Complexation of CXCL12, FGF-2 and VEGF with Heparin Modulates the Protein Release from Alginate Microbeads.
Ontology highlight
ABSTRACT:
SUBMITTER: Adrian E
PROVIDER: S-EPMC8583835 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Periodontitis is one of the most common infectious diseases globally that, if untreated, leads to destruction of the tooth supporting tissues and finally results in tooth loss. Evidence shows that standard procedures as mechanical root cleaning could be supported by further treatment options such as locally applied substances. Due to gingival crevicular fluid flow, substances are commonly washed out off the periodontal pockets. The evaluation of administration techniques and the development of local drug releasing devices is thus an important aspect in periodontal research. This study describes the development and examination of a new alginate based, biodegradable and easily applicable drug delivery system for chlorhexidine (CHX). Different micro beads were produced and loaded with CHX and the release profiles were investigated by high performance liquid chromatography (HPLC). The in vitro-demonstrated release of CHX from alginate based beads shows comparable releasing characteristics as clinically approved systems. Yet many characteristics of this new delivery system show to be favourable for periodontal therapy. Easy application by injection, low production costs and multifunctional adaptions to patient related specifics may improve the usage in routine care.
| S-EPMC5626444 | biostudies-other
Project description:Host reactivity to biocompatible immunoisolation devices is a major challenge for cellular therapies, and a human screening model would be of great value. We designed new types of surface modified barium alginate microspheres, and evaluated their inflammatory properties using human whole blood, and the intraperitoneal response after three weeks in Wistar rats. Microspheres were modified using proprietary polyallylamine (PAV) and coupled with macromolecular heparin conjugates (Corline Heparin Conjugate, CHC). The PAV-CHC strategy resulted in uniform and stable coatings with increased anti-clot activity and low cytotoxicity. In human whole blood, PAV coating at high dose (100 µg/ml) induced elevated complement, leukocyte CD11b and inflammatory mediators, and in Wistar rats increased fibrotic overgrowth. Coating of high dose PAV with CHC significantly reduced these responses. Low dose PAV (10 µg/ml) ± CHC and unmodified alginate microbeads showed low responses. That the human whole blood inflammatory reactions paralleled the host response shows a link between inflammatory potential and initial fibrotic response. CHC possessed anti-inflammatory activity, but failed to improve overall biocompatibility. We conclude that the human whole blood assay is an efficient first-phase screening model for inflammation, and a guiding tool in development of new generation microspheres for cell encapsulation therapy.
| S-EPMC5600981 | biostudies-literature
Project description:Alginate hydrogels have been investigated for a broad variety of medical applications. The ability to assemble hydrogels at neutral pH and mild temperatures makes alginate a popular choice for the encapsulation and delivery of cells and proteins. Alginate has been studied extensively for the delivery of islets as a treatment for type 1 diabetes. However, poor stability of the encapsulation systems after implantation remains a challenge. In this paper, alginate was modified with 2-aminoethyl methacrylate hydrochloride (AEMA) to introduce groups that can be photoactivated to generate covalent bonds. This enabled formation of dual crosslinked structure upon exposure to ultraviolet light following initial ionic crosslinking into bead structures. The degree of methacrylation was varied and in vitro stability, long term swelling, and cell viability examined. At low levels of the methacrylation, the beads could be formed by first ionic crosslinks followed by exposure to ultraviolet light to generate covalent bonds. The methacrylated alginate resulted in more stable beads and cells were viable following encapsulation. Alginate microbeads, ionic (unmodified) and dual crosslinked, were implanted into a rat omentum pouch model. Implantation was performed with a local injection of 100?µl of 50?µg/ml of Lipopolysaccharide (LPS) to stimulate a robust inflammatory challenge in vivo. Implants were retrieved at 1 and 3?weeks for analysis. The unmodified alginate microbeads had all failed by week 1, whereas the dual-crosslinked alginate microbeads remained stable up through 3?weeks. The modified alginate microbeads may provide a more stable alternative to current alginate-based systems for cell encapsulation. STATEMENT OF SIGNIFICANCE:Alginate, a naturally occurring polysaccharide, has been used for cell encapsulation to prevent graft rejection of cell transplants for people with type I diabetes. Although some success has been observed in clinical trials, the lack of reproducibility and failure to reach insulin dependence for longer periods of time indicates the need for improvements in the procedure. A major requirement for the long-term function of alginate encapsulated cells is the mechanical stability of microcapsules. Insufficient mechanical integrity of the capsules can lead to immunological reactions in the recipients. In this work, alginate was modified to allow photoactivatable groups in order to allow formation of covalent crosslinks in addition to ionic crosslinking. The dual crosslinking design prevents capsule breakdown following implantation in vivo.
| S-EPMC5902406 | biostudies-literature
Project description:Lymphatic dysfunction is associated with the progression of many cardiovascular disorders due to their role in maintaining tissue fluid homeostasis. Promoting new lymphatic vessels (lymphangiogenesis) is a promising strategy to reverse these cardiovascular disorders via restoring lymphatic function. Vascular endothelial growth factor (VEGF) members VEGF-C and VEGF-D are both potent candidates for stimulating lymphangiogenesis, though maintaining spatial and temporal control of these factors represents a challenge to developing efficient therapeutic lymphangiogenic applications. Injectable alginate hydrogels have been useful for the controlled delivery of many angiogenic factors, including VEGF-A, to stimulate new blood vasculature. However, the utility of these tunable hydrogels for delivering lymphangiogenic factors has never been closely examined. Thus, the objective of this study was to utilize ionically cross-linked alginate hydrogels to deliver VEGF-C and VEGF-D for potential lymphangiogenic applications. We demonstrated that lymphatic endothelial cells (LECs) are sensitive to temporal presentation of VEGF-C and VEGF-D but with different responses between the factors. The greatest LEC mitogenic and sprouting response was observed for constant concentrations of VEGF-C and a high initial concentration that gradually decreased over time for VEGF-D. Additionally, alginate hydrogels provided sustained release of radiolabeled VEGF-C and VEGF-D. Finally, VEGF-C and VEGF-D released from these hydrogels promoted a similar number of LEC sprouts as exogenously added growth factors and new vasculature in vivo via a chick chorioallantoic membrane (CAM) assay. Overall, these findings demonstrate that alginate hydrogels can provide sustained and bioactive release of VEGF-C and VEGF-D which could have applications for therapeutic lymphangiogenesis.
| S-EPMC5517064 | biostudies-other
Project description:Quorum sensing, in which bacteria communities use signaling molecules for inter- and intracellular communication, has been intensively studied in recent decades. In order to fabricate highly sensitive easy-to-handle point of care biosensors that detect quorum sensing molecules, we have developed, as is reported here, reporter bacteria loaded alginate-methacrylate (alginate-MA) hydrogel beads. The alginate-MA beads, which were obtained by electrostatic extrusion, were reinforced by photo-cross-linking to increase stability and thereby to reduce bacteria leaching. In these beads the genetically engineered fluorescent reporter bacterium Escherichia coli pTetR-LasR-pLuxR-GFP (E. coli pLuxR-GFP) was encapsulated, which responds to the autoinducer N-(3-oxododecanoyl)homoserine lactone secreted by Pseudomonas aeruginosa. After encapsulation in alginate-MA hydrogel beads with diameters in the range of 100-300 μm that were produced by an electrostatic extrusion method and rapid photo-cross-linking, the E. coli pLuxR-GFP were found to possess a high degree of viability and sensing activity. The encapsulated bacteria could proliferate inside the hydrogel beads, when exposed to bacteria culture medium. In media containing the autoinducer N-(3-oxododecanoyl)homoserine lactone, the encapsulated reporter bacteria responded with a strong fluorescence signal due to an increased green fluorescent protein (GFP) expression. A prototype dipstick type sensor developed here underlines the potential of encapsulation of viable and functional reporter bacteria inside reinforced alginate-methacrylate hydrogel beads for whole cell sensors for bacteria detection.
| S-EPMC5741077 | biostudies-literature
Project description:Grape pomace is a byproduct of wineries and a sustainable source of bioactive phenolic compounds. Encapsulation of phenolics with a well-chosen coating may be a promising means of delivering them to the intestine, where they can then be absorbed and exert their health-promoting properties, including antioxidant, anti-inflammatory, anticancer, cardioprotective, and antimicrobial effects. Ionic gelation of grape pomace extract with natural coatings (sodium alginate and its combination with maltodextrins, gelatin, chitosan, gums Tragacanth and Arabic) was performed, and the resulting hydrogel microbeads were then air-, vacuum-, and freeze-dried to prevent spoilage. Freeze-drying showed advantages in preserving the geometrical parameters and morphology of the microbeads compared to other drying techniques. A good relationship was found between the physicochemical properties of the dried microbeads and the in vitro release of phenolics. Freeze-dried microbeads showed the highest cumulative release of phenols in the intestinal phase (23.65-43.27 mgGAE/gMB), while the most suitable release dynamics in vitro were observed for alginate-based microbeads in combination with gelatin, gum Arabic, and 1.5% (w/v) chitosan. The results highlight the importance of developing encapsulated formulations containing a natural source of bioactive compounds that can be used in various functional foods and pharmaceutical products.
| S-EPMC10671312 | biostudies-literature
Project description:Myocardial infarction (MI) is one of cardiovascular diseases that pose a serious threat to human health. The pathophysiology of MI is complex and contains several sequential phases including blockage of a coronary artery, necrosis of myocardial cells, inflammation, and myocardial fibrosis. Aiming at the treatment of different stages of MI, in this work, an injectable alginate based composite hydrogel is developed to load vascular endothelial active factor (VEGF) and silk fibroin (SF) microspheres containing bone morphogenetic protein 9 (BMP9) for releasing VEGF and BMP9 to realize their respective functions. The results of in vitro experiments indicate a rapid initial release of VEGF during the first few days and a relatively slow and sustained release of BMP9 for days, facilitating the formation of blood vessels in the early stage and inhibiting myocardial fibrosis in the long-term stage, respectively. Intramyocardial injection of such composite hydrogel into the infarct border zone of mice MI model via multiple points promotes angiogenesis and reduces the infarction size. Taken together, these results indicate that the dual-release of VEGF and BMP9 from the composite hydrogel results in a collaborative effect on the treatment of MI and improvement of heart function, showing a promising potential for cardiac clinical application. Graphical abstract Image 1 Highlights • An injectable alginate based composite hydrogel containing VEGF and silk fibroin microspheres encapsulated with BMP9 was developed. .• The composite hydrogel could rapidly release VEGF to facilitate angiogenesis in the early stage of myocardial infarction and then sustainably release BMP9 to inhibit fibrosis formation in the long-term stage of myocardial infarction, respectively. .• Injection of this composite hydrogel could effectively accelerate the vessel formation and inhibit the fibrosis formation in a myocardial infarction mouse model to improve cardiac functions.
| S-EPMC7492819 | biostudies-literature
Project description:Functional tissue regeneration using synthetic biomaterials requires proliferation and heterotypic differentiation of stem/progenitor cells within a specialized heterogeneous (biophysical-biochemical) microenvironment. The current techniques have limitations to develop synthetic hydrogels, mimicking native extracellular matrix porosity along with heterogeneous microenvironmental cues of matrix mechanics, degradability, microstructure and cell-cell interactions. Here, we have developed a microenvironment modulating system to fabricate in situ porous hydrogel matrix with two or more distinct tailored microenvironmental niches within microbeads and the hydrogel matrix for multicellular tissue regeneration. Electrosprayed pectin-gelatin blended microbeads and crosslinked alginate hydrogel system help to tailor microenvironmental niches of encapsulated cells where two different cells are surrounded by a specific microenvironment. The effect of different microenvironmental parameters associated with the microbead/hydrogel matrix was evaluated using human umbilical-cord mesenchymal stem cells (hUCMSCs). The osteogenic differentiation of hUCMSCs in the hydrogel matrix was evaluated for bone tissue regeneration. This will be the first report on microenvironment modulating microbead-hydrogel system to encapsulate two/more types of cells in a hydrogel, where each cell is surrounded with distinct niches for heterogeneous tissue regeneration.
| S-EPMC8271062 | biostudies-literature
Project description:Imaging pHe of the tumor microenvironment has paramount importance for characterizing aggressive, invasive tumors, as well as therapeutic responses. Here, a robust approach to image pH changes in the tumor microenvironment longitudinally and during sodium bicarbonate treatment was reported. The pH-sensing microbeads were designed and prepared based on materials approved for clinical use, i.e., alginate microbead-containing computed tomography (CT) contrast-agent (iopamidol)-loaded liposomes (Iop-lipobeads). This Iop-lipobead prepared using a customized microfluidic device generated a CEST contrast of 10.6% at 4.2 ppm at pH 7.0, which was stable for 20 days in vitro. The CEST contrast decreased by 11.8% when the pH decreased from 7.0 to 6.5 in vitro. Optimized Iop-lipobeads next to tumors showed a significant increase of 19.7 ± 6.1% (p < 0.01) in CEST contrast at 4.2 ppm during the first 3 days of treatment and decreased to 15.2 ± 4.8% when treatment stopped. Notably, percentage changes in Iop-lipobeads were higher than that of amide CEST (11.7% and 9.1%) in tumors during and after treatment. These findings demonstrated that the Iop-lipobead could provide an independent and sensitive assessment of the pHe changes for a noninvasive and longitudinal monitoring of the treatment effects using multiple CEST contrast.
| S-EPMC9756293 | biostudies-literature
Project description:Smart hydrogels that can respond to external stimuli such as temperature and pH have attracted tremendous interest for biological and biomedical applications. In this work, we synthesized two alginate-graft-poly(N-isopropylacrylamide) (Alg-g-PNIPAAm) copolymers and aimed to prepare smart hydrogels through formation of polyelectrolyte complex (PEC) between the negatively charged Alg-g-PNIPAAm copolymers and the positively charged chitosan (Cts) in aqueous solutions. The hydrogels were expected to be able to respond to both temperature and pH changes due to the nature of Alg-g-PNIPAAm and chitosan. The hydrogel formation was determined by a test tube inverting method and confirmed by the rheological measurements. The rheological measurements showed that the PEC hydrogels formed at room temperature could be further enhanced by increasing temperature over the lower critical solution temperature (LCST) of PNIPAAm, because PNIPAAm would change from hydrophilic to hydrophobic upon increasing temperature over its LCST, and the hydrophobic interaction between the PNIPAAm segments may act as additional physical crosslinking. The controlled release properties of the hydrogels were studied by using the organic dye rhodamine B (RB) as a model drug at different pH. The PEC hydrogels could sustain the RB release more efficiently at neutral pH. Both low pH and high pH weakened the PEC hydrogels, and resulted in less sustained release profiles. The release kinetics data were found to fit well to the Krosmyer-Peppas power law model. The analysis of the release kinetic parameters obtained by the modelling indicates that the release of RB from the PEC hydrogels followed mechanisms combining diffusion and dissolution of the hydrogels, but the release was mainly governed by diffusion with less dissolution at pH 7.4 when the PEC hydrogels were stronger and stabler than those at pH 5.0 and 10.0. Therefore, the PEC hydrogels are a kind of smart hydrogels holding great potential for drug delivery applications.
| S-EPMC9315676 | biostudies-literature