High Swelling Ratio Research Articles

Biodegradable cellulose-based superabsorbent as potent hemostatic agent

This study aims to engineer a novel developed superabsorbent (NDS) as potent hemostatic agent. NDS induces coagulation process due to the high adhesion affinity to the wet tissue, high swelling ratio and clotting potency. NDS controls massive bleedings by inducing the red blood cells accumulation, platelets aggregation and fibrin network formation at the site of bleeding. • NDS acts as brilliant superabsorbent that absorb 60 g of blood per one g of NDS. • NDS as a powerful hemostatic agents activated coagulation cascade process. • Biochemical, hematological, and pathological results didn’t show toxic effects. Engineering of effective and biocompatible hemostatic materials to control massive bleeding is one of the interesting research fields. Herein, cellulose-based polymer modified by silica aerogel and calcium chloride was used for suitable control of bleeding. Novel developed superabsorbent (NDS) was synthesized by chemical and physical cross-linking methods. NDS not only quickly absorbs a high amount of blood component (60 g/g), but it can also adhere strongly (~90 KPa) to damaged tissue. The contributions of the freeze-drying method and presence of silica aerogel as structural modifiers led to the creation of a superabsorbent with a porosity percentage of 70% which creates a significant ability to absorb blood cells. NDS negative surface charge and presence of silica nanoparticles and calcium ions accelerate activation of the coagulation cascade process. Superior hemostatic ability of NDS compared to commercial hemostatic powder (Gelita-Cel® and Traumastem®) was proved by complementary tests such as blood absorption content, RBC attachment, blood clotting index (BCI), platelet adhesion, clotting time test and partial thromboplastin time (PTT). In vivo study results demonstrate that the NDS could successfully decrease bleeding time and blood loss amount in Wistar rat’s cut-out femoral artery, 2.25 and 4.3 fold better than Gelita-Cel® and 2.13 and 4.4 fold better than Traumastem®. NDS biodegradability was proved by its implantation inside the Wistar rat's body during 14 days. Biochemical, hematological, and pathological tests did not show inflammation and toxic effects in the liver and renal tissues, skin tissues, and alteration in complete blood count parameters (CBC) in NDS treated Wistar rats. In conclusion, the cellulose-based NDS hemostatic biomaterial is suggested for future clinical trial studies due to its powerful ability in bleeding control.

Fabrication and characterization of biodegradable KH560 crosslinked chitin hydrogels with high toughness and good biocompatibility

Chitin hydrogels have multiple advantages of nontoxicity, biocompatibility, biodegradability, and three-dimensional hydrophilic polymer network structure similar to the macromolecular biological tissue. However, the mechanical strength of chitin hydrogels is relatively weak. Construction of chitin hydrogels with high mechanical strength and good biocompatibility is essential for the successful applications in biomedical field. Herein, we developed double crosslinked chitin hydrogels by dissolving chitin in KOH/urea aqueous solution with freezing-thawing process, then using KH560 as cross-linking agent and coagulating in ethanol solution at low temperature. The obtained chitin/ KH560 (CK) hydrogels displayed good transparency and toughness with compressed nanofibrous network and porous structure woven with chitin nanofibers. Moreover, the optimal CK hydrogels exhibited excellent mechanical properties (σb = 1.92 ± 0.21 Mpa; εb = 71 ± 5 %), high swelling ratio, excellent blood compatibility, biocompatibility and biodegradability, which fulfill the requirements of biomedical materials and showing potential applications in biomedicine.

Hyaluronidase Inhibitor-Incorporated Cross-Linked Hyaluronic Acid Hydrogels for Subcutaneous Injection.

Hyaluronidase (HAase) inhibitor-incorporated hyaluronic acid (HA) hydrogel cross-linked with 1,4-butanediol diglycidyl ether (BDDE) was designed to reduce the toxicity risk induced by BDDE and its biodegradation rate in subcutaneous tissue. The formulation composition of hydrogel and its preparation method were optimized to have a high swelling ratio and drug content. Quercetin (QCT) and quetiapine (QTP), as an HAase inhibitor and model drug, respectively, were incorporated into the cross-linked hydrogel using the antisolvent precipitation method for extending their release after subcutaneous injection. The cross-linked HA (cHA)-based hydrogels displayed appropriate viscoelasticity and injectability for subcutaneous injection. The incorporation of QCT (as an HAase inhibitor) in the cHA hydrogel formulation resulted in slower in vitro and in vivo degradation profiles compared to the hydrogel without QCT. Single dosing of optimized hydrogel injected via a subcutaneous route in rats did not induce any acute toxicities in the blood chemistry and histological staining studies. In the pharmacokinetic study of rats following subcutaneous injection, the cHA hydrogel with QCT exhibited a lower maximum QTP concentration and longer half-life and mean residence time values compared to the hydrogel without QCT. All of these results support the designed HAase inhibitor-incorporated cHA hydrogel being a biocompatible subcutaneous injection formulation for sustained drug delivery.

Tyrosinase-mediated rapid and permanent chitosan/gelatin and chitosan/gelatin/nanohydroxyapatite hydrogel

Chitosan/gelatin and chitosan/gelatin/nanohydroxyapatite hydrogels were rapidly and stably prepared without any crosslinking materials by using an engineered tyrosinase (mTyr-CNK) with high catalytic activity for tyrosine/DOPA-tethered polymeric biomaterials throughout a broad pH range. A dual-barrel syringe with one part containing chitosan/mTyr-CNK solution and the other containing gelatin solution with/without nanohydroxyapatite was successfully used to form homogeneous hydrogels at room temperature followed by 37 °C to simulate an in situ injection approach. The obtained hydrogels exhibited an average pore size greater than 150 µm and high swelling ratios with similar mechanical properties to other chemically crosslinked chitosan/gelatin hydrogels. The in vitro degradation properties and cellular viability suggested that the hydrogels could be used as biodegradable and biocompatible scaffolds for biomedical applications, such as space filling biomaterials and delivery vehicles for bioactive molecules and cells. These results demonstrated that mTyr-CNK-mediated hydrogels have remarkable promise as an injectable scaffold biomaterial.

Structural and biological investigation of chitosan/hyaluronic acid with silanized-hydroxypropyl methylcellulose as an injectable reinforced interpenetrating network hydrogel for cartilage tissue engineering

Cartilage damage continues to pose a threat to humans, but no treatment is currently available to fully restore cartilage function. In this study, a new class of composite hydrogels derived from water-soluble chitosan (CS)/hyaluronic acid (HA) and silanized-hydroxypropyl methylcellulose (Si-HPMC) (CS/HA/Si-HPMC) has been synthesized and tested as injectable hydrogels for cartilage tissue engineering when combined without the addition of a chemical crosslinking agent. Mechanical studies of CS/HA and CS/HA/Si-HPMC hydrogels showed that as Si-HPMC content increased, swelling rate and rheological properties were higher, compressive strength decreased and degradation was faster. Our results demonstrate that the CS and HA-based hydrogel scaffolds, especially the ones with 3.0% (w/v) Si-HPMC and 2.5/4.0% (w/v) CS/HA, have suitable physical performance and bioactive properties, thus provide a potential opportunity to be used for cartilage tissue engineering. In vitro studies of CS/HA and CS/HA/Si-HPMC hydrogels encapsulated in chondrocytes have shown that the proper amount of Si-HPMC increases the proliferation and deposition of the cartilage extracellular matrix. The regeneration rate of the CS/HA/Si-HPMC (3%) hydrogel reached about 79.5% at 21 days for long retention periods, indicating relatively good in vivo bone regeneration. These CS/HA/Si-HPMC hydrogels are promising candidates for tissue compatibility injectable scaffolds. The data provide proof of the principle that the resulting hydrogel has an excellent ability to repair joint cartilage using a tissue-engineered approach. RESEARCH HIGHLIGHTS An injectable hydrogel based on CS/HA/Si-HPMC composites was developed. The CS/HA/Si-HPMC hydrogel displays the tunable rheological with mechanical properties. The CS/HA/Si-HPMC hydrogel is highly porous with high swelling and degradation ratio. Increasing concentration of Si-HPMC promote an organized network in CS/HA/Si-HPMC hydrogels. Injectable CS/HA/Si-HPMC hydrogels have a high potential for cartilage tissue engineering.

Synthesis and Characterization of Hydrogel of Chitosan-Poly (N-Vinyl-2-Pirrolidone) (PVP)- Alginate for Ibuprofen Release

Hydrogels chitosan-poly-(N-vinyl-pyrrolidone)-alginate (Ch/PVP/Alg) have been synthesized with Ca2+, Zn2+ and formaldehyde as crosslinker. Hydrogels with ratio polymer 70:20:10 give a high swelling ratio and good network. The Ch/PVP/Alg/Ca2+ has 463.73% swelling ratio and 80.59% gel. Ch/PVP/Alg/Zn has 489.21% swelling ratio and 81.67% gel. Ch/PVP/Alg crosslinked with formaldehyde result 488.03% swelling ratio and 85.34% gel. Dissolution test of hydrogels in pH 1.2 releases ibuprofen less than 30%. Whereas in the pH 7.4, the release of ibuprofen by hydrogels are relatively high. Ch/PVP/Alg/Ca reach up to 34.63% in 30 minutes and 40.86% for Ch/PVP/Alg/Zn. Meanwhile Ch/PVP/Alg/CH2O can release 44.92% of ibuprofen in 30 minutes. The obtained hydrogel was characterized using infrared (FTIR) spectrophotometry, differential scanning calorimetry (DSC) and scanning electron microscopy (SEM).

High-Efficient Nanocomposite Ion Exchange Membranes for Lithium Polysulfide (Li-PS) Redox Flow Battery (RFB)

Redox flow batteries (RFBs) have attracted extensive research interest in recent years due to their low cost, safe operation condition, design flexibility, and easy scalability for large scale energy storage applications. Among all the RFBs, the lithium polysulfide redox flow battery (Li-PS RFB) has been considered as one of the most promising new energy storage systems because of their high theoretical energy density (~2600 Wh/kg and 2199 Wh/L for elemental Li and S) and low material cost.However, despite their great promise, the practical application of Li-PS RFBs has been hindered mainly by the dissolution and shuttling of intermediate polysulfides species that cause rapid capacity decay, low coulombic efficiency, and undesired electrode fouling. This shuttling effect is more detrimental in Li-PS RFBs which doesn’t have carbon matrix to immobilize the solid-state sulfur. To address these issues, an effective strategy is to employ a highly selective membrane separator which can suppress polysulfide crossover while allowing fast lithium-ion conductance. Unfortunately, commercial porous battery separators (e.g. Celgard) cannot be adopted due to their low rejection for polysulfide (PSn-) active species and fast capacity decay. Recent few research works revealed the feasibility of using ion exchange membranes (IEMs) as a barrier layer to selectively transport Li+ ions and block PSn- ions. However, most commercial IEMs are unstable in the organic polysulfide electrolyte because of its high swelling ratio which can cause the electrolytes crossover. Hence, there is a critical need to develop high-performance membrane materials for Li-PS RFB applications.In this work, we will present our recent progress on developing high-performance nanoengineered IEM materials for the Li-PS RFBs which can greatly suppress the polysulfide shuttling while maintaining high Li+ conductivity and mechanical stability. Our biphenyl polymer membrane (BPSA) presents excellent stability for the DOL/DME organic electrolyte solution, exhibiting potential for Li-PS RFBs application. To further improve the selectivity of Li-ion over PS, we developed nanocomposite membranes consisting of carbon nanotubes (CNT), boron nitride nanotubes (BNNT), and BPSA. The CNT layer can act as a PS shielding layer as well as reducing the interfacial resistance of membranes, while the BNNT layer can facilitate heat dissipation and suppressing the lithium dendrite formation. Our composite membranes greatly reduce PS crossover which is lower than commercial Celgard 2325 by 4-order of magnitude (3.5×10-7 cm2/sec vs. 2.2×10-7 cm2/sec), while areal resistance is only 3 times higher than Celgard 2325 (15.12 Ω cm2 vs. 4.64 Ω cm2). As a result, the performance of the Li-PS RFB single cell with our composite membranes is superior to that of Celgard and other commercial IEMs (e.g. Nafion 215) under the same condition. At the 100th cycle, the LiPS RFB capacity with Celgard 2325 loses all initial capacity at 40 cycles, while our composite membrane keeps around 95% of the initial capacity after 100 cycles. More detailed descriptions of ion transport properties, electrochemical properties, and battery performance of the membrane separators will be presented.

Preparation and characterization of okara nanocellulose fabricated using sonication or high-pressure homogenization treatments

Nanocellulose was isolated from okara using either ultrasound or high-pressure homogenization treatments. Dynamic light scattering, Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy, swelling behavior, rheological properties, and thermal analysis were used to characterize the physical-chemical and structural properties of the cellulose obtained. Sonication at 600 W for 15 min led to a cellulose material with a small mean particle diameter (d =0.22 μm), narrow polydispersity index (PDI = 0.21), strong negative charge (ζ = −36 mV), high swelling ratio (SR = 7.6), high crystallinity index (CI = 72 %), and formed viscous solutions. The initial pyrolysis temperature of the cellulose increased from 212 to 225 ℃, while the pyrolysis residue decreased from 26 to 12 %, after the sonication/homogenization treatment. The cellulose material produced in this study may be applied in various food and non-food applications as a texture modifier, stabilizer, structural component, or digestion modifier.

Enhanced Interfacial Adhesion of Polydimethylsiloxane (PDMS) by Control of the Crosslink Density.

In this paper, we report a simple, fast, and one-step approach to improve the adhesion force of polydimethylsiloxane (PDMS) by incorporating inorganic nanoparticles that can control the physical, mechanical, and adhesion properties of the PDMS. An organic/inorganic PDMS-based composite was fabricated by the hydrosilylation of vinyl-decorated silica nanoparticles (v-SNPs) and the PDMS. The v-SNP/PDMS composite showed a significantly decreased elastic modulus and increased elongation compared with that of pristine SNPs incorporated with the PDMS composite (SNP/PDMS) and pristine PDMS. Furthermore, the v-SNP/PDMS composite exhibited a low glass-transition temperature and sharp crystallization and melting peaks in the differential scanning calorimetry curve compared with those of pristine PDMS and the SNP/PDMS composite. Moreover, the v-SNP/PDMS composite showed a high swelling ratio and crosslinked molecular weight and low gel fraction. These results may originate from the suppression of the PDMS-curing networks as the addition of the v-SNPs creates a low curing density because of the chemical bonding between PDMS and the v-SNPs. Finally, the v-SNP/PDMS composite showed an improvement of ~426% in the adhesion force compared with pristine PDMS and the SNP/PDMS composite. We anticipate that this v-SNP/PDMS composite could be used as a highly adhesive and hydrophobic coating material for various applications in industry.

Aromatic nonpolar organogels for efficient and stable perovskite green emitters

Existing gels are mostly polar, whose nature limits their role in soft devices. The intermolecular interactions of nonpolar polymer-liquid system are typically weak, which makes the gel brittle. Here we report highly soft and transparent nonpolar organogels. Even though their elements are only carbon and hydrogen, their elastic modulus, transparency, and stretchability are comparable to common soft hydrogels. A key strategy is introducing aromatic interaction into the polymer-solvent system, resulting in a high swelling ratio that enables efficient plasticization of the polymer networks. As a proof of applicability, soft perovskite nanocomposites are synthesized, where the nonpolar environment of organogels enables stable formation and preservation of highly concentrated perovskite nanocrystals, showing high photoluminescence efficiency (~99.8%) after water-exposure and environmental stabilities against air, water, acid, base, heat, light, and mechanical deformation. Their superb properties enable the demonstration of soft electroluminescent devices that stably emit bright and pure green light under diverse deformations.

Hydroxyethyl cellulose hydrogel modified with tannic acid as methylene blue adsorbent

AbstractThis work developed an effective way to improve the methylene blue (MB) adsorption performance of cellulose‐based hydrogel by modified with tannic acid (TA). HEC‐co‐p(AA‐AM)/TA hydrogel was synthesized by grafting of acrylic acid (AA) and acrylamide (AM) onto hydroxyethyl cellulose (HEC), followed by modified with TA. Fourier transform infrared spectroscopy manifested that AA and AM were successfully grafted onto the hydrogel, and TA was immobilized in the hydrogel. Field emission scanning electron microscope demonstrated that the hydrogel after TA modification had a homogeneous pore structure. Brunauer‐Emmett‐Teller (BET) surface areas, total pore volume, and average pore diameters of the hydrogel are 11.821 m2g−1, 0.0641 cm3g−1, and 2.538 nm, respectively. The high swelling ratio (1179.2 g g−1in deionized water) was in favor of the MB adsorption. The results of the adsorption experiments illustrated that HEC‐co‐p(AA/AM) hydrogel had excellent MB adsorption performance. As the pH increases, the electrostatic attraction is enhanced, and the adsorption capacity is improved. The adsorption process was more fit with pseudo‐second‐order kinetics, and the maximum adsorption capacity (3438.27 mg g−1) was determined by Langmuir model. Thermodynamic studies suggested that the adsorption process is spontaneous, exothermic, and entropy reduction. X‐ray photoelectron spectroscopy analysis confirmed that MB molecules were reacted with the oxygen atoms in hydroxyl and carboxyl groups by ion‐exchange. High reusability demonstrated that the hydrogel could be a potential candidate for removal cationic dye from industrial effluents.

Regulation of the Morphological and Physical Properties of a Soft Tissue Scaffold by Manipulating DD and DS of O-Carboxymethyl Chitin.

To improve the biocompatibility/biodegradability as well as to lower the cost of the popular glycosaminoglycan/collagen scaffold, a monocomponent's polysaccharide scaffold based on biomimetic chemical modification of chitin from lower organisms was developed creatively. O-Carboxymethyl chitin (O-CMCH) was prepared by chloroacetic acid substitution of alkalized chitin. The cross-linked O-CMCH soft tissue scaffold was constructed by a sol-gel freeze-drying method. The key parameters of the O-CMCH molecular structure, the degree of deacetylation (DD), and the degree of substitution (DS) were used to regulate the morphology and physical properties of the scaffold. The optimized scaffolds were implanted subcutaneously in mice, and the inflammation reaction of surrounding tissues, dermal tissue growth, and scaffold degradation were observed dynamically by light microscopy and scanning electron microscopy. The results showed that the micropores of the scaffold constructed by O-CMCH with DD = 0.53 and DS = 0.61 were uniformly distributed and in communication with each other, and the pore size was 100-150 μm, with high porosity (93.52 ± 4.68%), high swelling ratio (1402 ± 70%), and high skeleton cross-linking degree (93.4 ± 4.6%). Its tensile strength reached 0.183 ± 0.009 MPa, and its elongation at break was 18.7 ± 0.9%. Furthermore, it could be degraded to less than 10% after 16 days in phosphate buffer solution (pH = 7.4) with 0.2 mg/mL lysozymes (≥ 20 000 U/mg). The early inflammation after implanting the optimized scaffolds in mice showed no difference compared with the control. The scaffold material induced dermal tissues to grow over it and was degraded gradually in vivo. The optimized scaffold regulated by DD and DS of O-CMCH possessed suitable morphology and physical properties for soft tissue engineering technology and exhibited a high applicable value.

Sub-nanoscaled Metal Oxide Cluster-Integrated Polymer Network for Quasi-Homogeneous Catalysis.

The simultaneous improvement of catalytic activity and recyclability of metal oxides is exciting, however challenging, due to the paradox for particle size requirements. Herein, we report the design of polymer nanocomposites (PNCs) by covalently integrating a sub-nanoscaled metal oxide cluster (∼0.7 nm) into a polymer network with superelasticity. Due to the ultrasmall sizes of loaded clusters and the high swelling ratios (SRs) of PNCs, the swelled organogels from PNCs claim similar catalytic efficiencies to homogeneous catalysts, while their recyclability can be simply achieved after the catalytic reactions. Thanks to their robust mechanical properties, the PNCs can be processed into microgel particles for column reactors, enabling large-scale and continuous-flow catalysis.

Engineering a Biopolymer-Based Ultrafast Permeable Aerogel Membrane Decorated with Task-Specific Fe-Al Nanocomposites for Robust Water Purification.

The present work demonstrates an innovative strategy for robust water purification using an engineered aerogel membrane fabricated from biopolymers and task-specific Fe-Al-based nanocomposites. The as-prepared ethylenediaminetetraacetate dianhydride cross-linked chitosan- and agarose (7:3 weight ratio)-based aerogel membrane decorated with α-FeOOH- and γ-AlOOH-based nanocomposites was characterized using various analytical tools, which suggested formation of a highly stable network interconnected through covalent and electrostatic interactions. The optimized bionanocomposite-based aerogel (BNC-AG-0.1) membrane showed macroporous and partial unidirectional short-range channels with an ultralow density of 0.021 g·m-2, a high swelling ratio of 1974%, and a remarkable pure water flux of 19,228 L·m-2·h-1 (>6-fold higher flux compared to the reported aerogel membranes). The aerogel membranes were successfully utilized for purification of diverse pollutants such as dyes, emerging pollutants (EPs), arsenate, and fluoride in a continuous flow method under gravitational force. The BNC-AG-0.1 membrane exhibits high rejection (95-98.6%) for both cationic and anionic dyes with a flux rate of 1150-1375 L·m-2·h-1 and a rejection of 89-92% for EPs with a flux rate of 1098-1165 L·m-2·h-1. Moreover, the BNC-AG-0.1 membrane showed a qmax of 102.45 mg·g-1 (at pH 6.5) for As(V) with >93% rejection at a flow rate of 1000 L·m-2·h-1. Furthermore, the aerogel membrane showed an excellent removal efficiency (92%) of arsenic up to the 10th cycle and hence demonstrated as a potential adsorption-based membrane for arsenic-free potable water. On the other hand, the BNC-AG-0.1 membrane showed a qmax of 81.56 mg·g-1 (at pH 6.5) for F- removal with >99% rejection at a flow rate of 250 L·m-2·h-1. When applied for real-water purification, approximately 4734 L of safe drinking water (the F- concentration is less than the WHO permissible limit) per square meter of the aerogel membrane can be obtained with a flux rate of 250 L·m-2·h-1. Overall, the prepared aerogel membrane showed robust removal of a variety of contaminants with ultrafast water permeation and established excellent recyclability.

Fabrication of chitosan/polyvinylpyrrolidone hydrogel scaffolds containing PLGA microparticles loaded with dexamethasone for biomedical applications

One of the most effective approaches for treatment of chronic rhinosinusitis is the use of hydrogel scaffolds with the sustained release of a given required drug. With this in mind, first, we synthesized and characterized poly (lactide-co-glycolide) (PLGA) micro and nano particles loaded with dexamethasone (DEX). We observed a 7-day release of DEX from nanoparticles, while the microparticles showed a 22-day release profile. Due to their slower rate of release, the PLGA microparticles loaded with DEX (PLGADEX microparticles) were specifically chosen for this study. As a second step, chitosan/polyvinylpyrrolidone (PVP) based hydrogels were prepared in various weight ratios and the PLGADEX microparticles were optimized in their structure based on variable gelation times. The morphological studies showed PLGADEX microparticles homogenously dispersed in the hydrogels. Moreover, the effect of weight ratio in the presence and absence of optimum percentage of PLGADEX microparticles was studied. The resultant hydrogels demonstrated a range of advantages, including good mechanical strength, porous morphology, amorphous structure, high swelling ratio, controlled biodegradability rate, and antibacterial activity. Additionally, a cytotoxicity analysis confirmed that the hydrogel scaffolds do not have adverse effects on the cells; our release studies in the hydrogel with the highest PVP content also showed 80% release after 30 days. Based on these results we were able to predict and control some of the mechanical properties, including the microstructure of the scaffolds, as well as the drug release, by optimizing the polymers - microparticle concentration, plus their resulting interactions. This optimized hydrogel can become part of a suitable alternative for treatment of allergic rhinitis and chronic sinusitis.

Dual-enzymatically crosslinked hyaluronic acid hydrogel as a long-time 3D stem cell culture system

Stem cell-based tissue engineering shows enormous potential for regenerative medicine. Three-dimensional (3D) stem cell culture is the most basic aspect of tissue engineering. However, achievement of a perfect scaffold for highly efficient 3D cell culture is currently still limited. Herein, a new hyaluronic acid hydrogel dual-enzymatically crosslinked by horseradish peroxidase and choline oxidase is developed as a 3D stem cell culture system. This hydrogel possesses superior stability over two months, controllable biodegradability with hyaluronidases, a high swelling ratio exceeding 6000%, and excellent cytocompatibility in vitro and biocompatibility in vivo. More importantly, a long-time and highly cellular activity 3D culture of bone marrow-derived mesenchymal stem cells was achieved in vitro over 20 days. All these encouraging results highlight the great potential of this new hydrogel for 3D culture and tissue engineering.

Photografting and Patterning of Poly(ethylene glycol) Methacrylate Hydrogel on Glass for Biochip Applications.

An efficient procedure for chemical initiator-free, in situ synthesis of a functional polyethylene glycol methacrylate (PEG MA) hydrogel on regular glass substrates is reported. It is demonstrated that self-initiated photografting and photopolymerization driven by UV irradiation can yield tens of nanometer-thick coatings of carboxy-functionalized PEG MA on the aldehyde-terminated borosilicate glass surface. The most efficient formulation for hydrogel synthesis contained methyl methacrylic acid (MAA), 2-hydroxyethyl methacrylate (HEMA), and PEG methacrylate (PEG10MA) monomers (1:1:1). The resulting HEMA/PEG10MA/MAA (HPMAA) coatings had a defined thickness in the range from 11 to 50 nm. The physicochemical properties of the synthesized HPMAA coatings were analyzed by combining water contact angle measurements, stylus profilometry, imaging null ellipsometry, and atomic force microscopy (AFM). The latter technique was employed in the quantitative imaging mode not only for direct probing of the surface topography but also for swelling behavior characterization in the pH range from 4.5 to 8.0. The estimated high swelling ratios of the HPMAA hydrogel (up to 3.2) together with its good stability and resistance to nonspecific protein binding were advantageous in extracellular matrix mimetics via patterning of fibronectin (FN) at a resolution close to 200 nm. It was shown that the fabricated FN micropatterns on HPMAA were equally suitable for single-cell arraying, as well as controlled cell culture lasting at least for 96 h.

3D printed artificial cornea for corneal stromal transplantation

The aim of this study is to understand the optical, biocompatible, and mechanical properties of chitosan (CS) and polyvinyl-alcohol (PVA) based corneal stroma constructs using 3D printing process. Corneal stroma is tested for biocompatibility with human adipose tissue-derived mesenchymal stem cells (hASCs). Physico-chemical and chemical characterization of the construct was performed using scanning electron microscopy (SEM), fourier transforms infrared spectroscopy (FTIR). Optical transmittance was analyzed using UV-Spectrophotometer. Results showed fabricated constructs have required shape and size. SEM images showed construct has thickness of 400 µm. The FTIR spectra demonstrated the presence of various predicted peaks. The swelling and degradation studies of 13%(wt)PVA and 13%(wt)PVA/(1, 3, 5)%(wt)CS showed to have high swelling ratios of 7 days and degradation times of 30 days, respectively. The light transmittance values of the fabricated cornea constructs decreased with CS addition slightly. Tensile strength values decreased with increasing CS ratio, but we found to support intraocular pressure (IOP) which ranges from 12 to 22 mm-Hg. Preliminary biostability studies showed that composite constructs were compatible with hASCs even after 30 days’ of degradation, showing potential for these cells to be differentiated to stroma layer in future. This study has implications for the rapid and custom fabrication of various cornea constructs for clinical applications.

Assessment of various crosslinking agents on collagen/chitosan scaffolds for myocardial tissue engineering

Suitable material for scaffolds that support cell attachment, proliferation, vascularization and contraction has always been a challenge in myocardial tissue engineering. Much research effort has been focused on natural polymers including collagen, gelatin, chitosan, fibrin, alginate, etc. Among them, a collagen/chitosan composite scaffold was widely used for myocardial tissue engineering. Due to the non-proliferative and contractile characteristics of cardiomyocytes, the biocompatibility and mechanical properties of the scaffolds are extremely important for supporting intercellular connection and tissue function for myocardial tissue engineering. To the best of our knowledge, the three crosslinking agents (glutaraldehyde (GTA), genipin (GP), tripolyphosphate (TPP)) have not yet been comparatively studied in myocardial tissue engineering. Thus, the aim of this study is to compare and identify the crosslinking effect of GTA, GP and TPP for myocardial tissue engineering. The collagen/chitosan scaffolds prepared with various crosslinking agents were fabricated and evaluated for physical characteristics, biocompatibility and contractile performance. All the groups of scaffolds exhibited high porosity (>65%) and good swelling ratio suitable for myocardial tissue engineering. TPP crosslinked scaffolds showed excellent mechanical properties, with their elastic modulus (81.0 ± 8.1 kPa) in the physiological range of native myocardium (20∼100 kPa). Moreover, GP and TPP crosslinked scaffolds exhibited better biocompatibility than GTA crosslinked scaffolds, as demonstrated by the live/dead staining and proliferation assay. In addition, cardiomyocytes within TPP crosslinked scaffolds showed the highest expression of cardiac-specific marker protein and the best contractile performance. To conclude, of the three crosslinking agents, TPP was recommended as the most suitable crosslinking agent for collagen/chitosan scaffold in myocardial tissue engineering.

Engineering PEG-based hydrogels to foster efficient endothelial network formation in free-swelling and confined microenvironments

In vitro tissue engineered models are poised to have significant impact on disease modeling and preclinical drug development. Reliable methods to induce microvascular networks in such microphysiological systems are needed to improve the size and physiological function of these models. By systematically engineering several physical and biomolecular properties of the cellular microenvironment (including crosslinking density, polymer density, adhesion ligand concentration, and degradability), we establish design principles that describe how synthetic matrix properties influence vascular morphogenesis in modular and tunable hydrogels based on commercial 8-arm poly (ethylene glycol) (PEG8a) macromers. We apply these design principles to generate endothelial networks that exhibit consistent morphology throughout depths of hydrogel greater than 1 mm. These PEG8a-based hydrogels have relatively high volumetric swelling ratios (>1.5), which limits their utility in confined environments such as microfluidic devices. To overcome this limitation, we mitigate swelling by incorporating a highly functional PEG-grafted alpha-helical poly (propargyl-l-glutamate) (PPLGgPEG) macromer along with the canonical 8-arm PEG8a macromer in gel formation. This hydrogel platform supports enhanced endothelial morphogenesis in neutral-swelling environments. Finally, we incorporate PEG8a-PPLGgPEG gels into microfluidic devices and demonstrate improved diffusion kinetics and microvascular network formation in situ compared to PEG8a-based gels.