scholarly journals Anti-Inflammatory Properties of Injectable Betamethasone-Loaded Tyramine-Modified Gellan Gum/Silk Fibroin Hydrogels

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1456
Author(s):  
Isabel Matos Oliveira ◽  
Cristiana Gonçalves ◽  
Myeong Eun Shin ◽  
Sumi Lee ◽  
Rui Luis Reis ◽  
...  

Rheumatoid arthritis is a rheumatic disease for which a healing treatment does not presently exist. Silk fibroin has been extensively studied for use in drug delivery systems due to its uniqueness, versatility and strong clinical track record in medicine. However, in general, natural polymeric materials are not mechanically stable enough, and have high rates of biodegradation. Thus, synthetic materials such as gellan gum can be used to produce composite structures with biological signals to promote tissue-specific interactions while providing the desired mechanical properties. In this work, we aimed to produce hydrogels of tyramine-modified gellan gum with silk fibroin (Ty–GG/SF) via horseradish peroxidase (HRP), with encapsulated betamethasone, to improve the biocompatibility and mechanical properties, and further increase therapeutic efficacy to treat rheumatoid arthritis (RA). The Ty–GG/SF hydrogels presented a β-sheet secondary structure, with gelation time around 2–5 min, good resistance to enzymatic degradation, a suitable injectability profile, viscoelastic capacity with a significant solid component and a betamethasone-controlled release profile over time. In vitro studies showed that Ty–GG/SF hydrogels did not produce a deleterious effect on cellular metabolic activity, morphology or proliferation. Furthermore, Ty–GG/SF hydrogels with encapsulated betamethasone revealed greater therapeutic efficacy than the drug applied alone. Therefore, this strategy can provide an improvement in therapeutic efficacy when compared to the traditional use of drugs for the treatment of rheumatoid arthritis.

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1184
Author(s):  
Seongwon Lee ◽  
Joohee Choi ◽  
Jina Youn ◽  
Younghun Lee ◽  
Wooyoup Kim ◽  
...  

Hydrogel is in the spotlight as a useful biomaterial in the field of drug delivery and tissue engineering due to its similar biological properties to a native extracellular matrix (ECM). Herein, we proposed a ternary hydrogel of gellan gum (GG), silk fibroin (SF), and chondroitin sulfate (CS) as a biomaterial for cartilage tissue engineering. The hydrogels were fabricated with a facile combination of the physical and chemical crosslinking method. The purpose of this study was to find the proper content of SF and GG for the ternary matrix and confirm the applicability of the hydrogel in vitro and in vivo. The chemical and mechanical properties were measured to confirm the suitability of the hydrogel for cartilage tissue engineering. The biocompatibility of the hydrogels was investigated by analyzing the cell morphology, adhesion, proliferation, migration, and growth of articular chondrocytes-laden hydrogels. The results showed that the higher proportion of GG enhanced the mechanical properties of the hydrogel but the groups with over 0.75% of GG exhibited gelling temperatures over 40 °C, which was a harsh condition for cell encapsulation. The 0.3% GG/3.7% SF/CS and 0.5% GG/3.5% SF/CS hydrogels were chosen for the in vitro study. The cells that were encapsulated in the hydrogels did not show any abnormalities and exhibited low cytotoxicity. The biochemical properties and gene expression of the encapsulated cells exhibited positive cell growth and expression of cartilage-specific ECM and genes in the 0.5% GG/3.5% SF/CS hydrogel. Overall, the study of the GG/SF/CS ternary hydrogel with an appropriate content showed that the combination of GG, SF, and CS can synergistically promote articular cartilage defect repair and has considerable potential for application as a biomaterial in cartilage tissue engineering.


2021 ◽  
Vol 22 (17) ◽  
pp. 9226
Author(s):  
Lidia Gómez-Cid ◽  
María Luisa López-Donaire ◽  
Diego Velasco ◽  
Víctor Marín ◽  
María Isabel González ◽  
...  

Stem-cell-derived extracellular vesicles (EVs) have demonstrated multiple beneficial effects in preclinical models of cardiac diseases. However, poor retention at the target site may limit their therapeutic efficacy. Cardiac extracellular matrix hydrogels (cECMH) seem promising as drug-delivery materials and could improve the retention of EVs, but may be limited by their long gelation time and soft mechanical properties. Our objective was to develop and characterize an optimized product combining cECMH, polyethylene glycol (PEG), and EVs (EVs–PEG–cECMH) in an attempt to overcome their individual limitations: long gelation time of the cECMH and poor retention of the EVs. The new combined product presented improved physicochemical properties (60% reduction in half gelation time, p < 0.001, and threefold increase in storage modulus, p < 0.01, vs. cECMH alone), while preserving injectability and biodegradability. It also maintained in vitro bioactivity of its individual components (55% reduction in cellular senescence vs. serum-free medium, p < 0.001, similar to EVs and cECMH alone) and increased on-site retention in vivo (fourfold increase vs. EVs alone, p < 0.05). In conclusion, the combination of EVs–PEG–cECMH is a potential multipronged product with improved gelation time and mechanical properties, increased on-site retention, and maintained bioactivity that, all together, may translate into boosted therapeutic efficacy.


2020 ◽  
Vol 16 (11) ◽  
pp. 1588-1599
Author(s):  
Yiping Li ◽  
Ying Zhu ◽  
Shiyao Luo ◽  
Yue He ◽  
Zhewei Huang ◽  
...  

In this study, we report a new ultrashort peptide (LOC), which forms a redox-sensitive hydrogel after cross-linking with the mild oxidant H2 O2 and used it for tumor-targeted delivery of doxorubicin hydrochloride (DOX). LOC gelled within a few minutes in low-concentration H2 O2 solution. The concentration of H2 O2 significantly altered the gelation time and mechanical properties of the hydrogel. The in vitro micromorphology, secondary structure and rheology characterization of cross-linked hydrogels confirmed the sensitivity and injectability to reducing agent. The cross-linked hydrogel had a strong drug loading capacity, and the drug was released in a GSH concentration-dependent manner, following the Fick diffusion model. In addition, the cross-linked hydrogel showed no cytotoxicity to normal fibroblasts, and no damage to the subcutaneous tissue of mice was observed. In vitro cytotoxicity experiments showed that the DOX-hydrogel system exhibited good anti-cancer efficacy. In vivo studies using 4T1 tumor-bearing mice showed that the DOX-hydrogel system had a significant inhibitory effect on tumors. Therefore, the newly designed redox-sensitive hydrogel can effectively enhance the therapeutic efficacy of DOX and reduce toxicity, making it an attractive biological material.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Rossella Barenghi ◽  
Szabolcs Beke ◽  
Ilaria Romano ◽  
Paola Gavazzo ◽  
Balázs Farkas ◽  
...  

One of the main open issues in modern vascular surgery is the nonbiodegradability of implants used for stent interventions, which can lead to small caliber-related thrombosis and neointimal hyperplasia. Some new, resorbable polymeric materials have been proposed to substitute traditional stainless-steel stents, but so far they were affected by poor mechanical properties and low biocompatibility. In this respect, a new material, polypropylene fumarate (PPF), may be considered as a promising candidate to implement the development of next generation stents, due to its complete biodegradability, and excellent mechanical properties and the ease to be precisely patterned. Besides all these benefits, PPF has not been tested yet for vascular prosthesis, mainly because it proved to be almost inert, while the ability to elicit a specific biological function would be of paramount importance in such critical surgery applications. Here, we propose a biomimetic functionalization process, aimed at obtaining specific bioactivation and thus improved cell-polymer interaction. Porous PPF-based scaffolds produced by deep-UV photocuring were coated by elastin and the functionalized scaffolds were extensively characterized, revealing a stable bound between the protein and the polymer surface. Both 3T3 and HUVEC cell lines were used forin vitrotests displaying an enhancement of cells adhesion and proliferation on the functionalized scaffolds.


Nanomedicine ◽  
2021 ◽  
Author(s):  
Eleesha Sana ◽  
Mahira Zeeshan ◽  
Qurat Ul Ain ◽  
Ashraf Ullah Khan ◽  
Irshad Hussain ◽  
...  

Aim: To fabricate and evaluate curcumin-loaded transfersomes (Cur-TF) for the targeted delivery and enhanced therapeutic efficacy of curcumin for the treatment of rheumatoid arthritis (RA). Methods: Modified thin-film hydration method was used to prepare Cur-TF which were then embedded into carbopol-934 gel. They were further evaluated through in vitro techniques and in an in vivo arthritis model. Results: Cur-TF had optimal particle size, spherical morphology, high encapsulation efficiency and sustained drug release profiles. The Cur-TF gel had better in vitro skin penetration than plain curcumin. In vivo findings demonstrated improved clinical, histological and x-ray scores and reduced pro-inflammatory cytokines through NF-κβ inhibition. Conclusion: Cur-TF gel delivered curcumin to the arthritic dermal tissue through a topical route and demonstrated promising therapeutic efficacy by significantly alleviating complete Freud's adjuvant (CFA)-induced arthritis.


2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Emily Mulvany ◽  
Sara McMahan ◽  
Jiazhu Xu ◽  
Narges Yazdani ◽  
Rebecca Willits ◽  
...  

Introduction: Cardiac extracellular matrix (cECM) hydrogel has been explored to treat myocardial infarction (MI). It possesses organ specific microenvironmental cues for resident cells and can be minimally invasive delivered into the heart using a transendocardial catheter. Recent clinical studies demonstrated the safety and feasibility of using cECM for treating MI patients. However, little is known about whether the region of cardiac tissue harvesting is critical for downstream applications. We performed in vitro studies to compare cECM hydrogels derived from porcine whole heart (WH), left ventricle (LV), and right ventricle (RV). Materials and Methods: Adult porcine hearts were obtained from a local USDA approved abattoir. The tissues were separated into 3 major categories: LV, RV, and WH tissues. Following our published protocol, tissues were decellularized and solubilized. The complete decellularization was confirmed by H&E staining and DNA content measurement. Chemical composition was examined using SDS-PAGE electrophoresis as well as Collagen and GAGs measurements. The gelation time, SEM (hydrogel microstructures), and mechanical properties (storage and complex modulus) were studied. Human cardiomyocytes (CMs) and mesenchymal stem cells (MSCs) were separately seeded on the hydrogels to examine their responses. Cell viability and vascular differentiation of human MSCs were examined. Results and Discussion: The cECM from WH has more complex chemical composition compared with cECM from LV and RV. All three types of cECM hydrogels share many similarities in terms of their microstructure, gelation time and mechanical properties. WH-derived cECM hydrogels have larger variations in storage modulus (G’) and complex modulus (G*) compared with the other two types of cECM hydrogels. Both human CMs and MSCs could maintain high cell viability on all hydrogels. Regardless of harvesting sites, all cECM hydrogels have equivalent potency in directing vascular differentiation of seeded human MSCs. Conclusions: The cECM hydrogels from WH, LV and RV exhibited similarity in material properties and cell response in vitro . Future fabrication of cECM hydrogels from WH would increase the yield and decrease production cost.


Materials ◽  
2020 ◽  
Vol 13 (16) ◽  
pp. 3507
Author(s):  
Justyna Kozlowska ◽  
Weronika Prus-Walendziak ◽  
Natalia Stachowiak ◽  
Anna Bajek ◽  
Lukasz Kazmierski ◽  
...  

Because consumers are nowadays focused on their health and appearance, natural ingredients and their novel delivery systems are one of the most developing fields of pharmacy, medicine, and cosmetics. The main goal of this study was to design, prepare, and characterize composite materials obtained by incorporation of microspheres into the porous polymer materials consisting of collagen, gelatin, and hydroxyethyl cellulose. Microspheres, based on gellan gum and xanthan gum with encapsulated Calendula officinalis flower extract, were produced by two methods: extrusion and emulsification. The release profile of the extract from both types of microspheres was compared. Then, obtained microparticles were incorporated into polymeric materials with a porous structure. This modification had an influence on porosity, density, swelling properties, mechanical properties, and stability of materials. Besides, in vitro tests were performed using mouse fibroblasts. Cell viability was assessed with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The obtained materials, especially with microspheres prepared by emulsion method, can be potentially helpful when designing cosmetic forms because they were made from safely for skin ingredients used in this industry and the herbal extract was successfully encapsulated into microparticles.


RSC Advances ◽  
2017 ◽  
Vol 7 (13) ◽  
pp. 7954-7963 ◽  
Author(s):  
Yi Yang ◽  
Xili Ding ◽  
Tongqiang Zou ◽  
Ge Peng ◽  
Haifeng Liu ◽  
...  

A conductive fibrous scaffold made of silk fibroin and graphene was developed using electrospinning technique. The 3% G/SF scaffolds showed improved electroactivity and mechanical properties. Moreover, they could support the cell growth in vitro.


Author(s):  
Iulian PĂDURARU ◽  
Vasile BRIA ◽  
Adrian CÎRCIUMARU

In this paper impact resistance is a key parameter for composite materials. Composite structures can experience impact loads either accidentally in the designed life or in an anticipated hostile service environment. That is why the manufacturing technology is very important. For materials manufacture were established: the type of polymer matrix, the types of fabrics and additives which will be used to improve impact resistance and also analysis of mechanical properties of formed composite materials (bending and tensile tests). Knowledge of the mechanical properties of polymeric materials is necessary in all areas of their applicability. Thus, rigidity and mechanical strength are key properties for most applications in which polymeric matrix composites are used.


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