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1
Wen, Jie, Xiaopeng Zhang, Mingwang Pan, Jinfeng Yuan, Zhanyu Jia, and Lei Zhu. "A Robust, Tough and Multifunctional Polyurethane/Tannic Acid Hydrogel Fabricated by Physical-Chemical Dual Crosslinking." Polymers 12, no. 1 (January 19, 2020): 239. http://dx.doi.org/10.3390/polym12010239.
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Commonly synthetic polyethylene glycol polyurethane (PEG–PU) hydrogels possess poor mechanical properties, such as robustness and toughness, which limits their load-bearing application. Hence, it remains a challenge to prepare PEG–PU hydrogels with excellent mechanical properties. Herein, a novel double-crosslinked (DC) PEG–PU hydrogel was fabricated by combining chemical with physical crosslinking, where trimethylolpropane (TMP) was used as the first chemical crosslinker and polyphenol compound tannic acid (TA) was introduced into the single crosslinked PU network by simple immersion process. The second physical crosslinking was formed by numerous hydrogen bonds between urethane groups of PU and phenol hydroxyl groups in TA, which can endow PEG–PU hydrogel with good mechanical properties, self-recovery and a self-healing capability. The research results indicated that as little as a 30 mg·mL−1 TA solution enhanced the tensile strength and fracture energy of PEG–PU hydrogel from 0.27 to 2.2 MPa, 2.0 to 9.6 KJ·m−2, respectively. Moreover, the DC PEG–PU hydrogel possessed good adhesiveness to diverse substrates because of TA abundant catechol groups. This work shows a simple and versatile method to prepare a multifunctional DC single network PEG–PU hydrogel with excellent mechanical properties, and is expected to facilitate developments in the biomedical field.
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Lu, Qiqi, Mirali Pandya, Abdul Jalil Rufaihah, Vinicius Rosa, Huei Jinn Tong, Dror Seliktar, and Wei Seong Toh. "Modulation of Dental Pulp Stem Cell Odontogenesis in a Tunable PEG-Fibrinogen Hydrogel System." Stem Cells International 2015 (2015): 1–9. http://dx.doi.org/10.1155/2015/525367.
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Injectable hydrogels have the great potential for clinical translation of dental pulp regeneration. A recently developed PEG-fibrinogen (PF) hydrogel, which comprises a bioactive fibrinogen backbone conjugated to polyethylene glycol (PEG) side chains, can be cross-linked after injection by photopolymerization. The objective of this study was to investigate the use of this hydrogel, which allows tuning of its mechanical properties, as a scaffold for dental pulp tissue engineering. The cross-linking degree of PF hydrogels could be controlled by varying the amounts of PEG-diacrylate (PEG-DA) cross-linker. PF hydrogels are generally cytocompatible with the encapsulated dental pulp stem cells (DPSCs), yielding >85% cell viability in all hydrogels. It was found that the cell morphology of encapsulated DPSCs, odontogenic gene expression, and mineralization were strongly modulated by the hydrogel cross-linking degree and matrix stiffness. Notably, DPSCs cultured within the highest cross-linked hydrogel remained mostly rounded in aggregates and demonstrated the greatest enhancement in odontogenic gene expression. Consistently, the highest degree of mineralization was observed in the highest cross-linked hydrogel. Collectively, our results indicate that PF hydrogels can be used as a scaffold for DPSCs and offers the possibility of influencing DPSCs in ways that may be beneficial for applications in regenerative endodontics.
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Henise, Jeff, Shaun D. Fontaine, Brian R. Hearn, Samuel J. Pfaff, Eric L. Schneider, Julia Malato, Donghui Wang, Byron Hann, Gary W. Ashley, and Daniel V. Santi. "In Vitro-In Vivo Correlation for the Degradation of Tetra-PEG Hydrogel Microspheres with Tunable β-Eliminative Crosslink Cleavage Rates." International Journal of Polymer Science 2019 (February 10, 2019): 1–7. http://dx.doi.org/10.1155/2019/9483127.
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The degradation of Tetra-PEG hydrogels containing β-eliminative crosslinks has been studied in order to provide an in vitro-in vivo correlation for the use of these hydrogels in our chemically controlled drug delivery system. We measured time-dependent gel mass loss and ultrasound volume changes of 13 subcutaneously implanted Tetra-PEG hydrogel microspheres having degradation times ranging from ~3 to 250 days. Applying a previously developed model of Tetra-PEG hydrogel degradation, the mass changes correlate well with the in vitro rates of crosslink cleavage and hydrogel degelation. These results allow prediction of in vivo biodegradation properties of these hydrogels based on readily obtained in vitro rates, despite having degradation times that span 2 orders of magnitude. These results support the optimization of drug-releasing hydrogels and their development into long-acting therapeutics. The use of ultrasound volume measurements further provides a noninvasive technique for monitoring hydrogel degradation in the subcutaneous space.
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Sousa, Gustavo F., Samson Afewerki, Dalton Dittz, Francisco E. P. Santos, Daniele O. Gontijo, Sérgio R. A. Scalzo, Ana L. C. Santos, et al. "Catalyst-Free Click Chemistry for Engineering Chondroitin Sulfate-Multiarmed PEG Hydrogels for Skin Tissue Engineering." Journal of Functional Biomaterials 13, no. 2 (April 18, 2022): 45. http://dx.doi.org/10.3390/jfb13020045.
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The quest for an ideal biomaterial perfectly matching the microenvironment of the surrounding tissues and cells is an endless challenge within biomedical research, in addition to integrating this with a facile and sustainable technology for its preparation. Engineering hydrogels through click chemistry would promote the sustainable invention of tailor-made hydrogels. Herein, we disclose a versatile and facile catalyst-free click chemistry for the generation of an innovative hydrogel by combining chondroitin sulfate (CS) and polyethylene glycol (PEG). Various multi-armed PEG-Norbornene (A-PEG-N) with different molecular sizes were investigated to generate crosslinked copolymers with tunable rheological and mechanical properties. The crosslinked and mechanically stable porous hydrogels could be generated by simply mixing the two clickable Tetrazine-CS (TCS) and A-PEG-N components, generating a self-standing hydrogel within minutes. The leading candidate (TCS-8A-PEG-N (40 kD)), based on the mechanical and biocompatibility results, was further employed as a scaffold to improve wound closure and blood flow in vivo. The hydrogel demonstrated not only enhanced blood perfusion and an increased number of blood vessels, but also desirable fibrous matrix orientation and normal collagen deposition. Taken together, these results demonstrate the potential of the hydrogel to improve wound repair and hold promise for in situ skin tissue engineering applications.
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Mazzarotta, Alessia, Tania Mariastella Caputo, Edmondo Battista, Paolo Antonio Netti, and Filippo Causa. "Hydrogel Microparticles for Fluorescence Detection of miRNA in Mix-Read Bioassay." Sensors 21, no. 22 (November 18, 2021): 7671. http://dx.doi.org/10.3390/s21227671.
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Herein we describe the development of a mix-read bioassay based on a three-dimensional (3D) poly ethylene glycol—(PEG)-hydrogel microparticles for the detection of oligonucleotides in complex media. The key steps of hydrogels synthesis and molecular recognition in a 3D polymer network are elucidated. The design of the DNA probes and their density in polymer network were opportunely optimized. Furthermore, the diffusion into the polymer was tuned adjusting the polymer concentration and consequently the characteristic mesh size. Upon parameters optimization, 3D-PEG-hydrogels were synthetized in a microfluidic system and provided with fluorescent probe. Target detection occurred by double strand displacement assay associated to fluorescence depletion within the hydrogel microparticle. Proposed 3D-PEG-hydrogel microparticles were designed for miR-143-3p detection. Results showed 3D-hydrogel microparticles with working range comprise between 10−6–10−12 M, had limit of detection of 30 pM and good specificity. Moreover, due to the anti-fouling properties of PEG-hydrogel, the target detection occurred in human serum with performance comparable to that in buffer. Due to the approach versatility, such design could be easily adapted to other short oligonucleotides detection.
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Wang, Xiaoyan, Yu Zhang, Wei Xue, Hong Wang, Xiaozhong Qiu, and Zonghua Liu. "Thermo-sensitive hydrogel PLGA-PEG-PLGA as a vaccine delivery system for intramuscular immunization." Journal of Biomaterials Applications 31, no. 6 (November 25, 2016): 923–32. http://dx.doi.org/10.1177/0885328216680343.
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In this work, we explored the potential of thermo-sensitive PLGA-PEG-PLGA with sol-gel transition temperature around 32℃ as an intramuscular vaccine delivery system by using ovalbumin as a model antigen. First, in vitro release test showed that the PLGA-PEG-PLGA-deriving hydrogels could release ovalbumin in vitro in a more sustainable way. From fluorescence living imaging, 50–200 mg/mL of PLGA-PEG-PLGA formulations could release antigen in a sustainable manner in vivo, suggesting that the PLGA-PEG-PLGA hydrogel worked as an antigen-depot. Further, the sustainable antigen release from the PLGA-PEG-PLGA hydrogels increased antigen availability in the spleens of the immunized mice. The intramuscular immunization results showed that 50–200 mg/mL of PLGA-PEG-PLGA formulations promoted significantly more potent antigen-specific IgG immune response. In addition, 200 mg/mL of PLGA-PEG-PLGA formulation significantly enhanced the secretion of both Th1 and Th2 cytokines. From in vitro splenocyte proliferation assay, 50–200 mg/mL of PLGA-PEG-PLGA formulations all initiated significantly higher splenocyte activation. These results indicate that the thermo-sensitive and injectable PLGA-PEG-PLGA hydrogels (particularly, 200 mg/mL of PLGA-PEG-PLGA-based hydrogel) own promising potential as an intramuscular vaccine delivery system.
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Tanaka, Shizuma, Shinsuke Yukami, Yuhei Hachiro, Yuichi Ohya, and Akinori Kuzuya. "Application of DNA Quadruplex Hydrogels Prepared from Polyethylene Glycol-Oligodeoxynucleotide Conjugates to Cell Culture Media." Polymers 11, no. 10 (October 2, 2019): 1607. http://dx.doi.org/10.3390/polym11101607.
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Application of Na+-responsive DNA quadruplex hydrogels, which utilize G-quadruplexes as crosslinking points of poly(ethylene glycol) (PEG) network as cell culture substrate, has been examined. PEG-oligodeoxynucleotide (ODN) conjugate, in which four deoxyguanosine (dG4) residues are tethered to both ends of PEG, was prepared by modified high-efficiency liquid phase (HELP) synthesis of oligonucleotides and used as the macromonomer. When mixed with equal volume of cell culture media, the solution of PEG-ODN turned into stiff hydrogel (G-quadruplex hydrogel) as the result of G-quadruplex formation by the dG4 segments in the presence of Na+. PEG-ODN itself did not show cytotoxicity and the resulting hydrogel was stable enough under cell culture conditions. However, L929 fibroblast cells cultured in G-quadruplex hydrogel remained spherical for a week, yet alive, without proliferation. The cells gradually sedimented through the gel day by day, probably due to the reversible nature of G-quadruplex formation and the resulting slow rearrangement of the macromonomers. Once they reached the bottom glass surface, the cells started to spread and proliferate.
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Güney, Aysun, Christina Gardiner, Andrew McCormack, Jos Malda, and Dirk Grijpma. "Thermoplastic PCL-b-PEG-b-PCL and HDI Polyurethanes for Extrusion-Based 3D-Printing of Tough Hydrogels." Bioengineering 5, no. 4 (November 14, 2018): 99. http://dx.doi.org/10.3390/bioengineering5040099.
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Novel tough hydrogel materials are required for 3D-printing applications. Here, a series of thermoplastic polyurethanes (TPUs) based on poly(ɛ-caprolactone)-b-poly(ethylene glycol)-b-poly(ɛ-caprolactone) (PCL-b-PEG-b-PCL) triblock copolymers and hexamethylene diisocyanate (HDI) were developed with PEG contents varying between 30 and 70 mol%. These showed excellent mechanical properties not only when dry, but also when hydrated: TPUs prepared from PCL-b-PEG-b-PCL with PEG of Mn 6 kg/mol (PCL7-PEG6-PCL7) took up 122 wt.% upon hydration and had an E-modulus of 52 ± 10 MPa, a tensile strength of 17 ± 2 MPa, and a strain at break of 1553 ± 155% in the hydrated state. They had a fracture energy of 17976 ± 3011 N/mm2 and a high tearing energy of 72 kJ/m2. TPUs prepared using PEG with Mn of 10 kg/mol (PCL5-PEG10-PCL5) took up 534% water and were more flexible. When wet, they had an E-modulus of 7 ± 2 MPa, a tensile strength of 4 ± 1 MPa, and a strain at break of 147 ± 41%. These hydrogels had a fracture energy of 513 ± 267 N/mm2 and a tearing energy of 16 kJ/m2. The latter TPU was first extruded into filaments and then processed into designed porous hydrogel structures by 3D-printing. These hydrogels can be used in 3D printing of tissue engineering scaffolds with high fracture toughness.
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Cao, Ye, Bae Hoon Lee, Scott Alexander Irvine, Yee Shan Wong, Havazelet Bianco Peled, and Subramanian Venkatraman. "Inclusion of Cross-Linked Elastin in Gelatin/PEG Hydrogels Favourably Influences Fibroblast Phenotype." Polymers 12, no. 3 (March 17, 2020): 670. http://dx.doi.org/10.3390/polym12030670.
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The capacity of a biomaterial to innately modulate cell behavior while meeting the mechanical property requirements of the implant is a much sought-after goal within bioengineering. Here we covalently incorporate soluble elastin into a gelatin–poly (ethylene glycol) (PEG) hydrogel for three-dimensional (3D) cell encapsulation to achieve these properties. The inclusion of elastin into a previously optimized gelatin–PEG hydrogel was then evaluated for effects on entrapped fibroblasts, with the aim to assess the hydrogel as an extracellular matrix (ECM)-mimicking 3D microenvironment for cellular guidance. Soluble elastin was incorporated both physically and covalently into novel gelatin/elastin hybrid PEG hydrogels with the aim to harness the cellular interactivity and mechanical tunability of both elastin and gelatin. This design allowed us to assess the benefits of elastin-containing hydrogels in guiding fibroblast activity for evaluation as a potential dermal replacement. It was found that a gelatin–PEG hydrogel with covalently conjugated elastin, supported neonatal fibroblast viability, promoted their proliferation from 7.3% to 13.5% and guided their behavior. The expression of collagen alpha-1(COL1A1) and elastin in gelatin/elastin hybrid gels increased 16-fold and 6-fold compared to control sample at day 9, respectively. Moreover, cells can be loaded into the hydrogel precursor solution, deposited, and the matrix cross-linked without affecting the incorporated cells adversely, thus enabling a potential injectable system for dermal wound healing.
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Yao, Fang, Xiao Xia Ji, Bao Ping Lin, and Guo Dong Fu. "Synthesis of High Strength and Well-Defined PEG-Based Hydrogel Networks via Click Chemistry." Advanced Materials Research 304 (July 2011): 131–34. http://dx.doi.org/10.4028/www.scientific.net/amr.304.131.
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Click Chemistry was used to synthesize a series of PEG-based hydrogel networks. Attributable to the controlled nature and the quantitative yields of Click Chemistry, the prepared PEG-based hydrogels have the well-defined structures, which resulted in the improved mechanical properties and the high swelling ratios of hydrogels
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Hamid, Zuratul Ain Abdul, Anton Blencowe, Greg Qiao, and Geoff Stevens. "Effect of EDA/PEGDGE Mole Ratios on PEG-Based Hydrogel Scaffolds Properties." Advanced Materials Research 626 (December 2012): 681–85. http://dx.doi.org/10.4028/www.scientific.net/amr.626.681.
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The synthesis of biocompatible hydrogel based on poly (ethylene glycol) (PEG) and ethylene diamine (EDA) using epoxy-amine chemistry was conducted. PEG was chosen as the base material (or monomer) to synthesise hydrogels in this study due to its high hydrophilicity, biocompatibility and low toxicity properties. The effects of mole ratios of EDA to PEGDGE on the hydrogel scaffolds properties (i.e., gelling time, swelling) were investigated. It was found out for hydrogel scaffolds prepared at 1.2 and 1.4 M [PEGDG and an EDA/PEGDGE mol ratio of 0.5 in DMSO gave the optimum hydrogel properties. Swelling studies has confirmed that hydrogel prepared at 0.5 mole ratios consist of highly cross-linked network as expected.
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Gori, M., S. M. Giannitelli, G. Vadalà, R. Papalia, L. Zollo, A. Rainer, and V. Denaro. "A POLY(SBMA) ZWITTERIONIC HYDROGEL COATING OF POLYIMIDE SURFACES TO REDUCE THE FOREIGN BODY REACTION TO INVASIVE NEURAL INTERFACES." Orthopaedic Proceedings 105-B, SUPP_7 (April 4, 2023): 20. http://dx.doi.org/10.1302/1358-992x.2023.7.020.
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Intraneural electrodes can be harnessed to control neural prosthetic devices in human amputees. However, in chronic implants we witness a gradual loss of device functionality and electrode isolation due to a nonspecific inflammatory response to the implanted material, called foreign body reaction (FBR). FBR may eventually lead to a fibrous encapsulation of the electrode surface. Poly(ethylene glycol) (PEG) is one of the most common low-fouling materials used to coat and protect electrode surfaces. Yet, PEG can easily undergo encapsulation and oxidative damage in long-term in vivo applications. Poly(sulfobetaine methacrylate) - poly(SBMA) - zwitterionic hydrogels may represent more promising alternatives to minimize the FBR due to their ultra-low fouling features. Here, we tested and compared the poly(SBMA) zwitterionic hydrogel coating with the PEG coating in reducing adhesion and activation of pro-inflammatory and pro-fibrotic cells to polyimide surfaces, which are early hallmarks of FBR. We aimed to coat polyimide surfaces with a hydrogel thin film and analysed the release of a model drug from the hydrogel.We performed hydrogel synthesis, mechanical characterization and biocompatibility analysis. Cell adhesion, viability and morphology of human myofibroblasts cultured on PEG- and hydrogel-coated surfaces were evaluated through confocal microscopy-based high-content analysis (HCA). Reduced activation of pro-inflammatory human macrophages cultured on hydrogels was assessed as well as the hydrogel drug release profile.Because of its high hydration, biocompatibility, low stiffness and ultra-low fouling characteristics the hydrogel enabled lower adhesion and activation of pro-inflammatory and pro-fibrotic cells vs. polystyrene controls, and showed a long-term release of the anti-fibrotic drug Everolimus. Furthermore, a polyimide surface was successfully coated with a hydrogel thin film.Our soft zwitterionic hydrogel could outperform PEG as more suitable coating material of neural electrodes for mitigating the FBR. Such poly(SBMA)-based biomaterial could also be envisioned as long-term delivery system for a sustained release of anti-inflammatory and anti-fibrotic drugs in vivo.
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Steinman, Noam Y., and Abraham J. Domb. "Instantaneous Degelling Thermoresponsive Hydrogel." Gels 7, no. 4 (October 14, 2021): 169. http://dx.doi.org/10.3390/gels7040169.
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Responsive polymeric hydrogels have found wide application in the clinic as injectable, biocompatible, and biodegradable materials capable of controlled release of therapeutics. In this article, we introduce a thermoresponsive polymer hydrogel bearing covalent disulfide bonds. The cold aqueous polymer solution forms a hydrogel upon heating to physiological temperatures and undergoes slow degradation by hydrolytic cleavage of ester bonds. The disulfide functionality allows for immediate reductive cleavage of the redox-sensitive bond embedded within the polymer structure, affording the option of instantaneous hydrogel collapse. Poly(ethylene glycol)-b-poly(lactic acid)-S-S-poly(lactic acid)-b-poly(ethylene glycol) (PEG-PLA-SS-PLA-PEG) copolymer was synthesized by grafting PEG to PLA-SS-PLA via urethane linkages. The aqueous solution of the resultant copolymer was a free-flowing solution at ambient temperatures and formed a hydrogel above 32 °C. The immediate collapsibility of the hydrogel was displayed via reaction with NaBH4 as a relatively strong reducing agent, yet stability was displayed even in glutathione solution, in which the polymer degraded slowly by hydrolytic degradation. The polymeric hydrogel is capable of either long-term or immediate degradation and thus represents an attractive candidate as a biocompatible material for the controlled release of drugs.
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Subramani, Karthikeyan, and M. A. Birch. "Micropatterning of Poly (Ethylene Glycol)-Diacrylate (PEG-DA) Hydrogel by Soft-Photolithography for Analysis of Cell-Biomaterial Interactions." Journal of Biomimetics, Biomaterials and Tissue Engineering 2 (May 2009): 3–14. http://dx.doi.org/10.4028/www.scientific.net/jbbte.2.3.
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Poly (ethylene glycol) hydrogel (PEG) micropatterns fabricated by photolithography and various other microfabrication techniques have been used as a platform to analyze cell-biomaterial interactions in cell culture studies. Numerous innovative techniques have been described about photolithography and the use of Poly (dimethyl siloxane) stamp (PDMS) based pressure moulding technique for the microfabrication of PEG hydrogel micropatterns. We herein this literature describe a simple and a versatile method for fabricating Poly (ethylene glycol) hydrogel-diacrylate (PEG-DA) hydrogel micropatterns using the ‘Soft-photolithography’ technique which is a combination of pressure moulding using a PDMS stamp and photolithography. Using this simple technique, PEG-DA hydrogel micropatterns were fabricated on a silicon substrate of varying dimensions from 40μm to 10μm within the same substrate. Such a three-dimensional microenvironment with varying sizes can serve as an excellent platform to study cell behaviour in culture. These PEG-DA hydrogel micropatterns can further be functionalized by adding a variety of biomolecular cues within the PEG-DA hydrogel matrix or these biomolecules can be patterned on the PEG-DA micropatterns after photopolymerization using micro-contact printing for analysis of cell-biomaterial interactions and tissue engineering purposes.
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Yang, Xin, Bronwin Dargaville, and Dietmar Hutmacher. "Elucidating the Molecular Mechanisms for the Interaction of Water with Polyethylene Glycol-Based Hydrogels: Influence of Ionic Strength and Gel Network Structure." Polymers 13, no. 6 (March 10, 2021): 845. http://dx.doi.org/10.3390/polym13060845.
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The interaction of water within synthetic and natural hydrogel systems is of fundamental importance in biomaterial science. A systematic study is presented on the swelling behavior and states of water for a polyethylene glycol-diacrylate (PEGDA)-based model neutral hydrogel system that goes beyond previous studies reported in the literature. Hydrogels with different network structures are crosslinked and swollen in different combinations of water and phosphate-buffered saline (PBS). Network variables, polyethylene glycol (PEG) molecular weight (MW), and weight fraction are positively correlated with swelling ratio, while “non-freezable bound water” content decreases with PEG MW. The presence of ions has the greatest influence on equilibrium water and “freezable” and “non-freezable” water, with all hydrogel formulations showing a decreased swelling ratio and increased bound water as ionic strength increases. Similarly, the number of “non-freezable bound water” molecules, calculated from DSC data, is greatest—up to six molecules per PEG repeat unit—for gels swollen in PBS. Fundamentally, the balance of osmotic pressure and non-covalent bonding is a major factor within the molecular structure of the hydrogel system. The proposed model explains the dynamic interaction of water within hydrogels in an osmotic environment. This study will point toward a better understanding of the molecular nature of the water interface in hydrogels.
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Hasan, Md Mahmudul, Md Forhad Uddin, Nayera Zabin, Md Salman Shakil, Morshed Alam, Fahima Jahan Achal, Most Hosney Ara Begum, Md Sakib Hossen, Md Ashraful Hasan, and Md Mahbubul Morshed. "Fabrication and Characterization of Chitosan-Polyethylene Glycol (Ch-Peg) Based Hydrogels and Evaluation of Their Potency in Rat Skin Wound Model." International Journal of Biomaterials 2021 (October 14, 2021): 1–11. http://dx.doi.org/10.1155/2021/4877344.
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Thermal burns are a major cause of death and suffering around the globe. They can cause debilitating, life-altering injuries as well as lead to significant psychological and financial consequences. Several research works have been conducted in attempt to find a wound healing therapy that is successful. At present, hydrogels have been widely used in cutting-edge research for this purpose because they have suitable properties. This study aimed to see how therapy with chitosan-polyethylene glycol (Ch-Peg) based hydrogels affected the healing of burn wounds in rats. With the concern of public health, xanthan gum (X), boric acid (B), gelatin (Ge), polyethylene glycol (Peg), chitosan (Ch), glutaraldehyde (G), and HPLC-grade water were prepared using X : Ge : G, X : Ge : Peg : G, X : Ge : Ch : G, X : Ge : Peg : Ch : G, X : Ge : B : Ch : G, X : Ge : B : Peg : G, and X : Ge : B : Peg : Ch : G. The produced composite hydrogels were examined for swelling ability, biodegradability, rheological characteristics, and porosity. The 3D structure of the hydrogel was revealed by scanning electron microscopy (SEM). After that, the structural characterization technique named Fourier-transform infrared spectroscopy (FTIR) was used to describe the composites (SEM). Lastly, in a rat skin wound model, the efficacy of the produced hydrogels was studied. Swelling ability, biodegradability, rheological properties, and porosity were all demonstrated in composite hydrogels that contained over 90% water. Hydrogels with good polymeric networks and porosity were observed using SEM. The existence of bound water and free, intra- and intermolecule hydrogen-linked OH and NH in the hydrogels was confirmed using FTIR. In a secondary burned rat model, all hydrogels showed significant wound healing effectiveness when compared to controls. When compared to other composite hydrogels, wounds treated with X : Ge : Peg : Ch : G, X : Ge : B : Peg : G, and X : Ge : B : Peg : Ch:G recovered faster after 28 days. In conclusion, this research suggests that X : Ge : Peg : Ch : G, X : Ge : B : Peg : G, and X : Ge : B : Peg : Ch : G could be used to treat skin injuries in the clinic.
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Kim, Young Ho, Jeong Woo Sohn, Youngjae Woo, Joo Hyun Hong, and Juyoung Park. "Fabrication of PEG Hydrogel and PDMS Microstructures by a Simple UV Curing Process for Nanobio-Chip Applications." Advanced Materials Research 941-944 (June 2014): 404–10. http://dx.doi.org/10.4028/www.scientific.net/amr.941-944.404.
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Polyethylene glycol (PEG) hydrogel microstructures with various shapes and sizes on a glass chip were prepared by a simple and rapid ultraviolet (UV) irradiation method using a metal mask. Photocurable PEG solution prepared by mixing 95 wt.% polyethylene glycol diacrylate and 5 wt.% 2-hydroxy-2-methylpropiophenone as a photo-initiator was injected to the gap between bottom and upper glasses in a simply assembled glass chip. After a metal mask with line-and-space or complex patterns was placed on the glass chip, UV light from a spot UV irradiation device was exposed to the glass chip through the metal mask for 7 seconds at UV intensity of 26 mW/cm2. Then the PEG hydrogel micropatterns on the glass chip were obtained after removing unreacted PEG solution by air blowing. To prepare more rigid microstructure, the prepared PEG micropatterned chip was exposed under UV light for 20 seconds. Then the PEG hydrogel micropattern chip was fabricated by a simple and rapid procedure. Micropattern transferring was performed from the PEG hydrogel chip to polydimethyl siloxane (PDMS) replica by a solution casting. The prepared micropatterned PDMS replicas showed similar shape and size of microstructures compared to that of the corresponded PEG hydrogel chip. Thus the PEG hydrogel microstructures on a glass chip could be used as a mold to fabricate micropattern PDMS chips for nanobio-chip applications. Furthermore, the present method provides large scale chip fabrication, more than 4 cm-length and 4 cm-width in a single step, not only PEG hydrogel chips but also PDMS chips.
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Zuo, Baoyan, Mingxue Cao, Xiumei Tao, Xiaoyu Xu, Hongfei Leng, Yali Cui, and Kaishun Bi. "Metabolic Study of Tetra-PEG-Based Hydrogel after Pelvic Implantation in Rats." Molecules 27, no. 18 (September 14, 2022): 5993. http://dx.doi.org/10.3390/molecules27185993.
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In vivo metabolism of polyethylene glycol (PEG) hydrogels has rarely been studied. In this study, we prepared a chemically crosslinked hydrogel formulation using 14C-labeled tetra-armed poly (ethylene glycol) succinimidyl succinate (Tetra-PEG-SS) and 3H-labeled crosslinking agent for implantation into the pelvis of Sprague-Dawley (SD) rats. This radioactive labeling technique was used to investigate the radioactivity excretion rates in of feces and urine, the blood exposure time curve, and the radioactivity recovery rate in each tissue over time. We showed that the primary excretion route of the hydrogel was via urine (3H: about 86.4%, 14C: about 90.0%), with fewer portion through feces (3H: about 6.922%, 14C: about 8.16%). The hydrogel metabolites exhibited the highest distribution in the kidney, followed by the jejunal contents; The 3H and 14C radioactivity exposures in the remaining tissues were low. We also showed that the 3H and 14C radioactivity recovery rates in the blood were usually low (<0.10% g−1 at 12 h after implantation), even though, in theory, the hydrogel could be absorbed into the blood through the adjacent tissues. By using a combination of HPLC-MS/MS and offline radioactivity counting method, we established that the tetra-PEG-based hydrogel was mainly metabolized to lower-order PEG polymers and other low-molecular-weight substances in vivo.
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Sun, Yang, Adiel F. Perez, Ivy L. Cardoza, Nina Baluyot-Reyes, and Yong Ba. "Mucoadhesive and Rheological Studies on the Co-Hydrogel Systems of Poly(Ethylene Glycol) Copolymers with Fluoroalkyl and Poly(Acrylic Acid)." Polymers 13, no. 12 (June 12, 2021): 1956. http://dx.doi.org/10.3390/polym13121956.
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A self-assembled co-hydrogel system with sol-gel two-phase coexistence and mucoadhesive properties was developed based on the combined properties of fluoroalkyl double-ended poly(ethylene glycol) (Rf-PEG-Rf) and poly(acrylic acid) (PAA), respectively. We have synthesized an Rf-PEG-g-PAA (where g denotes grafted) copolymer and integrated it into the Rf-PEG-Rf physically cross-linked micellar network to form a co-hydrogel system. Tensile strengths between the co-hydrogel surfaces and two different sets of mucosal surfaces were acquired. One mucosal surface was made of porcine stomach mucin Type II, while the other one is a pig small intestine. The experimental results show that the largest maximum detachment stresses (MDSs) were obtained when the Rf-PEG-g-PAA’s weight percent in the dehydrated polymer mixture is ~15%. Tensile experiments also found that MDSs are greater in acidic conditions (pH = 4–5) (123.3 g/cm2 for the artificial mucus, and 43.0 g/cm2 for pig small intestine) and basic conditions (pH = 10.6) (126.9 g/cm2, and 44.6 g.cm2, respectively) than in neutral pH (45.4 g/cm2, and 30.7 g.cm2, respectively). Results of the rheological analyses using shear strain amplitude sweep and frequency sweep reveal that the Rf-PEG-g-PAA was physically integrated into the Rf-PEG-Rf micellar network, and the co-hydrogels remain physically cross-linked in three-dimensional micellar networks with long-term physical dispersion stability. Therefore, the co-hydrogel system is promising for drug delivery applications on mucosal surfaces.
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Wang, Shan, Zhicun Wang, Cheng Xu, Lin Cui, Guihua Meng, Shengchao Yang, Jianning Wu, Zhiyong Liu, and Xuhong Guo. "PEG-α-CD/AM/liposome @amoxicillin double network hydrogel wound dressing—Multiple barriers for long-term drug release." Journal of Biomaterials Applications 35, no. 9 (February 20, 2021): 1085–95. http://dx.doi.org/10.1177/0885328221991948.
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Wound infection and poor wound healing are the major challenges of wound treatment. Antibiotic drug treatment is the effective way to inhibit wound infection. It is necessary to achieve sustained release of antibiotics to get a longer treatment for wound infection. The double network hydrogels based on liposome, polyethylene glycol (PEG), α- cyclodextrin ( α-CD) and acrylamide (AM) were developed, in which liposome acts as amoxicillin repository. Because the drug would release from the multiple barriers including two cavities of liposome and α-CD, as well as polyethylene glycol - α- cyclodextrin/acrylamide (PEG-CD/AM) double network, the PEG- α-CD/AM/liposome @amoxicillin double network hydrogels could achieve sustained drug release. The drug release assay showed that the dressing could release amoxicillin continuously until 12 days, than that of 8th day for single-network hydrogel releasing. The antibacterial ratio of the hydrogel could reach above 80%. What’s more, the hydrogels present adjustable mechanical strength by changing the ratio of the components. The swelling ratio proved that the hydrogel had potential ability to absorb wound exudates. The cytotoxicity test of the hydrogels demonstrated excellent biocompatibility. These results indicated that this study can provide a new thought for antibacterial wound dressing and has a broad application prospect.
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Wang, Jun, Guangna Qu, Xiangbin Liu, Qin Yu, and Na Zhang. "Preparation and swelling behavior of end-linked hydrogels prepared from linear poly(ethylene glycol) and dendrimer-star polymers." Journal of Polymer Engineering 41, no. 3 (February 1, 2021): 202–10. http://dx.doi.org/10.1515/polyeng-2020-0220.
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Abstract Linear diepoxide-terminated poly(ethylene glycol) (PEG) of molar mass 600, 1000 and 2000 g mol−1 was end-linked with dendrimer-star polymer (PAMAM) of generations 1.0 in water to prepare architecturally well-defined copolymer hydrogels. The structures and properties of the products were characterized using infrared, 1H NMR, DSC measurements, scanning electron microscopy (SEM) and swelling behavior tests. The swelling behavior of these hydrogels was tested in distilled water at constant temperature and the equilibrium swelling ratio (ESR) was determined for structurally different hydrogels and various environmental conditions, which showed that ESR was influenced by the molecular weight of PEG, the molar ratio of H amine groups/epoxy groups, temperature and pH. Higher ESR was obtained for either longer-chain PEG, non-stoichiometric H amine/epoxy groups ratio, acidic pH or lower temperatures. When the hydrogel was switched from 10 °C to 65 °C and pH 3.5 to 11.5, the swelling behavior of the hydrogels showed good reversibility for swelling–deswelling. When the molecular weight of PEG was changed in the range of 600–2000, the lower critical solution temperature (LCST) of hydrogel increased from 30 to 40 °C. When the molar ratio of H amine/epoxy groups was changed, the LCST was not significantly changed.
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Ohya, Yuichi, Hiroyuki Suzuki, Koji Nagahama, Akihiro Takahashi, Tatsuro Ouchi, and Akinori Kuzuya. "Design of Biodegradable Injectable Polymers Exhibiting Temperature-Responsive Sol-Gel Transition." Advances in Science and Technology 86 (September 2012): 9–16. http://dx.doi.org/10.4028/www.scientific.net/ast.86.9.
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Starburst triblock copolymers consisting of 8-arm poly(ethylene glycol) (8-arm PEG), poly(L-lactide) (PLLA) or its enantiomer poly(D-lactide) (PDLA) and terminal PEG, 8-arm PEG-b-PLLA-b-PEG (Stri-L) and 8-arm PEG-b- PDLA-b-PEG (Stri-D), were synthesized. An aqueous solution of a 1:1 mixture (Stri-Mix) of Stri-L and Stri-D assumed a sol state at room temperature, but instantaneously formed a physically cross-linked hydrogel in response to increasing temperature. The resulting hydrogel exhibited a high storage modulus at 37 °C. The rapid temperature-triggered hydrogel formation, high mechanical strength, and degradation behavior render this polymer system suitable for use in injectable drug delivery system or a biodegradable scaffold for tissue engineering.
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Shih, Han, Hung-Yi Liu, and Chien-Chi Lin. "Improving gelation efficiency and cytocompatibility of visible light polymerized thiol-norbornene hydrogels via addition of soluble tyrosine." Biomaterials Science 5, no. 3 (2017): 589–99. http://dx.doi.org/10.1039/c6bm00778c.
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A biomimetic PEG-peptide hydrogel was developed through tyrosine-assisted visible-light thiol-norbornene crosslinking. Soluble tyrosine improves crosslinking and enhances the cytocompatibility of hydrogels.
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GONG, C., S. SHI, P. DONG, B. KAN, M. GOU, X. WANG, X. LI, F. LUO, X. ZHAO, and Y. WEI. "Synthesis and characterization of PEG-PCL-PEG thermosensitive hydrogel." International Journal of Pharmaceutics 365, no. 1-2 (January 5, 2009): 89–99. http://dx.doi.org/10.1016/j.ijpharm.2008.08.027.
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Abdul Hamid, Zuratul Ain, Hanafi Ismail, and Zulkifli Ahmad. "The Development of Macroporous PEG-Based Hydrogel Scaffolds for Tissue Engineering Applications." Materials Science Forum 819 (June 2015): 361–66. http://dx.doi.org/10.4028/www.scientific.net/msf.819.361.
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The fabrication of porous poly (ethylene glycol) (PEG)-based hydrogel scaffolds via epoxy-amine crosslinked polymerization was conducted in this research works. PEG was chosen as the main component of the hydrogel scaffolds due to their unique characteristic including high hydrophilicity, biocompatibility and low toxicity properties. The effects of different solvents ((water, dimethylsulfoxide (DMSO), triethylene glycol dimethyl ether (TGDME), etc) toward physical and mechanical properties of fabricated PEG-based hydrogel scaffolds were investigated to identify the suitable solvent for fabrication of porous hydrogel scaffolds. From the results obtained, DMSO was selected as the solvent because the produced hydrogels scaffolds possessed the optimum physical properties as compared to other solvents. In tissue engineering field, porosity of scaffolds play key role for cell attachment, grow and proliferation consequently help in regeneration of new tissues. Therefore, in this study the macroporous hydrogel scaffolds were produced via introduction of fused salt templates in the range sizes of 100–300 μm (small) and 300–600 μm (large) in the fabrication process. Improved interconnectivity of pores was achieved and pores sizes obtained were according to the size of salt particles utilized in the template. Modification of the scaffolds pore morphology resulted in a reduction in the mechanical properties as we expected.
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Sagle, Alyson C., Hao Ju, Benny D. Freeman, and Mukul M. Sharma. "PEG-based hydrogel membrane coatings." Polymer 50, no. 3 (January 2009): 756–66. http://dx.doi.org/10.1016/j.polymer.2008.12.019.
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Stealey, Samuel, Mariam Khachani, and Silviya Petrova Zustiak. "Adsorption and Sustained Delivery of Small Molecules from Nanosilicate Hydrogel Composites." Pharmaceuticals 15, no. 1 (January 1, 2022): 56. http://dx.doi.org/10.3390/ph15010056.
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Two-dimensional nanosilicate particles (NS) have shown promise for the prolonged release of small-molecule therapeutics while minimizing burst release. When incorporated in a hydrogel, the high surface area and charge of NS enable electrostatic adsorption and/or intercalation of therapeutics, providing a lever to localize and control release. However, little is known about the physio-chemical interplay between the hydrogel, NS, and encapsulated small molecules. Here, we fabricated polyethylene glycol (PEG)-NS hydrogels for the release of model small molecules such as acridine orange (AO). We then elucidated the effect of NS concentration, NS/AO incubation time, and the ability of NS to freely associate with AO on hydrogel properties and AO release profiles. Overall, NS incorporation increased the hydrogel stiffness and decreased swelling and mesh size. When individual NS particles were embedded within the hydrogel, a 70-fold decrease in AO release was observed compared to PEG-only hydrogels, due to adsorption of AO onto NS surfaces. When NS was pre-incubated and complexed with AO prior to hydrogel encapsulation, a >9000-fold decrease in AO release was observed due to intercalation of AO between NS layers. Similar results were observed for other small molecules. Our results show the potential for use of these nanocomposite hydrogels for the tunable, long-term release of small molecules.
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Dey, Kamol, Silvia Agnelli, and Luciana Sartore. "Designing Viscoelastic Gelatin-PEG Macroporous Hybrid Hydrogel with Anisotropic Morphology and Mechanical Properties for Tissue Engineering Application." Micro 3, no. 2 (April 11, 2023): 434–57. http://dx.doi.org/10.3390/micro3020029.
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The mechanical properties of scaffolds play a vital role in regulating key cellular processes in tissue development and regeneration in the field of tissue engineering. Recently, scaffolding material design strategies leverage viscoelasticity to guide stem cells toward specific tissue regeneration. Herein, we designed and developed a viscoelastic Gel-PEG hybrid hydrogel with anisotropic morphology and mechanical properties using a gelatin and functionalized PEG (as a crosslinker) under a benign condition for tissue engineering application. The chemical crosslinking/grafting reaction was mainly involved between epoxide groups of PEG and available functional groups of gelatin. FTIR spectra revealed the hybrid nature of Gel-PEG hydrogel. The hybrid hydrogel showed good swelling behavior (water content > 600%), high porosity and pore interconnectivity suitable for tissue engineering application. Simple unidirectional freezing followed by a freeze-drying technique allowed the creation of structurally stable 3D anisotropic macroporous architecture that showed tissue-like elasticity and was capable of withstanding high deformation (50% strain) without being damaged. The tensile and compressive modulus of Gel-PEG hybrid hydrogel were found to be 0.863 MPa and 0.330 MPa, respectively, which are within the range of normal human articular cartilage. In-depth mechanical characterizations showed that the Gel-PEG hybrid hydrogel possessed natural-tissue-like mechanics such as non-linear and J-shaped stress-strain curves, stress softening effect, high fatigue resistance and stress relaxation response. A month-long hydrolytic degradation test revealed that the hydrogel gradually degraded in a homogeneous manner over time but maintained its structural stability and anisotropic mechanics. Overall, all these interesting features provide a potential opportunity for Gel-PEG hybrid hydrogel as a scaffold in a wide range of tissue engineering applications.
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Park, Yeonju, Minkyoung Kim, Isao Noda, and Young Mee Jung. "Understanding Thermal Behavior of Poly(ethylene glycol)-block-poly(N-isopropylacrylamide) Hydrogel Using Two-Dimensional Correlation Infrared Spectroscopy." Applied Spectroscopy 75, no. 8 (April 8, 2021): 957–62. http://dx.doi.org/10.1177/00037028211006681.
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In this study, one of the thermoresponsive polymers, block copolymer consisting of poly(ethylene glycol) and poly( N-isopropylacylamide), was investigated using Fourier transform infrared (FT-IR) spectroscopy, principal component analysis (PCA), and two-dimensional correlation spectroscopy (2D-COS). The apparent trend of the spectral changes in the temperature-dependent FT-IR spectra of poly(ethylene glycol)- block-poly( N-isopropylacylamide) (PEG- b-PNiPAAm) hydrogel during the heating process looks similar to that during the cooling process. The results of the PCA and 2D-COS, however, clearly indicate an irreversible phase transition mechanism of PEG- b-PNiPAAm hydrogel during the heating and cooling processes. It has been also shown that PEG affects the phase transition mechanism of PEG- b-PNiPAAm hydrogel, especially during the heating process. Consequently, we can successfully determine the phase transition temperature and the mechanism of PEG- b-PNiPAAm hydrogel during the heating and cooling processes using PCA and 2D-COS, respectively.
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Liu, Hung-Yi, and Chien-Chi Lin. "A Diffusion-Reaction Model for Predicting Enzyme-Mediated Dynamic Hydrogel Stiffening." Gels 5, no. 1 (March 13, 2019): 17. http://dx.doi.org/10.3390/gels5010017.
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Hydrogels with spatiotemporally tunable mechanical properties have been increasingly employed for studying the impact of tissue mechanics on cell fate processes. These dynamic hydrogels are particularly suitable for recapitulating the temporal stiffening of a tumor microenvironment. To this end, we have reported an enzyme-mediated stiffening hydrogel system where tyrosinase (Tyrase) was used to stiffen orthogonally crosslinked cell-laden hydrogels. Herein, a mathematical model was proposed to describe enzyme diffusion and reaction within a highly swollen gel network, and to elucidate the critical factors affecting the degree of gel stiffening. Briefly, Fick’s second law of diffusion was used to predict enzyme diffusion in a swollen poly(ethylene glycol) (PEG)-peptide hydrogel, whereas the Michaelis–Menten model was employed for estimating the extent of enzyme-mediated secondary crosslinking. To experimentally validate model predictions, we designed a hydrogel system composed of 8-arm PEG-norbornene (PEG8NB) and bis-cysteine containing peptide crosslinker. Hydrogel was crosslinked in a channel slide that permitted one-dimensional diffusion of Tyrase. Model predictions and experimental results suggested that an increasing network crosslinking during stiffening process did not significantly affect enzyme diffusion. Rather, diffusion path length and the time of enzyme incubation were more critical in determining the distribution of Tyrase and the formation of additional crosslinks in the hydrogel network. Finally, we demonstrated that the enzyme-stiffened hydrogels exhibited elastic properties similar to other chemically crosslinked hydrogels. This study provides a better mechanistic understanding regarding the process of enzyme-mediated dynamic stiffening of hydrogels.
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Schröder, Romina, Hannah Pohlit, Timo Schüler, Martin Panthöfer, Ronald E. Unger, Holger Frey, and Wolfgang Tremel. "Transformation of vaterite nanoparticles to hydroxycarbonate apatite in a hydrogel scaffold: relevance to bone formation." Journal of Materials Chemistry B 3, no. 35 (2015): 7079–89. http://dx.doi.org/10.1039/c5tb01032b.
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Vaterite nanoparticles incorporated in a biodegradable PEG hydrogel transform to hydroxycarbonate apatite upon incubation in simulated body fluid. The vaterite-loaded hydrogels did not have inflammatory effects on endothelial cells.
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Lu, Quanfang, Jie Yu, Jinzhang Gao, Wu Yang, and Yan Li. "A promising absorbent of acrylic acid/poly(ethylene glycol) hydrogel prepared by glow-discharge electrolysis plasma." Open Chemistry 10, no. 4 (August 1, 2012): 1349–59. http://dx.doi.org/10.2478/s11532-012-0055-9.
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AbstractAn acrylic acid/poly(ethylene glycol) (AAc/PEG) hydrogel was synthesized in aqueous solution by a simple one-step method using glow-discharge electrolysis plasma (GDEP) technique. The structure of AAc/PEG hydrogel was characterized by Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS). Factors influencing the adsorption of heavy-metal ions such as solution pH, contact time, initial heavy-metal ion concentration were examined systematically by batch experiments. Results showed that both chemical complexation and ion exchange played an important role for heavy-metal ion adsorption onto AAc/PEG hydrogel. The adsorption isothermals followed the Langmuir isotherm and the adsorption kinetics fitted the pseudo-second-order model at 25°C with a pH 6. In addition, AAc/PEG hydrogel can be also regenerated and re-used.
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Yang, Hang, Xianyu Lan, and Yuzhu Xiong. "In Situ Growth of Zeolitic Imidazolate Framework-L in Macroporous PVA/CMC/PEG Composite Hydrogels with Synergistic Antibacterial and Rapid Hemostatic Functions for Wound Dressing." Gels 8, no. 5 (May 1, 2022): 279. http://dx.doi.org/10.3390/gels8050279.
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Although many advances have been made in medicine, traumatic bleeding and wound infection are two of the most serious threats to human health. To achieve rapid hemostasis and prevent infection by pathogenic microbes, the development of new hemostatic and antibacterial materials has recently gained significant attention. In this paper, safe, non-toxic, and biocompatible polyvinyl alcohol (PVA); carboxymethyl cellulose (CMC), which contains several carboxyl and hydroxyl groups; and polyethylene glycol (PEG), which functions as a pore-forming agent, were used to prepare a novel PVA/CMC/PEG-based composite hydrogel with a macroporous structure by the freeze-thaw method and the phase separation technique. In addition, a PVA/CMC/PEG@ZIF-L composite hydrogel was prepared by the in situ growth of zeolitic imidazolate framework-L (ZIF-L). ZIF-L grown in situ on hydrogels released Zn2+ and imidazolyl groups. They elicited a synergistic antibacterial effect in hemostasis with PVA and CMC, rendering the PVA/CMC/PEG@ZIF-L hydrogel with a good antibacterial effect against Staphylococcus aureus. At the same time, the macroporous structure enabled the rapid release of Zn2+ and imidazolyl groups in ZIF-L and promoted cell proliferation at an early stage, enhancing the coagulation efficiency. A rat liver injury model was used to confirm its rapid hemostasis capacity.
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Ito, Kiyoshi, Tetsuyoshi Horiuchi, Kiyomitsu Oyanagi, Tetsuo Nomiyama, and Kazuhiro Hongo. "Comparative study of fibrin and chemical synthetic sealant on dural regeneration and brain damage." Journal of Neurosurgery: Spine 19, no. 6 (December 2013): 736–43. http://dx.doi.org/10.3171/2013.8.spine12998.
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Object Several materials, such as polyethylene glycol (PEG) hydrogel and fibrin glue, have been used to seal dural incisions after brain and spinal surgeries. Although the use of PEG sealant is gaining popularity, it can be associated with postoperative cerebrospinal fluid leakage and infection. However, the reasons for this association are currently unknown. The present study aimed to investigate the effects of PEG sealant and fibrin glue on wound healing and brain damage in vivo. Methods Oval-shaped bone defects and dural defects were created bilaterally over the parietal lobes of 22 Japanese white rabbits. The dural defects were covered with 0.5 ml of fibrin glue on one side and 0.5 ml of PEG sealant on the other side. Dural regeneration and brain damage were investigated in each harvested brain and dura mater using light microscopy. Results Dural regeneration was more effective in the presence of fibrin glue than it was with PEG sealant (p = 0.014). Of the 22 rabbits, 11 showed thick (Grades ++ and +++) dural regeneration by 28 days postsurgery in the hemisphere where fibrin glue was used, whereas Grade +++ dural regeneration was not observed in the PEG hydrogel hemisphere, and only 4 rabbits showed Grade ++ regeneration. Abscess and granulation formation also tended to be more severe when PEG hydrogel sealant was used. No Grade ++ granulation/abscess formation was observed with fibrin glue, and Grade + was only observed in 13 of 22 rabbits. Conversely, with PEG hydrogel sealant, only 2 rabbits did not show granulation/abscess formation, and Grade +, ++, and +++ granulation/abscess formation was observed in 8, 7, and 5 rabbits, respectively. The extent of cortical damage was significantly greater in rabbits with abscesses and granulations, compared with rabbits without these lesions (p = 0.007). Conclusions Dural regeneration tended to occur more rapidly with fibrin glue, whereas granulation was more likely with PEG hydrogel sealant, which led to postoperative complications. Histological analysis indicated that PEG hydrogel sealant inhibited the normal tissue healing process and that outcomes were improved by the use of fibrin glue.
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Noh, Soyoung, Hye Yeon Gong, Hyun Jong Lee, and Won-Gun Koh. "Electrically Conductive Micropatterned Polyaniline-Poly(ethylene glycol) Composite Hydrogel." Materials 14, no. 2 (January 8, 2021): 308. http://dx.doi.org/10.3390/ma14020308.
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Hydrogel substrate-based micropatterns can be adjusted using the pattern shape and size, affecting cell behaviors such as proliferation and differentiation under various cellular environment parameters. An electrically conductive hydrogel pattern system mimics the native muscle tissue environment. In this study, we incorporated polyaniline (PANi) in a poly(ethylene glycol) (PEG) hydrogel matrix through UV-induced photolithography with photomasks, and electrically conductive hydrogel micropatterns were generated within a few seconds. The electrical conductance of the PANi/PEG hydrogel was 30.5 ± 0.5 mS/cm. C2C12 myoblasts were cultured on the resulting substrate, and the cells adhered selectively to the PANi/PEG hydrogel regions. Myogenic differentiation of the C2C12 cells was induced, and the alignment of myotubes was consistent with the arrangement of the line pattern. The expression of myosin heavy chain on the line pattern showed potential as a substrate for myogenic cell functionalization.
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Noh, Soyoung, Hye Yeon Gong, Hyun Jong Lee, and Won-Gun Koh. "Electrically Conductive Micropatterned Polyaniline-Poly(ethylene glycol) Composite Hydrogel." Materials 14, no. 2 (January 8, 2021): 308. http://dx.doi.org/10.3390/ma14020308.
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Hydrogel substrate-based micropatterns can be adjusted using the pattern shape and size, affecting cell behaviors such as proliferation and differentiation under various cellular environment parameters. An electrically conductive hydrogel pattern system mimics the native muscle tissue environment. In this study, we incorporated polyaniline (PANi) in a poly(ethylene glycol) (PEG) hydrogel matrix through UV-induced photolithography with photomasks, and electrically conductive hydrogel micropatterns were generated within a few seconds. The electrical conductance of the PANi/PEG hydrogel was 30.5 ± 0.5 mS/cm. C2C12 myoblasts were cultured on the resulting substrate, and the cells adhered selectively to the PANi/PEG hydrogel regions. Myogenic differentiation of the C2C12 cells was induced, and the alignment of myotubes was consistent with the arrangement of the line pattern. The expression of myosin heavy chain on the line pattern showed potential as a substrate for myogenic cell functionalization.
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Khan, Rahima, Muhammad Zaman, Ahmad Salawi, Mahtab Ahmad Khan, Muhammad Omer Iqbal, Romana Riaz, Muhammad Masood Ahmed, et al. "Synthesis of Chemically Cross-Linked pH-Sensitive Hydrogels for the Sustained Delivery of Ezetimibe." Gels 8, no. 5 (May 1, 2022): 281. http://dx.doi.org/10.3390/gels8050281.
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In recent years, pH-sensitive hydrogels have been developed for the delivery of therapeutic agents to specific target sites that have a defined pH range. The use of pH-responsive polymers in hydrogels allows drug delivery to the desired pH range of the target organ. The primary aim is to increase the retention time of the drug in the small intestine by utilizing the swelling mechanism of the hydrogel at intestinal pH. In this study, polyethylene glycol (PEG) was used as a polymer to formulate a pH-sensitive hydrogel of Ezetimibe to deliver the drug to the small intestine where it inhibits the absorption of cholesterol. Design Expert software was applied to design and optimize the trial formulations in order to obtain an optimized formulation that has all the desired characteristics of the hydrogels. The PEG/Acrylic Acid hydrogels showed the maximum swelling at pH 6.8, which is consistent with the pH of the small intestine (pH 6–7.4). The maximum entrapment efficiency of the hydrogels was 99%. The hydrogel released 80–90% of the drug within 24 h and followed first-order release kinetics, which showed that the release from the drug was sustained. Hence, the results showed that the choice of a suitable polymer can lead to the development of an efficient drug-loaded hydrogel that can deliver the drug at the specific pH of the target organ.
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Giliomee, Johnel, Lisa C. du Toit, Pradeep Kumar, Bert Klumperman, and Yahya E. Choonara. "Evaluation of Composition Effects on the Physicochemical and Biological Properties of Polypeptide-Based Hydrogels for Potential Application in Wound Healing." Polymers 13, no. 11 (May 31, 2021): 1828. http://dx.doi.org/10.3390/polym13111828.
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In this study, the effect of crosslinking and concentration on the properties of a new library of low-concentration poly(Lys60-ran-Ala40)-based hydrogels for potential application in wound healing was investigated in order to correlate the hydrogel composition with the desired physicochemical and biofunctional properties to expand the assortment of poly-l-lysine (PLL)-based hydrogels suitable for wound healing. Controlled ring-opening polymerization (ROP) and precise hydrogel compositions were used to customize the physicochemical and biofunctional properties of a library of new hydrogels comprising poly(l-lysine-ran-l-alanine) and four-arm poly(ethylene glycol) (P(KA)/4-PEG). The chemical composition and degree of crosslinking via free amine quantification were analyzed for the P(KA)/4-PEG hydrogels. In addition, the rheological properties, pore morphology, swelling behavior and degradation time were characterized. Subsequently, in vitro cell studies for evaluation of the cytotoxicity and cell adhesion were performed. The 4 wt% 1:1 functional molar ratio hydrogel with P(KA) concentrations as low as 0.65 wt% demonstrated low cytotoxicity and desirable cell adhesion towards fibroblasts and thus displayed a desirable combination of properties for wound healing application.
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Wang, Shiwen, Guanjiang Liu, Bei Yang, Zifeng Zhang, Debo Hu, Chenchen Wu, Yaling Qin, Qian Dou, Qing Dai, and Wenping Hu. "Low-fouling CNT-PEG-hydrogel coated quartz crystal microbalance sensor for saliva glucose detection." RSC Advances 11, no. 37 (2021): 22556–64. http://dx.doi.org/10.1039/d1ra02841c.
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We successfully achieved the direct detection of saliva glucose by a CNT-PEG-hydrogel. The top CNT-PEG layer provides channels for transporting glucose molecules and filters macromolecular impurities and the bottom base PBA-hydrogel film provides the glucose binding sites.
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Cosgrove, G. Rees, Johnny B. Delashaw, J. Andre Grotenhuis, John M. Tew, Harry van Loveren, Robert F. Spetzler, Troy Payner, et al. "Safety and efficacy of a novel polyethylene glycol hydrogel sealant for watertight dural repair." Journal of Neurosurgery 106, no. 1 (January 2007): 52–58. http://dx.doi.org/10.3171/jns.2007.106.1.52.
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Object The authors prospectively evaluated the safety and efficacy of a novel polyethylene glycol (PEG) hydrogel sealant in patients undergoing elective cranial surgery with documented cerebrospinal fluid (CSF) leakage after sutured dural repair. Methods The PEG hydrogel sealant was used at 11 different study sites in 111 patients with documented intraoperative CSF leakage after neurosurgical dural repair for a variety of conditions. Intraoperative CSF leakage was either spontaneous or induced by a Valsalva maneuver. Patients were monitored for 3 months postoperatively with physical examinations, clinical laboratory analyses, and diagnostic imaging. The PEG hydrogel sealant was 100% effective in stopping CSF leakage in all patients. There were no sealant-related adverse events and all clinical outcomes were consistent with expectations for seriously ill patients undergoing prolonged neurosurgical procedures. Conclusions The PEG hydrogel sealant provides a safe and effective watertight closure when used as an adjunct to sutured dural repair during cranial surgery.
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Bock, Nathalie, Farzaneh Forouz, Luke Hipwood, Julien Clegg, Penny Jeffery, Madeline Gough, Tirsa van Wyngaard, et al. "GelMA, Click-Chemistry Gelatin and Bioprinted Polyethylene Glycol-Based Hydrogels as 3D Ex Vivo Drug Testing Platforms for Patient-Derived Breast Cancer Organoids." Pharmaceutics 15, no. 1 (January 12, 2023): 261. http://dx.doi.org/10.3390/pharmaceutics15010261.
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3D organoid model technologies have led to the development of innovative tools for cancer precision medicine. Yet, the gold standard culture system (Matrigel®) lacks the ability for extensive biophysical manipulation needed to model various cancer microenvironments and has inherent batch-to-batch variability. Tunable hydrogel matrices provide enhanced capability for drug testing in breast cancer (BCa), by better mimicking key physicochemical characteristics of this disease’s extracellular matrix. Here, we encapsulated patient-derived breast cancer cells in bioprinted polyethylene glycol-derived hydrogels (PEG), functionalized with adhesion peptides (RGD, GFOGER and DYIGSR) and gelatin-derived hydrogels (gelatin methacryloyl; GelMA and thiolated-gelatin crosslinked with PEG-4MAL; GelSH). Within ranges of BCa stiffnesses (1–6 kPa), GelMA, GelSH and PEG-based hydrogels successfully supported the growth and organoid formation of HR+,−/HER2+,− primary cancer cells for at least 2–3 weeks, with superior organoid formation within the GelSH biomaterial (up to 268% growth after 15 days). BCa organoids responded to doxorubicin, EP31670 and paclitaxel treatments with increased IC50 concentrations on organoids compared to 2D cultures, and highest IC50 for organoids in GelSH. Cell viability after doxorubicin treatment (1 µM) remained >2-fold higher in the 3D gels compared to 2D and doxorubicin/paclitaxel (both 5 µM) were ~2.75–3-fold less potent in GelSH compared to PEG hydrogels. The data demonstrate the potential of hydrogel matrices as easy-to-use and effective preclinical tools for therapy assessment in patient-derived breast cancer organoids.
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Lee, Woo Tak, Johyun Yoon, Sung Soo Kim, Hanju Kim, Nguyen Thi Nguyen, Xuan Thien Le, Eun Seong Lee, Kyung Taek Oh, Han-Gon Choi, and Yu Seok Youn. "Combined Antitumor Therapy Using In Situ Injectable Hydrogels Formulated with Albumin Nanoparticles Containing Indocyanine Green, Chlorin e6, and Perfluorocarbon in Hypoxic Tumors." Pharmaceutics 14, no. 1 (January 8, 2022): 148. http://dx.doi.org/10.3390/pharmaceutics14010148.
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Combined therapy using photothermal and photodynamic treatments together with chemotherapeutic agents is considered one of the most synergistic treatment protocols to ablate hypoxic tumors. Herein, we sought to fabricate an in situ-injectable PEG hydrogel system having such multifunctional effects. This PEG hydrogel was prepared with (i) nabTM-technique-based paclitaxel (PTX)-bound albumin nanoparticles with chlorin-e6 (Ce6)-conjugated bovine serum albumin (BSA-Ce6) and indocyanine green (ICG), named ICG/PTX/BSA-Ce6-NPs (~175 nm), and (ii) an albumin-stabilized perfluorocarbon (PFC) nano-emulsion (BSA-PFC-NEs; ~320 nm). This multifunctional PEG hydrogel induced moderate and severe hyperthermia (41−42 °C and >48 °C, respectively) at the target site under two different 808 nm laser irradiation protocols, and also induced efficient singlet oxygen (1O2) generation under 660 nm laser irradiation supplemented by oxygen produced by ultrasound-triggered PFC. Due to such multifunctionality, our PEG hydrogel formula displayed significantly enhanced killing of three-dimensional 4T1 cell spheroids and also suppressed the growth of xenografted 4T1 cell tumors in mice (tumor volume: 47.7 ± 11.6 and 63.4 ± 13.0 mm3 for photothermal and photodynamic treatment, respectively, vs. PBS group (805.9 ± 138.5 mm3), presumably based on sufficient generation of moderate heat as well as 1O2/O2 even under hypoxic conditions. Our PEG hydrogel formula also showed excellent hyperthermal efficacy (>50 °C), ablating the 4T1 tumors when the irradiation duration was extended and output intensity was increased. We expect that our multifunctional PEG hydrogel formula will become a prototype for ablation of otherwise poorly responsive hypoxic tumors.
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Mhessn, R. Jameel, L. Abd-Alredha, R. Al-Rubaie, and A. Fuad Khudair Aziz. "Preparation of Tannin Based Hydrogel for Biological Application." E-Journal of Chemistry 8, no. 4 (2011): 1638–43. http://dx.doi.org/10.1155/2011/763295.
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Polymeric blends as potential wound dressing were prepared. Natural polymer (Tannin) and synthetic polymers (PVA and PEG) were used to prepare heterogeneous blends. The product was identified by spectrophotometry. A diaphragm cell was used to measure the diffusion coefficient (D). The result shown the PEG-PVA disk was very faster permeability for all solution. The D of PVA/ PEG-Tannin blend was 0.184x10-3cm2/s higher than Tannin-PEG blend was 0.038x10-3cm2/s. The natural phenolic compounds that can be used artificial membrane to inhibit growth or kill microorganism such as bacteria or fungi.
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Roumani, Sandra, Charlotte Jeanneau, Thomas Giraud, Aurélie Cotten, Marc Laucournet, Jérôme Sohier, Martine Pithioux, and Imad About. "Osteogenic Potential of a Polyethylene Glycol Hydrogel Functionalized with Poly-Lysine Dendrigrafts (DGL) for Bone Regeneration." Materials 16, no. 2 (January 16, 2023): 862. http://dx.doi.org/10.3390/ma16020862.
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Resorbable hydrogels are widely used as scaffolds for tissue engineering. These hydrogels can be modified by grafting dendrimer-linked functionalized molecules (dendrigrafts). Our aim was to develop a tunable poly(L-lysine) dendrigrafts (DGL)/PEG-based hydrogel with an inverse porosity and to investigate its osteogenic potential. DGL/PEG hydrogels were emulsified in a surfactant-containing oil solution to form microspheres. The toxicity was evaluated on Human Vascular Endothelial Cells (HUVECs) and Bone Marrow Mesenchymal Stem Cells (hMSCs) with Live/Dead and MTT assays. The effects on HUVECs were investigated through C5 Complement expression by RT-PCR and C5a/TGF-β1 secretion by ELISA. Recruitment of hMSCs was investigated using Boyden chambers and their osteogenic differentiation was studied by measuring Alkaline Phosphatase activity (ALP) and BMP-2 secretion by ELISA. Adjusting the stirring speed during the emulsification allowed to obtain spherical microspheres with tunable diameters (10–1600 µm). The cell viability rate with the hydrogel was 95 and 100% with HUVECs and hMSCs, respectively. Incubating HUVECs with the biomaterial induced a 5-fold increase in TGF-β1 and a 3-fold increase in Complement C5a release. Furthermore, HUVEC supernatants obtained after incubation with the hydrogel induced a 2.5-fold increase in hMSC recruitment. The hydrogel induced a 3-fold increase both in hMSC ALP activity and BMP-2 secretion. Overall, the functionalized hydrogel enhanced the osteogenic potential by interacting with endothelial cells and hMSCs and represents a promising tool for bone tissue engineering.
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Lee, Hwajung, Hye Jin Hong, Sujeong Ahn, Dohyun Kim, Shin Hyuk Kang, Kanghee Cho, and Won-Gun Koh. "One-Pot Synthesis of Double-Network PEG/Collagen Hydrogel for Enhanced Adipogenic Differentiation and Retrieval of Adipose-Derived Stem Cells." Polymers 15, no. 7 (April 3, 2023): 1777. http://dx.doi.org/10.3390/polym15071777.
Full textAbstract:
Hydrogels are widely used in stem cell therapy due to their extensive tunability and resemblance to the extracellular matrix (ECM), which has a three-dimensional (3D) structure. These features enable various applications that enhance stem cell maintenance and function. However, fast and simple hydrogel fabrication methods are desirable for stem cells for efficient encapsulation and to reduce adverse effects on the cells. In this study, we present a one-pot double-crosslinked hydrogel consisting of polyethylene glycol (PEG) and collagen, which can be prepared without the multi-step sequential synthesis of each network, by using bio-orthogonal chemistry. To enhance the adipogenic differentiation efficiency of adipose-derived stem cells (ADSCs), we added degradable components within the hydrogel to regulate matrix stiffness through cell-mediated degradation. Bio-orthogonal reactions used for hydrogel gelation allow rapid gel formation for efficient cell encapsulation without toxic by-products. Furthermore, the hybrid network of synthetic (PEG) and natural (collagen) components demonstrated adequate mechanical strength and higher cell adhesiveness. Therefore, ADSCs grown within this hybrid hydrogel proliferated and functioned better than those grown in the single-crosslinked hydrogel. The degradable elements further improved adipogenesis in ADSCs with dynamic changes in modulus during culture and enabled the retrieval of differentiated cells for potential future applications.
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Xie, Pengfei, Lifang You, Yahao Ma, Tianyin Chen, and Xiaoying Wang. "Thermo-tunable Injectable Thermosensitive Hydrogel and its Application as Protein Carriers." International Journal of Biology and Life Sciences 3, no. 2 (July 12, 2023): 19–22. http://dx.doi.org/10.54097/ijbls.v3i2.10088.
Full textAbstract:
It is known that polymer chemistries determine mechanical and physical properties of hydrogels and thus its drug delivery performance. In order to achieve desired drug release behavior, triblock copolyester PCT-PEG-PCT with proper hydrogel formulation has to be synthesized. This research has demonstrated a way to adjust hydrogel mechanical and gelation properties by simply physically mixing amphiphilic copolymers with different composition to achieve desired protein carriers. Tri-block copolymer poly (CL-co-TOSUO)-PEG-poly (CL-co-TOSUO), briefed as (PCT-PEG-PCT) with different composition have been successfully synthesized. These copolymers are thermosensitive and can form hydrogels in aqueous solution. Copolymers with higher percentage hydrophobic PCT blocks show higher mechanical stiffness and yet lower solubility. To reduce the crystallinity of the hydrophobic block and soften the hydrogel, the copolymer with long PCT blocks was physically mixed with ones with shorter PCT blocks. The polymer mixture demonstrated a moderated mechanical stiffness and desired solubility. The polymer mixture also achieved a gelation temperature at 37°C, which is desirable for drug delivery. Macromolecular drug, bovine serum albumin (BSA) was used as model drug for its release study. This protein drug was successfully loaded into the polymer mixture, and the drug release study shows the polymer mixture is able to extend a stable drug release for over 48 hours. This result confirms physical mixing of PCT-PET-PCT thermosensitive copolymers can tune gel properties and improve drug delivery performance without redesigning and synthesizing new polymers.
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Shao, Meiling, Zhan Shi, Bin Zhai, Xiangfei Zhang, and Zhongyi Li. "Preparation and Performance Analysis of Bacterial Cellulose-Based Composite Hydrogel Based on Scanning Electron Microscope." Scanning 2022 (August 6, 2022): 1–7. http://dx.doi.org/10.1155/2022/8750394.
Full textAbstract:
In order to better prepare and analyze bacterial cellulose-based composite hydrogels, an experimental method based on scanning electron microscopy was proposed. The specific content of the method is to observe the hydrogel through scanning electron microscope, to observe the space between molecules through experiments, and to improve the effect of bacterial cellulose preparation of hydrogel. The experimental results show that the gel preparation effect is best when PEG concentration is not more than observed by scanning electron microscope. It is better to prepare bacterial cellulose complex hydrogel by scanning electron microscopy.
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Xie, Cangyou, Fatma Rashed, Yosuke Sasaki, Masud Khan, Jia Qi, Yuri Kubo, Yoshiro Matsumoto, et al. "Comparison of Osteoconductive Ability of Two Types of Cholesterol-Bearing Pullulan (CHP) Nanogel-Hydrogels Impregnated with BMP-2 and RANKL-Binding Peptide: Bone Histomorphometric Study in a Murine Calvarial Defect Model." International Journal of Molecular Sciences 24, no. 11 (June 5, 2023): 9751. http://dx.doi.org/10.3390/ijms24119751.
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The receptor activator of NF-κB ligand (RANKL)-binding peptide is known to accelerate bone morphogenetic protein (BMP)-2-induced bone formation. Cholesterol-bearing pullulan (CHP)-OA nanogel-crosslinked PEG gel (CHP-OA nanogel-hydrogel) was shown to release the RANKL-binding peptide sustainably; however, an appropriate scaffold for peptide-accelerated bone formation is not determined yet. This study compares the osteoconductivity of CHP-OA hydrogel and another CHP nanogel, CHP-A nanogel-crosslinked PEG gel (CHP-A nanogel–hydrogel), in the bone formation induced by BMP-2 and the peptide. A calvarial defect model was performed in 5-week-old male mice, and scaffolds were placed in the defect. In vivo μCT was performed every week. Radiological and histological analyses after 4 weeks of scaffold placement revealed that the calcified bone area and the bone formation activity at the defect site in the CHP-OA hydrogel were significantly lower than those in the CHP-A hydrogel when the scaffolds were impregnated with both BMP-2 and the RANKL-binding peptide. The amount of induced bone was similar in both CHP-A and CHP-OA hydrogels when impregnated with BMP-2 alone. In conclusion, CHP-A hydrogel could be an appropriate scaffold compared to the CHP-OA hydrogel when the local bone formation was induced by the combination of RANKL-binding peptide and BMP-2, but not by BMP-2 alone.
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Guo, Wenlai, Bingbing Pei, Zehui Li, Xiao Lan Ou, Tianwen Sun, and Zhe Zhu. "PLGA-PEG-PLGA hydrogel with NEP1-40 promotes the functional recovery of brachial plexus root avulsion in adult rats." PeerJ 9 (November 1, 2021): e12269. http://dx.doi.org/10.7717/peerj.12269.
Full textAbstract:
Adult brachial plexus root avulsion can cause serious damage to nerve tissue and impair axonal regeneration, making the recovery of nerve function difficult. Nogo-A extracellular peptide residues 1-40 (NEP1-40) promote axonal regeneration by inhibiting the Nogo-66 receptor (NgR1), and poly (D, L-lactide-co-glycolide)-poly (ethylene glycol)-poly (D, L-lactide-co-glycolide) (PLGA-PEG-PLGA) hydrogel can be used to fill in tissue defects and concurrently function to sustain the release of NEP1-40. In this study, we established an adult rat model of brachial plexus nerve root avulsion injury and conducted nerve root replantation. PLGA-PEG-PLGA hydrogel combined with NEP1-40 was used to promote nerve regeneration and functional recovery in this rat model. Our results demonstrated that functional recovery was enhanced, and the survival rate of spinal anterior horn motoneurons was higher in rats that received a combination of PLGA-PEG-PLGA hydrogel and NEP1-40 than in those receiving other treatments. The combined therapy also significantly increased the number of fluorescent retrogradely labeled neurons, muscle fiber diameter, and motor endplate area of the biceps brachii. In conclusion, this study demonstrates that the effects of PLGA-PEG-PLGA hydrogel combined with NEP1-40 are superior to those of other therapies used to treat brachial plexus nerve root avulsion injury. Therefore, future studies should investigate the potential of PLGA-PEG-PLGA hydrogel as a primary treatment for brachial plexus root avulsion.
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Li, Li, Dongyu Lei, Jiaojiao Zhang, Lu Xu, Jiashan Li, Lu Jin, and Le Pan. "Dual-Responsive Alginate Hydrogel Constructed by Sulfhdryl Dendrimer as an Intelligent System for Drug Delivery." Molecules 27, no. 1 (January 3, 2022): 281. http://dx.doi.org/10.3390/molecules27010281.
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Intelligent stimulus-triggered release and high drug-loading capacity are crucial requirements for drug delivery systems in cancer treatment. Based on the excessive intracellular GSH expression and pH conditions in tumor cells, a novel glutathione (GSH) and pH dual-responsive hydrogel was designed and synthesized by conjugates of glutamic acid-cysteine dendrimer with alginate (Glu-Cys-SA) through click reaction, and then cross-linked with polyethylene glycol (PEG) through hydrogen bonds to form a 3D-net structure. The hydrogel, self-assembled by the inner disulfide bonds of the dendrimer, is designed to respond to the GSH heterogeneity in tumors, with a remarkably high drug loading capacity. The Dox-loaded Glu-Cys-SA hydrogel showed controlled drug release behavior, significantly with a release rate of over 76% in response to GSH. The cytotoxicity investigation indicated that the prepared DOX-loaded hydrogel exhibited comparable anti-tumor activity against HepG-2 cells with positive control. These biocompatible hydrogels are expected to be well-designed GSH and pH dual-sensitive conjugates or polymers for efficient anticancer drug delivery.