Effect of Thermosensitive Hydrogel Injection on Mechanical Behavior of Porcine Myocardium

2013 ◽  
Author(s):  
Bo Wang ◽  
Robbin Bertucci ◽  
Zhenqing Li ◽  
Raj Prabhu ◽  
Lakiesha Williams ◽  
...  
Keyword(s):  
Mechanical Behavior ◽  
The United States ◽  
Myocardial Infarctions ◽  
Thermosensitive Hydrogel ◽  
Thermally Responsive ◽  
Vitro Model ◽  
Biodegradable Biomaterials ◽  
Responsive Hydrogels

Myocardial infarctions (MI) afflict approximately 1.1 million individuals in the United States each year and exhibit an increasing prevalence worldwide due to the improvement of economic levels. Injection therapies for MI using biodegradable biomaterials with/without cells have been recognized to stabilize and preserve mechanical properties in the infarcted area in pre-clinical animal models. Recently, thermally responsive hydrogels, which can be injected from a syringe below 37 °C and then solidified at body temperature, are considered an attractive material for injection therapy.[1] The advantages of using an injectable hydrogel lie in its high moldability, capability of filling irregular shaped defects, and ability to be delivered to the in vivo environment by limited surgical invasion. However, it is still not very clear how the injection of thermosensitive hydrogel affects local tissue structure and mechanics. Thus, the goal of this study is to investigate possible alterations in myocardial structure and mechanical behavior after hydrogel injection using a well-controlled in vitro model.

scholarly journals Thermo-Responsive Hydrogels Based on Methylcellulose/Persian Gum Loaded With Taxifolin Enhance Bone Regeneration: An in Vitro / in Vivo Study

2021 ◽  
Author(s):  
Zahra Sadat Sajadi-Javan ◽  
Jaleh Varshosaz ◽  
Mina Mirian ◽  
Maziar Manshaei ◽  
Atousa Aminzadeh
Keyword(s):  
Animal Studies ◽  
Bone Defects ◽  
Halloysite Nanotubes ◽  
Thermosensitive Hydrogel ◽  
Alizarin Red ◽  
The Impact ◽  
Responsive Hydrogels

Abstract In-situ forming hydrogels have gained noticeable attention to encapsulate osteogenic agents and regenerate irregular-shape bone defects. In this study, a novel thermosensitive hydrogel based on blended methylcellulose (MC) with Persian gum (PG) was fabricated and enriched with taxifolin (TAX) loaded halloysite nanotubes (HNTs) to enhance mechanical and biological characteristics of the hydrogel in bone tissue engineering. The injectability, mechanical and rheological tests were performed for different hydrogel formulations containing 0.25-1.5 w/v% PG and 1-7 w/v% HNTs. Also, to evaluate the impact of PG and HNTs on hydrogel behavior, the degradation rate and swelling degree of hydrogels were assessed. The optimized MC/PG/HNTs hydrogel containing 1% PG and 3% HNTs (MC/PG-1/HNTs 3%) was easily injectable and gelled rapidly at physiological temperature, while it had the highest mechanical strength due to the existence of PG and HNTs. In vitro release study of TAX from this system also revealed more sustained release compared to HNTs-TAX nanoparticles. Furthermore, the interaction of cells with hydrogel and osteo-conductivity was studied using osteoblast-like cells (MG-63). Results showed higher cell adhesion, proliferation, and gene expression for MC/PG-1/HNTs-TAX hydrogel compared to MC/PG-1 and MC/PG-1/HNTs 3% possibly due to the synergic effect of HNTs and TAX. In addition, Alizarin Red S staining and alkaline phosphatase measurements indicated that the existence of HNTs-TAX promoted osteogenic differentiation. Eventually, animal studies on the femoral defects indicated improved remedy when using the MC/PG-1/HNTs-TAX hydrogel carrying MG-63 cells.

Repurposing N,N-Dimethylacetamide (DMA), a Pharmaceutical Excipient, as a Prototype Novel Anti-inflammatory Agent for the Prevention and/or Treatment of Preterm Birth

2018 ◽  
Vol 24 (9) ◽  
pp. 989-992 ◽  
Author(s):  
Samir Gorasiya ◽  
Juliet Mushi ◽  
Ryan Pekson ◽  
Sabesan Yoganathan ◽  
Sandra E. Reznik
Keyword(s):  
Preterm Birth ◽  
Ex Vivo ◽  
The United States ◽  
Occurrence Rate ◽  
Pharmaceutical Excipient ◽  
Ongoing Work ◽  
Exciting Line ◽  
Pregnant Mice

Background: Preterm birth (PTB), or birth that occurs before 37 weeks of gestation, accounts for the majority of perinatal morbidity and mortality. As of 2016, PTB has an occurrence rate of 9.6% in the United States and accounts for up to 18 percent of births worldwide. Inflammation has been identified as the most common cause of PTB, but effective pharmacotherapy has yet to be developed to prevent inflammation driven PTB. Our group has discovered that N,N-dimethylacetamide (DMA), a readily available solvent commonly used as a pharmaceutical excipient, rescues lipopolysaccharide (LPS)-induced timed pregnant mice from PTB. Methods: We have used in vivo, ex vivo and in vitro approaches to investigate this compound further. Results: Interestingly, we found that DMA suppresses cytokine secretion by inhibiting nuclear factor-kappa B (NF-κB). In ongoing work in this exciting line of investigation, we are currently investigating structural analogs of DMA, some of them novel, to optimize this approach focused on the inflammation associated with PTB. Conclusion: Successful development of pharmacotherapy for the prevention of PTB rests upon the pursuit of multiple strategies to solve this important clinical challenge.

scholarly journals Functional and Transcriptional Adaptations of Blood Monocytes Recruited to the Cystic Fibrosis Airway Microenvironment In Vitro

2021 ◽  
Vol 22 (5) ◽  
pp. 2530
Author(s):  
Bijean D. Ford ◽  
Diego Moncada Giraldo ◽  
Camilla Margaroli ◽  
Vincent D. Giacalone ◽  
Milton R. Brown ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bactericidal Activity ◽  
Scavenger Receptor ◽  
Receptor Expression ◽  
Blood Monocytes ◽  
Bacterial Killing ◽  
Blood Neutrophils ◽  
Vitro Model

Cystic fibrosis (CF) lung disease is dominated by the recruitment of myeloid cells (neutrophils and monocytes) from the blood which fail to clear the lung of colonizing microbes. In prior in vitro studies, we showed that blood neutrophils migrated through the well-differentiated lung epithelium into the CF airway fluid supernatant (ASN) mimic the dysfunction of CF airway neutrophils in vivo, including decreased bactericidal activity despite an increased metabolism. Here, we hypothesized that, in a similar manner to neutrophils, blood monocytes undergo significant adaptations upon recruitment to CFASN. To test this hypothesis, primary human blood monocytes were transmigrated in our in vitro model into the ASN from healthy control (HC) or CF subjects to mimic in vivo recruitment to normal or CF airways, respectively. Surface phenotype, metabolic and bacterial killing activities, and transcriptomic profile by RNA sequencing were quantified post-transmigration. Unlike neutrophils, monocytes were not metabolically activated, nor did they show broad differences in activation and scavenger receptor expression upon recruitment to the CFASN compared to HCASN. However, monocytes recruited to CFASN showed decreased bactericidal activity. RNASeq analysis showed strong effects of transmigration on monocyte RNA profile, with differences between CFASN and HCASN conditions, notably in immune signaling, including lower expression in the former of the antimicrobial factor ISG15, defensin-like chemokine CXCL11, and nitric oxide-producing enzyme NOS3. While monocytes undergo qualitatively different adaptations from those seen in neutrophils upon recruitment to the CF airway microenvironment, their bactericidal activity is also dysregulated, which could explain why they also fail to protect CF airways from infection.

scholarly journals Radiofrequency Irradiation Modulates TRPV1-Related Burning Sensation in Rosacea

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1424
Author(s):  
Seyeon Oh ◽  
Myeongjoo Son ◽  
Joonhong Park ◽  
Donghwan Kang ◽  
Kyunghee Byun
Keyword(s):  
Burning Sensation ◽  
In Vivo Model ◽  
Molecular Evidence ◽  
Exposed Skin ◽  
Heat Treated ◽  
Vitro Model ◽  
Effective Use ◽  
Inflammatory Molecules

Rosacea is a skin inflammatory condition that is accompanied by not only redness and flushing but also unseen symptoms, such as burning, stinging, and itching. TRPV1 expression in UVB-exposed skin can lead to a painful burning sensation. Upregulated TRPV1 expression helps release neuropeptides, including calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide, and vasoactive intestinal peptide, which can activate macrophage and inflammatory molecules. In this study, we found that radiofrequency (RF) irradiation reduced TRPV1 activation and neuropeptide expression in a UVB-exposed in vivo model and UVB- or heat-treated in an in vitro model. RF irradiation attenuated neuropeptide-induced macrophage activation and inflammatory molecule expression. Interestingly, the burning sensation in the skin of UVB-exposed mice and patients with rosacea was significantly decreased by RF irradiation. These results can provide experimental and molecular evidence on the effective use of RF irradiation for the burning sensation in patients with rosacea.

scholarly journals Generation of a Novel In Vitro Model to Study Endothelial Dysfunction from Atherothrombotic Specimens

2021 ◽  
Author(s):  
Susan Gallogly ◽  
Takeshi Fujisawa ◽  
John D. Hung ◽  
Mairi Brittan ◽  
Elizabeth M. Skinner ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
In Vitro Model ◽  
Umbilical Vein ◽  
Coronary Syndrome ◽  
Coronary Endothelial Cells ◽  
Vitro Model ◽  
Umbilical Vein Endothelial Cells

Abstract Purpose Endothelial dysfunction is central to the pathogenesis of acute coronary syndrome. The study of diseased endothelium is very challenging due to inherent difficulties in isolating endothelial cells from the coronary vascular bed. We sought to isolate and characterise coronary endothelial cells from patients undergoing thrombectomy for myocardial infarction to develop a patient-specific in vitro model of endothelial dysfunction. Methods In a prospective cohort study, 49 patients underwent percutaneous coronary intervention with thrombus aspiration. Specimens were cultured, and coronary endothelial outgrowth (CEO) cells were isolated. CEO cells, endothelial cells isolated from peripheral blood, explanted coronary arteries, and umbilical veins were phenotyped and assessed functionally in vitro and in vivo. Results CEO cells were obtained from 27/37 (73%) atherothrombotic specimens and gave rise to cells with cobblestone morphology expressing CD146 (94 ± 6%), CD31 (87 ± 14%), and von Willebrand factor (100 ± 1%). Proliferation of CEO cells was impaired compared to both coronary artery and umbilical vein endothelial cells (population doubling time, 2.5 ± 1.0 versus 1.6 ± 0.3 and 1.2 ± 0.3 days, respectively). Cell migration was also reduced compared to umbilical vein endothelial cells (29 ± 20% versus 85±19%). Importantly, unlike control endothelial cells, dysfunctional CEO cells did not incorporate into new vessels or promote angiogenesis in vivo. Conclusions CEO cells can be reliably isolated and cultured from thrombectomy specimens in patients with acute coronary syndrome. Compared to controls, patient-derived coronary endothelial cells had impaired capacity to proliferate, migrate, and contribute to angiogenesis. CEO cells could be used to identify novel therapeutic targets to enhance endothelial function and prevent acute coronary syndromes.

scholarly journals 3D Environment Is Required In Vitro to Demonstrate Altered Bone Metabolism Characteristic for Type 2 Diabetics

2021 ◽  
Vol 22 (6) ◽  
pp. 2925
Author(s):  
Victor Häussling ◽  
Romina H Aspera-Werz ◽  
Helen Rinderknecht ◽  
Fabian Springer ◽  
Christian Arnscheidt ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
In Vitro Model ◽  
Bone Diseases ◽  
3D Environment ◽  
Type 2 Diabetics ◽  
Mineralized Matrix ◽  
Vitro Model

A large British study, with almost 3000 patients, identified diabetes as main risk factor for delayed and nonunion fracture healing, the treatment of which causes large costs for the health system. In the past years, much progress has been made to treat common complications in diabetics. However, there is still a lack of advanced strategies to treat diabetic bone diseases. To develop such therapeutic strategies, mechanisms leading to massive bone alterations in diabetics have to be well understood. We herein describe an in vitro model displaying bone metabolism frequently observed in diabetics. The model is based on osteoblastic SaOS-2 cells, which in direct coculture, stimulate THP-1 cells to form osteoclasts. While in conventional 2D cocultures formation of mineralized matrix is decreased under pre-/diabetic conditions, formation of mineralized matrix is increased in 3D cocultures. Furthermore, we demonstrate a matrix stability of the 3D carrier that is decreased under pre-/diabetic conditions, resembling the in vivo situation in type 2 diabetics. In summary, our results show that a 3D environment is required in this in vitro model to mimic alterations in bone metabolism characteristic for pre-/diabetes. The ability to measure both osteoblast and osteoclast function, and their effect on mineralization and stability of the 3D carrier offers the possibility to use this model also for other purposes, e.g., drug screenings.

scholarly journals Photosensitizing Medications and Skin Cancer: A Comprehensive Review

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2344
Author(s):  
Elisabeth A. George ◽  
Navya Baranwal ◽  
Jae H. Kang ◽  
Abrar A. Qureshi ◽  
Aaron M. Drucker ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Cancer Risk ◽  
Cell Carcinoma ◽  
The United States ◽  
In Vivo Studies ◽  
Cancer Risk Factors ◽  
Skin Cancer Risk ◽  
Number Of Patients

(1) The incidence of skin cancer is increasing in the United States (US) despite scientific advances in our understanding of skin cancer risk factors and treatments. In vitro and in vivo studies have provided evidence that suggests that certain photosensitizing medications (PSMs) increase skin cancer risk. This review summarizes current epidemiological evidence on the association between common PSMs and skin cancer. (2) A comprehensive literature search was conducted to identify meta-analyses, observational studies and clinical trials that report on skin cancer events in PSM users. The associated risks of keratinocyte carcinoma (squamous cell carcinoma and basal cell carcinoma) and melanoma are summarized, for each PSM. (3) There are extensive reports on antihypertensives and statins relative to other PSMs, with positive and null findings, respectively. Fewer studies have explored amiodarone, metformin, antimicrobials and vemurafenib. No studies report on the individual skin cancer risks in glyburide, naproxen, piroxicam, chlorpromazine, thioridazine and nalidixic acid users. (4) The research gaps in understanding the relationship between PSMs and skin cancer outlined in this review should be prioritized because the US population is aging. Thus the number of patients prescribed PSMs is likely to continue to rise.

scholarly journals Multi-responsive nanofibers composite gel for local drug delivery to inhibit recurrence of glioma after operation

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yufu Zhu ◽  
Jun Jia ◽  
Gang Zhao ◽  
Xuyang Huang ◽  
Lansheng Wang ◽  
...  
Keyword(s):  
Malignant Gliomas ◽  
Postoperative Recurrence ◽  
Local Drug Delivery ◽  
Recurrent Glioma ◽  
Mixed Solution ◽  
Composite Gel ◽  
Poly Propylene ◽  
Responsive Hydrogels

Abstract Background The postoperative recurrence of malignant gliomas has presented a clinical conundrum currently. Worse, there is no standard treatment for these recurrent tumours. Therefore, novel promising methods of clinical treatment are urgently needed. Methods In this study, we synthesized reactive oxygen species (ROS)-triggered poly(propylene sulfide)60 (PPS60) mixed with matrix metalloproteinases (MMPs)-responsive triglycerol monostearate (T) lipids and TMZ. The mixed solution could self-assemble at 50 ℃ to generate hydrogels with MMPs- and ROS-responsiveness. We explored whether the T/PPS + TMZ hydrogel could achieve the MMP- and ROS-responsive delivery of TMZ and exert anti-glioma regrowth effects in vitro and in vivo. These results demonstrated that the T/PPS + TMZ hydrogel significantly improved the curative effect of TMZ to inhibit postsurgical recurrent glioma. Results The results confirmed the responsive release of TMZ encapsulated in the T/PPS + TMZ hydrogel, and the hydrogel showed excellent performance against glioma in an incomplete glioma operation model, which indicated that the T/PPS + TMZ hydrogel effectively inhibited the growth of recurrent glioma. Conclusion In summary, we successfully developed injectable MMPs- and ROS-responsive hydrogels that could achieve the sustained release of TMZ in the surgical cavity to inhibit local recurrent glioma after surgery. Graphic abstract

scholarly journals Role of the C5a-C5a receptor axis in the inflammatory responses of the lungs after experimental polytrauma and hemorrhagic shock

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shinjini Chakraborty ◽  
Veronika Eva Winkelmann ◽  
Sonja Braumüller ◽  
Annette Palmer ◽  
Anke Schultze ◽  
...  
Keyword(s):  
Hemorrhagic Shock ◽  
Inflammatory Responses ◽  
Experimental Models ◽  
Lung Damage ◽  
C5a Receptor ◽  
Cytokine Levels ◽  
Vitro Model

AbstractSingular blockade of C5a in experimental models of sepsis is known to confer protection by rescuing lethality and decreasing pro-inflammatory responses. However, the role of inhibiting C5a has not been evaluated in the context of sterile systemic inflammatory responses, like polytrauma and hemorrhagic shock (PT + HS). In our presented study, a novel and highly specific C5a L-aptamer, NoxD21, was used to block C5a activity in an experimental murine model of PT + HS. The aim of the study was to assess early modulation of inflammatory responses and lung damage 4 h after PT + HS induction. NoxD21-treated PT + HS mice displayed greater polymorphonuclear cell recruitment in the lung, increased pro-inflammatory cytokine levels in the bronchoalveolar lavage fluids (BALF) and reduced myeloperoxidase levels within the lung tissue. An in vitro model of the alveolar-capillary barrier was established to confirm these in vivo observations. Treatment with a polytrauma cocktail induced barrier damage only after 16 h, and NoxD21 treatment in vitro did not rescue this effect. Furthermore, to test the exact role of both the cognate receptors of C5a (C5aR1 and C5aR2), experimental PT + HS was induced in C5aR1 knockout (C5aR1 KO) and C5aR2 KO mice. Following 4 h of PT + HS, C5aR2 KO mice had significantly reduced IL-6 and IL-17 levels in the BALF without significant lung damage, and both, C5aR1 KO and C5aR2 KO PT + HS animals displayed reduced MPO levels within the lungs. In conclusion, the C5aR2 could be a putative driver of early local inflammatory responses in the lung after PT + HS.

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