Methacrylic Acid Hydrogels Research Articles

Gelatin Methacrylic Acid Hydrogel-Based Nerve Growth Factors Enhances Neural Stem Cell Growth and Differentiation to Promote Repair of Spinal Cord Injury.

The challenge in treating irreversible nerve tissue damage has resulted in suboptimal outcomes for spinal cord injuries (SCI), underscoring the critical need for innovative treatment strategies to offer hope to patients. In this study, gelatin methacrylic acid hydrogel scaffolds loaded with nerve growth factors (GMNF) were prepared and used to verify the performance of SCI. The physicochemical and biological properties of the GMNF were tested. The effect of GMNF on activity of neuronal progenitor cells (NPCs) was investigated in vitro. Histological staining and motor ability was carried out to assess the ability of SCI repair in SCI animal models. Achieving nerve growth factors sustained release, GMNF had good biocompatibility and could effectively penetrate into the cells with good targeting permeability. GMNF could better enhance the activity of NPCs and promote their directional differentiation into mature neuronal cells in vitro, which could exert a good neural repair function. In vivo, SCI mice treated with GMNF recovered their motor abilities more effectively and showed better wound healing by macroscopic observation of the coronal surface of their SCI area. Meanwhile, the immunohistochemistry demonstrated that the GMNF scaffolds effectively promoted SCI repair by better promoting the colonization and proliferation of neural stem cells (NSCs) in the SCI region and targeted differentiation into mature neurons. The application of GMNF composite scaffolds shows great potential in SCI treatment, which are anticipated to be a potential therapeutic bioactive material for clinical application in repairing SCI in the future.

PH-sensitive semi-interpenetrating network of microcrystalline cellulose and methacrylic acid hydrogel for the oral delivery of insulin

Insulin is commonly administered to diabetic patients subcutaneously and has shown poor patient compliance. Due to this, research has been carried out extensively to find molecules that could deliver insulin orally. In this context, a new type of pH-responsive hydrogel, composed of microcrystalline cellulose and methacrylic acid-based hydrogels, has been developed and studied for the oral delivery of insulin. These hydrogels were prepared by free radical polymerization using potassium persulphate as initiator and N, N’-methylenebisacrylamide as a cross-linker. These pH-sensitive hydrogels showed swelling in distilled water as high as 5800 %. The hydrogels were investigated for swelling in saline and glucose solutions, and pH sensitivity was confirmed by swelling in solutions of different pH. The morphological shape was established by SEM, and the structure was analyzed by FTIR. Thermal degradation was investigated by TGA. In vitro release studies have confirmed pH sensitivity, showing lower insulin release at pH 1.2 than at pH 6.8. The encapsulation efficiency was determined to be 56.00 ± 0.04 %. It was further validated by in-vivo investigations for which insulin was loaded into hydrogels and administered orally to healthy and diabetic Wistar rats at 40 IU/kg, showing maximum hypoglycemic effect at 6 h, which was sustained for 24 h. In the stomach’s acidic environment, the gels remained unaffected due to the formation of intermolecular polymer complexes. Insulin remained in the gel and was protected from proteolytic degradation. Thus, pH-responsive methacrylic acid-based hydrogels are promising for biomedical applications, especially oral drug delivery.

Immunomodulation by subcutaneously injected methacrylic acid-based hydrogels and tolerogenic dendritic cells in a mouse model of autoimmune diabetes

Type 1 diabetes is an autoimmune disease associated with the destruction of insulin-producing β cells. Immunotherapies are being developed to mitigate autoimmune diabetes. One promising option is the delivery of tolerogenic dendritic cells (DCs) primed with specific β-cell-associated autoantigens. These DCs can combat autoreactive cells and promote expansion of β-cell-specific regulatory immune cells, including Tregs. Tolerogenic DCs are typically injected systemically (or near target lymph nodes) in suspension, precluding control over the microenvironment surrounding tolerogenic DC interactions with the host. In this study we show that degradable, synthetic methacrylic acid (MAA)-based hydrogels are an inherently immunomodulating delivery vehicle that enhances tolerogenic DC therapy in the context of autoimmune diabetes. MAA hydrogels were found to affect the local recruitment and activation state of macrophages, DCs, T cells and other cells. Delivering tolerogenic DCs in the MAA hydrogel improved the local host response (e.g., fewer cytotoxic T cells) and enhanced peripheral Treg expansion. Non obese diabetic (NOD) mice treated with tolerogenic DCs subcutaneously injected in MAA hydrogels showed a delay in onset of autoimmune diabetes compared to control vehicles. Our findings further demonstrate the usefulness of MAA-based hydrogels as platforms for regenerative medicine in the context of type 1 diabetes.

Synthesis of core-shell structure based on silica nanoparticles and methacrylic acid via RAFT method: An efficient pH-sensitive hydrogel for prolonging doxorubicin release

In recent years, much attention has been received on stimuli-responsive nanocarriers in nanomedicine. In this work, a pH-responsive core-shell system based on silica nanoparticles (SNPs) as core and methacrylic acid hydrogels as shell were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Methacrylic acid hydrogel through bulk and RAFT polymerization was developed as a model to compare with core-shell hydrogel. The synthesized nanocarriers were characterized by TGA, FT-IR, SEM, TEM, and DLS techniques. To investigate the synthesized core-shell nanoparticles as anticancer nanocarriers, Doxorubicin (DOX) was used as a model drug. In-vitro drug release manner at physiological barriers (pH 7.4) and cancer cell conditions (pH 4.8) illustrates a pH-controlled release for the nanocarriers over 15 days. The study of drug release kinetics reveals that the release mechanism of the carriers followed by the Gompertz model. In addition, the DOX-loaded nanocarriers have notable cytotoxicity against human breast MCF-7 cells with 0.7866 μM IC50 for core-shell nanocarrier. The obtained results showed that the prepared pH-responsive core-shell hydrogel has a high potential to be employed as a sustained pH-sensitive drug release system.

Novel Graphene Oxide Nanohybrid Doped Methacrylic Acid Hydrogels for Enhanced Swelling Capability and Cationic Adsorbability.

Novel versatile hydrogels were designed and composited based on covalent bond and noncovalent bond self-assembly of poly(methacrylic acid) (PMAA) networks and nanohybrids doped with graphene oxide (GO). The structures and properties of the neat PMAA and the prepared PMAA/GO hydrogels were characterized and analyzed in detail, using X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, swelling and cationic absorption, etc. The swelling results showed that the water penetration follows the non-Fick transport mechanism based on swelling kinetics and diffusion theory. The swelling capacity of PMAA and composited PMAA/GO hydrogels toward pH, Na+, Ga2+, and Fe3+ was investigated; the swelling ratio was tunable between 4.44 and 36.44. Taking methylene blue as an example, the adsorption capacity of PMAA/GO hydrogels was studied. Nanohybrid doped GO not only self-associated with PMAA via noncovalent bonding interactions and had a tunable swelling ratio, but also interacted with water molecules via electrostatic repulsion, offering a pH response of both the network and dye absorption. Increases in pH caused a rise in equilibrium swelling ratios and reduced the cumulative cationic dye removal.

Injectable and degradable methacrylic acid hydrogel alters macrophage response in skeletal muscle

After severe trauma, skeletal muscle cannot repair itself leading to scar tissue formation and functional impairment. A novel approach to overcome this issue is to alter the fibrotic response in muscle using regenerative biomaterials, such as those containing methacrylic acid (MAA). In the skin, MAA-based materials have been shown to promote wound healing and new vessel formation, through endogenous mechanisms, including macrophage polarization; however, MAA has yet to be studied outside the skin. To study the innate immune response to MAA in skeletal muscle, MAA-poly(ethylene glycol) (MAA-PEG) hydrogels were synthesized with degradation rates of either 2 (fast-degrading) or 7 days (slow-degrading). When injected into the tibialis anterior muscle of mice, both slow- and fast-degrading MAA hydrogels increased the expression of Il-10, Tnfα and M2 macrophage markers (Fizz1 and Arg for slow-and fast-degrading, respectively). Moreover, the slow degrading MAA hydrogel decreased the number of pro-inflammatory MHCII+ macrophages. An unbiased t-distributed stochastic neighbor embedding (tSNE) analysis suggested the involvement of other immune cells beyond just macrophages in the effect of MAA on skeletal muscle. Overall, this study shows that MAA hydrogels bias macrophages towards a pro-regenerative phenotype.

Development of Acyclovir Loaded β‐Cyclodextrin‐g‐Poly Methacrylic Acid Hydrogel Microparticles: An In Vitro Characterization

AbstractIn this work, successful efforts have been performed for solubility enhancement of acyclovir. pH‐sensitive β‐Cyclodextrin‐g‐poly methacrylic acid (MAA) hydrogel microparticles were developed. β‐Cyclodextrin, MAA, N,N‐methylene bisacrylamide were used as polymer, monomer, and cross‐linker, respectively. Nine different formulations (BM‐1 to BM‐9) were prepared by aqueous free radical polymerization. Developed microparticles were characterized for FTIR, Differential Scanning Calorimetry/Thermo Gravimetric Analysis, PXRD, energy‐dispersive x‐ray spectroscopy, SEM, TEM, optical microscopy, zeta sizer, percent equilibrium swelling (%ES), solubility studies, and in vitro drug release studies. Higher swelling results (83.68%) were obtained at pH 7.4 in less than 3 h. Porous surfaces with drug were seen in TEM images. Maximum release was observed at pH 7.4 (89.51%). Solubility enhancement was 7.38‐fold in water as compared to pure acyclovir. Thermal stability of grafted microparticles was increased up to 440.13°C. A potential approach for solubility enhancement was successfully developed.

Preparation of injectable poly methacrylic acid hydrogels and study of their vascular regenerative effect in vivo

Event Abstract Back to Event Preparation of injectable poly methacrylic acid hydrogels and study of their vascular regenerative effect in vivo Redouan Mahou1* and Michael V. Sefton1, 2* 1 University of Toronto, Institute of Biomaterials and Biomedical Engineering, Canada 2 University of Toronto, Department of Chemical Engineering and Applied Chemistry , Canada Introduction: Progress in the field of tissue engineering and regenerative medicine has been hampered because of limited vascularization. Current approaches to overcome this issue include delivery of angiogenic growth factors (GF), transplantation of endothelial cell, gene delivery, or the utilization of decellularized scaffolds[1]. Our lab discovered a unique material based on poly methacrylic acid (PMAA) that induced the formation of blood vessels instead of a fibrous capsule, without the addition of GF or cells[2]-[4]. Here we report on the properties of a new injectable PMAA-based hydrogel that we envisage can be used for cell delivery. Materials and Methods: In our approach, poly(ethylene glycol) (PEG) was used as an injectable “delivery vehicle” to administer water-soluble, linear poly(MAA) in vivo. A liquid solution containing multi-arm PEG-vinyl sulfone and poly(MAA) gels upon the addition of a stoichiometric amount of a thiol cross-linker, via Michael-type addition[5]. The resulting material is a semi-interpenetrating polymer network (SIPN), where PMAA is physically “entrapped” in a 3D network made of PEG. Results and Discussion: Interpenetrating networks (SIPN) of PEG and poly(MAA) were prepared with well-controllable physical properties. At room temperature, gelation times ranged from >11 min to <30 s when changing the nature of the cross-linker or altering the hydrogel formulation, as shown in Figure 1A. SIPN exhibited tunable water uptake accompanied by swelling at 37°C, which did not change over a period of three weeks indicating a stable 3D networks (Figure 1B and C). Two formulations were prepared by changing the mass ratio of PEG to PMAA (80/20 and 60/40) and compared to the base PEG vehicle. Figure 1: Gelation times (A) and water uptakes (B) of hydrogels prepared from different cross-linkers: 2arms PEG-SH (P-2); 4arms PEG-SH (P-4); 8arms PEG-SH (P-8); and dithiothreitol (DTT). The equilibrium swelling of hydrogels prepared with DTT remains stable for at least 21 days (C). The generation of blood vessels in the surrounding tissue upon subcutaneous injection of the SIPN in CD1 mice is being investigated, as shown in Figure 2. Studies are underway to optimize the formulation of the SIPN and test its suitability for cell delivery purposes. Chemical modification of PMAA to allow the preparation of injectable PMAA hydrogels without PEG vehicle is also under consideration. Figure 2: Generation of blood vessels at periphery of hydrogels upon subcutaneous injection is evaluated in vivo. SIPN PEG60-PMAA40 (right) and pure PEG (left). Both hydrogels were prepared using DTT as cross-linker. Conclusions: A new type of injectable hydrogel made of the vascular regenerating methacrylic acid was prepared. The vascularizing capacity and the suitability for cell delivery purposes is investigated. The findings create the basis for the selective production of such hydrogels for future application in the field of cell-based therapy. The authors acknowledge the financial support of the Ontario Research Fund

An electro-responsive hydrogel for intravascular applications: an in vitro and in vivo evaluation.

There is a growing interest in using hydrogels for biomedical applications, because of more favourable characteristics. Some of these hydrogels can be activated by using particular stimuli, for example electrical fields. These stimuli can change the hydrogel shape in a predefined way. It could make them capable of adaptation to patient-specific anatomy even post-implantation. This is the first paper aiming to describe in vivo studies of an electro-responsive, Pluronic F127 based hydrogel, for intravascular applications. Pluronic methacrylic acid hydrogel (PF127/MANa) was in vitro tested for its haemolytic and cytotoxic effects. Minimal invasive implantation in the carotid artery of sheep was used to evaluate its medium-term biological effects, through biochemical, macroscopic, radiographic, and microscopic evaluation. Indirect and direct testing of the material gave no indication of the haemolytic effects of the material. Determination of fibroblast viability after 24 h of incubation in an extract of the hydrogel showed no cytotoxic effects. Occlusion was obtained within 1 h following in vivo implantation. Evaluation at time of autopsy showed a persistent occlusion with no systemic effects, no signs of embolization and mild effects on the arterial wall. An important proof-of-concept was obtained showing biocompatibility and effectiveness of a pluronic based electro-responsive hydrogel for obtaining an arterial occlusion with limited biological impact. So the selected pluronic-methacrylic acid based hydrogel can be used as an endovascular occlusion device. More importantly it is the first step in further development of electro-active hydrogels for a broad range of intra-vascular applications (e.g. system to prevent endoleakage in aortic aneurysm treatment, intra-vascular drug delivery).

Enzyme‐Modified Hydrogel Coatings with Self‐Cleaning Abilities for Low Fouling PDMS Devices

Enzyme-containing hydrogel coatings with abilities to automatically degrade proteins are developed by covalently binding proteases onto poly(ethylene glycol)/methacrylic acid hydrogel surfaces. Such active coatings can be easily applied to hydrophobic polydimethylsiloxane (PDMS) surfaces to impart long-term hydrophilicity and self-cleaning ability, providing an effective and environmentally friendly way to resist protein fouling in the biologically related application of PDMS-based devices. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Development of a Calcium-Chelating Hydrogel for Treatment of Superficial Burns and Scalds

Superficial burns and scalds are usually managed conservatively with traditional dressings. Failure to heal within 3 weeks leads to their management by skin grafting. Our aim was to develop a biomaterial to actively promote keratinocyte migration in superficial burns by modulating local cation concentrations to accelerate keratinocyte migration and deter wounds from contracting, thus potentially reducing the number of such wounds requiring grafting. We investigated polymeric hydrogels for their Ca(2+) chelating properties and enhancement of keratinocyte migration in human tissue-engineered skin models. Dimethylaminoethyl methacrylate:methacrylic acid hydrogel coupled with elevated [Mg(2+)] reduced media [Ca(2+)], potentiating keratinocyte migration in tissue-engineered skin models, it also significantly reduced wound model contraction. Dimethylaminoethyl methacrylate:methacrylic acid hydrogels could promote wound healing and reduce wound contraction, a significant complication in burn wound healing.

Immobilization of Myoglobin from Horse Skeletal Muscle in Hydrophilic Polymer Networks.

This work examines the immobilization of myoglobin from horse skeletal muscle in hydrophilic polymer networks. Due to specific changes in the spectroscopic properties of hemoproteins during ligand binding, they could be employed in optical sensing devices. Two immobilization techniques were considered: imbibition and entrapment. Anionic hydrogels composed of methacrylic acid (MAA), cationic hydrogels composed of dimethylamino ethyl methacrylate (DMAEM), and neutral hydrogels composed of poly(ethylene glycol) monomethyl ether monomethacrylate (PEGMA; molecular weight = 200, 400, or 1000), all crosslinked with poly(ethylene glycol) dimethacrylate (PEGDMA) (molecular weight = 200, 600, or 1000), were synthesized by free-radical solution polymerization. By the imbibition method, MAA-based hydrogels incorporated the highest amount of myoglobin in comparison with PEGMA or DMAEM polymers. The evaluation of the correlation length of the networks revealed that MAA hydrogels had the highest correlation length in comparison with PEGMA-containing matrices or DMAEM hydrogels. Release experiments from MAA hydrogels at pHs 5.8 and 7.0 showed that the solute-transport mechanism was a combination of Fickian and chain relaxation diffusion. Myoglobin-loaded MAA hydrogels retained their heme reactivity after the immobilization process. The release of myoglobin incorporated by entrapment in MAA-PEGDMA hydrogels was highly influenced by the chain relaxation process. The diffusion coefficients of myoglobin incorporated by entrapment into anionic hydrogels were 2 orders of magnitude smaller (~10-13) than those for myoglobin incorporated by imbibition (10-11), both evaluated at pH 7.0. Substrate binding studies indicated that the protein biological activity was not compromised in those hydrogels loaded by the imbibition method, whereas prepolymeric solutions showed detrimental effects on protein stability.

Synthesis, characterization and adsorption study of the uranyl ions by hydrogels based on polyethylene glycol and methacrylic acid copolymers

The water swelling polymeric hydrogels were obtained by γ-initiated radiation copolymerization of polyethylene glycol (PEG) with methacrylic acid (MAA) and three-ethylene glycol dimethacrylate (TEGDMA) as cross-linking agent. The main regularities of PEG–MAA network formation, deformation properties, structure and thermal characteristics depending on copolymer composition, molecular weight of PEG have been studied. The sorption of uranyl ions by PEG–MAA hydrogels in comparison with homopolymer PMAA was investigated. The effect of uranyl ions concentration on sorption efficiency of hydrogels was shown. The ability to regeneration in desorption process was demonstrated for PEG–MAA hydrogels in comparison with PMAA gel.

Radiation-induced graft copolymerization of methacrylic acid on to poly (vinyl chloride) films and their thrombogenicity

Methacrylic acid (MAA) was radiation grafted on to poly(vinyl chloride) (PVC) films to improve the blood compatibility of PVC. The thromobogenicity of MAA grafted PVC was evaluated by thrombus formation, platelet adhesion and haemolytic activity in vitro. The hydrophilicity of grafted PVC films was investigated by contact angle measurement. Methacrylic acid grafted PVC film showed lower thrombogenicity than that of PVC. It was found that the weight of thrombus formed on grafted PVC was less than that of PVC and glass and decreased with the increase in the graft level. The adhesion of platelets on grafted PVC was retarded after grafting with MAA hydrogels.