Pharmaceutical formulation and polymer chemistry for cell encapsulation applied to the creation of a lab-on-a-chip bio-microsystem.

2021 ◽  
Author(s):  
Armin Mooranian ◽  
Melissa Jones ◽  
Corina Mihaela Ionescu ◽  
Daniel Walker ◽  
Susbin Raj Wagle ◽  
...  
Keyword(s):  
Immune System ◽  
Cell Survival ◽  
Bile Acids ◽  
Lab On A Chip ◽  
Cell Encapsulation ◽  
Polymer Chemistry ◽  
Organ Development ◽  
Active Materials ◽  
Formulation Design ◽  
Bioartificial Organs

Microencapsulation of formulation designs further expands the field and offers the potential for use in developing bioartificial organs via cell encapsulation. Combining formulation design and encapsulation requires ideal excipients to be determined. In terms of cell encapsulation, an environment which allows growth and functionality is paramount to ensuring cell survival and incorporation into a bioartificial organ. Hence, excipients are examined for both individual properties and benefits, and compatibility with encapsulated active materials. Polymers are commonly used in microencapsulation, offering protection from the immune system. Bile acids are emerging as a tool to enhance delivery, both biologically and pharmaceutically. Therefore, this review will focus on bile acids and polymers in formulation design via microencapsulation, in the field of bioartificial organ development.

scholarly journals Topoisomerase II is regulated by translationally controlled tumor protein for cell survival during organ growth in Drosophila

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Dae-Wook Yang ◽  
Jung-Wan Mok ◽  
Stephanie B. Telerman ◽  
Robert Amson ◽  
Adam Telerman ◽  
...  
Keyword(s):  
Cell Survival ◽  
Topoisomerase Ii ◽  
Wing Disc ◽  
Organ Development ◽  
Translationally Controlled Tumor Protein ◽  
Protein Levels ◽  
Eye Disc ◽  
Mutual Regulation

AbstractRegulation of cell survival is critical for organ development. Translationally controlled tumor protein (TCTP) is a conserved protein family implicated in the control of cell survival during normal development and tumorigenesis. Previously, we have identified a human Topoisomerase II (TOP2) as a TCTP partner, but its role in vivo has been unknown. To determine the significance of this interaction, we examined their roles in developing Drosophila organs. Top2 RNAi in the wing disc leads to tissue reduction and caspase activation, indicating the essential role of Top2 for cell survival. Top2 RNAi in the eye disc also causes loss of eye and head tissues. Tctp RNAi enhances the phenotypes of Top2 RNAi. The depletion of Tctp reduces Top2 levels in the wing disc and vice versa. Wing size is reduced by Top2 overexpression, implying that proper regulation of Top2 level is important for normal organ development. The wing phenotype of Tctp RNAi is partially suppressed by Top2 overexpression. This study suggests that mutual regulation of Tctp and Top2 protein levels is critical for cell survival during organ development.

scholarly journals Comparison of Linear Poly Ethylene Imine (LPEI) and Poly L-Lysine (PLL) in Fabrication of CHOK1 Cell-Loaded Multilayer Alginate Microcapsules

2020 ◽  
Vol 10 (2) ◽  
pp. 290-296
Author(s):  
Fariba Hajifathaliha ◽  
Arash Mahboubi ◽  
Elham Mohit ◽  
Noushin Bolourchian ◽  
Vahid Khalaj ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Survival ◽  
Metabolic Activity ◽  
Encapsulation Efficiency ◽  
Cell Encapsulation ◽  
High Price ◽  
Ethylene Imine ◽  
Linear Poly ◽  
Cellular Metabolic Activity ◽  
Poly Ethylene

Purpose: Poly l-lysine (PLL) has been introduced as a strengthening covering layer for alginate microcapsules which are the most convenient way for cell encapsulation. Some disadvantages of PLL such as high price and low biocompatibility have prompted scientists to find better alternatives. Linear poly ethylene imine (LPEI), thanks to its highly similar structure to PLL, could be considered as a proper cost-effective alternative. In this study LPEI and PLL were compared as covering layers of cell-loaded alginate-LPEI-alginate (cALA) and alginate-PLL-alginate (cAPA) microcapsules. Methods: In addition to the physico-mechanical properties, the encapsulation efficiency, cell survival post encapsulation, cell viability, and cellular metabolic activity within the microcapsules were evaluated using trypan blue, live/dead cell staining, and MTT test, respectively. Results: Physico-mechanical evaluation of the microcapsules revealed that the cell microencapsulation process did not affect their shape, size, and mechanical stability. Although the encapsulation efficiency for cALA and cAPA was not different (P>0.05), cell survival post encapsulation was higher in cALA than in cAPA (P<0.05) which could be the reason for the higher cell viability and also cellular metabolic activity within these microcapsules in comparison to cAPA. Conclusion: Here, based on these results, ALA could be introduced as a preferable alternative to APA for cell encapsulation.

Rational formulation design of injectable thermosensitive chitosan-based hydrogels for cell encapsulation and delivery

2021 ◽  
pp. 118836
Author(s):  
Phuong Anh Dang ◽  
Carla Palomino-Durand ◽  
Mohamed Elsafi Mabrouk ◽  
Pierre Marquaille ◽  
Clément Odier ◽  
...  
Keyword(s):  
Cell Encapsulation ◽  
Formulation Design

scholarly journals A Low-Cost Open Source Device for Cell Microencapsulation

Materials ◽  
2020 ◽  
Vol 13 (22) ◽  
pp. 5090
Author(s):  
Miriam Salles Pereira ◽  
Liana Monteiro da Fonseca Cardoso ◽  
Tatiane Barreto da Silva ◽  
Ayla Josma Teixeira ◽  
Saul Eliahú Mizrahi ◽  
...  
Keyword(s):  
Immune System ◽  
Cell Therapy ◽  
Open Source ◽  
Low Cost ◽  
Cell Encapsulation ◽  
Host Cells ◽  
Host Immune System ◽  
Middle Income ◽  
Encapsulated Cells ◽  
Cell Microencapsulation

Microencapsulation is a widely studied cell therapy and tissue bioengineering technique, since it is capable of creating an immune-privileged site, protecting encapsulated cells from the host immune system. Several polymers have been tested, but sodium alginate is in widespread use for cell encapsulation applications, due to its low toxicity and easy manipulation. Different cell encapsulation methods have been described in the literature using pressure differences or electrostatic changes with high cost commercial devices (about 30,000 US dollars). Herein, a low-cost device (about 100 US dollars) that can be created by commercial syringes or 3D printer devices has been developed. The capsules, whose diameter is around 500 µm and can decrease or increase according to the pressure applied to the system, is able to maintain cells viable and functional. The hydrogel porosity of the capsule indicates that the immune system is not capable of destroying host cells, demonstrating that new studies can be developed for cell therapy at low cost with microencapsulation production. This device may aid pre-clinical and clinical projects in low- and middle-income countries and is lined up with open source equipment devices.

Abstract 15060: Protein-Engineered Hydrogels for Improved Efficacy of Stem Cell-Based Injection Therapy in a Murine Model of Peripheral Arterial Disease

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Lei Cai ◽  
Ruby Dewi ◽  
Zachary Strassberg ◽  
Luqia Hou ◽  
Abbygail Foster ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Arterial Disease ◽  
Cell Viability ◽  
Cell Survival ◽  
Cell Encapsulation ◽  
Arterial Disease ◽  
Cell Injection ◽  
Invasive Approach ◽  
Peripheral Arterial ◽  
Hydrogel System

Introduction: Stem cell injection is a minimally invasive approach for treatment of cardiovascular diseases including peripheral arterial disease (PAD), which affects over 8 million patients in the US. However, poor cell survival and low cell retention at injection site are critical bottlenecks to the efficacy of stem cell therapy. We developed a shear-thinning and self-healing hydrogel system with controllable rigidity for stem cell encapsulation so as to enhance transplant cell viability. Hypothesis: The injectable hydrogel system will prolong cell survival under ischemic conditions and maintain cellular phenotype, in comparison to cell injection in saline. Methods: We developed a hydrogel comprised of two complementary engineered proteins that self-assemble upon simple mixing. The hydrogel network incorporates a polyethylene glycol physical crosslinker that modulates hydrogel stiffness and degradation. Bioluminescently-labeled human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) were encapsulated within the hydrogel with controllable stiffness (G'~10-800 Pa) under conditions of hypoxia (1% O2). The cells within hydrogel were then subjected to an in vitro model of injection and assayed for cell survival, proliferation, and endothelial phenotype for up to 14 days. To verify these results in an experimental model of PAD, 10^6 cells were injected in saline or in 400 Pa hydrogel into the ischemic limb in SCID mice. Results: Acutely after injection, the survival of iPSC-ECs in saline was 65%, whereas survival of iPSC-ECs in hydrogels with stiffnesses of 10, 100, 400, and 800 Pa was 94%. Bioluminescence imaging of cell viability in hypoxia for 14 days demonstrated the highest proliferation in the hydrogel with 400 Pa stiffness. In the 400 Pa hydrogel, iPSC-ECs maintained elongated morphology with robust expression of endothelial phenotypic marker, CD31. In the ischemic hindlimb, iPSC-EC retention was markedly increased with hydrogel encapsulation, compared to saline delivery. Conclusions: These findings demonstrate that stem cell encapsulation within this protein hydrogel improves cell viability, which may have therapeutic benefit for treatment of PAD and broadly to myocardial ischemia.

scholarly journals Single-Cellular Biological Effects of Cholesterol-Catabolic Bile Acid-Based Nano/Micro Capsules as Anti-Inflammatory Cell Protective Systems

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 73
Author(s):  
Armin Mooranian ◽  
Corina Mihaela Ionescu ◽  
Daniel Walker ◽  
Melissa Jones ◽  
Susbin Raj Wagle ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cell Viability ◽  
Bile Acids ◽  
Chemical Stability ◽  
Targeted Delivery ◽  
Biological Activities ◽  
Biological Effects ◽  
Cell Encapsulation ◽  
Viable Cell ◽  
Thermal And Chemical Stability

Recent studies in our laboratories have shown promising effects of bile acids in ➀ drug encapsulation for oral targeted delivery (via capsule stabilization) particularly when encapsulated with Eudragit NM30D® and ➁ viable-cell encapsulation and delivery (via supporting cell viability and biological activities, postencapsulation). Accordingly, this study aimed to investigate applications of bile acid-Eudragit NM30D® capsules in viable-cell encapsulation ready for delivery. Mouse-cloned pancreatic β-cell line was cultured and cells encapsulated using bile acid-Eudragit NM30D® capsules, and capsules’ images, viability, inflammation, and bioenergetics of encapsulated cells assessed. The capsules’ thermal and chemical stability assays were also assessed to ascertain an association between capsules’ stability and cellular biological activities. Bile acid-Eudragit NM30D® capsules showed improved cell viability (e.g., F1 < F2 & F8; p < 0.05), insulin, inflammatory profile, and bioenergetics as well as thermal and chemical stability, compared with control. These effects were formulation-dependent and suggest, overall, that changes in ratios of bile acids to Eudragit NM30D® can change the microenvironment of the capsules and subsequent cellular biological activities.

scholarly journals Effect of High Dose of Bile Acids Supplementation in Broiler Feed on Growth Performance, Clinical Blood Metabolites, and Organ Development

2018 ◽  
Vol 27 (4) ◽  
pp. 532-539 ◽  
Author(s):  
Wenqing Lai ◽  
Aizhi Cao ◽  
Juntao Li ◽  
Wenjuan Zhang ◽  
Liying Zhang
Keyword(s):  
Growth Performance ◽  
Bile Acids ◽  
Blood Metabolites ◽  
High Dose ◽  
Organ Development ◽  
Broiler Feed

scholarly journals Advanced Biotechnology for Cell Cryopreservation

2019 ◽  
Vol 26 (6) ◽  
pp. 409-423
Author(s):  
Jing Yang ◽  
Lei Gao ◽  
Min Liu ◽  
Xiaojie Sui ◽  
Yingnan Zhu ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cell ◽  
Cell Therapy ◽  
Organic Solvent ◽  
Cell Survival ◽  
Assisted Reproduction ◽  
Stem Cell Therapy ◽  
Future Development ◽  
Cell Encapsulation ◽  
Cell Printing

AbstractCell cryopreservation has evolved as an important technology required for supporting various cell-based applications, such as stem cell therapy, tissue engineering, and assisted reproduction. Recent times have witnessed an increase in the clinical demand of these applications, requiring urgent improvements in cell cryopreservation. However, cryopreservation technology suffers from the issues of low cryopreservation efficiency and cryoprotectant (CPA) toxicity. Application of advanced biotechnology tools can significantly improve post-thaw cell survival and reduce or even eliminate the use of organic solvent CPAs, thus promoting the development of cryopreservation. Herein, based on the different cryopreservation mechanisms available, we provide an overview of the applications and achievements of various biotechnology tools used in cell cryopreservation, including trehalose delivery, hydrogel-based cell encapsulation technique, droplet-based cell printing, and nanowarming, and also discuss the associated challenges and perspectives for future development.

scholarly journals Microfluidic-assisted synthesis and modelling of monodispersed magnetic nanocomposites for biomedical applications

2020 ◽  
Vol 9 (1) ◽  
pp. 1397-1407
Author(s):  
Omid Sartipzadeh ◽  
Seyed Morteza Naghib ◽  
Farhad Shokati ◽  
Mehdi Rahmanian ◽  
Keivan Majidzadeh-A ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tissue Engineering ◽  
Biomedical Applications ◽  
Lab On A Chip ◽  
Cell Encapsulation ◽  
Cell Isolation ◽  
Two Phase ◽  
Experimental Procedure ◽  
Velocity Flow

Abstract Droplet microfluidic was devoted to design and fabricate robust devices in the field of biosensing, tissue engineering, drug delivery, cell encapsulation, cell isolation, and lab-on-a-chip. Chitosan was widely used for different biomedical applications because of its unique characteristics such as antibacterial bioactivities, immune-enhancing influences, and anticancer bioactivities. In this research, a model is used for investigating the formation and size of composite droplets in a microfluidic device. The role of the velocity flow ratio in the composite droplet characteristics such as the generation rate and composite droplet size is described. According to the results, a desirable protocol is developed to control the properties of the composite droplets and to compare the size and rate of the composite droplets in a micro device. Furthermore, the level set laminar two-phase flow approach is exploited for studying the composite droplet-breaking procedure. An experimental procedure is used for validation of the simulation process. Various sizes and geometries of the composite droplets are fabricated to depict a potential in biomedical applications such as bioimaging, biosensing, tissue engineering, drug delivery, cell encapsulation, cancer cell isolation, and lab-on-a-chip.

scholarly journals Critical roles of bile acids in regulating intestinal mucosal immune responses

2021 ◽  
Vol 14 ◽  
pp. 175628482110180
Author(s):  
Ruicong Sun ◽  
Chunjin Xu ◽  
Baisui Feng ◽  
Xiang Gao ◽  
Zhanju Liu
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Bile Acids ◽  
Molecular Diversity ◽  
New Drugs ◽  
Daily Diet ◽  
Intestinal Immune System ◽  
Long Time ◽  
Inflammatory Bowel ◽  
Secondary Bile Acids

Bile acids are a class of cholesterol derivatives that have been known for a long time for their critical roles in facilitating the digestion and absorption of lipid from the daily diet. The transformation of primary bile acids produced by the liver to secondary bile acids appears under the action of microbiota in the intestine, greatly expanding the molecular diversity of the intestinal environment. With the discovery of several new receptors of bile acids and signaling pathways, bile acids are considered as a family of important metabolites that play pleiotropic roles in regulating many aspects of human overall health, especially in the maintenance of the microbiota homeostasis and the balance of the mucosal immune system in the intestine. Accordingly, disruption of the process involved in the metabolism or circulation of bile acids is implicated in many disorders that mainly affect the intestine, such as inflammatory bowel disease and colon cancer. In this review, we discuss the different metabolism profiles in diseases associated with the intestinal mucosa and the diverse roles of bile acids in regulating the intestinal immune system. Furthermore, we also summarize recent advances in the field of new drugs that target bile acid signaling and highlight the importance of bile acids as a new target for disease intervention.

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