scholarly journals 3D Encapsulation Made Easy: A Coaxial-Flow Circuit for the Fabrication of Hydrogel Microfibers Patches

2019 ◽  
Vol 6 (2) ◽  
pp. 30 ◽  
Author(s):  
Chiara Campiglio ◽  
Francesca Ceriani ◽  
Lorenza Draghi

To fully exploit the potential of hydrogel micro-fibers in the design of regenerative medicinal materials, we designed a simple, easy to replicate system for cell embedding in degradable fibrous scaffolds, and validated its effectiveness using alginate-based materials. For scaffold fabrication, cells are suspended in a hydrogel-precursor and injected in a closed-loop circuit, where a pump circulates the ionic cross-linking solution. The flow of the cross-linking solution stretches and solidifies a continuous micro-scaled, cell-loaded hydrogel fiber that whips, bends, and spontaneously assembles in a self-standing, spaghetti-like patch. After investigation and tuning of process- and solution-related parameters, homogeneous microfibers with controlled diameters and consistent scaffolds were obtained from different alginate concentrations and blends with biologically favorable macromolecules (i.e., gelatin or hyaluronic acid). Despite its simplicity, this coaxial-flow encapsulation system allows for the rapid and effortless fabrication of thick, well-defined scaffolds, with viable cells being homogeneously distributed within the fibers. The reduced fiber diameter and the inherent macro-porous structure that is created from the random winding of fibers can sustain mass transport, and support encapsulated cell survival. As different materials and formulations can be processed to easily create homogeneously cell-populated structures, this system appears as a valuable platform, not only for regenerative medicine, but also, more in general, for 3D cell culturing in vitro.

Polymers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1138
Author(s):  
Lixuan Wang ◽  
Shiyan Dong ◽  
Yutong Liu ◽  
Yifan Ma ◽  
Jingjing Zhang ◽  
...  

Injectable hydrogels have been widely applied in the field of regenerative medicine. However, current techniques for injectable hydrogels are facing a challenge when trying to generate a biomimetic, porous architecture that is well-acknowledged to facilitate cell behaviors. In this study, an injectable, interconnected, porous hyaluronic acid (HA) hydrogel based on an in-situ bubble self-generation and entrapment process was developed. Through an amide reaction between HA and cystamine dihydrochloride activated by EDC/NHS, CO2 bubbles were generated and were subsequently entrapped inside the substrate due to a rapid gelation-induced retention effect. HA hydrogels with different molecular weights and concentrations were prepared and the effects of the hydrogel precursor solution’s concentration and viscosity on the properties of hydrogels were investigated. The results showed that HA10-10 (10 wt.%, MW 100,000 Da) and HA20-2.5 (2.5 wt.%, MW 200,000 Da) exhibited desirable gelation and obvious porous structure. Moreover, HA10-10 represented a high elastic modulus (32 kPa). According to the further in vitro and in vivo studies, all the hydrogels prepared in this study show favorable biocompatibility for desirable cell behaviors and mild host response. Overall, such an in-situ hydrogel with a self-forming bubble and entrapment strategy is believed to provide a robust and versatile platform to engineer injectable hydrogels for a variety of applications in tissue engineering, regenerative medicine, and personalized therapeutics.


2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Assunta Borzacchiello ◽  
Luisa Russo ◽  
Birgitte M. Malle ◽  
Khadija Schwach-Abdellaoui ◽  
Luigi Ambrosio

Hyaluronic acid (HA) hydrogels, obtained by cross-linking HA molecules with divinyl sulfone (DVS) based on a simple, reproducible, and safe process that does not employ any organic solvents, were developed. Owing to an innovative preparation method the resulting homogeneous hydrogels do not contain any detectable residual cross-linking agent and are easier to inject through a fine needle. HA hydrogels were characterized in terms of degradation and biological properties, viscoelasticity, injectability, and network structural parameters. They exhibit a rheological behaviour typical of strong gels and show improved viscoelastic properties by increasing HA concentration and decreasing HA/DVS weight ratio. Furthermore, it was demonstrated that processes such as sterilization and extrusion through clinical needles do not imply significant alteration of viscoelastic properties. Both SANS and rheological tests indicated that the cross-links appear to compact the network, resulting in a reduction of the mesh size by increasing the cross-linker amount. In vitro degradation tests of the HA hydrogels demonstrated that these new hydrogels show a good stability against enzymatic degradation, which increases by increasing HA concentration and decreasing HA/DVS weight ratio. Finally, the hydrogels show a good biocompatibility confirmed by in vitro tests.


Author(s):  
Enrico Tognana ◽  
Lanfranco Callegaro

Tissue engineering strategies have recently emerged as the most advanced therapeutic option presently available in regenerative medicine. Tissue engineering encompasses the use of cells and their molecules in artificial constructs that compensate for lost or impaired body functions. It is based upon scaffoldguided tissue regeneration and involves the seeding of porous, biodegradable scaffolds with donor cells, which become differentiated and mimic naturally occurring tissues. These tissue-engineered constructs are then implanted into the patient to replace diseased or damaged tissues. Our approach to regenerative medicine is based on hyaluronan derivative polymers. HYAFF® is a class of hyaluronan derivative polymers obtained by coupling reaction. The strategy behind the creation of these polymers was to improve the stability of the polymer by esterifying the free carboxyl group of glucuronic acid, frequently repeated along the hyaluronic acid chain, with different types of alcohols. Once esterification of the polymer has been obtained, the material can easily be processed to produce membranes, fibres, sponges, microspheres and other devices, by extrusion, lyophilization or spray drying. A broad variety of polymers can be subsequently generated either by changing the type of ester group introduced or the extent of the esterification. The benzyl esters of hyaluronan, termed HYAFF®-11, are one of the most characterized HYAFF® polymers, from both the physicochemical and biological viewpoints, produced starting from hyaluronan of about 200 KDa. The ideal scaffold for tissue engineering should provide an immediate support to cells and have mechanical properties matching those of the tissue being repaired. Gradually then the material should be resorbed, as the cells begin secreting their own extracellular matrix, thus allowing for an optimal integration between newformed and existing tissue. Extensive biocompatibility studies have demonstrated the safety of HYAFF® scaffolds and their ability to be resorbed in the absence of an inflammatory response. Moreover, when implanted tend to promote the recapitulation of the events that facilitate tissue repair. HYAFF®-11 three-dimensional matrices support the in vitro growth of highly viable chondrocytes and fibroblasts. Similarly, micro-perforated membrane supports the growth and differentiation of keratinocytes. These cells, previously expanded on plastic and hence seeded into the HYAFF® scaffold, produce a characteristic extracellular matrix rich in proteoglycans expressing the typical markers of the tissues of their origin. Hyaluronan presents a variety of multi-functional activity being both a structural and informational molecule. Investigation of hyaluronan synthesis and degradation, the identification of new receptors and binding proteins and the elucidation of hyaluronan-dependent signaling pathways keep providing novel insights into the true biological functions of this intriguing polymer. The possibility to elaborate this natural polymer in different physical forms, as HYAFF® biopolymers family is allowing to do, has given the opportunity to translate tissue engineering strategies in clinical practice providing a biomaterial that induces and modulates the sequence of events that lead to damage tissue restoration. The following chapter will report how tissue engineering approach and hyaluronic acid technology could improve the biological function of cell transplantation in the treatment of tissue defects, in particular for skin and cartilage tissue restoration.


2021 ◽  
Vol 22 (5) ◽  
Author(s):  
Shahla Mirzaeei ◽  
Shiva Taghe ◽  
Kofi Asare-Addo ◽  
Ali Nokhodchi

AbstractA novel nanofiber insert was prepared with a modified electrospinning method to enhance the ocular residence time of ofloxacin (OFX) and to provide a sustained release pattern by covering hydrophilic polymers, chitosan/polyvinyl alcohol (CS/PVA) nanofibers, with a hydrophobic polymer, Eudragit RL100 in layers, and by glutaraldehyde (GA) cross-linking of CS-PVA nanofibers for the treatment of infectious conjunctivitis. The morphology of the prepared nanofibers was studied using scanning electron microscopy (SEM). The average fiber diameter was found to be 123 ± 23 nm for the single electrospun nanofiber with no cross-linking (OFX-O). The single nanofibers, cross-linked for 10 h with GA (OFX-OG), had an average fiber diameter of 159 ± 30 nm. The amount of OFX released from the nanofibers was measured in vitro and in vivo using UV spectroscopy and microbial assay methods against Staphylococcus aureus, respectively. The antimicrobial efficiency of OFX formulated in cross-linked and non-cross-linked nanofibers was affirmed by observing the inhibition zones of Staphylococcus aureus and Escherichia coli. In vivo studies using the OFX nanofibrous inserts on a rabbit eye confirmed a sustained release pattern for up to 96 h. It was found that the cross-linking of the nanofibers by GA vapor could reduce the burst release of OFX from OFX-loaded CS/PVA in one layer and multi-layered nanofibers. In vivo results showed that the AUC0–96 for the nanofibers was 9–20-folds higher compared to the OFX solution. This study thus demonstrates the potential of the nanofiber technology is being utilized to sustained drug release in ocular drug delivery systems.


2019 ◽  
Vol 34 (4-5) ◽  
pp. 321-330
Author(s):  
Hyeong Sup Yu ◽  
Mijin Koo ◽  
Sung-Wook Choi ◽  
Kun Na ◽  
Kyung Taek Oh ◽  
...  

In this study, we designed and synthesized polysaccharidic nanogels comprising starch cross-linked with hyaluronic acid. These hyaluronated starch nanogels were prepared by cross-linking primary hydroxyl groups in polysaccharides (starch and hyaluronic acid) and epoxide groups in 1,4-butanediol diglycidyl ether (used as a cross-linking agent). The nanogels take advantage of hyaluronic acid as a specific ligand for CD44 receptors overexpressed on tumors and the hyaluronic acid/starch core as a compartment for the encapsulation of docetaxel (as model antitumor drug). Here, hyaluronic acid can be enzymatically degraded by tumor cell–specific enzyme (e.g. hyaluronidase-1), which could significantly accelerate docetaxel release from the nanogels. Our experimental results demonstrate that the nanogels promote the release of docetaxel content in the presence of hyaluronidase-1 enzyme. As a result, the nanogels selectively inhibited MCF-7 (with CD44 receptor and hyaluronidase-1 enzyme) tumor cell growth in vitro, suggesting their therapeutic potential for efficient tumor ablation.


1997 ◽  
Vol 77 (05) ◽  
pp. 0959-0963 ◽  
Author(s):  
Lisa Seale ◽  
Sarah Finney ◽  
Roy T Sawyer ◽  
Robert B Wallis

SummaryTridegin is a potent inhibitor of factor Xllla from the leech, Haementeria ghilianii, which inhibits protein cross-linking. It modifies plasmin-mediated fibrin degradation as shown by the absence of D-dimer and approximately halves the time for fibrinolysis. Plasma clots formed in the presence of Tridegin lyse more rapidly when either streptokinase, tissue plasminogen activator or hementin is added 2 h after clot formation. The effect of Tridegin is markedly increased if clots are formed from platelet-rich plasma. Platelet-rich plasma clots are lysed much more slowly by the fibrinolytic enzymes used and if Tridegin is present, the rate of lysis returns almost to that of platelet- free clots. These studies indicate the important role of platelets in conferring resistance to commonly used fibrinolytic enzymes and suggest that protein cross-linking is an important step in this effect. Moreover they indicate that Tridegin, a small polypeptide, may have potential as an adjunct to thrombolytic therapy.


2019 ◽  
Author(s):  
Yong Mao ◽  
Tyler Hoffman ◽  
Sandeep Dhall ◽  
Amit Singal ◽  
Malathi Sathyamoorthy ◽  
...  

2019 ◽  
Vol 13 (2) ◽  
pp. 114-128 ◽  
Author(s):  
Gayatri Patel ◽  
Bindu K.N. Yadav

Background: The purpose of this study was to formulate, characterize and conduct in vitro cytotoxicity of 5-fluorouracil loaded polymeric electrospun nanofibers for the treatment of skin cancer. The patents on electrospun nanofibers (US9393216B2), (US14146252), (WO2015003155A1) etc. helped in the selection of polymers and method for the preparation of nanofibers. Methods: In the present study, the fabrication of nanofibers was done using a blend of chitosan with polyvinyl alcohol and processed using the electrospinning technique. 5-fluorouracil with known chemotherapeutic potential in the treatment of skin cancer was used as a drug carrier. 24-1 fractional factorial screening design was employed to study the effect of independent variables like the concentration of the polymeric solution, applied voltage (kV), distance (cm), flow rate (ml / hr) on dependent variables like % entrapment efficiency and fiber diameter. Results: Scanning electron microscopy was used to characterize fiber diameter and morphology. Results showed that the fiber diameter of all batches was found in the range of 100-200 nm. The optimized batch results showed the fiber diameter of 162.7 nm with uniform fibers. The tensile strength obtained was 190±37 Mpa. Further in vitro and ex vivo drug release profile suggested a controlled release mechanism for an extended period of 24 hr. The 5-fluorouracil loaded electrospun nanofibers were found to decrease cell viability up to ≥50% over 24 hr, with the number of cells dropping by ~ 10% over 48 hr. As the cell viability was affected by the release of 5-fluorouracil, we believe that electrospun nanofibers are a promising drug delivery system for the treatment of Basal Cell Carcinoma (BCC) skin cancer. Conclusion: These results demonstrate the possibility of delivering 5-Fluorouracil loaded electrospun nanofiber to skin with enhanced encapsulation efficiency indicating the effectiveness of the formulation for the treatment of basal cell carcinoma type of skin cancer.


Polymers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 948
Author(s):  
Nicola Zerbinati ◽  
Sabrina Sommatis ◽  
Cristina Maccario ◽  
Maria Chiara Capillo ◽  
Giulia Grimaldi ◽  
...  

(1) Background: Injectable hyaluronic acid (HA) dermal fillers are used to restore volume, hydration and skin tone in aesthetic medicine. HA fillers differ from each other due to their cross-linking technologies, with the aim to increase mechanical and biological activities. One of the most recent and promising cross-linkers is polyethylene glycol diglycidyl ether (PEGDE), used by the company Matex Lab S.p.A., (Brindisi, Italy) to create the HA dermal filler PEGDE family. Over the last few years, several studies have been performed to investigate the biocompatibility and biodegradability of these formulations, but little information is available regarding their matrix structure, rheological and physicochemical properties related to their cross-linking technologies, the HA content or the degree of cross-linking. (2) Methods: Seven different injectable HA hydrogels were subjected to optical microscopic examination, cohesivity evaluation and rheological characterization in order to investigate their behavior. (3) Results: The analyzed cross-linked dermal fillers showed a fibrous “spiderweb-like” matrix structure, with each medical device presenting different and peculiar rheological features. Except for HA non cross-linked hydrogel 18 mg/mL, all showed an elastic and cohesive profile. (4) Conclusions: The comparative analysis with other literature works makes a preliminary characterization of these injectable medical devices possible.


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