Design and fabrication of heart muscle using scaffold-based tissue engineering

Cardiac tissue engineering strategies are based on the development of functional models of heart muscle in vitro . Our research is focused on evaluating the feasibility of different tissue engineering platforms to support the formation of heart muscle. Our previous work was focused on developing three-dimensional (3D) models of heart muscle using self-organization strategies and biodegradable hydrogels. To build on this work, our current study describes a third tissue engineering platform using polymer-based scaffolding technology to engineer functional heart muscle in vitro . Porous scaffolds were fabricated by solubilizing chitosan in dilute glacial acetic acid, transferring the solution to a mold, freezing the mold at −80°C followed by overnight lyophilization. The scaffolds were rehydrated in sodium hydroxide to neutralize the pH, sterilized in 70% ethanol and cellularized using primary cardiac myocytes. Several variables were studied: effect of polymer concentration and chitosan solution volume (i.e., scaffold thickness) on scaffold fabrication, effect of cell number and time in culture on active force generated by cardiomyocyte-seeded scaffolds and the effect of lysozyme on scaffold degradation. Histology (hematoxylin and eosin) and contractility (active, baseline and specific force, electrical pacing) were evaluated for the cellularized constructs under different conditions. We found that a polymer concentration in the range 1.0–2.5% (w/v) was most suitable for scaffold fabrication while a scaffold thickness of 200 Μm was optimal for cardiac cell functionality. Direct injection of the cells on the scaffold did not result in contractile constructs due to low cell retention. Fibrin gel was required to retain the cells within the constructs and resulted in the formation of contractile constructs. We found that lower cell seeding densities, in the range of 1–2 million cells, resulted in the formation of contractile heart muscle, termed s mart m aterial i ntegrated h eart m uscle (SMIHMs). Chitosan concentration of 1–2% (w/v) did not have a significant effect on the active twitch force of SMIHMs. We found that scaffold thickness was an important variable and only the thinnest scaffolds evaluated (200 Μm) generated any measurable active twitch force upon electrical stimulation. The maximum active force for SMIHMs was found to be 439.5 ΜN while the maximum baseline force was found to be 2850 ΜN, obtained after 11 days in culture. Histological evaluation showed a fairly uniform cell distribution throughout the thickness of the scaffold. We found that lysozyme concentration had a profound effect on scaffold degradation with complete scaffold degradation being achieved in 2 h using a lysozyme concentration of 1 mg/mL. Slower degradation times (in the order of weeks) were achieved by decreasing the lysozyme concentration to 0.01 mg/mL. In this study, we provide a detailed description for the formation of contractile 3D heart muscle utilizing scaffold-based methods. We demonstrate the effect of several variables on the formation and culture of SMIHMs. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58652/1/31642_ftp.pd

Possum Scoring in Predicting the Mortality and Morbidity of Patients Undergoing Emergency Laparotomy in Tirunelveli Medical College Hospital

INTRODUCTION: The Physiological and Operative Severity Score for the enumeration of Mortality and morbidity (POSSUM) is a scoring system that is used to predict 30 day mortality and morbidity rates in patients who are undergoing surgery. POSSUM stands for Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity. It was developed by Copeland in 1991. Emergency laparotomy is a common procedure having mortality rate considerably greater than that of elective laparotomy. Measuring the outcome of emergency laparotomy is crucial for both the patient and health providers, in which improvementin the health service can be achieved. AIM OF THE STUDY: 1. Evaluation of POSSUM equation in patients undergoing EMERGENCY LAPAROTOMY 2. To identify high risk patients who could be benefited from preoperative optimization to provide better surgical care to the patients. MATERIALS AND METHODS: A prospective cross-sectional study that include patients who is undergoing Emergency Laparotomy from seven general surgical units at TVMCH from the period of December 2017- June 2019. Data was collected prospectively on a proforma prepared for the study, from the patients undergoing emergency laparotomy. All such patients would have their physiological score recorded on admission. An operative severity score was calculated based on findings recorded on the proforma. The risk of mortality was calculated using POSSUM equation. RESULTS: In this study, we studied 170 patients who underwent Emergency Laparotomy during the period of December 2017-June 2019 with follow up for 30 days, To observe the mortality and morbidity and possible intervention to improve the prognosis of the high risk patient. Most common indication for emergency laparotomy in this study is Duodenal perforation (74), secondly Gastric perforation (17) followed by ileal perforation (10). Male were the predominantly affected with total 133 patients and 37 females. Most common age group affected is 40 to 60. In our study we observed total of 16 deaths 9.6% and 63 patients with complications 36.4%. Most common cause for death is Duodenal perforation. Most common complications follow by Emergency surgery is Surgical Site Infection 11.2% followed by LRI 5.9%. Possum scoring system was applied to predict the post operative mortality and morbidity. On analyzing observed and predicted value, there was no statistically significant difference between the observed and predicted value of mortality (P=1) and morbidity (P=0.56). CONCLUSION: In Surgical Audit Crude mortality and morbidity is an unreliable indicator so with the use of Possum scoring system patient specific mortality and morbidity can be assessed. Possum scoring system is one of the dependable scoring system to assess the post operative patient. High risk patients can be benefited from peri-operative optimization. In our study there was No statistically significant variation noted between the observed as well as predicted Morbidity (P=0.56) and Mortality (P=1.00). Hence the current study suggests that the POSSUM scoring system is a most reliable for predicting post-operative mortality and morbidity and which may help to improve the prognosis of the patients

Development of a Novel Bioreactor for the Mechanical Loading of Tissue-Engineered Heart Muscle

Objective: In this study, we describe a novel bioreactor system to deliver controlled stretch protocols to bioengineered heart muscle (BEHM) constructs. Our primary objective was to evaluate the effect of mechanical stretch on the contractile properties of three-dimensional cardiac constructs in vitro. Methods: BEHMs were formed by culturing primary neonatal cardiac myocytes in a fibrin gel using a method previously developed in our laboratory. A custom bioreactor system was designed using SolidWorks (Concord, MA) and structural components were manufactured using fusion deposition modeling. We utilized the bioreactor to evaluate the effect of 2-, 6-, and 24-hour stretch protocols on the stretch-induced changes in contractile function of BEHMs. Results: We were able to demonstrate compatibility of the bioreactor system with BEHMs and were able to stretch all the constructs with zero incidence of failure. We found that loading the constructs for 2, 6, and 24 hours during a 24-hour period using a stretch protocol of 1 Hz, 10% stretch did not result in any significant change in the active force, specific force, pacing characteristics, and morphological features. Conclusions: In this study, we demonstrate compatibility of a novel bioreactor system with BEHMs and the stability of the BEHMs in response to stretch protocols.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63267/1/ten.2006.0359.pd

Generalization of Linearized Gouy-Chapman-Stern Model of Electric Double Layer for Nanostructured and Porous Electrodes: Deterministic and Stochastic Morphology

We generalize linearized Gouy-Chapman-Stern theory of electric double layer for nanostructured and morphologically disordered electrodes. Equation for capacitance is obtained using linear Gouy-Chapman (GC) or Debye-$\rm{\ddot{u}}$ckel equation for potential near complex electrode/electrolyte interface. The effect of surface morphology of an electrode on electric double layer (EDL) is obtained using "multiple scattering formalism" in surface curvature. The result for capacitance is expressed in terms of the ratio of Gouy screening length and the local principal radii of curvature of surface. We also include a contribution of compact layer, which is significant in overall prediction of capacitance. Our general results are analyzed in details for two special morphologies of electrodes, i.e. "nanoporous membrane" and "forest of nanopillars". Variations of local shapes and global size variations due to residual randomness in morphology are accounted as curvature fluctuations over a reference shape element. Particularly, the theory shows that the presence of geometrical fluctuations in porous systems causes enhanced dependence of capacitance on mean pore sizes and suppresses the magnitude of capacitance. Theory emphasizes a strong influence of overall morphology and its disorder on capacitance. Finally, our predictions are in reasonable agreement with recent experimental measurements on supercapacitive mesoporous systems

Elastically and Plastically Foldable Electrothermal Micro‐Origami for Controllable and Rapid Shape Morphing

Integrating origami principles within traditional microfabrication methods can produce shape morphing microscale metamaterials and 3D systems with complex geometries and programmable mechanical properties. However, available micro‐origami systems usually have slow folding speeds, provide few active degrees of freedom, rely on environmental stimuli for actuation, and allow for either elastic or plastic folding but not both. This work introduces an integrated fabrication–design–actuation methodology of an electrothermal micro‐origami system that addresses the above‐mentioned challenges. Controllable and localized Joule heating from electrothermal actuator arrays enables rapid, large‐angle, and reversible elastic folding, while overheating can achieve plastic folding to reprogram the static 3D geometry. Because the proposed micro‐origami do not rely on an environmental stimulus for actuation, they can function in different atmospheric environments and perform controllable multi‐degrees‐of‐freedom shape morphing, allowing them to achieve complex motions and advanced functions. Combining the elastic and plastic folding enables these micro‐origami to first fold plastically into a desired geometry and then fold elastically to perform a function or for enhanced shape morphing. The proposed origami systems are suitable for creating medical devices, metamaterials, and microrobots, where rapid folding and enhanced control are desired.An elastically and plastically foldable micro‐origami is developed and tested to create controllable and functional 3D shape morphing systems with multiple active degrees of freedom. The work demonstrates a versatile design–fabrication–actuation method to achieve rapid folding, enhanced control, and function in different atmospheric environments, enabling applications in microrobots, medical devices, and metamaterials.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163442/2/adfm202003741.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163442/1/adfm202003741-sup-0001-SuppMat.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163442/3/adfm202003741_am.pd

Drug induced Parkinson’s: A comprehensive review of the issues and measures required to tackle the same

Drug-inducedParkinsonism(DIP) closelyresemblesParkinson'sdisease(PD)inmotorsymptoms butiscausedbyspecificmedicationsdisruptingdopaminereceptorsandneurotransmitterbalance. PD involves a complex interplay of genetic, environmental, and biochemical factors resulting in the gradual degeneration of dopaminergic neurons. Environmental toxins and genetic mutations, such as LRRK2 and SNCA, contribute to the risk of developing PD. DIP primarily occurs due to the obstruction of dopamine receptors by certain drugs, notably antipsychotics and antiemetics, affecting dopamine transmission and causing Parkinsonian symptoms. Toxin-induced Parkinsonism(TIP)arisesfromexposuretosubstanceslikemanganese,herbicides,pesticides,and specific drugs, disrupting dopaminergic pathways and altering neurotransmission. This study examines various cases of DIP, emphasizing the significance of timely identification and intervention. A thorough understanding and proactive management of DIP are crucial for alleviatingsymptomsandimprovingpatientoutcomes.Healthcareprofessionalsneedtodiligently monitor patients using medications associated with DIP, adjust treatment plans, and educate patientsaboutpotentialsideeffects. Further researchisimperativetounravelthepathophysiology of DIP, considering genetic, environmental, and drug-related factors, to enhance clinical practices and optimize patient care. Addressing DIP requires a multifaceted approach, including early recognition, thoughtful management, and patient-centred care

Caecal metastasis from breast cancer presenting as intestinal obstruction

<p>Abstract</p> <p>Background</p> <p>Gastrointestinal metastsasis from the breast cancer are rare. We report a patient who presented with intestinal obstruction due to solitary caecal metastasis from infiltrating ductal carcinoma of breast. We also review the available literature briefly.</p> <p>Case presentation</p> <p>A 72 year old lady with past history of breast cancer presented with intestinal obstruction due to a caecal mass. She underwent an emergency right hemicolectomy. The histological examination of the right hemicolectomy specimen revealed an adenocarcinoma in caecum staining positive for Cytokeratin 7 and Carcinoembryonic antigen and negative for Cytokeratin 20, CDX2 and Estrogen receptor. Eight out of 11 mesenteric nodes showed tumour deposits. A histological diagnosis of metastatic breast carcinoma was given.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first case report of solitary metastasis to caecum from infiltrating ductal carcinoma of breast. Awareness of this possibility will aid in appropriate management of such patients.</p

Bioreactors as engineering support to treat cardiac muscle and vascular disease

Cardiovascular disease is the leading cause of morbidity and mortality in the Western World. The inability of fully differentiated, load-bearing cardiovascular tissues to in vivo regenerate and the limitations of the current treatment therapies greatly motivate the efforts of cardiovascular tissue engineering to become an effective clinical strategy for injured heart and vessels. For the effective production of organized and functional cardiovascular engineered constructs in vitro, a suitable dynamic environment is essential, and can be achieved and maintained within bioreactors. Bioreactors are technological devices that, while monitoring and controlling the culture environment and stimulating the construct, attempt to mimic the physiological milieu. In this study, a review of the current state of the art of bioreactor solutions for cardiovascular tissue engineering is presented, with emphasis on bioreactors and biophysical stimuli adopted for investigating the mechanisms influencing cardiovascular tissue development, and for eventually generating suitable cardiovascular tissue replacements

Effect of mineral-enriched diet and medicinal herbs on Fe, Mn, Zn, and Cu uptake in chicken

<p>Abstract</p> <p>Background</p> <p>The goal of our study was to evaluate the effects of different medicinal herbs rich in polyphenol (Lemon balm, Sage, St. John's wort and Small-flowered Willowherb) used as dietary supplements on bioaccumulation of some essential metals (Fe, Mn, Zn and Cu) in different chicken meats (liver, legs and breast).</p> <p>Results</p> <p>In different type of chicken meats (liver, legs and breast) from chickens fed with diets enriched in minerals and medicinal herbs, beneficial metals (Fe, Mn, Zn and Cu) were analysed by flame atomic absorption spectrometry. Fe is the predominant metal in liver and Zn is the predominant metal in legs and breast chicken meats. The addition of metal salts in the feed influences the accumulations of all metals in the liver, legs and breast chicken meat with specific difference to the type of metal and meat. The greatest influences were observed in legs meat for Fe and Mn. Under the influence of polyphenol-rich medicinal herbs, accumulation of metals in the liver, legs and breast chicken meat presents specific differences for each medicinal herb, to the control group that received a diet supplemented with metal salts only. Great influence on all metal accumulation factors was observed in diet enriched with sage, which had significantly positive effect for all type of chicken meats.</p> <p>Conclusions</p> <p>Under the influence of medicinal herbs rich in different type of polyphenol, accumulation of metals in the liver, legs and breast chicken meat presents significant differences from the group that received a diet supplemented only with metal salts. Each medicinal herb from diet had a specific influence on the accumulation of metals and generally moderate or poor correlations were observed between total phenols and accumulation of metals. This may be due to antagonism between metal ions and presence of other chelating agents (amino acids and protein) from feeding diets which can act as competitor for complexation of metals and influence accumulation of metals in chicken meat.</p> <p><b>Graphical abstract</b></p