectable hybrid hydrogels were cross-linked multi-arm amino-terminated poly(ethylene glycol) (PEG) with aldehyde hyaluronic acid (HA) upon mixing, without the addition of a chemical crosslinking agent. The gelation is attributed to the Schiff-base reaction between amino and aldehyde groups of PEG and oxidized HA. In the current work, 4-arm and 8-arm amino-terminated PEG crosslinked with aldehyde HA were characterized.In vitrogelation time, morphologies, swelling ratio, weight loss and compressive modulus of multi-arm PEG/HA hydrogels in phosphate buffered saline at 37°C were studied. Results demonstrated that the 4-arm PEG/HA hydrogel showed a faster gelation time, higher water uptake and lower weight loss comparing to the 8-arm PEG/HA hydrogel. Drug delivery results demonstrated that there was a significantly lower release of dexamethasone detected from the 4-arm PEG/HA hydrogel than the 8-arm PEG/HA hydrogel. Human adipose-derived stem cells were seeded into the 4-arm and 8-arm PEG/HA hydrogelsin vitroto assess the biological performance and applicability of the gels as cell carriers. The 4-arm PEG hydrogel resulted in significantly enhanced cell adhesion and proliferation as compared to the 8-arm PEG hydrogel. Overall, these characteristics provide a potential opportunity for hybrid multi-arm PEG/HA hydrogels as injectable scaffolds in adipose tissue engineering application. [ABSTRACT FROM PUBLISHER]

Injectable hydrogels have attracted a lot of attention in drug delivery, however, their capacity to deliver water-insoluble or hydrophobic anti-cancer drugs is limited. Here, we developed injectable graphene oxide/graphene composite supramolecular hydrogels to deliver anti-cancer drugs. Pluronic F-127 was used to stabilize graphene oxide (GO) and reduced graphene oxide (RGO) in solution, which was mixed with α-cyclodextrin (α-CD) solution to form hydrogels. Native hydrogel was used as control. GO or RGO slightly shortened gelation time. The storage and loss moduli of the hydrogels were tracked by dynamic force measurement. The storage modulus of GO or RGO composite hydrogels was larger than that of the native hydrogel. Hydrogels were unstable in solution and eroded gradually. GO or RGO in Pluronic F-127 solution could potentially improve the solubility of the water-insoluble anti-cancer drug camptothecin (CPT), especially with large drug-loaded CPT amount. Drug release behaviors from solutions and hydrogels were characterized. The nanocomponents (GO or RGO) were able to bind more drug molecules either for CPT or for doxorubicin hydrochloride (DXR) in solution. Therefore, GO or RGO composite hydrogel could potentially enable better controlled and gentler drug release (for both CPT and DXR) than native hydrogel. [ABSTRACT FROM PUBLISHER]

The chitosan-human-like collagen/β-sodium glycerophosphate (CS-HLC/β-GP) hydrogel, is sensitive to pH and temperature changes and has proved to be a potential candidate as an injectable filling biomaterial in plastic and reconstruction surgery. The formation and pH/temperature-sensitivity mechanism of the novel CS-HLC/β-GP hydrogel were explored by Fourier transform infrared spectroscopy (FTIR) and swelling tests. Our results showed that an amide bond (-CONH) is formed between the carbonyl (CO) of HLC and the amino of CS and -NRH2+is formed between the amide bond and β-GP; the temperature sensitivity depended on the hydrophobic-hydrophilic interaction of molecular chains, and the pH sensitivity depended on the electrostatic interaction of ionic groups (-NRH2+and -OPO32-). The properties of the novel CS-HLC/β-GP hydrogel were also examined using the tube inverting method, the swelling test, the liquid displacement method, and mechanical testing. The gelling time before and after addition of HLC is 30 min and 8 min, respectively, at 37°C. Compared with conventional CS/β-GP hydrogels, such as CS-AC (animal-derived collagen)/β-GP hydrogel, the CS-HLC/β-GP hydrogel showed a desirable porosity level, swelling ratio, pH/temperature sensitivity, a smooth surface, regular porous networks, and adequate mechanical strength and cross-linking densities. Therefore, the CS–HLC/β-GP hydrogels are excellent candidates for use in biomedical fields, such as in soft tissue defect filling and drug delivery. [ABSTRACT FROM AUTHOR]

Injectable hydrogels have advantages over preformed hydrogels in biomedical applications. In our previous study, we showed usefulness of sugar beet pectin (SBP) as an injectable gel material. However, the in vivo biodegradability of the gels was low because animals lack suitable hydrolytic enzymes of SBP. In this study, we developed SBP-based injectable gels with higher in vivo biodegradability than the previous SBP gels by incorporating biodegradable gelatin into the latter. An aqueous solution with dissolved SBP and gelatin rapidly (<1 min) formed gels through a horseradish peroxidase-catalyzed oxidative coupling reaction between feruloyl moieties on the SBP molecules and phenolic moieties on the gelatin molecules. Gelation time and mechanical properties of the gels were tunable by adjusting the polymer concentrations. The gels containing doxorubicin, an anticancer drug, successfully suppressed the growth of a solid tumor created by subcutaneous injection of mouse melanoma B16F1 cells into nude mice. These results indicate that injectable and biodegradable SBP/gelatin gels are useful in biomedical applications. [ABSTRACT FROM AUTHOR]

Injectable hydrogels are increasingly being developed for biomedical applications due to their ability to be delivered in a minimally invasive manner. One potential use for such materials is in cell delivery for cardiac regeneration. While the materials' properties are often characterized, how these properties (and in particular gelation) are affected by the addition of the therapeutic agent(s) they are designed to deliver is often overlooked. The aim of this study was to examine the interactive effects between collagen-based hydrogels and different additives (cells and microspheres). The results demonstrated that the incorporation of either cells or microspheres to a collagen hydrogel decreased its gelation time and increased its viscosity. Increased concentrations of the EDC/NHS cross-linker resulted in greater loss of cell viability. However, it was found that this cell loss could be minimized by delivering cells with the cross-linker scavenger glycine. A better understanding of how materials and cells (and other additives) respond to each other will help towards the goal of improving scaffolds being developed for regenerative therapy. [ABSTRACT FROM AUTHOR]

Vitrectomy is a common procedure for treating ocular-related diseases. The surgery involves removing the vitreous humor from the center of the eye, and vitreous substitutes are needed to replace the vitreous humor after vitrectomy. In the present study, we developed a colorless, transparent and injectable hydrogel with appropriate refractive index as a vitreous substitute. The hydrogel is formed by oxidated hyaluronic acid (oxi-HA) cross-linked with adipic acid dihydrazide (ADH). Hyaluronic acid (HA) was oxidized by sodium periodate to create aldehyde functional groups, which could be cross-linked by ADH. The refractive index of this hydrogel ranged between 1.3420 and 1.3442, which is quite similar to human vitreous humor (1.3345). The degradation tests demonstrated that the hydrogel could maintain the gel matrix over 35 days, depending on the ADH concentration. In addition, the cytotoxicity was evaluated on retina pigmented epithelium (RPE) cells cultivated following the ISO standard (tests for in vitro cytotoxicity), and the hydrogel was found to be non-toxic. In a preliminary animal study, the oxi-HA/ADH hydrogel was injected into the vitreous cavity of rabbit eyes. The evaluations of slit-lamp observation, intraocular pressure, cornea thickness and histological examination showed no significant abnormal biological reactions for 3 weeks. This study suggests that the injectable oxi-HA/ADH hydrogel should be a potential vitreous substitute. [ABSTRACT FROM AUTHOR]

We designed and synthesized water-soluble biocompatible and biodegradable polymers composed of 2-methacryroyloxyethyl phosphorylcholine and oligo(L- or D-lactic acid) macromonomers to develop an injectable hydrogel matrix. Aqueous solutions containing the polymers with oligo(L-lactic acid) (OLLA) and oligo(D-lactic acid) (ODLA) chains underwent spontaneous gelation when mixed together. This was due to the formation of a stereocomplex between the OLLA and ODLA side-chains, which act as cross-linking components in the hydrogel. Therefore, the hydrogel could be re-dissolved in a buffer solution by hydrolysis of the oligo(lactic acid) chains. We obtained an injectable, biocompatible and degradable hydrogel, and we anticipate that it will be used in applications involving the controlled release of bioactive molecules and cell-based tissue engineering. [ABSTRACT FROM AUTHOR]

Alginate hydrogels have been widely utilized as cell carriers due to their simplicity for fabricating cell-immobilized gel beads or 3-dimentional porous scaffolds, biocompatibility and non-toxicity to cells. Generally alginate hydrogels have been produced by contacting alginate solution with CaCl2 as a cross-linking agent. However, the major disadvantages of this system are that the gelation rate is too fast and hard to control, and the prepared alginate gels cannot be injected. Injectable alginates have been prepared by using CaSO4 or CaCO3 as a cross-linking agent. However, the gelation rate of alginate with CaCO3 is slow owing to the low solubility of CaCO3 in water, while that with CaSO4 is too fast to form uniform gels. In this study, we prepared injectable alginate/polyvinyl alcohol (PVA) blend hydrogels with controllable gelation rate by using CaSO4 as a cross-linking agent and Na2HPO4 as a cross-linking retardation agent. The gelation rate could be controlled by adjusting CaSO4/Na2HPO4 ratio in the solution. The alginate and PVA showed good compatibility in aqueous solutions or gels. The gelation rate of alginate increased with increasing Na2HPO4 and decreasing CaSO4 concentrations, as expected. The PVA itself in the alginate/PVA blend did not affect the gelation rate. All alginate/PVA hydrogels demonstrated some extraction of PVA, but the extraction extent was not much even after 7 days immersion in water. The alginate/PVA hydrogels were examined for their in vitro cell compatibility by the culture of chondrocytes (human chondrocyte cell line) in the gels up to 28 days. The cells were grown almost linearly in the alginate/PVA hydrogels with higher PVA compositions showing better cell growth. The GAG contents from the cells in the hydrogels did not show dramatic changes with culture time, however, they also increased gradually in the alginate/PVA hydrogels with higher PVA composition. The PVA in the hydrogels seemed to play positive roles for the growth and activity of chondrocytes. The alginate/PVA hydrogels with controllable gelation rate are expected to be applicable as injectable cell carriers. [ABSTRACT FROM AUTHOR]

In these experiments, the effects of the drying history of hydrogels made from a novel polymer, oligo(poly(ethylene glycol) fumarate) (OPF) with two different poly(ethylene glycol) (PEG) molecular weights (approximately 920 (1K) and 9110 (10K) g/mol), were investigated. The hydrogels were either formed, dried and then swelled, representing what may occur in the case of a pre-formed membrane for guided tissue regeneration, or were formed and swelled immediately, as may occur with an injectable material for such applications. Subsequently, swelling properties, sol fraction and polymer network structure (as indicated by differential scanning calorimetry), as well as attachment of human dermal fibroblasts to these hydrogels at 4 and 24 h was examined. It was found that drying before swelling caused a significant reduction in final fold swelling of OPF hydrogels, regardless of OPF formulation or method of drying (air-dried or vacuum-dried) (e.g. PEG 10K swollen first: 13.94 ± 0.35 vs. vacuum first: 6.53 ± 0.12; PEG 1K swollen first: 8.99 ± 0.47 vs. vacuum first: 2.26 ± 0.08). This decreased swelling correlated to significantly higher cell attachment (% seeded) to these hydrogels at 24 h (PEG 10K vacuum first: 21.1 ± 4.7% vs. swollen first: 7.1 ± 5.5%; PEG 1K vacuum first: 58.2 ± 2% vs. swollen first: 7.4 ± 2.2%). LIVE/DEAD staining followed by microscopic analysis revealed attached cells were viable, yet rounded, and that, in the case of the PEG 1K dried-first samples, undulations in the surface visible in the hydrated state may have affected cell adhesion. Regardless of treatment, all hydrogels showed significantly less cell attachment than the tissue culture polystyrene control after 24 h (104.9 ± 4.4%). These results suggest that, by altering the PEG molecular weight used in synthesis, OPF hydrogels may be tailored to produce desired swelling properties and reduce non-specific cell adhesion for either injectable or pre-formed applications, thus providing a potential alternative material for use in guided tissue regeneration procedures. [ABSTRACT FROM AUTHOR]