scholarly journals Affinity-Controlled Double-Network Hydrogel Facilitates Long-Term Release of Anti-Human Papillomavirus Protein

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1298
Author(s):  
Chenjia Zhao ◽  
Jingyuan Ji ◽  
Tianjun Yin ◽  
Jing Yang ◽  
Yuan Pang ◽  
...  

Hydrogels have recently received attention as delivery carriers owing to their good biocompatibility and structural similarity to natural extracellular matrices. However, the utilization of traditional single-network (SN) hydrogels is limited by poor mechanical properties and burst drug release. Therefore, we developed a novel double-network (DN) hydrogel, which employs an alginate (ALG)/polyethylene glycol diacrylate (PEGDA) network to adjust the mechanical strength and a positively charged monomer AETAC (2-(acryloyloxy)ethyl]trimethyl-ammonium chloride) to regulate the release curve of the electronegative anti-human papillomavirus (HPV) protein (bovine β-lactoglobulin modified with 3-hydroxyphthalic anhydride) based on an affinity-controlled delivery mechanism. The results show that the double-network hydrogel strongly inhibits the burst release, and the burst release amount is about one-third of that of the single-network hydrogel. By changing the concentration of the photoinitiator, the mechanical strength of the DN hydrogels can be adjusted to meet the stiffness requirements for various tissues within the range of 0.71 kPa to 10.30 kPa. Compared with the SN hydrogels, the DN hydrogels exhibit almost twice the mechanical strength and have smaller micropores. Cytotoxicity tests indicated that these SN and DN hydrogels were not cytotoxic with the result of over 100% relative proliferation rate of the HUVECs. Furthermore, DN hydrogels can significantly alleviate the burst release of antiviral proteins and prolong the release time to more than 14 days. Finally, we utilized digital light processing (DLP) technology to verify the printability of the DN hydrogel. Our study indicates that ALG/PEGDA-AETAC DN hydrogels could serve as platforms for delivering proteins and show promise for diverse tissue engineering applications.

2022 ◽  
Vol 12 (2) ◽  
pp. 771
Author(s):  
Anusha Wei Asohan ◽  
Rokiah Hashim ◽  
Ku Marsilla Ku Ishak ◽  
Zuratul Ain Abdul Hamid ◽  
Nurshafiqah Jasme ◽  
...  

In this study, we aimed to prepare and characterise hydrogel formulations using cellulose nanocrystals (CNCs), alginate (Alg), and polyethylene glycol diacrylate (PEGDA). The CNC/Alg/PEGDA formulations were formed using a double network crosslinking approach. Firstly, CNC was extracted from oil palm trunk, and the size and morphology of the CNCs were characterised using TEM analysis. Secondly, different formulations were prepared using CNCs, Alg, and PEGDA. The mixtures were crosslinked with Ca2+ ions and manually extruded using a syringe before being subjected to UV irradiation at 365 nm. The shear-thinning properties of the formulations were tested prior to any crosslinking, while the determination of storage and loss modulus was conducted post extrusion after the Ca2+ ion crosslink using a rheometer. For the analysis of swelling behaviour, the constructs treated with UV were immersed in PBS solution (pH 7.4) for 48 h. The morphology of the UV crosslinked construct was analysed using SEM imaging. The extracted CNC exhibited rod-like structures with an average diameter and length of around 7 ± 2.4 and 113 ± 20.7 nm, respectively. Almost all CNC/Alg/PEGDA formulations (pre-gel formulation) displayed shear-thinning behaviour with the power-law index η < 1, and the behaviour was more prominent in the 1% [w/v] Alg formulations. The CNC/Alg/PEGDA with 2.5% and 4% [w/v] Alg displayed a storage modulus dominance over loss modulus (G′ > G″) which suggests good shape fidelity. After the hydrogel constructs were subjected to UV treatment at 365 nm, only the F8 construct [4% CNC: 4% Alg: 40% PEGDA] demonstrated tough and flexible characteristics that possibly mimic the native articular cartilage property due to a similar water content percentage (79.5%). In addition, the small swelling ratio of 4.877 might contribute to a minimal change of the 3D construct’s geometry. The hydrogel revealed a rough and wavy surface, and the pore size ranged from 3 to 20 µm. Overall, the presence of CNCs in the double network hydrogel demonstrated importance and showed positive effects towards the fabrication of a potentially ideal 3D bioprinted scaffold.


Polymers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 845
Author(s):  
Xin Yang ◽  
Bronwin Dargaville ◽  
Dietmar Hutmacher

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.


Micromachines ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 293
Author(s):  
José M. Acosta-Cuevas ◽  
José González-García ◽  
Mario García-Ramírez ◽  
Víctor H. Pérez-Luna ◽  
Erick Omar Cisneros-López ◽  
...  

Photopolymerized microparticles are made of biocompatible hydrogels like Polyethylene Glycol Diacrylate (PEGDA) by using microfluidic devices are a good option for encapsulation, transport and retention of biological or toxic agents. Due to the different applications of these microparticles, it is important to investigate the formulation and the mechanical properties of the material of which they are made of. Therefore, in the present study, mechanical tests were carried out to determine the swelling, drying, soluble fraction, compression, cross-linking density (Mc) and mesh size (ξ) properties of different hydrogel formulations. Tests provided sufficient data to select the best formulation for the future generation of microparticles using microfluidic devices. The initial gelation times of the hydrogels formulations were estimated for their use in the photopolymerization process inside a microfluidic device. Obtained results showed a close relationship between the amount of PEGDA used in the hydrogel and its mechanical properties as well as its initial gelation time. Consequently, it is of considerable importance to know the mechanical properties of the hydrogels made in this research for their proper manipulation and application. On the other hand, the initial gelation time is crucial in photopolymerizable hydrogels and their use in continuous systems such as microfluidic devices.


Author(s):  
Jinhui Zhang ◽  
Eiji Kamio ◽  
Masayuki Kinoshita ◽  
Atsushi Matsuoka ◽  
Keizo Nakagawa ◽  
...  

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 55
Author(s):  
Cheolheon Park ◽  
Junghyun Bae ◽  
Yeongjae Choi ◽  
Wook Park

We demonstrate that it is possible to produce microparticles with high deformability while maintaining a high effective volume. For significant particle deformation, a particle must have a void region. The void fraction of the particle allows its deformation under shear stress. Owing to the importance of the void fraction in particle deformation, we defined an effective volume index (V*) that indicates the ratio of the particle’s total volume to the volumes of the void and material structures. We chose polyethylene glycol diacrylate (Mn ~ 700) for the fabrication of the microparticles and focused on the design of the particles rather than the intrinsic softness of the material (E). We fabricated microparticles with four distinct shapes: discotic, ring, horseshoe, and spiral, with various effective volume indexes. The microparticles were subjected to shear stress as they were pushed through a tapered microfluidic channel to measure their deformability. The deformation ratio R was introduced as R = 1−Wdeformed/Doriginal to compare the deformability of the microparticles. We measured the deformation ratio by increasing the applied pressure. The spiral-shaped microparticles showed a higher deformation ratio (0.901) than those of the other microparticles at the same effective volume index.


TECHNOLOGY ◽  
2014 ◽  
Vol 02 (02) ◽  
pp. 144-152 ◽  
Author(s):  
Peng Xue ◽  
David Chen Loong Yeo ◽  
Yon Jin Chuah ◽  
Hong Liang Tey ◽  
Yuejun Kang ◽  
...  

Keloid is a long-term dermatological scarring disease characterized by disfiguring lesions resulting from overgrowth of dense fibrous tissue. Current therapeutics are ineffective, require clinical supervision and can be costly. This study investigated the use of microneedle technology in the self-management of keloid lesions. Specifically, a microneedle patch comprising of polyethylene glycol diacrylate (PEGDA) and encapsulating 5-fluorouracil (5-FU) has been developed for transdermal delivery. The microneedle patches showed requisite mechanical strength (hardness 45 ± 11 MPa, elastic modulus 0.66 ± 0.16 GPa) and were able to puncture porcine epidermis. The choice of PEGDA substrate enabled conformability to non-planar anatomical regions (e.g. elbow), with about 50% of the loaded 5-FU released during the first 12 hours. Thereafter, the microneedle efficacy was evaluated on in vitro keloid fibroblast culture models, where 5-FU loaded microneedles effectively abolished keloid fibroblast proliferation activity. In summary, we have developed a microneedle device with a good potential as an effective, economical and self-applied therapy for keloid scars.


Polymers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1263 ◽  
Author(s):  
June-Yo Chen ◽  
Joanne Hwang ◽  
Wai-Sam Ao-Ieong ◽  
Yung-Che Lin ◽  
Yi-Kong Hsieh ◽  
...  

As acrylated polymers become more widely used in additive manufacturing, their potential applications toward biomedicine also raise the demand for biodegradable, photocurable polymeric materials. Polycaprolactone diacrylate (PCLDA) and poly(ethylene glycol) diacrylate (PEGDA) are two popular choices of materials for stereolithography (SLA) and digital light processing additive manufacturing (DLP-AM), and have been applied to many biomedical related research. However, both materials are known to degrade at a relatively low rate in vivo, limiting their applications in biomedical engineering. In this work, biodegradable, photocurable copolymers are introduced by copolymerizing PCLDA and/or PEGDA with poly(glycerol sebacate) acrylate (PGSA) to form a network polymer. Two main factors are discussed: the effect of degree of acrylation in PGSA and the weight ratio between the prepolymers toward the mechanical and degradation properties. It is found that by blending prepolymers with various degree of acrylation and at various weight ratios, the viscosity of the prepolymers remains stable, and are even more 3D printable than pure substances. The formation of various copolymers yielded a database with selectable Young’s moduli between 0.67–10.54 MPa, and the overall degradation rate was significantly higher than pure substance. In addition, it is shown that copolymers fabricated by DLP-AM fabrication presents higher mechanical strength than those fabricated via direct UV exposure. With the tunable mechanical and degradation properties, the photocurable, biodegradable copolymers are expected to enable a wider application of additive manufacturing toward tissue engineering.


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