Structurally and mechanically tuned macroporous hydrogels for scalable mesenchymal stem cell-extracellular matrix spheroid production.

Mesenchymal stem cells (MSCs) are essential in regenerative medicine. However, conventional expansion and harvesting methods often fail to maintain the essential extracellular matrix (ECM) components, which are crucial for their functionality and efficacy in therapeutic applications. Here, we introduce a bone marrow-inspired macroporous hydrogel designed for the large-scale production of MSC-ECM spheroids. Through a soft-templating approach leveraging liquid-liquid phase separation, we engineer macroporous hydrogels with customizable features, including pore size, stiffness, bioactive ligand distribution, and enzyme-responsive degradability. These tailored environments are conducive to optimal MSC proliferation and ease of harvesting. We find that soft hydrogels enhance mechanotransduction in MSCs, establishing a standard for hydrogel-based 3D cell culture. Within these hydrogels, MSCs exist as both cohesive spheroids, preserving their innate vitality, and as migrating entities that actively secrete functional ECM proteins. Additionally, we also introduce a gentle, enzymatic harvesting method that breaks down the hydrogels, allowing MSCs and secreted ECM to naturally form MSC-ECM spheroids. These spheroids display heightened stemness and differentiation capacity, mirroring the benefits of a native ECM milieu. Our research underscores the significance of sophisticated materials design in nurturing distinct MSC subpopulations, facilitating the generation of MSC-ECM spheroids with enhanced therapeutic potential.

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing.

Cryogels are macroporous polymeric structures formed from the cryogelation of monomers/polymers in a solvent below freezing temperature. Due to their inherent interconnected macroporosity, ease of preparation, and biocompatibility, they are increasingly being investigated for use in biomedical applications such as 3D-bioprinting, drug delivery, wound healing, and as injectable therapeutics. This review highlights the fundamentals of macroporous cryogel preparation, cryogel properties that can be useful in the highlighted biomedical applications, followed by a comprehensive review of recent studies in these areas. Research evaluated includes the use of cryogels to combat various types of cancer, for implantation without surgical incision, and use as highly effective wound dressings. Furthermore, conclusions and outlooks are discussed for the use of these promising and durable macroporous cryogels.

Tannic Acid Incorporated Antibacterial Polyethylene Glycol Based Hydrogel Sponges for Management of Wound Infections.

Conventional wound dressings fail to provide features that can assist the healing process of chronic wounds. Multifunctional wound dressings address this issue by incorporating attributes including antibacterial and antioxidant activity, and the ability to enhance wound healing. Herein, polyethylene glycol (PEG)-based antibacterial hydrogel sponge dressings are prepared by a rapid and facile gas foaming method based on an acid chloride/alcohol reaction where tannic acid (TA) is included as a reactant to impart antibacterial efficacy as well as to enhance the mechanical properties of the samples. The results reveal that the TA-integrated sponges possess excellent antibacterial properties against both Escherichia coli and Staphylococcus aureus with approximately 6-8 log reduction in the microbial colony count after 6 h, indicating their high potential for management of infection-prone wounds. Compared to the control sample, TA incorporation increases the elastic modulus by twofold. As the samples also exhibit biocompatibility, antioxidant activity, and wound healing capacity, the novel TA-incorporated hydrogels can be an alternative to traditional wound dressings for wounds with low-to-moderate exudate.

Emulsion-Templated Gelatin/Amino Acids/Chitosan Macroporous Hydrogels with Adjustable Internal Dimensions for Three-Dimensional Stem Cell Culture.

The demand for macroporous hydrogel scaffolds with interconnected porous and open-pore structures is crucial for advancing research and development in cell culture and tissue regeneration. Existing techniques for creating 3D porous materials and controlling their porosity are currently constrained. This study introduces a novel approach for producing highly interconnected aspartic acid-gelatin macroporous hydrogels (MHs) with precisely defined open pore structures using a one-step emulsification polymerization method with surface-modified silica nanoparticles as Pickering stabilizers. Macroporous hydrogels offer adjustable pore size and pore throat size within the ranges of 50 to 130 µm and 15 to 27 µm, respectively, achieved through variations in oil-in-water ratio and solid content. The pore wall thickness of the macroporous hydrogel can be as thin as 3.37 µm and as thick as 6.7 µm. In addition, the storage modulus of the macroporous hydrogels can be as high as 7250 Pa, and it maintains an intact rate of more than 92% after being soaked in PBS for 60 days, which is also good performance for use as a biomedical scaffold material. These hydrogels supported the proliferation of human dental pulp stem cells (hDPSCs) over a 30 day incubation period, stretching the cell morphology and demonstrating excellent biocompatibility and cell adhesion. The combination of these desirable attributes makes them highly promising for applications in stem cell culture and tissue regeneration, underscoring their potential significance in advancing these fields.

In situ forming macroporous biohybrid hydrogel for nucleus pulposus cell delivery.

Degenerative intervertebral disc disease is a common source of chronic pain and reduced quality of life in people over the age of 40. While degeneration occurs throughout the disc, it most often initiates in the nucleus pulposus (NP). Minimally invasive delivery of NP cells within hydrogels that can restore and maintain the disc height while regenerating the damaged NP tissue is a promising treatment strategy for this condition. Towards this goal, a biohybrid ABA dimethacrylate triblock copolymer was synthesized, possessing a lower critical solution temperature below 37 °C and which contained as its central block an MMP-degradable peptide flanked by poly(trimethylene carbonate) blocks bearing pendant oligoethylene glycol groups. This triblock prepolymer was used to form macroporous NP cell-laden hydrogels via redox initiated (ammonium persulfate/sodium bisulfite) crosslinking, with or without the inclusion of thiolated chondroitin sulfate. The resulting macroporous hydrogels had water and mechanical properties similar to those of human NP tissue and were mechanically resilient. The hydrogels supported NP cell attachment and growth over 28 days in hypoxic culture. In hydrogels prepared with the triblock copolymer but without the chondroitin sulfate the NP cells were distributed homogeneously throughout in clusters and deposited collagen type II and sulfated glycosaminoglycans but not collagen type I. This hydrogel formulation warrants further investigation as a cell delivery vehicle to regenerate degenerated NP tissue. STATEMENT OF SIGNIFICANCE: The intervertebral disc between the vertebral bones of the spine consists of three regions: a gel-like central nucleus pulposus (NP) within the annulus fibrosis, and bony endplates. Degeneration of the intervertebral disc is a source of chronic pain in the elderly and most commonly initiates in the NP. Replacement of degenerated NP tissue with a NP cell-laden hydrogel is a promising treatment strategy. Herein we demonstrate that a crosslinkable polymer with a lower critical solution temperature below 37 °C can be used to form macroporous hydrogels for this purpose. The hydrogels are capable of supporting NP cells, which deposit collagen II and sulfated glycosaminoglycans, while also possessing mechanical properties matching those of human NP tissue.

Macroporous Adhesive Nano-Enabled Hydrogels Generated from Air-in-Water Emulsions.

Developing nanocomposite hydrogel with multi-functions including adjustable mechanical property, tissue-adhesion, and blood coagulation property to accelerate wound healing is highly desirable in surgical application. Here a macroporous adhesive nano-enabled hydrogel constructed from gelatin methacryloyl stabilized air-in-water emulsions incorporated with dopamine-grafted-gelatin (GelDA) and Laponite nanoclay is reported. The hydrogel exhibits interconnected macroporous structure. The physical/chemical cross-linked network formed among the various components contributes to the good mechanical strength of hydrogel, which could be further regulated by adjusting the concentration of Laponite nanoclay. Furthermore, the nanocomposite macroporous hydrogel is endowed with self-healing properties and tissue adhesion by the intermolecular hydrogen bonds, ionic interactions among Laponite nanoclay and polymers, as well as the catechol functional groups. The in vitro studies demonstrate that the macroporous hydrogel has good biocompatibility and could significantly reduce blood clotting time, which is expected to be applied for the rapid sealing and hemostasis of bleeding wounds.

Macroporous methacrylated hyaluronic acid hydrogel with different pore sizes forin vitroandin vivoevaluation of vascularization.

Vascularization of thick hydrogel scaffolds is still a big challenge, because the submicron- or nano-sized pores seriously restrict endothelial cells adhesion, proliferation and migration. Therefore, porous hydrogels have been fabricated as a kind of promising hydrous scaffolds for enhancing vascularization during tissue repairing. In order to investigate the effects of pore size on vascularization, macroporous methacrylated hyaluronic acid (HAMA) hydrogels with different pore sizes were fabricated by a gelatin microspheres (GMS) template method. After leaching out GMS templates, uniform and highly interconnected macropores were formed in hydrogels, which provided an ideal physical microenvironment to induce human umbilical vein endothelial cells (HUVECs) migration and tissue vascularization.In vitroresults revealed that macroporous hydrogels facilitated cells proliferation and migration compared with non-macroporous hydrogels. Hydrogels with middle pore size of 200-250 µm (HAMA250 hydrogels) supported the best cell proliferation and furthest 3D migration of HUVECs. The influences of pore sizes on vascularization were then evaluated with subcutaneous embedding.In vivoresults illustrated that HAMA250 hydrogels exhibited optimum vascularization behavior. Highest number of newly formed blood vessels and expression of CD31 could be found in HAMA250 hydrogels rather than in other hydrogels. In summary, our results concluded that the best pore size for endothelial cells migration and tissue vascularization was 200-250 µm. This research provides a new insight into the engineering vascularized tissues and may find utility in designing regenerative biomaterial scaffolds.

Macroporous Hydrogel for High-Performance Atmospheric Water Harvesting.

Simple, low-cost, and high-performance atmospheric water harvesting (AWH) still remains challenging in the context of global water shortage. Here, we present a simple and low-cost macroporous hydrogel for high-performance AWH to address this challenge. We employed an innovative strategy of pore foaming and vacuum drying to rationally fabricate a macroporous hydrogel. The hydrogel is endowed with a macroporous structure and a high specific surface area, enabling sufficient contact of the inner sorbent with outside air and high-performance AWH. The experiments demonstrate that macroporous hydrogels can achieve high-performance AWH with a broad range of sorption humidity [relative humidity (RH) from 100% to even lower than 20%], high water sorption capacity (highest 433.72% of hydrogel's own weight at ∼98% RH, 25 °C within 60 h), rapid vapor capturing (the sorption efficiency is as high as 0.32 g g-1 h-1 in the first 3 h at 90% RH, 25 °C), unique durability, low desorption temperature (∼50 °C, lowest), and high water-releasing rate (release 99.38% of the sorbed water under 500 W m-2 light for 6 h). The results show that this macroporous hydrogel can sorb water more than 193.46% of its own weight overnight (13 h) at a RH of ∼90%, 25 °C and release as high as 99.38% of the sorbed water via the photothermal effect. It is estimated that the daily water yield can reach up to approximately 2.56 kg kg-1 day-1 in real outdoor conditions, enabling daily minimum water consumption of an adult. Our simple, affordable, and easy-to-scale-up macroporous hydrogel can not only unleash the unlimited possibilities for large-scale and high-performance AWH but also offer promising opportunities for functional materials, soft matter, flexible electronics, tissue engineering, and biomedical applications.

Dissolvable microgel-templated macroporous hydrogels for controlled cell assembly.

Mesenchymal stem cells (MSCs)-based therapies have been widely used to promote tissue regeneration and to modulate immune/inflammatory response. The therapeutic potential of MSCs can be further improved by forming multi-cellular spheroids. Meanwhile, hydrogels with macroporous structures are advantageous for improving mass transport properties for the cell-laden matrices. Herein, we report the fabrication of MSC-laden macroporous hydrogel scaffolds through incorporating rapidly dissolvable spherical cell-laden microgels. Dissolvable microgels were fabricated by tandem droplet-microfluidics and thiol-norbornene photopolymerization using a novel fast-degrading macromer poly(ethylene glycol)-norbornene-dopamine (PEGNB-Dopa). The cell-laden PEGNB-Dopa microgels were subsequently encapsulated within another bulk hydrogel matrix, whose porous structure was generated efficiently by the rapid degradation of the PEGNB-Dopa microgels. The cytocompatibility of this in situ pore-forming approach was demonstrated with multiple cell types. Furthermore, adjusting the stiffness and cell adhesiveness of the bulk hydrogels afforded the formation of solid cell spheroids or hollow spheres. The assembly of solid or hollow MSC spheroids led to differential activation of AKT pathway. Finally, MSCs solid spheroids formed in situ within the macroporous hydrogels exhibited robust secretion of HGF, VEGF-A, IL-6, IL-8, and TIMP-2. In summary, this platform provides an innovative method for forming cell-laden macroporous hydrogels for a variety of future biomedical applications.

DLP-based bioprinting of void-forming hydrogels for enhanced stem-cell-mediated bone regeneration.

The integration of 3D bioprinting and stem cells is of great promise in facilitating the reconstruction of cranial defects. However, the effectiveness of the scaffolds has been hampered by the limited cell behavior and functions. Herein, a therapeutic cell-laden hydrogel for bone regeneration is therefore developed through the design of a void-forming hydrogel. This hydrogel is prepared by digital light processing (DLP)-based bioprinting of the bone marrow stem cells (BMSCs) mixed with gelatin methacrylate (GelMA)/dextran emulsion. The 3D-bioprinted hydrogel can not only promote the proliferation, migration, and spreading of the encapsulated BMSCs, but also stimulate the YAP signal pathway, thus leading to the enhanced osteogenic differentiation of BMSCs. In addition, the in vivo therapeutic assessments reveal that the void-forming hydrogel shows great potential for BMSCs delivery and can significantly promote bone regeneration. These findings suggest that the unique 3D-bioprinted void-forming hydrogels are promising candidates for applications in bone regeneration.

Long-Term Recruitment of Endogenous M2 Macrophages by Platelet Lysate-Rich Plasma Macroporous Hydrogel Scaffold for Articular Cartilage Defect Repair.

After cartilage damage, a large number of monocytes/macrophages infiltrate into adjacent synovium and the resident macrophages in synovial tissue transform to activated macrophages (M1), which secrete pro-inflammatory cytokines to induce sustained inflammation and chondrocyte apoptotic. However, current clinical therapies for cartilage repair can rarely achieve long-term anti-inflammatory regulation and satisfactory outcomes. Herein, a platelet lysate-rich plasma macroporous hydrogel (PLPMH) scaffold with around 100 µm pore size and 1.25 MPa Young's modulus is developed to sustainedly recruit and polarize endogenous anti-inflammatory macrophages (M2) for improving cartilage defect repair. PLPMH scaffold can steadily release sphingosine1-phosphate and proteins via gradual degradation, thus inducing M2 macrophages migration or resting (M0) macrophages migration and then polarization to M2 phenotype, and improving the secretion of anti-inflammatory cytokines. Furthermore, PLPMH scaffold exhibits negligible inflammatory responses in vivo and promotes endogenous M2 macrophage infiltration in large numbers and long-time duration to provide a local anti-inflammatory microenvironment, which even lasts for 42 d. In a rabbit model of cartilage defect, PLPMH scaffold increases the ratio of M2 macrophages and improves cartilage tissue regeneration. These studies support that PLPMH scaffold may have a great potential in articular cartilage tissue engineering by providing an anti-inflammatory and pro-regenerative microenvironment.

Novel Synthesis, Characterization and Amoxicillin Release Study of pH-Sensitive Nanosilica/Poly(acrylic acid) Macroporous Hydrogel with High Swelling.

The effect of SiO2 nanoparticles on the formation of PAA (poly acrylic acid) gel structure was investigated with seeded emulsion polymerization method used to prepare SiO2/PAA nanoparticles. The morphologies of the nanocomposite nanoparticles were studied by transmission electron microscopy (TEM). Fourier-transform infrared (FTIR) spectroscopy results indicated that the PAA was chemically bonded to the surface of the SiO2 nanoparticles. Additionally, the resulting morphology of the nanocomposite nanoparticles confirmed the co-crosslinking role of the SiO2 nanoparticles in the formation of the 3D structure and hydrogel of PAA. SiO2/PAA nanocomposite hydrogels were synthesized by in situ solution polymerization with and without toluene. The morphology studies by field emission scanning electron microscopy (FESEM) showed that when the toluene was used as a pore forming agent in the polymerization process, a macroporous hydrogel structure was achieved. The pH-sensitive swelling behaviors of the nanocomposite hydrogels showed that the formation of pores in the gels structure was a dominant factor on the water absorption capacity. In the current research the absorption capacity was changed from about 500 to 4000 g water/g dry hydrogel. Finally, the macroporous nanocomposite hydrogel sample was tested as an amoxicillin release system in buffer solutions with pHs of 3, 7.2, and 9 at 37 °C. The results showed that the percentage cumulative release of amoxicillin from the hydrogels was higher in neutral and basic mediums than in the acidic medium and the amoxicillin release rate was decreased with increasing pH. Additionally, the release results were very similar to swelling results and hence amoxicillin release was a swelling controlled-release system.

Effect of Chitosan on Alginate-Based Macroporous Hydrogels for the Capture of Glioblastoma Cancer Cells.

Glioblastoma multiforme is a type of brain cancer associated with a very low survival rate since a large number of cancer cells remain infiltrated in the brain despite the treatments currently available. This work presents a macroporous hydrogel trap, destined to be implanted in the surgical cavity following tumor resection and designed to attract and retain cancer cells, in order to eliminate them afterward with a lethal dose of stereotactic radiotherapy. The biocompatible hydrogel formulation comprises sodium alginate (SA) and chitosan (CHI) bearing complementary electrostatic charges and stabilizing the gels in saline and cell culture media, as compared to pristine SA gels. The highly controlled and interconnected porosity, characterized by X-ray microCT, yields mechanical properties comparable to those of brain tissues and allows F98 glioblastoma cells to penetrate the gels within the entire volume, as confirmed by fluorescence microscopy. The addition of a grafted -RGD peptide on SA, combined with CHI, significantly enhances the adhesion and retention of F98 cells within the gels. Overall, the best compromise between low proliferation and a high level of accumulation and retention of F98 cells was obtained with the hydrogel formulated with 1% SA and 0.2% CHI, without the -RGD adhesion peptide.

An alginate-based macroporous hydrogel matrix to trap cancer cells.

To overcome the radioresistance of glioblastoma (GBM) cells infiltrated in the brain, we propose to attract these cancer cells into a trap to which a lethal radiation dose can be delivered safely. Herein, we have prepared and characterized a sodium alginate-based macroporous hydrogel as a potential cancer cell trap. Microcomputed X-ray tomography shows that the hydrogel matrices comprise interconnected pores with an average diameter of 300 µm. The F98 GBM cells migrated in the pores and mainly accumulated in the center of the matrix. Depending on the number of cancer cells added, the grafting of RGD cell-adhesion peptides to the alginate resulted in a 4 to 10 times increase in the number of F98 cells (which overexpress the associated αvß3 and αvß5 binding integrins) retained in the matrix. Finally, a radiation dose of 25 Gy eliminated all F98 cells trapped in the matrix, without significantly altering the matrix mechanical properties.

Macroporous Hydrogels for Stable Sequestration and Sustained Release of Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor Using Nucleic Acid Aptamers.

Macroporous hydrogels have been widely studied for biological and biomedical applications such as drug delivery and tissue engineering. However, these hydrogels cannot stably sequester molecules of interest due to their high permeability. The purpose of this work was to study the feasibility of using two aptamers to sequester two protein drugs, quantify the apparent diffusivity of protein drugs in aptamer-functionalized macroporous hydrogels, and evaluate the function of aptamer-functionalized macroporous hydrogels in controlling protein release for angiogenesis. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were used as model proteins. The data show that anti-VEGF and anti-bFGF aptamers could be uniformly incorporated into macroporous hydrogels for stable and specific sequestration of VEGF and bFGF. The aptamers could reduce the apparent diffusivity of VEGF and bFGF in the macroporous hydrogels by approximately three orders of magnitude. Moreover, as the aptamers could prolong the release of these growth factors, dual aptamer-functionalized macroporous hydrogels could stimulate synergistic angiogenesis. Therefore, this work has successfully demonstrated that aptamer-functionalized macroporous hydrogels hold great potential of stably sequestering multiple molecules of interest for various biological and biomedical applications.

Construction of Injectable Self-Healing Macroporous Hydrogels via a Template-Free Method for Tissue Engineering and Drug Delivery.

Because of their ease of handling and excellent biocompatibility, injectable macroporous hydrogels have received a considerable interest in the fields of tissue engineering and drug delivery systems because of their unique application in minimally invasive surgical procedures. In this study, in situ forming, injectable, macroporous, self-healing gelatin (GE)/oxidized alginate (OSA)/adipic acid dihydrazide (ADH) hydrogels were prepared using a high-speed shearing treatment and were stabilized by Schiff base reaction and acylhydrazone bonds. Their injectability, self-healing ability, rheology, microstructure, equilibrium water content, and in vitro biodegradation were investigated. We found that the injectable GE/OSA/ADH precursors remained in a liquid form and flowed easily for several minutes at room temperature, but however, gelled rapidly at body temperature. The gelation time could be regulated by varying the ratio of GE, OSA, and ADH. The obtained hydrogels had an interconnected macroporous structure and self-healing ability. The porosity of hydrogels was in the range of approximately 60-83%, and pore size varied from approximately 125-380 µm. The porous structure of hydrogel was visualized by field-emission scanning electron microscope, micro-computed tomography, and laser confocal microscope. Human epidermal growth factor was loaded by in situ mixing in GE/OSA/ADH hydrogels and was released with good bioactivity as evaluated by ELISA. Moreover, L929 cells proliferated on GE/OSA/ADH hydrogels, as verified by Cell Counting Kit-8 and LIVE/DEAD assays. Furthermore, encapsulation of NIH 3T3 cells within GE/OSA/ADH hydrogels demonstrated that the hydrogel can support cell survival, proliferation, and migration. In vivo studies showed that the hydrogels had a good injectability, in situ gelation, and tissue biocompatibility. Therefore, GE/OSA/ADH hydrogel represented a novel and safe injectable macroporous self-healing hydrogel for tissue engineering scaffold and drug delivery vehicle purposes.

Enhanced formation of hydroxyapatites in gelatin/imogolite macroporous hydrogels.

HYPOTHESIS: Gelatin is widely investigated for the fabrication of synthetic scaffolds in bone tissue engineering. Practical limitations to its use are mainly due to the fast dissolution rate in physiological conditions and to the lack of pores with suitable dimensions for cell permeation. The aim of this work is to exploit imogolite clays as nucleation sites for the growth of calcium phosphates in gelatin-based hydrogels and to take advantage of a cryogenic treatment to obtain pores of ∼100µm. EXPERIMENTS: We evaluated the effect of imogolites and a biocompatible cross-linker on the gelatin network in terms of morphology, thermal and rheological behavior. The hydrogels were cryogenically-treated and characterized to investigate the modification of the polymer network, both at the micro- and nano-scale. The samples were mineralized to investigate the effect of imogolites on the formation of calcium phosphates. FINDINGS: The interaction between gelatin, imogolite and cross-linker leads to the modification of the hydrogel structure at the micro-scale, while minor effects are detected at the nano-scale. The cryogenic procedure is successful in generating pores with the desired size, while the presence of imogolites in the hydrogel promotes hydroxyapatites formation. These results demonstrate that imogolites can be effectively employed as functional fillers in polymer-based scaffolds.

Injectable Macroporous Ferrogel Microbeads with a High Structural Stability for Magnetically Actuated Drug Delivery.

Macroporous hydrogels are an attractive material platform that can provide shortened interfacial diffusion pathways and high biomacromolecule loading. Recently, macroporous ferrogels have shown high potential for use in the on-demand delivery of bioactive molecules, resulting from their reversible and large volumetric deformation upon magnetic stimulation. However, these macroporous ferrogels require surgical placement in the body due to their large size; an injectable form of macroporous ferrogels has not yet been reported. In this study, injectable macroporous ferrogel microbeads loaded with iron oxide nanoparticles have been prepared on the basis of alginate microbeads for on-demand drug release. A simple solvent exchange and subsequent covalent cross-linking of the alginate chains in hydrogel microbeads induced a high polymer density on the hydrogel network and led to enhanced mechanical properties even after the generation of macropores in the microbeads. The macroporous ferrogel microbeads exhibited good mechanical stability and were stable during needle injection. The increased loading of large biomolecules due to the macroporosity of the microbeads and their large reversible volumetric deformation response to the external magnetic field enabled their potential for use in the on-demand delivery of drugs of assorted sizes by magnetic actuation. As a result of their structural stability, injectable size, and ability for on-demand drug delivery, ferrogel microbeads have promising potential for application in many biomedical fields.

Fabrication of magnetic macroporous chitosan-g-poly (acrylic acid) hydrogel for removal of Cd2+ and Pb2.

A novel macroporous magnetic macroporous chitosan-g-poly (acrylic acid) hydrogel adsorbent was fabricated from the Pickering high internal emulsions template stabilized by modified Fe3O4 nanoparticles. The structure and composition of modified Fe3O4 and macroporous magnetic hydrogel were characterized by TEM, XRD, TG and SEM techniques. The characterization results suggest that the Fe3O4 nanoparticles have been modified successfully with organosilane of 3-aminopropyltrimethoxysilane (APTES), and the porous structure of the macroporous hydrogel can be tuned with the amount of stabilized particles, volume fraction of dispersed phase and the amount of the cosurfactant. Adsorption experiments indicate that the adsorption equilibrium was rapidly reached within 20min and the maximal adsorption capacities were determined to be 308.84mg/g for Cd2+ and 695.22mg/g for Pb2+. After five adsorption-desorption cycles, the adsorbent can retain its high adsorption capacity. The introduction of Fe3O4 is beneficial to the recycle of adsorbent after usage.

Rapid and selective removal of preservative from ophthalmic formulations during eyedrops instillation.

About 70% of eyedrops contain benzalkonium chloride (BAK) as a preservative to prevent the growth of microorganisms. While preservatives are mandated to maintain sterility, many patients exhibit irritation and toxicity to such compounds. We propose to mitigate the ocular toxicity in the ocular formulations without compromising sterility by designing a device that can be incorporated into an eyedrops bottle to selectively remove the preservatives during the process of drop instillation. Here, we specifically focus on macroporous poly(2-hydroxyethyl methacrylate) (pHEMA) gel due to its excellent biocompatibility and high partition coefficient for BAK. In addition to specific selectivity for BAK, the device also requires high hydraulic permeability to allow drop dispensing without excessive pressure drop. The pHEMA monolith can remove nearly 100% of contained BAK from a 25 ml, 0.012% BAK solution with negligible uptake of the hydrophilic drugs such as timolol and dorzolamide. The filter, however, had to be pre-equilibrated with hydrophobic drugs to reach a high separation of BAK without reducing the concentration of the active drug. The average hydraulic permeability of the filter was 0.025 Darcy, which is about 5-fold lower than the ideal value. Incorporation of a pHEMA macroporous gel into an eyedrops bottle can virtually eliminate the exposure of the eyes to the preservatives without compromising the sterility. Our novel design can eliminate the preservative induced toxicity from eyedrops thereby impacting hundreds of millions of patients with chronic ophthalmic diseases such as glaucoma and dry eyes.