Novel injectable gallium-based self-setting glass-alginate hydrogel composite for cardiovascular tissue engineering.

Composite biomaterials offer a new approach for engineering novel, minimally-invasive scaffolds with properties that can be modified for a range of soft tissue applications. In this study, a new way of controlling the gelation of alginate hydrogels using Ga-based glass particles is presented. Through a comprehensive analysis, it was shown that the setting time, mechanical strength, stiffness and degradation properties of this composite can all be tailored for various applications. Specifically, the hydrogel generated through using a glass particle, wherein toxic aluminium is replaced with biocompatible gallium, exhibited enhanced properties. The material's stiffness matches that of soft tissues, while it displays a slow and tuneable gelation rate, making it a suitable candidate for minimally-invasive intra-vascular injection. In addition, it was also found that this composite can be tailored to deliver ions into the local cellular environment without affecting platelet adhesion or compromising viability of vascular cells in vitro.

A Self-Assembling Peptide Gel as a Vitreous Substitute: A Rabbit Study.

Purpose: To evaluate a self-assembling peptide gel as a potential vitreous substitute. Methods: PanaceaGel SPG-178, a self-assembling peptide gel, was diluted with distilled water and a balanced salt solution to achieve a final peptide concentration of 0.1%. The gel's refractive index, visible light transmission rate, and rheologic properties were investigated. The gel's biocompatibility was evaluated by examining the cellular viability (live and dead staining) and proliferation rate (alamarBlue assay). A 25-G pars plana vitrectomy was performed on the right eye of 21 New Zealand white rabbits. The gel was then injected into the vitreous cavity of 15 eyes. Six eyes were injected with a balanced salt solution (BSS) and served as controls. Toxicity was examined using electroretinography and histologic analysis after the injection of the gel. Results: The gel's physical properties closely resembled those of human vitreous. The gel showed no apparent toxicity. When the gel was injected into the vitreous cavity, fragmentation was not observed. Additionally, the gel remained transparent in the vitreous cavity and no complications were observed for 3 months after the injection. Electroretinography and histology confirmed the gel's biocompatibility. Conclusions: This diluted self-assembling peptide gel could be provide a promising vitreous substitute.

Effects of free radical initiators on polyethylene glycol dimethacrylate hydrogel properties and biocompatibility.

Many studies have utilized Irgacure 2959 photopolymerized poly(ethylene glycol) (PEG) hydrogels for tissue engineering application development. Due to the limited penetration of ultraviolet light through tissue, Irgacure 2959 polymerized hydrogels are not suitable for use in tissues where material injection is desirable, such as the spinal cord. To address this, several free radical initiators (thermal initiator VA044, ammonium persulfate (APS)/TEMED reduction-oxidation reaction, and Fenton chemistry) are evaluated for their effects on the material and mechanical properties of PEG hydrogels compared with Irgacure 2959. To emulate the effects of endogenous thiols on in vivo polymerization, the effects of chain transfer agent (CTA) dithiothreitol on gelation rates, material properties, Young's and shear modulus, are examined. Mouse embryonic stem cells and human induced pluripotent stem cell derived neural stem cells were used to investigate the cytocompatibility of each polymerization. VA044 and Fenton chemistry polymerization of PEG hydrogels both had gelation rates and mechanical properties that were highly susceptible to changes in CTA concentration and showed poor cytocompatibility. APS/TEMED polymerized hydrogels maintained consistent gelation rates and mechanical properties at high CTA concentration and had a similar cytocompatibility as Irgacure 2959 when cells were encapsulated within the PEG hydrogels. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3059-3068, 2017.

A High Strength Self-Healable Antibacterial and Anti-Inflammatory Supramolecular Polymer Hydrogel.

There is a significant cost to mitigate the infection and inflammation associated with the implantable medical devices. The development of effective antibacterial and anti-inflammatory biomaterials with novel mechanism of action has become an urgent task. In this study, a supramolecular polymer hydrogel is synthesized by the copolymerization of N-acryloyl glycinamide and 1-vinyl-1,2,4-triazole in the absence of any chemical crosslinker. The hydrogel network is crosslinked through the hydrogen bond interactions between dual amide motifs in the side chain of N-acryloyl glycinamide. The prepared hydrogels demonstrate excellent mechanical properties-high tensile strength (≈1.2 MPa), large stretchability (≈1300%), and outstanding compressive strength (≈11 MPa) at swelling equilibrium state. A simulation study elaborates the changes of hydrogen bond interactions when 1-vinyl-1,2,4-triazole is introduced into the gel network. It is demonstrated that the introduction of 1-vinyl-1,2,4-triazole endowes the supramolecular hydrogels with self-repairability, thermoplasticity, and reprocessability over a lower temperature range for 3D printing of different shapes and patterns under simplified thermomelting extrusion condition. In addition, these hydrogels exhibit antimicrobial and anti-inflammatory activities, and in vitro cytotoxicity assay and histological staining following in vivo implantation confirm the biocompatibility of the hydrogel. These hydrogels with integrated multifunctions hold promising potential as an injectable biomaterial for treating degenerated soft supporting tissues.

Preparation of a Salecan/poly(2-acrylamido-2-methylpropanosulfonic acid-co-[2-(methacryloxy)ethyl]trimethylammonium chloride) Semi-IPN Hydrogel for Drug Delivery.

Salecan is a water-soluble bacterial polysaccharide consisting of glucopyranosyl units linked by α-1,3 and ß-1,3 glycosidic bonds. salecan is suitable for the development of hydrogels for biomedical applications, given its outstanding physicochemical and biological profiles. In this study we designed a new semi-interpenetrating polymer network hydrogel that introduces the salecan polysaccharide into a stimuli-responsive poly(2-acrylamido-2-methylpropanosulfonic acid-co-[2-(methacryloxy)ethyl]trimethylammonium chloride) (PAM) hydrogel matrix for controlled insulin release. We found that salecan not only tunes the structure and pore size of the PAM hydrogels, but also endows them with adjustable water release rates. More importantly, in vitro drug loading/release assays demonstrated that insulin is efficiently loaded into the resulting hydrogels and can be released in an on-demand manner by controlling the pH and salecan dose. Furthermore, cell viability and cell adhesion experiments verified the cell compatibility of these hydrogel carriers. Together, these results make salecan-incorporated PAM hydrogels promising materials for drug delivery.

Preparation of Quantum Dots Hydrogel Nanocomposites with Improved Cytotoxicity.

Nanocomposites are materials with unique properties and a wide range of applications. The combination of different nanostructures with traditional materials gives a variety of possibilities that should be analyzed. Especially, functional fluorescent semiconductor quantum dots (QDs) embedded in polymeric matrices have shown promising fluorescence and biocompatibility properties. These hybrid materials can be used in medical applications such as biodiagnostic and bioimaging. In this study, two hydrogels, one of polyethylene glycol diacrylate (PEGDA) and other of polyacrylamide (PAAm), were prepared with quantum dots of CdTe (4 nm of diameter) and characterized. The aim of this research was to analyze the optical properties of the nanocomposites and their cell viability. QDs nanocomposites were fabricated by a free radical polymerization process. The optical studies showed that the nanocomposites have well defined properties of fluorescence. To study the biocompatibility of the nanocomposites, metastatic B16f10 cell line were used and MTT assay was performed. The nanocomposites had a significant improved cell viability compared with QDs solutions.

Assessment of degradation and biocompatibility of electrodeposited chitosan and chitosan-carbon nanotube tubular implants.

Designing three-dimensional tubular materials made of chitosan is still a challenging task. Availability of such forms is highly desired by tissue engineering, especially peripheral nerve tissue engineering. Aiming at this problem, we use an electrodeposition phenomenon in order to obtain chitosan and chitosan-carbon nanotube hydrogel tubular implants. The in vitro biocompatibility of the fabricated structures is assessed using a mouse hippocampal cell line (mHippoE-18). As both implants do not induce significant cytotoxicity, they are next subjected to in vitro degradation studies in the environment simulating in vivo conditions for specified periods of time: 7, 14, and 28 days. The mass loss of implants indicates their stability at the tested time period; therefore, the materials are subcutaneously implanted in Sprague Dawley rats. The explants are collected after 7, 14, and 28 days. The assessment of composition and changes in tissues surrounding the implanted materials is made in respect to surrounding tissue thickness as well as the number of blood vessels, macrophages, lymphocytes, and neutrophils. No symptoms of acute inflammation are noticed at any point in time. The observed regular healing process allows concluding that both chitosan and chitosan-carbon hydrogel tubular implants are biocompatible with high application potential in tissue engineering. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2701-2711, 2016.

Thermosensitive injectable in-situ forming carboxymethyl chitin hydrogel for three-dimensional cell culture.

Injectable hydrogels have gained great attentions for cell therapy and tissue regeneration as a result of the applications in minimally invasive surgical procedures with the ease of handling and complete filling of the defect area. Here, a novel biodegradable, thermosensitive and injectable carboxymethyl chitin (CMCH) hydrogel was developed for three-dimensional (3D) cell culture. The obtained CMCH solution remained transparent liquid flowing easily at low temperatures and gelled rapidly at 37°C. The gelation time of CMCH hydrogels could be easily tuned by varying temperature and the degree of carboxymethylation, which facilitates the cell encapsulation process at room temperature and in-situ forming hydrogel at body temperature. Moreover, the CMCH-14 hydrogels in PBS buffer remained stable and continuous porous structure and could be degraded in the presence of lysozyme or hyaluronidase. HeLa cells proliferated sustainably and self-assembled to form 3D multicellular spheroids with high cell activity on the surface of CMCH-14 hydrogel. Encapsulation of COS-7 cells within the in-situ forming CMCH hydrogel demonstrated that CMCH hydrogels promoted cell survival and proliferation. In vivo mouse study of the CMCH hydrogels showed good in-situ gel formation and tissue biocompatibility. Thus, the biodegradable thermosensitive injectable CMCH hydrogels hold potential for 3D cell culture and biomedical applications. STATEMENT OF SIGNIFICANCE: Biodegradable hydrogels have been widely studied for cell therapy and tissue regeneration. Herein, we report a novel thermosensitive injectable carboxymethyl chitin (CMCH) hydrogel for 3D cell culture, which was synthesized homogeneously from the bioactive natural chitin through the "green" process avoiding using organic solvent. The CMCH solutions exhibited rapid thermoresponsive sol-to-gel phase transition behavior at 37°C with controllable gelation times, which facilitates the cell encapsulation process at room temperature and in-situ forming hydrogel at body temperature. Importantly, in vitro 3D cell culture and in vivo mouse study of the CMCH hydrogel showed promotion of cell survival and proliferation, good in-situ gel formation and biocompatibility. We believe that such thermosensitive injectable CMCH hydrogels would be very useful for biomedical applications, such as tumor model for cancer research, post-operative adhesion prevention, the regeneration of cartilage and central nervous system and so on.

Thermosensitive hydrogel containing dexamethasone micelles for preventing postsurgical adhesion in a repeated-injury model.

Tissue adhesion is a common complication after surgery. In this work, a dexamethasone loaded polymeric micelles in thermosensitive hydrogel composite (Dex hydrogel) was prepared, which combined the anti-adhesion barrier with controlled release of anti-adhesion drug. Dexamethasone (Dex) was encapsulated in polymeric micelles (Dex micelles), and then the Dex micelles were loaded into biodegradable and thermosensitive hydrogel. The obtained Dex hydrogel showed a temperature-dependent sol-gel-sol phase transition behavior. The Dex hydrogel could form a non-flowing gel in situ upon subcutaneous injection and gradually degrade in about 20 days. In addition, Dex hydrogel was assigned for anti-adhesion studies in a more rigorous recurrent adhesion animal model. Compared with normal saline (NS) and Dex micelles group, tissue adhesions in hydrogel and Dex hydrogel group were significantly alleviated. In Dex hydrogel group, the media adhesion score is 0, which was dramatically lower than that in blank hydrogel group (2.50, P < 0.001). In histopathological examination and scanning electron microscopy (SEM) analysis, an integral neo-mesothelial cell layer with microvilli on their surface was observed, which revealed that the injured parietal and visceral peritoneum were fully recovered without the concerns of adhesion formation. Our results suggested that Dex hydrogel may serve as a potential anti-adhesion candidate.

Fabrication of three-dimensional bioplotted hydrogel scaffolds for islets of Langerhans transplantation.

In clinical islet transplantation, allogeneic islets of Langerhans are transplanted into the portal vein of patients with type 1 diabetes, enabling the restoration of normoglycemia. After intra-hepatic transplantation several factors are involved in the decay in islet mass and function mainly caused by an immediate blood mediated inflammatory response, lack of vascularization, and allo- and autoimmunity. Bioengineered scaffolds can potentially provide an alternative extra-hepatic transplantation site for islets by improving nutrient diffusion and blood supply to the scaffold. This would ultimately result in enhanced islet viability and functionality compared to conventional intra portal transplantation. In this regard, the biomaterial choice, the three-dimensional (3D) shape and scaffold porosity are key parameters for an optimal construct design and, ultimately, transplantation outcome. We used 3D bioplotting for the fabrication of a 3D alginate-based porous scaffold as an extra-hepatic islet delivery system. In 3D-plotted alginate scaffolds the surface to volume ratio, and thus oxygen and nutrient transport, is increased compared to conventional bulk hydrogels. Several alginate mixtures have been tested for INS1E ß-cell viability. Alginate/gelatin mixtures resulted in high plotting performances, and satisfactory handling properties. INS1E ß-cells, human and mouse islets were successfully embedded in 3D-plotted constructs without affecting their morphology and viability, while preventing their aggregation. 3D plotted scaffolds could help in creating an alternative extra-hepatic transplantation site. In contrast to microcapsule embedding, in 3D plotted scaffold islets are confined in one location and blood vessels can grow into the pores of the construct, in closer contact to the embedded tissue. Once revascularization has occurred, the functionality is fully restored upon degradation of the scaffold.

Injectable and Self-Healing Carbohydrate-Based Hydrogel for Cell Encapsulation.

With the fast development of cell therapy, there has been a shift toward the development of injectable hydrogels as cell carriers that can overcome current limitations in cell therapy. However, the hydrogels are prone to damage during use, inducing cell apoptosis. Therefore, this study was carried out to develop an injectable and self-healing hydrogel based on chondroitin sulfate multiple aldehyde (CSMA) and N-succinyl-chitosan (SC). By varying the CSMA to SC ratio, the hydrogel stiffness, water content, and kinetics of gelation could be controlled. Gelation readily occurred at physiological conditions, predominantly due to a Schiff base reaction between the aldehyde groups on CSMA and amino groups on SC. Meanwhile, because of the dynamic equilibrium of Schiff base linkage, the hydrogel was found to be self-healing. Cells encapsulated in the hydrogel remained viable and metabolically active. In addition, the hydrogel produced minimal inflammatory response when injected subcutaneously in a rat model and showed biodegradability in vivo. This work establishes an injectable and self-healing hydrogel derived from carbohydrates with potential applications as a cell carrier and in tissue engineering.

Biodistribution and Toxicity Studies of PRINT Hydrogel Nanoparticles in Mosquito Larvae and Cells.

Mosquito-borne diseases continue to remain major threats to human and animal health and impediments to socioeconomic development. Increasing mosquito resistance to chemical insecticides is a great public health concern, and new strategies/technologies are necessary to develop the next-generation of vector control tools. We propose to develop a novel method for mosquito control that employs nanoparticles (NPs) as a platform for delivery of mosquitocidal dsRNA molecules to silence mosquito genes and cause vector lethality. Identifying optimal NP chemistry and morphology is imperative for efficient mosquitocide delivery. Toward this end, fluorescently labeled polyethylene glycol NPs of specific sizes, shapes (80 nm x 320 nm, 80 nm x 5000 nm, 200 nm x 200 nm, and 1000 nm x 1000 nm) and charges (negative and positive) were fabricated by Particle Replication in Non-Wetting Templates (PRINT) technology. Biodistribution, persistence, and toxicity of PRINT NPs were evaluated in vitro in mosquito cell culture and in vivo in Anopheles gambiae larvae following parenteral and oral challenge. Following parenteral challenge, the biodistribution of the positively and negatively charged NPs of each size and shape was similar; intense fluorescence was observed in thoracic and abdominal regions of the larval body. Positively charged NPs were more associated with the gastric caeca in the gastrointestinal tract. Negatively charged NPs persisted through metamorphosis and were observed in head, body and ovaries of adults. Following oral challenge, NPs were detected in the larval mid- and hindgut. Positively charged NPs were more efficiently internalized in vitro than negatively charged NPs. Positively charged NPs trafficked to the cytosol, but negatively charged NPs co-localized with lysosomes. Following in vitro and in vivo challenge, none of the NPs tested induced any cytotoxic effects.

Evaluation of an alginate-gelatine crosslinked hydrogel for bioplotting.

Using additive manufacturing to create hydrogel scaffolds which incorporate homogeneously distributed, immobilized cells in the context of biofabrication approaches represents an emerging and expanding field in tissue engineering. Applying hydrogels for additive manufacturing must consider the material processing properties as well as their influence on the immobilized cells. In this work alginate-dialdehyde (ADA), a partially oxidized alginate, was used as a basic material to improve the physico-chemical properties of the hydrogel for cell immobilization. At first, the processing ability of the gel using a bioplotter and the compatibility of the process with MG-63 osteoblast like cells were investigated. The metabolic and mitochondrial activities increased at the beginning of the incubation period and they balanced at a relatively high level after 14-28 days of incubation. During this incubation period the release of vascular endothelial growth factor-A also increased. After 28 days of incubation the cell morphology showed a spreading morphology and cells were seen to move out of the scaffold struts covering the whole scaffold structure. The reproducible processing capability of alginate-gelatine (ADA-GEL) and the compatibility with MG-63 cells were proven, thus the ADA-GEL material is highlighted as a promising matrix for applications in biofabrication.

Design and formulation of a topical hydrogel integrating lemongrass-loaded nanosponges with an enhanced antifungal effect: in vitro/in vivo evaluation.

Lemongrass oil (LGO) is a volatile oil extracted from the leaves of Cymbopogon citratus that has become one of the most important natural oils in the pharmaceutical industry because of its diverse pharmacologic and clinical effects. However, LGO suffers from low aqueous solubility, which could lead to a reduced effect. Moreover, the instability of its major active constituent, citral, could lead to volatilization, reaction with other formulation ingredients, and consequently, skin irritation. To surmount these problems, this research aims to formulate lemongrass-loaded ethyl cellulose nanosponges with a topical hydrogel with an enhanced antifungal effect and decreased irritation. The minimal inhibitory concentration and minimal fungicidal concentration of LGO against Candida albicans strain ATC 100231, determined using the broth macrodilution method, were found to be 2 and 8 µL/mL, respectively. The emulsion solvent evaporation technique was used for the preparation of the nanosponges. The nanosponge dispersions were then integrated into carbopol hydrogels (0.4%). Nine formulations were prepared based on a 32 full factorial design employing the ethyl cellulose:polyvinyl alcohol ratio and stirring rate as independent variables. The prepared formulations were evaluated for particle size, citral content, and in vitro release. Results revealed that all the nanosponge dispersions were nanosized, with satisfactory citral content and sustained release profiles. Statistical analysis revealed that both ethyl cellulose:polyvinyl alcohol ratio and stirring rate have significant effects on particle size and percentage released after 6 hours; however, the effect of the stirring rate was more prominent on both responses. The selected hydrogel formulation, F9, was subjected to surface morphological investigations, using scanning and transmission electron microscopy, where results showed that the nanosponges possess a spherical uniform shape with a spongy structure, the integrity of which was not affected by integration into the hydrogel. Furthermore, the selected formulation, F9, was tested for skin irritation and antifungal activity against C. albicans, where results confirmed the nonirritancy and the effective antifungal activity of the prepared hydrogel.

GM-CSF-loaded chitosan hydrogel as an immunoadjuvant enhances antigen-specific immune responses with reduced toxicity.

BACKGROUND: The application of vaccine adjuvants has been vigorously studied for a diverse range of diseases in order to improve immune responses and reduce toxicity. However, most adjuvants have limited uses in clinical practice due to their toxicity. METHODS: Therefore, to reduce health risks associated with the use of such adjuvants, we developed an advanced non-toxic adjuvant utilizing biodegradable chitosan hydrogel (CH-HG) containing ovalbumin (OVA) and granulocyte-macrophage colony-stimulating factor (GM-CSF) as a local antigen delivery system. RESULTS: After subcutaneous injection into mice, OVA/GM-CSF-loaded CH-HG demonstrated improved safety and enhanced OVA-specific antibody production compared to oil-based adjuvants such as Complete Freund's adjuvant (CFA) or Incomplete Freund's adjuvant (IFA). Moreover, CH-HG system-mediated immune responses was characterized by increased number of OVA-specific CD4(+) and CD8(+) INF-γ(+) T cells, leading to enhanced humoral and cellular immunity. CONCLUSIONS: In this study, the improved safety and enhanced immune response characteristics of our novel adjuvant system suggest the possibility of the extended use of adjuvants in clinical practice with reduced apprehension about toxic side effects.

Preparation of novel biodegradable pHEMA hydrogel for a tissue engineering scaffold by microwave-assisted polymerization.

OBJECTIVE: To prepare a novel biodegradable poly(2-hydroxyethylmethacrilate) (pHEMA) hydrogel as tissue engineering scaffold. METHODS: The pHEMA hydrogel was synthesized by microwave-assisted polymerization using 2-hydroxyethyl methacrylate (HEMA) as the raw material, potassium persulfate as the initiator, and PCLX as the cross-linking additive. The hydrogels was characterized with FTIR and NMR spectroscopy. The physical and chemical properties of the prepared hydrogel were evaluated, and its degradation performance was tested. The cytotoxicity of the optimum composite hydrogel was measured by an MTT assay to confirm the feasibility of its use in tissue engineering. RESULTS: The optimum conditions under which the hydrogel was prepared by microwave-assisted polymerization are as follows: 1.5 g cross-linking additive, 0.3 g initiator, reaction temperature of 80 °C, and microwave power of 800 W. Degradation studies showed good degradation profiles with 75% in 17 days. Additionally, the hydrogels did not elicit any cytotoxic response in in vitro cytotoxic assays. CONCLUSION: A biodegradable pHEMA hydrogel was successfully prepared by microwave-assisted polymerization, as confirmed from FTIR and NMR results. The hydrogel shows promising applications in tissue engineering, and its healing ability and biocompatibility will be evaluated in detail in the future.

PEG-g-chitosan thermosensitive hydrogel for implant drug delivery: cytotoxicity, in vivo degradation and drug release.

Thermosensitive hydrogels based on chitosan are of great interests for injectable implant drug delivery. The poly(ethylene glycol)-grafted-chitosan (PEG-g-CS) hydrogel was reported as a potential thermosensitive system. The objective of the present study is to evaluate the cytotoxicity, in vivo degradation and drug release of PEG-g-CS hydrogel. Cytotoxicity was evaluated using L929 murine fibrosarcoma cell line. Degradation and drug release in vivo were investigated by subcutaneous injection of the hydrogel into Sprague-Dawley rats. PEG-g-CS polymer exhibits no significant cytotoxicity when its concentration is less than 3 mg mL(-1). After being implanted, PEG-g-CS hydrogel maintains its integrity for two weeks and collapses, merging into the tissue, in the third week. It causes moderate inflammatory response but no fibrous encapsulation around the hydrogel is found. The hydrogel presents a three-week sustained release of cyclosporine A with no significant burst release in vitro and produces the effective drug concentration in blood for more than five weeks in vivo, performing almost the same bioavailability to chitosan/glycerophosphate hydrogel. Further modifications of PEG-g-CS hydrogel might be necessary to modulate the degradation and to mitigate the fluctuations in blood drug concentration.

Injectable 3D hydrogel scaffold with tailorable porosity post-implantation.

Since rates of tissue growth vary significantly between tissue types, and also between individuals due to differences in age, dietary intake, and lifestyle-related factors, engineering a scaffold system that is appropriate for personalized tissue engineering remains a significant challenge. In this study, a gelatin-hydroxyphenylpropionic acid/carboxylmethylcellulose-tyramine (Gtn-HPA/CMC-Tyr) porous hydrogel system that allows the pore structure of scaffolds to be altered in vivo after implantation is developed. Cross-linking of Gtn-HPA/CMC-Tyr hydrogels via horseradish peroxidase oxidative coupling is examined both in vitro and in vivo. Post-implantation, further alteration of the hydrogel structure is achieved by injecting cellulase enzyme to digest the CMC component of the scaffold; this treatment yields a structure with larger pores and higher porosity than hydrogels without cellulase injection. Using this approach, the pore sizes of scaffolds are altered in vivo from 32-87 µm to 74-181 µm in a user-controled manner. The hydrogel is biocompatible to COS-7 cells and has mechanical properties similar to those of soft tissues. The new hydrogel system developed in this work provides clinicians with the ability to tailor the structure of scaffolds post-implantation depending on the growth rate of a tissue or an individual's recovery rate, and could thus be ideal for personalized tissue engineering.

Synthesis, characterization, and acute oral toxicity evaluation of pH-sensitive hydrogel based on MPEG, poly(ε-caprolactone), and itaconic acid.

A kind of chemically cross-linked pH-sensitive hydrogels based on methoxyl poly(ethylene glycol)-poly(caprolactone)-acryloyl chloride (MPEG-PCL-AC, PECA), poly(ethylene glycol) methyl ether methacrylate (MPEGMA, MEG), N,N-methylenebisacrylamide (BIS), and itaconic acid (IA) were prepared without using any organic solvent by heat-initiated free radical method. The obtained macromonomers and hydrogels were characterized by ¹H NMR and FT-IR, respectively. Morphology study of hydrogels was also investigated in this paper, and it showed that the hydrogels had good pH-sensitivity. The acute toxicity test and histopathological study were conducted in BALB/c mice. The results indicated that the maximum tolerance dose of the hydrogel was higher than 10,000 mg/kg body weight. No morality or signs of toxicity were observed during the whole 7-day observation period. Compared to the control groups, there were no important adverse effects in the variables of hematology routine test and serum chemistry analysis both in male or female treatment group. Histopathological study also did not show any significant lesions, including heart, liver, lung, spleen, kidney, stomach, intestine, and testis. All the results demonstrated that this hydrogel was nontoxic after gavage. Thus, the hydrogel might be the biocompatible potential candidate for oral drug delivery system.

Thermosensitive hydrogel from oligopeptide-containing amphiphilic block copolymer: effect of peptide functional group on self-assembly and gelation behavior.

We reveal that a slight change in the functional group of the oligopeptide block incorporated into the poloxamer led to drastically different hierarchical assembly behavior and rheological properties in aqueous media. An oligo(L-Ala-co-L-Phe-co-ß-benzyl L-Asp)-poloxamer-oligo(ß-benzyl-L-Asp-co-L-Phe-co-L-Ala) block copolymer (OAF-(OAsp(Bzyl))-PLX-(OAsp(Bzyl))-OAF, denoted as polymer 1), which possessed benzyl group on the aspartate moiety of the peptide block, was synthesized through ring-opening polymerization. The benzyl group on aspartate was then converted to carboxylic acid to yield oligo(L-Ala-co-L-Phe-co-L-Asp)-poloxamer-oligo(L-Asp-co-L-Phe-co-L-Ala) (OAF-(OAsp)-PLX-(OAsp)-OAF, denoted as polymer 2). Characterization of the peptide secondary structure in aqueous media by circular dichroism revealed that the oligopeptide block in polymer 1 exhibited mainly an α-helix conformation, whereas that in polymer 2 adopted predominantly a ß-sheet conformation at room temperature. The segmental dynamics of the PEG in polymer 1 remained essentially unperturbed upon heating from 10 to 50 °C; by contrast, the PEG segmental motion in polymer 2 became more constrained above ca. 35 °C, indicating an obvious change in the chemical environment of the block chains. Meanwhile, the storage modulus of the polymer 2 solution underwent an abrupt increase across this temperature, and the solution turned into a gel. Wet-cell TEM observation revealed that polymer 1 self-organized to form microgel particles of several hundred nanometers in size. The microgel particle was retained as the characteristic morphological entity such that the PEG chains did not experience a significant change of their chemical environment upon heating. The hydrogel formed by polymer 2 was found to contain networks of nanofibrils, suggesting that the hydrogen bonding between the carboxylic acid groups led to an extensive stacking of the ß sheets along the fibril axis at elevated temperature. The in vitro cytotoxicity of the polymer 2 aqueous solution was found to be low in human retinal pigment epithelial cells. The low cytotoxicity coupled with the sol-gel transition makes the corresponding hydrogel a good candidate for biomedical applications.