Publications by authors named "Ashutosh Agarwal"

68 Publications

Different Regenerative Responses of Two Platelet Concentrates in the Treatment of Human Periodontal Infrabony Defects: A Clinico-Radiographic Study.

Contemp Clin Dent 2020 Jul-Sep;11(3):217-222. Epub 2020 Nov 26.

Department of Oral and Maxillofacial Surgery, Institute of Dental Sciences, Bareilly, Uttar Pradesh, India.

Background: Platelet concentrates usage in the treatment of intrabony defects has been improved due to advancement of research. Many generation of platelet concentrates were used, but research regarding advanced platelet-rich fibrin (A-PRF) regarding periodontal treatment is scanty.

Aim: The purpose of the study was to evaluate and compare PRF and A-PRF in the treatment of human periodontal infrabony defects (IBDs) both clinically and radiographically.

Materials And Methods: Twenty-eight patients having IBDs were divided into Group A (PRF) and Group B (A-PRF). Clinical parameters such as plaque index, gingival index, probing pocket depth (PPD), and clinical attachment level (CAL) were recorded at baseline and 3 and 6 months and radiographic examination at baseline and 6 months were also recorded to evaluate defect fill, resolution, and change in the alveolar crest height. Then, all the data were tabulated in a Microsoft Excel sheet and subjected to statistical analysis. Mean and standard deviations of the clinical and radiographic parameters were calculated, and unpaired -test was performed to assess intergroup comparison at different time intervals.

Results: Intragroup comparison showed statistically significant improvement in PPD and CAL at 3 and 6 months while statistically significant improvement was observed in mean defect fill and resolution in Group B.

Conclusion: Individually, both the materials have shown promising results. However, statistically, PRF group (Group A) showed better treatment outcome in terms of bone fill and A-PRF group (Group B) in terms of soft tissue healing.
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http://dx.doi.org/10.4103/ccd.ccd_7_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989751PMC
November 2020

Correction to: A Chemically Defined Common Medium for Culture of C2C12 Skeletal Muscle and Human Induced Pluripotent Stem Cell Derived Spinal Spheroids.

Cell Mol Bioeng 2021 Feb 30;14(1):131. Epub 2020 Nov 30.

Department of Biomedical Engineering, DJTMF Biomedical Nanotechnology Institute, University of Miami, 1251 Memorial Dr, MEA 203, Coral Gables, FL 33146 USA.

[This corrects the article DOI: 10.1007/s12195-020-00624-1.].
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http://dx.doi.org/10.1007/s12195-020-00662-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878659PMC
February 2021

Modular Microphysiological System for Modeling of Biologic Barrier Function.

Front Bioeng Biotechnol 2020 12;8:581163. Epub 2020 Nov 12.

Department of Biomedical Engineering, University of Miami, Coral Gables, FL, United States.

Microphysiological systems, also known as organs-on-chips, are microfluidic devices designed to model human physiology . Polydimethylsiloxane (PDMS) is the most widely used material for organs-on-chips due to established microfabrication methods, and properties that make it suitable for biological applications such as low cytotoxicity, optical transparency, gas permeability. However, absorption of small molecules and leaching of uncrosslinked oligomers might hinder the adoption of PDMS-based organs-on-chips for drug discovery assays. Here, we have engineered a modular, PDMS-free microphysiological system that is capable of recapitulating biologic barrier functions commonly demonstrated in PDMS-based devices. Our microphysiological system is comprised of a microfluidic chip to house cell cultures and pneumatic microfluidic pumps to drive flow with programmable pressure and shear stress. The modular architecture and programmable pumps enabled us to model multiple microenvironments. First, we demonstrate the ability to generate cyclic strain on the culture membrane and establish a model of the alveolar air-liquid interface. Next, we utilized three-dimensional finite element analysis modeling to characterize the fluid dynamics within the device and develop a model of the pressure-driven filtration that occurs at the glomerular filtration barrier. Finally, we demonstrate that our model can be used to recapitulate sphingolipid induced kidney injury. Together, our results demonstrate that a multifunctional and modular microphysiological system can be deployed without the use of PDMS. Further, the bio-inert plastic used in our microfluidic device is amenable to various established, high-throughput manufacturing techniques, such as injection molding. As a result, the development plastic organs-on-chips provides an avenue to meet the increasing demand for organ-on-chip technology.
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http://dx.doi.org/10.3389/fbioe.2020.581163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693638PMC
November 2020

A Chemically Defined Common Medium for Culture of C2C12 Skeletal Muscle and Human Induced Pluripotent Stem Cell Derived Spinal Spheroids.

Cell Mol Bioeng 2020 Dec 10;13(6):605-619. Epub 2020 Jun 10.

Department of Biomedical Engineering, DJTMF Biomedical Nanotechnology Institute, University of Miami, 1251 Memorial Dr, MEA 203, Coral Gables, FL 33146 USA.

Introduction: Multicellular platforms and linked multi organ on chip devices are powerful tools for drug discovery, and basic mechanistic studies. Often, a critical constraint is defining a culture medium optimal for all cells present in the system. In this study, we focused on the key cells of the neuromuscular junction i.e., skeletal muscle and motor neurons.

Methods: Formulation of a chemically defined medium for the co-culture of C2C12 skeletal muscle cells and human induced pluripotent stem cell (hiPSC) derived spinal spheroids (SpS) was optimized. C2C12 cells in 10 experimental media conditions and 2 topographies were evaluated over a 14-day maturation period to determine the ideal medium formulation for skeletal muscle tissue development.

Results: During early maturation, overexpression of genes for myogenesis and myopathy was observed for several media conditions, corresponding to muscle delamination and death. Together, we identified 3 media formulations that allowed for more controlled differentiation, healthier muscle tissue, and long-term culture duration. This evidence was then used to select media formulations to culture SpS and subsequently assessed axonal growth. As axonal growth in SpS cultures was comparable in all selected media conditions, our data suggest that the neuronal basal medium with no added supplements is the ideal medium formulation for both cell types.

Conclusions: Optimization using both topographical cues and culture media formulations provides a comprehensive analyses of culture conditions that are vital to future applications for NMJ models.
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http://dx.doi.org/10.1007/s12195-020-00624-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704992PMC
December 2020

Human-derived osteoblast-like cells and pericyte-like cells induce distinct metastatic phenotypes in primary breast cancer cells.

Exp Biol Med (Maywood) 2021 04 19;246(8):971-985. Epub 2020 Nov 19.

Department of Biomedical Engineering, DJTMF Biomedical Nanotechnology Institute, University of Miami, Miami, FL 33146, USA.

Approximately 70% of advanced breast cancer patients will develop bone metastases, which accounts for ∼90% of cancer-related mortality. Breast cancer circulating tumor cells (CTCs) establish metastatic tumors in the bone after a close interaction with local bone marrow cells including pericytes and osteoblasts, both related to resident mesenchymal stem/stromal cells (BM-MSCs) progenitors. recapitulation of the critical cellular players of the bone microenvironment and infiltrating CTCs could provide new insights into their cross-talk during the metastatic cascade, helping in the development of novel therapeutic strategies. Human BM-MSCs were isolated and fractionated according to CD146 presence. CD146+ cells were utilized as pericyte-like cells (PLCs) given the high expression of the marker in perivascular cells, while CD146- cells were induced into an osteogenic phenotype generating osteoblast-like cells (OLCs). Transwell migration assays were performed to establish whether primary breast cancer cells (3384T) were attracted to OLC. Furthermore, proliferation of 3384T breast cancer cells was assessed in the presence of PLC- and OLC-derived conditioned media. Additionally, conditioned media cultures as well as transwell co-cultures of each OLCs and PLCs were performed with 3384T breast cancer cells for gene expression interrogation assessing their induced transcriptional changes with an emphasis on metastatic potential. PLC as well as their conditioned media increased motility and invasion potential of 3384T breast cancer cells, while OLC induced a dormant phenotype, downregulating invasiveness markers related with migration and proliferation. Altogether, these results indicate that PLC distinctively drive 3384T cancer cells to an invasive and migratory phenotype, while OLC induce a quiescence state, thus recapitulating the different phases of the bone metastatic process. These data show that phenotypic responses from metastasizing cancer cells are influenced by neighboring cells at the bone metastatic niche during the establishment of secondary metastatic tumors.
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http://dx.doi.org/10.1177/1535370220971599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024509PMC
April 2021

Surgical Correction of Congenital Double Lip.

Ann Maxillofac Surg 2020 Jan-Jun;10(1):198-202. Epub 2020 Jun 8.

Department of Periodontology and Implantology, Institute of Dental Sciences, Bareilly, Uttar Pradesh, India.

Double lip is an unusual clinical finding, considered to be a developmental anomaly, and usually involving the upper lip more frequently than the lower lip. It may be seen in isolation or in association with Ascher's syndrome. It is caused by excessive areolar tissue and noninflammatory labial mucosa gland hyperplasia of pars villosa. During smiling, the lip is retracted, and the mucosa is positioned over the maxillary teeth, resulting in "cupid's bow" appearance. The incidence of this anomaly is not known. It has been reported in cleft patients, following lip trauma, and as a consequence of lip-biting habits. It might pose esthetic or functional problems and may be a reason for psychological stress to the affected individual because of over shown hyperplastic lip tissue. Surgical treatment is indicated for the correction of this disfigurement. Various surgical techniques have been suggested to address the double upper lip anomaly. All of these involve the excision of excessive mucosa and the underlying tissue. This case series puts forward the surgical management of this rare anomaly in a relatively simple manner. Double lip is a subject of interest to the dental clinicians because they usually are the first professionals to detect, identify, and treat this uncommon condition.
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http://dx.doi.org/10.4103/ams.ams_271_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433968PMC
June 2020

Relative frequency of oral focal reactive overgrowths: An institutional retrospective study.

J Oral Maxillofac Pathol 2020 Jan-Apr;24(1):76-80. Epub 2020 May 8.

Department of Oral Pathology and Microbiology, Bareilly International University, Institute of Dental Sciences, Bareilly, Uttar Pradesh, India.

Context: Focal fibrous hyperplasia, peripheral ossifying fibroma, pyogenic granuloma, peripheral giant cell granuloma, giant cell fibroma and focal reactive overgrowth (FROGs) are one of the foremost numerous benign soft-tissue growths in the oral cavity. Chronic irritation or trauma is with identified as the causative aspect. It may develop up to few centimeters in diameter, pedunculated or sessile and may arise on the gingiva or buccal mucosa. Treatment involves surgical excision, and recurrences are infrequent.

Aims: The aim of this study was to assess the prevalence of FROGs of oral mucosa in an institutional setup.

Subjects And Methods: All the histopathologically diagnosed cases of FROGs within a period of 10 years (January 2008-December 2017) were retrieved from the archives of the Department of Oral Pathology. The information such as age, sex, site, anatomical side and its prevalence were recorded on customized case history performa.

Statistical Analysis Used: The significance of difference was assessed using the Chi-square test and Fisher's exact test.

Results: A total of 2849 cases were identified, of which 449 (15%) were FROGs. The most prevalent lesion amid them were focal fibrous hyperplasia (277, 62%), followed by pyogenic granuloma (92, 20%), whereas the least common was giant cell fibroma with 2 (0.5%) cases. All the FROGs were distributed among 21-40 years of age showing female predominance. The commonly affected site was the right buccal mucosa.

Conclusions: Nevertheless, information of the frequency and distribution of these lesions is favorable when establishing a diagnosis and treatment plan in clinical practice.
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http://dx.doi.org/10.4103/jomfp.JOMFP_350_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269285PMC
May 2020

Microelectrode Array based Functional Testing of Pancreatic Islet Cells.

Micromachines (Basel) 2020 May 17;11(5). Epub 2020 May 17.

Department of Biomedical Engineering, University of Miami, Coral Gables, FL 33146, USA.

Electrophysiological techniques to characterize the functionality of islets of Langerhans have been limited to short-term, one-time recordings such as a patch clamp recording. We describe the use of microelectrode arrays (MEAs) to better understand the electrophysiology of dissociated islet cells in response to glucose in a real-time, non-invasive method over prolonged culture periods. Human islets were dissociated into singular cells and seeded onto MEA, which were cultured for up to 7 days. Immunofluorescent imaging revealed that several cellular subtypes of islets; β, δ, and γ cells were present after dissociation. At days 1, 3, 5, and 7 of culture, MEA recordings captured higher electrical activities of islet cells under 16.7 mM glucose (high glucose) than 1.1 mM glucose (low glucose) conditions. The fraction of the plateau phase (FOPP), which is the fraction of time with spiking activity recorded using the MEA, consistently showed distinguishably greater percentages of spiking activity with high glucose compared to the low glucose for all culture days. In parallel, glucose stimulated insulin secretion was measured revealing a diminished insulin response after day 3 of culture. Additionally, MEA spiking profiles were similar to the time course of insulin response when glucose concentration is switched from 1.1 to 16.7 mM. Our analyses suggest that extracellular recordings of dissociated islet cells using MEA is an effective approach to rapidly assess islet functionality, and could supplement standard assays such as glucose stimulate insulin response.
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http://dx.doi.org/10.3390/mi11050507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281363PMC
May 2020

Signature quality attributes of CD146 mesenchymal stem/stromal cells correlate with high therapeutic and secretory potency.

Stem Cells 2020 08 16;38(8):1034-1049. Epub 2020 May 16.

Department of Orthopaedics, UHealth Sports Medicine Institute, University of Miami, Miller School of Medicine, Miami, Florida, USA.

CD146 bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) play key roles in the perivascular niche, skeletogenesis, and hematopoietic support; however, comprehensive evaluation of therapeutic potency has yet to be determined. In this study, in vitro inflammatory priming to crude human BM-MSCs (n = 8) captured a baseline of signature responses, including enriched CD146 with coexpression of CD107a , CXCR4 , and LepR , transcriptional profile, enhanced secretory capacity, and robust immunomodulatory secretome and function, including immunopotency assays (IPAs) with stimulated immune cells. These signatures were significantly more pronounced in CD146 (POS)-sorted subpopulation than in the CD146 (NEG). Mechanistically, POS BM-MSCs showed a markedly higher secretory capacity with significantly greater immunomodulatory and anti-inflammatory protein production upon inflammatory priming compared with the NEG BM-MSCs. Moreover, IPAs with stimulated peripheral blood mononuclear cells and T lymphocytes demonstrated robust immunosuppression mediated by POS BM-MSC while inducing significant frequencies of regulatory T cells. in vivo evidence showed that POS BM-MSC treatment promoted pronounced M1-to-M2 macrophage polarization, ameliorating inflammation/fibrosis of knee synovium and fat pad, unlike treatment with NEG BM-MSCs. These data correlate the expression of CD146 with innately higher immunomodulatory and secretory capacity, and thus therapeutic potency. This high-content, reproducible evidence suggests that the CD146 (POS) MSC subpopulation are the mediators of the beneficial effects achieved using crude BM-MSCs, leading to translational implications for improving cell therapy and manufacturing.
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http://dx.doi.org/10.1002/stem.3196DOI Listing
August 2020

Integrated human pseudoislet system and microfluidic platform demonstrate differences in GPCR signaling in islet cells.

JCI Insight 2020 05 21;5(10). Epub 2020 May 21.

Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Pancreatic islets secrete insulin from β cells and glucagon from α cells, and dysregulated secretion of these hormones is a central component of diabetes. Thus, an improved understanding of the pathways governing coordinated β and α cell hormone secretion will provide insight into islet dysfunction in diabetes. However, the 3D multicellular islet architecture, essential for coordinated islet function, presents experimental challenges for mechanistic studies of intracellular signaling pathways in primary islet cells. Here, we developed an integrated approach to study the function of primary human islet cells using genetically modified pseudoislets that resemble native islets across multiple parameters. Further, we developed a microperifusion system that allowed synchronous acquisition of GCaMP6f biosensor signal and hormone secretory profiles. We demonstrate the utility of this experimental approach by studying the effects of Gi and Gq GPCR pathways on insulin and glucagon secretion by expressing the designer receptors exclusively activated by designer drugs (DREADDs) hM4Di or hM3Dq. Activation of Gi signaling reduced insulin and glucagon secretion, while activation of Gq signaling stimulated glucagon secretion but had both stimulatory and inhibitory effects on insulin secretion, which occur through changes in intracellular Ca2+. The experimental approach of combining pseudoislets with a microfluidic system allowed the coregistration of intracellular signaling dynamics and hormone secretion and demonstrated differences in GPCR signaling pathways between human β and α cells.
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http://dx.doi.org/10.1172/jci.insight.137017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259531PMC
May 2020

Chlorinated polyvinyl chloride (CPVC) assisted leaching of lithium and cobalt from spent lithium-ion battery in subcritical water.

J Hazard Mater 2020 Jul 22;393:122367. Epub 2020 Feb 22.

Department of Environment and Energy Engineering, Chonnam National University, Yongbong-ro 77, Buk-gu, Gwangju, 61186, Republic of Korea. Electronic address:

The objective of this study was to determine leaching efficiency of Li and Co from spent lithium-ion batteries (LIBs) by using waste chlorinated polyvinyl chloride (CPVC) in hydrothermal subcritical water process. Waste CPVC was used as the source of HCl to speed up leaching efficiency. Effects of temperature, time, LiCoO: CPVC mass ratio and liquid-solid ratio on leaching efficiencies of Li and Co were investigated. Solid residues were characterized by XRD and SEM-EDS elemental mapping to predict chemical compounds remained after leaching. Results showed that more than 98.71 % of Li and 97.69 % of Co were effectively leached from LiCoO powder under the following conditions: temperature of 250 °C, reaction time of 60 min, and LiCoO: CPVC mass ratio of 1:3. Results of this study suggest that recovery of Li and Co from spent LIBs using hydrothermal subcritical water is an efficient, environmental friendly and sustainable technology.
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http://dx.doi.org/10.1016/j.jhazmat.2020.122367DOI Listing
July 2020

Intra-Arterial Chemotherapy for Retinoblastoma: Four-Year Results from Tertiary Center in India.

Ocul Oncol Pathol 2020 Jan 4;6(1):66-73. Epub 2019 Jun 4.

Apollo Institute of Interventional Radiology, Apollo Hospital, Chennai, India.

Background: There are limited reports of intra-arterial chemotherapy (IAC) for retinoblastoma (RB) from developing world.

Objectives: In this study, we report our 4-year experience of IAC for RB from India.

Methods: Retrospective, interventional case series. Primary outcome measures included tumor regression, vitreous seeds and subretinal seeds control, and globe salvage. Secondary outcome measures were best-corrected visual acuity and treatment complications.

Results: Fifteen eyes underwent 53 IAC procedures over mean 28.6 ± 13.8 months (range 10-51 months). IAC was employed as primary ( = 6) or secondary ( = 9) chemotherapy. Following IAC, complete regression of main tumor was seen in 7 eyes (47%) and partial regression in 3 (20%) eyes. Enucleation was done in 5(33%) eyes. Globe salvage rates were achieved in 1 eye (100%) in group B, 2 eyes (67%) in group C ( = 3), 6 eyes (67%) in group D ( = 9), and 1 eye (50%) in group E ( = 2). Following IAC, Kaplan-Meier survival curve showed 93% globe survival rate at 1 year, 76% at 2 years, and 66% at 3, and 4 years.

Conclusion: IAC has enhanced globe salvage rates in eyes with RB. Multicenter studies with longer follow-up are necessary to better understand outcomes in the long term.
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http://dx.doi.org/10.1159/000500010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984160PMC
January 2020

Enzymatically crosslinked gelatin-laminin hydrogels for applications in neuromuscular tissue engineering.

Biomater Sci 2020 Jan;8(2):591-606

Department of Biomedical Engineering, University of Miami, 1251 Memorial Dr, MEA 203, Coral Gables, FL 33146, USA.

We report a water-soluble and non-toxic method to incorporate additional extracellular matrix proteins into gelatin hydrogels, while obviating the use of chemical crosslinkers such as glutaraldehyde. Gelatin hydrogels were fabricated using a range of gelatin concentrations (4%-10%) that corresponded to elastic moduli of approximately 1 kPa-25 kPa, respectively, a substrate stiffness relevant for multiple cell types. Microbial transglutaminase was then used to enzymatically crosslink a layer of laminin on top of gelatin hydrogels, resulting in 2-component gelatin-laminin hydrogels. Human induced pluripotent stem cell derived spinal spheroids readily adhered and rapidly extended axons on GEL-LN hydrogels. Axons displayed a more mature morphology and superior electrophysiological properties on GEL-LN hydrogels compared to the controls. Schwann cells on GEL-LN hydrogels adhered and proliferated normally, displayed a healthy morphology, and maintained the expression of Schwann cell specific markers. Lastly, skeletal muscle cells on GEL-LN hydrogels achieved long-term culture for up to 28 days without delamination, while expressing higher levels of terminal genes including myosin heavy chain, MyoD, MuSK, and M-cadherin suggesting enhanced maturation potential and myotube formation compared to the controls. Future studies will employ the superior culture outcomes of this hybrid substrate for engineering functional neuromuscular junctions and related organ on a chip applications.
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http://dx.doi.org/10.1039/c9bm01430fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141910PMC
January 2020

Engineering anisotropic cardiac monolayers on microelectrode arrays for non-invasive analyses of electrophysiological properties.

Analyst 2019 Dec;145(1):139-149

Department of Biomedical Engineering, University of Miami, Coral Gables, FL, USA.

A standard culture of cardiac cells as unorganized monolayers on tissue culture plastic or glass does not recapitulate the architectural or the mechanical properties of native myocardium. We investigated the physical and protein cues from the extracellular matrix to engineer anisotropic cardiac tissues as highly aligned monolayers on top of the microelectrode array (MEA). The MEA platform allows non-invasive measurement of beating rate and conduction velocity. The effect of different extracellular proteins was tested by using the most common extracellular matrix proteins in the heart, fibronectin and gelatin, after aligning myocytes using a microcontact (μC) printing technique. Both proteins showed similar electrophysiological results before the monolayer began to delaminate after the sixth day of culture. Additionally, there were no significant differences on day 4 between the two microcontact printed proteins in terms of sarcomere alignment and gap junction expression. To test the effect of substrate stiffness, a micromolded (μM) gelatin hydrogel was fabricated in different concentrations (20% and 2%), corresponding to the elastic moduli of approximately 33 kPa and 0.7 kPa, respectively, to cover both spectra of the in vivo range of myocardium. Cardiac monolayers under micromolded conditions beat in a much more synchronized fashion, and exhibited conduction velocity that was close to the physiological value. Both concentrations of gelatin hydrogel conditions yielded similar sarcomere alignment and gap junction expression on day 4 of culture. Ultimately, the 3D micromolded gelatin hydrogel that recapitulated myocardial stiffness improved the synchronicity and conduction velocity of neonatal rat ventricular myocytes (NRVM) without any stimulation. Identifying such microenvironmental factors will lead to future efforts to design heart on a chip platforms that mimic in vivo environment and predict potential cardiotoxicity when testing new drugs.
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http://dx.doi.org/10.1039/c9an01339cDOI Listing
December 2019

Evaluating Vascularization of Heterotopic Islet Constructs for Type 1 Diabetes Using an In Vitro Platform.

Integr Biol (Camb) 2019 11;11(8):331-341

Department of Biomedical Engineering, University of Miami, Coral Gables, FL, USA.

Type 1 diabetes (T1D) results from the autoimmune destruction of β-cells within the pancreatic islets of Langerhans. Clinical islet transplantation from healthy donors is proposed to ameliorate symptoms, improve quality of life, and enhance the life span of afflicted T1D patients. However, post-transplant outcomes are dependent on the survival of the transplanted islets, which relies on the engraftment of the islets with the recipient's vasculature among other factors. Treatment strategies to improve engraftment include combining islets with supporting cells including endothelial cells (EC) and mesenchymal stem cells (MSC), dynamic cells capable of robust immunomodulatory and vasculogenic effects. In this study, we developed an in vitro model of transplantation to investigate the cellular mechanisms that enhance rapid vascularization of heterotopic islet constructs. Self-assembled vascular beds of fluorescently stained EC served as reproducible in vitro transplantation sites. Heterotopic islet constructs composed of islets, EC, and MSC were transferred to vascular beds for modeling transplantation. Time-lapsed imaging was performed for analysis of the vascular bed remodeling for parameters of neo-vascularization. Moreover, sampling of media following modeled transplantation showed secretory profiles that were correlated with imaging analyses as well as with islet function using glucose-stimulated insulin secretion. Together, evidence revealed that heterotopic constructs consisting of islets, EC, and MSC exhibited the most rapid recruitment and robust branching of cells from the vascular beds suggesting enhanced neo-vascularization compared to islets alone and control constructs. Together, this evidence supports a promising cell transplantation strategy for T1D and also demonstrates a valuable tool for rapidly investigating candidate cellular therapies for transplantation.
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http://dx.doi.org/10.1093/intbio/zyz027DOI Listing
November 2019

Survival of Implants after Indirect Maxillary Sinus Elevation Procedure: A Two Years Longitudinal Study.

J Contemp Dent Pract 2019 Apr 1;20(4):504-507. Epub 2019 Apr 1.

Bali Dental Clinic, New Delhi, India.

Aim: The aim of the study was to evaluate the survival rate of two diverse implant systems with different implant surfaces with the same geometrical design.

Materials And Methods: One hundred fifty patients were included in the study in which 95 were males and 55 were females and 150 implants were placed using indirect sinus floor elevation technique and only one implant was placed in each subject and they were categorized into two groups of 100 in group A and 50 in group B as per two different implant systems. At review appointments, implants were tested clinically and radiographically and were examined for signs of infection. The patients were examined periodically after placement of the implants, and follow-up was conducted annually.

Results: Results of the Chi-square analysis showed no significant association between the type of implant surface and rate of success or failure of the implant. There was no significant difference between the observed and expected frequency of successful implants in group A as well as group B, indicating that the surface type of implant had no significant association with the success of the implant in group A and B.

Conclusion: To date, there is no consensus in the literature regarding the best surface and even on the macrotopography of the implants for better osseointegration. However, Surface treatments improve the result of osseointegration, especially in the early stages, benefiting bone affixation with qualitative and quantitative enhancements. In the present study, we achieved clinical success with both kinds of implant surfaces however Bioetched implant surface showed promising results comparable to Tiunite surface of Nobel BioCare Implants. In the future, more case-controlled studies with longer follow-up are needed to validate the results of the present findings.
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April 2019

Surgical outcomes of vitreoretinal surgery for rhegmatogenous retinal detachment in eyes with regressed retinopathy of prematurity.

Indian J Ophthalmol 2019 06;67(6):896-902

Shri Bhagwan Mahavir Vitreoretinal Services, Medical Research Foundation, Sankara Nethralaya, Chennai, Tamil Nadu, India.

Purpose: To report the anatomical and functional outcomes of vitreoretinal surgery in eyes with "regressed ROP" presenting with rhegmatogenous retinal detachment (RRD).

Methods: In this retrospective interventional case series, twenty-two eyes (of 22 patients) with regressed ROP, who underwent surgery for RD. Primary outcome measures were final anatomical and visual outcome for scleral buckling and pars plana vitrectomy (PPV). Visual outcomes were categorized into three groups: improved, remained stable, and deteriorated. Univariate binary logistic regression analysis was used to determine the risk factors for RD.

Results: Of 22 eyes in the study, overall anatomic success was achieved in 16 of 22 eyes (72.7%). The macula was attached in 17 of 22 eyes (77.3%) at final visit. In the scleral buckle (SB) group, overall anatomical success was achieved in six of seven eyes (85.7%). Overall, in the PPV group, anatomical success was seen in 10 of 15 eyes (66.7%) at final visit. At final follow-up, significant improvement in best-corrected visual acuity from baseline was seen in 11 cases (50%, P = 0.02), stable in 5 cases (22.7%), and significant visual deterioration was seen in 6 cases (27.3%, P = 0.02). The total mean follow-up duration of the patients was 45.5 months (range: 2.1 months to 11.2 years).

Conclusion: Early recognition and surgical intervention in such cases can lead to a high rate of anatomical success and can prevent the development of profound visual impairment in some patients.
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http://dx.doi.org/10.4103/ijo.IJO_706_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6552606PMC
June 2019

Prevalence of oral squamous cell carcinoma in Bareilly Region: A seven year institutional study.

J Exp Ther Oncol 2018 Nov;12(4):323-330

Department of Oral and Maxillofacial Pathology, Bareilly International University, Institute of Dental Sciences, Bareilly, (UP), India.

Background: Oral squamous cell carcinoma is a major contributor to disability and death caused by malignant tumors. Variations in social, cultural, and geographic factors affect the tumor behavior and response to treatment. In this study, we undertake a seven years institutional review and analysis of Oral squamous cell carcinoma cases in Bareilly.

Materials And Methods: A total of 1938 histologically diagnosed cases during the period of seven years i.e. from 2010 to 2016 were extracted from the archives of Department of Oral & Maxillofacial Pathology, Institute of Dental Sciences, Bareilly and evaluated to know the prevalence of Oral squamous cell carcinoma. The details like age, sex, habits and anatomical site were also recorded from the archived patient's case sheets.

Results: Out of the total 1938 cases, 318 were found to be Oral squamous cell carcinoma of which 232 were males and 86 were females. Incidence was highest in 40-49 year age group. The most common site was buccal mucosa (190 cases), followed by tongue (68 cases). Most lesions were well differentiated Oral squamous cell carcinoma (230 cases). Patients with poorly differentiated lesions had a comparatively lower mean age than their counterparts with other histological varieties.

Conclusion: The pattern of Oral squamous cell carcinoma differs from that of previous studies in relation to incidence and age correlation with the grade of carcinoma. The majority of the lesions were well differentiated. There is a need for intensive oral health awareness to encourage early presentation to cancer center as early detection will further enhance prognosis.
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November 2018

Outcome of vitreoretinal surgery for rhegmatogenous retinal detachment in X-linked juvenile retinoschisis.

Indian J Ophthalmol 2018 Dec;66(12):1825-1831

Medical Research Foundation, Sankara Nethralaya, Chennai, Tamil Nadu, India.

Purpose: Rhegmatogenous retinal detachment (RRD) is a vision-threatening complication of X-linked juvenile retinoschisis (XLRS). The aim of this study is to report the anatomical and functional outcomes of vitreoretinal surgery for the treatment of RRD in X-linked juvenile retinoschisis (XLRS).

Methods: This is a retrospective, interventional, consecutive case series in which case records of 34 eyes of 28 XLRS patients, who underwent surgery for RRD, were reviewed. Statistical analysis used is as follows: visual outcomes were categorized into three groups: improved, remained stable or deteriorated. Wilcoxon signed-rank test was used to determine the difference in visual acuity at baseline and at final visit. Univariate binary logistic regression analysis was used to determine the risk factors for retinal detachment. Any P value < 0.05 was considered as statistical significant.

Results: Mean age of the boys at presentation was 9.2 ± 3.5 years. Indication for surgery was RRD in all eyes. Concurrent vitreous haemorrhage was present in four eyes (11.8%). The primary surgical intervention was scleral buckle in 12 eyes and pars plana vitrectomy in 22 eyes. Persistence of subretinal fluid/redetachment was seen in 15 eyes of which 11 eyes underwent additional surgeries. At final follow up, 27 eyes (79.4%) were noted to have an attached retina. Of the total eyes, in 20, 6 and 8 eyes the visual acuity improved, stabilized and deteriorated, respectively.

Conclusion: Favourable outcomes are seen in a majority of eyes after vitreoretinal surgery for RRD in XLRS; however, multiple surgical interventions may be necessary.
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http://dx.doi.org/10.4103/ijo.IJO_607_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256875PMC
December 2018

Ultimate Control over Hydrogen Bond Formation and Reaction Rates for Scalable Synthesis of Highly Crystalline vdW MOF Nanosheets with Large Aspect Ratio.

Adv Mater 2018 Dec 2;30(52):e1802497. Epub 2018 Nov 2.

School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ, 85287, USA.

Large-scale synthesis of van der Waals (vdW) metal-organic framework (MOF) nanosheets with controlled crystallinity and interlayer coupling strength is one of the bottlenecks in 2D materials that has limited its successful transition to large-scale applications. Here, scalable synthesis of mBDC (m = Zn and Cu) 2D MOFs at large scales through a biphase method is demonstrated. The results show replacing water molecules with pyridine eliminates hydrogen bond formation at metal cluster sites. This prohibits tight coupling across adjacent MOF layers and sustains controllable 2D vdW MOF growth. It is further shown that control over the growth speed, crystallinity, and thickness can be achieved by addition of a controlled amount of triethylamine and formic acid to achieve highly crystalline vdW MOF nanosheets with extraordinarily high aspect ratio. The described synthesis route can easily be scaled up for large-scale production either by deposition onto desired substrates or in crystalline layered powder form. Owing to its large lateral size, vdW nature, and high crystallinity, it is possible to perform atomic force microscopy, Kelvin probe force microscopy, and Raman measurements on the 2D MOFs. The results not only establish their vibrational properties and layer-dependent responses but also show striking differences from other 2D inorganic materials.
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http://dx.doi.org/10.1002/adma.201802497DOI Listing
December 2018

Anomalous isoelectronic chalcogen rejection in 2D anisotropic vdW TiSSe trichalcogenides.

Nanoscale 2018 Aug;10(33):15654-15660

School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, Arizona 85287, USA.

Alloying in semiconductors has enabled many civilian technologies in electronics, optoelectronics, photonics, and others. While the alloying phenomenon is well established in traditional bulk semiconductors owing to a vast array of available ternary phase diagrams, alloying in 2D materials still remains at its seminal stages. This is especially true for transition metal trichalcogenides (TMTCs) such as TiS3 which has been recently predicted to be a direct gap, high carrier mobility, pseudo-1D semiconductor. In this work, we report on an unusual alloying rejection behavior in TiS3(1-x)Se3x vdW crystals. TEM, SEM, EDS, and angle-resolved Raman measurements show that only a miniscule amount (8%) of selenium can be successfully alloyed into a TiS3 host matrix despite vastly different precursor amounts as well as growth temperatures. This unusual behavior contrasts with other vdW systems such as TiS2(1-x)Se2x, MoS2(1-x)Se2x, Mo1-xWxS2, WS2(1-x)Se2x, where continuous alloying can be attained. Angle-resolved Raman and kelvin probe force microscopy measurements offer insights into how selenium alloying influences in-plane structural anisotropy as well as electron affinity values of exfoliated sheets. Our cluster expansion theory calculations show that only the alloys with a small amount of Se can be attained due to energetic instability above/below a certain selenium concentration threshold in the ternary phase diagrams. The overall findings highlight potential challenges in achieving stable Ti based TMTCs alloys.
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http://dx.doi.org/10.1039/c8nr04274hDOI Listing
August 2018

An Unusual Case of Split Cord Malformation with Simultaneous Ventral and Dorsal Bony Spur at a Single Site: A Technical Challenge.

J Pediatr Neurosci 2018 Apr-Jun;13(2):214-217

Department of Neurosurgery and Gamma Knife, All India Institute of Medical Sciences, New Delhi, India.

Split cord malformation (SCM) with simultaneous ventral and dorsal bony spur at a single site is an extremely rare entity with only one other case reported so far. We present a second such case in a 13-month-old female child, who presented with a skin dimple over the lumbar region with overlying hairy patch without any associated lower limb weakness or urinary complaints. Imaging demonstrated a complex Type I SCM with simultaneous ventral and dorsal bony spur at L4-L5 level. Intraoperatively, the patient was confirmed to have a Type Ic SCM with a ventrally based bony spur going dorsally to attach on the hypertrophied posterior arch of L4 and a dorsal spur going ventrally to attach on the L4 vertebral body. After meticulous microsurgical excision of the spur, the child was stable and developed no fresh neurological deficits. We discuss the relevant surgical implications and possible embryological mechanisms involved in such a complex SCM.
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http://dx.doi.org/10.4103/jpn.JPN_99_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057206PMC
August 2018

Circulating Tumor Cells: Strategies for Capture, Analyses, and Propagation.

Cancer J 2018 Mar/Apr;24(2):70-77

Circulating tumor cells (CTCs) play a central role in tumor dissemination and metastases, which are ultimately responsible for most cancer deaths. Technologies that allow for identification and enumeration of rare CTC from cancer patients' blood have already established CTC as an important clinical biomarker for cancer diagnosis and prognosis. Indeed, current efforts to robustly characterize CTC as well as the associated cells of the tumor microenvironment such as circulating cancer associated fibroblasts (cCAF), are poised to unmask key insights into the metastatic process. Ultimately, the clinical utility of CTC will be fully realized once CTC can be reliably cultured and proliferated as a biospecimen for precision management of cancer patients, and for discovery of novel therapeutics. In this review, we highlight the latest CTC capture and analyses technologies, and discuss in vitro strategies for culturing and propagating CTC.
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http://dx.doi.org/10.1097/PPO.0000000000000310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5880323PMC
March 2019

Traction force microscopy of engineered cardiac tissues.

PLoS One 2018 28;13(3):e0194706. Epub 2018 Mar 28.

Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, United States of America.

Cardiac tissue development and pathology have been shown to depend sensitively on microenvironmental mechanical factors, such as extracellular matrix stiffness, in both in vivo and in vitro systems. We present a novel quantitative approach to assess cardiac structure and function by extending the classical traction force microscopy technique to tissue-level preparations. Using this system, we investigated the relationship between contractile proficiency and metabolism in neonate rat ventricular myocytes (NRVM) cultured on gels with stiffness mimicking soft immature (1 kPa), normal healthy (13 kPa), and stiff diseased (90 kPa) cardiac microenvironments. We found that tissues engineered on the softest gels generated the least amount of stress and had the smallest work output. Conversely, cardiomyocytes in tissues engineered on healthy- and disease-mimicking gels generated significantly higher stresses, with the maximal contractile work measured in NRVM engineered on gels of normal stiffness. Interestingly, although tissues on soft gels exhibited poor stress generation and work production, their basal metabolic respiration rate was significantly more elevated than in other groups, suggesting a highly ineffective coupling between energy production and contractile work output. Our novel platform can thus be utilized to quantitatively assess the mechanotransduction pathways that initiate tissue-level structural and functional remodeling in response to substrate stiffness.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194706PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874032PMC
July 2018

Engineered Microenvironments for Maturation of Stem Cell Derived Cardiac Myocytes.

Theranostics 2018 1;8(1):124-140. Epub 2018 Jan 1.

Department of Biomedical Engineering, University of Miami.

Through the use of stem cell-derived cardiac myocytes, tissue-engineered human myocardial constructs are poised for modeling normal and diseased physiology of the heart, as well as discovery of novel drugs and therapeutic targets in a human relevant manner. This review highlights the recent bioengineering efforts to recapitulate microenvironmental cues to further the maturation state of newly differentiated cardiac myocytes. These techniques include long-term culture, co-culture, exposure to mechanical stimuli, 3D culture, cell-matrix interactions, and electrical stimulation. Each of these methods has produced various degrees of maturation; however, a standardized measure for cardiomyocyte maturation is not yet widely accepted by the scientific community.
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http://dx.doi.org/10.7150/thno.19441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743464PMC
November 2018

Hospital anxiety and depression scale assessment of 100 patients before and after using low vision care: A prospective study in a tertiary eye-care setting.

Indian J Ophthalmol 2017 Nov;65(11):1203-1208

Low Vision Care Clinic, Chennai, Tamil Nadu, India.

Purpose: Assessment of anxiety and depression in patients attending low vision care (LVC) using Hospital Anxiety and Depression Scale (HADS).

Methods: In this prospective, observational study, 100 patients with best-corrected visual acuity (BCVA) worse than 6/18 in the better eye or limitation of field of vision to <10° from center of fixation were assessed on the depression and anxiety subscales of HADS questionnaire before and after LVC. HADS is a 14-item scale with seven items each for anxiety and depression subscales. Scoring for each item ranges from zero to three. A subscale score >8 denotes anxiety or depression.

Results: Mean age at presentation was 38.2 years. Mean duration of symptoms was 9.6 years. Underlying etiology of visual impairment included retinal dystrophy/degeneration (n = 35), disorders of the optic nerve (n = 17), glaucoma (n = 10), diabetic retinopathy (n = 9), age-related macular degeneration (n = 5), uncorrected refractive errors (n = 5), and miscellaneous diseases (n = 19). Mean presenting BCVA in the better eye was 0.83 (±0.64) which improved significantly to 0.78 (±0.63) after LVC (P < 0.001). The HADS-Depression subscale score was comparable for severity of visual impairment for both distance (P = 0.57) and near vision (P = 0.61). Similarly, HADS-Anxiety scores were also comparable for severity of distance (P = 0.34) and near-visual impairment (NVI; P = 0.50). At baseline, mean HADS-Depression and HADS-Anxiety scores were 8.4 (±3.7) and 9.6 (±4.3) points, which improved significantly to 6.0 (±3.4) and 6.7 (±3.7), respectively, after low-vision correction (P < 0.001).

Conclusion: Low vision correction can significantly improve anxiety and depression indicators in visually impaired patients.
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http://dx.doi.org/10.4103/ijo.IJO_436_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700594PMC
November 2017

Microfilter-Based Capture and Release of Viable Circulating Tumor Cells.

Methods Mol Biol 2017 ;1634:93-105

Department of Biomedical Engineering, University of Miami, 1251 Memorial Drive, McArthur Engineering Building, Coral Gables, FL, 33146, USA.

Microfilters with slot-pore geometry can be used for size-based capture of circulating tumor cells (CTC) from the blood of cancer patients. The slot pore geometry reduces the shear stress that the cells would typically experience during filtration process and allows the cells to remain viable. The microfilter provides a platform capable of high CTC capture efficiency; however, the release of these cells from the filter following capture is nontrivial, possibly due to the strong nonspecific electrostatic adhesion of CTC to the microfilter surface. Techniques such as reverse flow or cell scraping result in recovery of only a small percentage of captured cells. We describe, in detail, a protocol for novel application of thermo-responsive polymer poly(N-iso-propylacrylamide) (PIPAAm) to release viable CTCs from microfilters with slot pores. Following fabrication of the microfilter, a coating of PIPAAm is applied to the surface to exploit its thermoresponsive interfacial properties to release the cells. Typically, cancer patient's blood is filtered at room temperature (below 32 °C) when PIPAAm is hydrophilic. Thereafter, the filter is placed in either culture medium or a buffer maintained at 37 °C, which renders PIPAAm hydrophobic, allowing subsequent release of the electrostatically bound cells with high efficiency. Using this method, viable CTC captured directly from cancer patients' blood can be subjected to downstream off-chip culture, analyses, and characterization.
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http://dx.doi.org/10.1007/978-1-4939-7144-2_7DOI Listing
April 2018

Enhanced microbubbles assisted cleaning of diesel contaminated sand.

Mar Pollut Bull 2017 Nov 25;124(1):331-335. Epub 2017 Jul 25.

Advanced Environmental Biotechnology Centre, Nanyang Environment and Water Research Institute, Nanyang Technological University, 1 Cleantech Loop, Singapore 637141, Singapore; School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore. Electronic address:

In this article, we investigated the effect of low intensity pulsed ultrasound (US), temperature and salinity on cleaning efficacy of fine bubbles with diameter <50μm for diesel contaminated sands. About 47% and 76% diesel removal was achieved from 10% (w/w) diesel contaminated fine and medium sands respectively, after 30min treatment with 40kHz low intensity intermittent pulsed US together with MBs in contrast to 41% and 68% diesel removal while treatment with MBs alone. The effect of high temperature was found to be prominent during the initial stages of cleaning. In addition, MBs generated in 599mM saline water efficiently removed 85% diesel from fine sand within 30min in contrast to only 41% diesel removal with MBs in fresh water. This study provides evidence for developing highly efficient MBs based chemical free technology for diesel contaminated sediments.
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http://dx.doi.org/10.1016/j.marpolbul.2017.07.041DOI Listing
November 2017

Identification and Quantitation of Circulating Tumor Cells.

Annu Rev Anal Chem (Palo Alto Calif) 2017 06 6;10(1):321-343. Epub 2017 Mar 6.

Department of Pathology, DJTMF Biomedical Nanotechnology Institute, University of Miami, Coral Gables, Florida 33146.

Circulating tumor cells (CTCs) are shed from the primary tumor into the circulatory system and act as seeds that initiate cancer metastasis to distant sites. CTC enumeration has been shown to have a significant prognostic value as a surrogate marker in various cancers. The widespread clinical utility of CTC tests, however, is still limited due to the inherent rarity and heterogeneity of CTCs, which necessitate robust techniques for their efficient enrichment and detection. Significant recent advances have resulted in technologies with the ability to improve yield and purity of CTC enrichment as well as detection sensitivity. Current efforts are largely focused on the translation and standardization of assays to fully realize the clinical utility of CTCs. In this review, we aim to provide a comprehensive overview of CTC enrichment and detection techniques with an emphasis on novel approaches for rapid quantification of CTCs.
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http://dx.doi.org/10.1146/annurev-anchem-061516-045405DOI Listing
June 2017

Resealable, optically accessible, PDMS-free fluidic platform for ex vivo interrogation of pancreatic islets.

Lab Chip 2017 02;17(5):772-781

Department of Biomedical Engineering, Department of Pathology & Laboratory Medicine, University of Miami, Miami, FL 33136, USA. and Diabetes Research Institute, University of Miami, USA.

We report the design and fabrication of a robust fluidic platform built out of inert plastic materials and micromachined features that promote optimized convective fluid transport. The platform is tested for perfusion interrogation of rodent and human pancreatic islets, dynamic secretion of hormones, concomitant live-cell imaging, and optogenetic stimulation of genetically engineered islets. A coupled quantitative fluid dynamics computational model of glucose stimulated insulin secretion and fluid dynamics was first utilized to design device geometries that are optimal for complete perfusion of three-dimensional islets, effective collection of secreted insulin, and minimization of system volumes and associated delays. Fluidic devices were then fabricated through rapid prototyping techniques, such as micromilling and laser engraving, as two interlocking parts from materials that are non-absorbent and inert. Finally, the assembly was tested for performance using both rodent and human islets with multiple assays conducted in parallel, such as dynamic perfusion, staining and optogenetics on standard microscopes, as well as for integration with commercial perfusion machines. The optimized design of convective fluid flows, use of bio-inert and non-absorbent materials, reversible assembly, manual access for loading and unloading of islets, and straightforward integration with commercial imaging and fluid handling systems proved to be critical for perfusion assay, and particularly suited for time-resolved optogenetics studies.
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http://dx.doi.org/10.1039/c6lc01504bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330806PMC
February 2017
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