Latest technologies from University of Tennessee Research Foundationhttp://utrf.technologypublisher.comBe the first to know about the latest inventions and technologies available from University of Tennessee Research Foundationen-USFri, 14 Dec 2018 09:24:44 GMTFri, 14 Dec 2018 09:24:44 GMThttps://cyber.harvard.edu/rss/rss.htmlsupport@inteum.comCopyright 2018, University of Tennessee Research FoundationGraded Cellular Materials with Improved Propertieshttp://utrf.technologypublisher.com/technology/27529The Problem:

Cellular materials possess unique combinations of strength, stiffness, and low density that traditional engineering materials cannot achieve. Graded cellular materials present superior combinations of static and dynamic properties when lightweight, stiff, and strong structures are needed. However, a simple method for designing and fabricating such complex materials that is also suitable for material extrusion additive manufacturing (AM) has been elusive until now. 

The Solution:

Researchers at the University of Tennessee have developed a method to fabricate graded cellular structures that is tailored for material extrusion AM processes. This method can create cellular structures having gradients in both density and cell shape, enabling an unprecedented range of properties using only one base material. The grading schemes allow the design of advanced materials with spatially varying stiffness and strength, incremental hardening or softening behavior to maximize energy absorption, and programmable collapse paths to protect designated regions in a structure. The novel method couples with existing material extrusion AM technology (i.e., fused deposition modeling and direct ink writing) to access a wider range of material properties and functionality than is currently available and is designed to be implemented within the process flow of existing commercial AM technology. 

Benefits:

  • Suited to existing material extrusion AM methods
  • Couples with existing grading schemes
  • Material properties can be tailored for a wide range of applications
  • Programmable failure behavior for maximized energy absorption
  • Creation of multifunctional parts with new combinations of static, dynamic, transport, and sensing properties
  • Potential to incorporate sub-cell functionality with macro-scale design

Inventor:

Dr. Brett Compton is an assistant professor in the mechanical engineering department at UTK.  He received his Ph.D. from the University of California Santa Barbara in 2012. His research interests include mechanical properties of advanced composite materials, developing high-performance materials for additive manufacturing, and understanding the fundamental processing-property-performance relationships in additive manufacturing materials. He has particular expertise in 3D-printable thermoset-based composite materials.

 

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Thu, 12 Apr 2018 06:26:19 GMTmdossant@utk.eduhttp://utrf.technologypublisher.com/technology/2752917104-03Thu, 12 Apr 2018 06:28:12 GMTBrettComptonAssistant ProfessorMABEOlegShyloAssistant ProfessorMichaelGoinUT Student AssistantMABEHesamShamsGrad Research AssistantAndreanaLeskovjanLicensing AssistantUTRFaleskovj@utk.edu865.974.1882EngineeringFalse
Silicone based denture adhesivehttp://utrf.technologypublisher.com/technology/27206The Problem:

 

Getting dentures to stay in place can be quite frustrating.  Most denture adhesives currently on the market are not completely effective at retaining dentures in place. Another frequent complaint with dentures is that over time, denture wearers are required have their dentures refitted in order to reestablish a tight seal between the wearer’s oral cavity and the dentures due to the natural changes in the gums and underlying boney structures that occur over time.  Dentures also generally require frequent cleaning, which involves not only removal of food particles and any adherent microorganisms, but can also involve removal of the adhesive that is employed to fix the dentures in the wearer’s mouth. 

Accordingly, it would be desirable to provide a new denture adhesive that provides strong hold, easy cleaning, and an ability to mitigate some of the physical changes to the underlying gums and/or bone that require dentures to be refitted.

 

The Technology:

Researchers in the College of Dentistry at the University of Tennessee have developed a silicone denture adhesive, Dentasil, which creates a substantially airtight gasket for a better hold.  The adhesive comprises a formulation that contains two separate silicone gels that are mixed together (See Figure 1.)

The adhesive gel is made with implant grade silicone, and is safe for use in the body for up to 30 days.  In addition to the silicone, each gel comprises a mixture of pigments, in amounts that provide a color desired by the denture wearer.  When the 2 gels are combined, the resulting mixture has a work time of 1 minute, a set time of 2 minutes, and a cure time of 3 minutes at room temperature.  The composition of the adhesive is designed such that the adhesiveness can be increased or decreased based on the preference of the user.  Another feature of the Dentasil is that, unlike most commercially available adhesives, it does not require cleaning to remove it because it peels off easily and cleanly.   

This adhesive formulation also acts a reliner. Often times, denture wearers will have their dentures refitted when they can no longer get a tight seal with denture adhesives.  The daily use of Dentasil provides daily relining of the dentures.

The researchers have compared Dentasil to commercially available denture adhesives. Initial testing shows that the adhesiveness is at least comparable to commercially available adhesives, but the gel removes more easily than the commercially available adhesives.  They will conduct additional studies to further elucidate the properties and characteristics of this novel adhesive.

 

 

Benefits and Features:

Provides strong hold

Adhesive and reliner all in one.

No cleaning required to remove adhesive.

 

 

 

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Fri, 23 Feb 2018 09:33:29 GMTmdossant@utk.eduhttp://utrf.technologypublisher.com/technology/2720617162-05Fri, 23 Feb 2018 09:33:29 GMTMaddieSingerDirector of AnaplastologyProsthondonticsLiangHongAssociate ProfessorTimothyHottelProfessorProsthondonticsFranklinGarcia-GodoyExecutive Dean of ResearchBioscience ResearchRussellWicksProfessor and ChairProsthodonticsDavidCagnaProsthodonticsDental product, Dentistry, LakitaCavinLicensing Associatelcavin@uthsc.edu901.44837825Human HealthFalse
Novel GPRC6A Agonists to Treat T2 Diabetes and Metabolic Syndromehttp://utrf.technologypublisher.com/technology/27112The Problem:

A critical barrier in preventing and treating T2D is the lack of a druggable target that simultaneously treats the multiple abnormalities associated with T2D that include impaired insulin secretion and chronic β-cell decompensation, owing to impaired glucose-sensing and insufficient increases in β-cell mass, and peripheral insulin resistance, due to alterations in muscle and liver metabolism. None of the currently prescribed drugs simultaneously target the multiple abnormalities, and they consequently have limited effectiveness, requiring multiple drug combinations.

 

The Technology Solution:

GPRC6A is a nutrient sensing receptor that regulates energy metabolism. The inventors found that activating GPRC6A yields a strong therapeutic effect for diabetes by directly stimulating insulin secretion from pancreatic β-cells and maintaining β-cell mass. That directly impacts peripheral tissue metabolic functions to increase insulin sensitivity in liver, muscle and adipose tissues. It drives hepatocytes to increase glucose and fatty acid uptake and stimulates the release of FGF-21 to enhance glucose uptake.

For the activation of GPRC6A we designed and synthesized novel GPRC6A agonists, starting from virtual high throughput screening hits. Functional analysis of these compounds in vitro confirmed their effect on GPRC6A activation. 

Going from hit to early discovery lead, SAR analysis identified the most active compounds that increased the insulin stimulation index ex-vivo in wild-type isolated pancreatic islets to a level similar to Osteocalcin, a benchmark ligand of GPRC6A (Fig 1 A).

In-vivo studies with the current lead reduced the blood glucose levels by 43.6% after 60 min at a dose of 10 mg/kg in wild-type mice (Fig. 1 B). Metformin, the first-line medication for T2D, resulted in similar reductions in blood glucose, but only at a much higher dose of 300 mg/kg, not 10 mg/kg as with our lead (Fig 1 D).

The project currently aims to de-risk leads with ADME/toxicity screens and find the compound with the best PK properties.

Related Publications:

MOLECULAR METABOLISM 6 (2017) 185-193

 

Patents:

Provisional Patent filed August 2017

 

Benefits:

  • Lowers blood glucose levels in vivo similar to first line medication Metformin at 30 x lower dose.
  • Increases insulin stimulation in pancreatic islets similar to benchmark ligand Osteocalcin.
  • Small molecule agonists with robust and reliable synthesis.

 

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Tue, 13 Feb 2018 16:22:28 GMTmdossant@utk.eduhttp://utrf.technologypublisher.com/technology/2711217161-05Tue, 28 Aug 2018 07:56:33 GMTL. DarrylQuarlesProfessorMedicineDuaneMillerProfessor EmeritusPharmaceutical SciencesMinPiAssociate ProfessorMedicineDong-Jin (Daniel)HwangPost-Doc Research TraineePharmaceutical SciencesJeromeBaudryAssistant ProfessorJeremySmithGovernor's Chair/ProfessorCtr for Molecular BiophysicsStefanSchweizerLicensing Associatesschwei1@uthsc.edu901-448-1146Human HealthFalse
Microemulsions for Topical Delivery of Water Soluable Drugshttp://utrf.technologypublisher.com/technology/27108The Problem:

Elevated intraocular pressure (IOP) is the most significant risk factor that contributes to visual field loss in primary open angle glaucoma (POAG). Despite glaucoma prevalence and its impact on society, current medications do not address the underlying pathophysiologies that cause elevated IOP, nor do they address genetic variations related to IOP modulation. Moreover, because of their short half-life and low corneal residence time, current medications require multiple daily topical applications, which are associated with poor patient compliance. Thus, an improved formulation is needed to improve patient compliance while at the same time maintaining and enhancing efficacy in lowering IOP.

 

The Technology Solution:

Researchers at the University of Tennessee have developed novel extended release topical bioadhesive microemulsion (ME) formulations to deliver pregabalin (preg) and that will allow for once daily dosing and better patient compliance. Through systems genetics investigations using the large BXD family of recombinant inbred mice as a genetic reference panel, they identified Cacna2d1 as a novel modulator of IOP. They discovered and confirmed that pregabalin is a specific modulator of CACNA2D1 that can lower IOP, and its IOP lowering effect is dependent upon the haplotype of Cacna2d1. They constructed multilayered w/o/w microemulsions with different polymers including alginate, chitosan, and carbopol; and loaded these microemulsions with pregabalin.  They have characterized these formulations, showing drug release profiles, corneal permeability, formulation safety, formulation efficacy, and other characteristics.  The release profiles (Fig. 1) show that all control formulations exhibited fast release behaviors that released 100% of the drug content within 3-8h. On the other hand, the tested MEs exhibited sustained release behaviors that last for up to 24h. Figure 2 shows that the ME-free formulation (Preg/water and Preg/ carbopol) possessed a higher permeation rate than the formulation containing ME. This is because of the natural ability of the drug to rapidly permeate through the cornea. This behavior is contrary to the required sustained release behavior. On the other hand, all formulations containing ME possessed a lower permeation rate. This is due to the special engineering of the ME, as the drug is located in the innermost aqueous layer of the multilayered ME. To be released, the drug must pass through two interfacesthe inner w/o interface and the outer o/w interfaceafter which it has to diffuse through the viscous hydrogel to be ready for permeation through the cornea. This behavior is ideal to support the sustained release of the formulation. In comparing the ME formulations, it was found that the formulation that contained carbopol possessed the lowest permeation rate among all tested formulations. This experiment confirmed the in vitro release data that carbopol ME can perfectly sustain pregabalin release to be suitable for once daily application.  Figure 3 shows the IOP profile of Dutch belted (DB) rabbits after a single application of different ME formulations. It is clear from the figure that the maximum IOP-reduction and the most extended effect was achieved with the carbopol ME, which may be due to the carbopol in situ gelling property at the physiological pH. The IOP did not return to baseline until after about 34h.  Figure 4 compares both carbopol formulations (gel and ME) in order to show the effect of ME on the duration of the drug effect. Overall, these data provide evidence that 1) pregabalin is an effective IOP lowering drug, and that 2) its lowering effects are enhanced and sustained by the ME formulations.  These data provide evidence of a potential new therapy for glaucoma that is both effective and sustained; thereby providing a feasible once daily dosing that would likely improve patient compliance.

 

 

 

 

 

 

 

 

Features and Benefits:

Novel sustained release formulation for treatment of glaucoma

ME is compatible with other hydrophilic drugs

Therapy based on systems genetics approach

Once daily dosing formulation

 

 

 

 

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Tue, 13 Feb 2018 09:48:21 GMTmdossant@utk.eduhttp://utrf.technologypublisher.com/technology/2710817057-05Mon, 19 Mar 2018 12:15:36 GMTMonicaJablonskiAssociate ProfessorOphthalmologyMohammedMoustafaPostdoctoral FellowOphthalmologyDrug Delivery, Formulation, Glaucoma, Ophthalmology, LakitaCavinLicensing Associatelcavin@uthsc.edu901.44837825Human HealthFalse
Radiosilhttp://utrf.technologypublisher.com/technology/27073The Problem:

The dental school requirement to collect human teeth and a requisite number of them has proven to be quite difficult to meet for most students. An alternative is to use plastic teeth to serve as proxies for actual human teeth. This presents a problem of its own in that plastic teeth are not visible radiographically. Dental students typically evaluate their work by viewing the teeth upon which they are working radiographically.    Plastic teeth, being much less radiopaque, provide significantly less feedback to the students with respect to the quality of their work. This is due to a relative inability to accurately interpret radiographs resulting from poor detail in radiographs. Accordingly, it would be desirable to increase the radiopacity of plastic teeth so that students can make a more accurate assessment of their work.

 

The Technology:

Researchers in the College of Dentistry at the University of Tennessee have developed a product which can be applied to the plastic teeth to allow students to evaluate their work radiographically. This novel composition, referred to as Radiosil, significantly enhances the radiopacity of plastic teeth. See figure 1.

 

Radiosil is a simple, quick, and easy composition that can be applied to plastic teeth.  It can be painted on to make a uniform covering of the plastic roots which then allows the student to evaluate his or her work radiographically.  Furthermore, Radiosil can be easily removed if the tooth is to be evaluated. Also, it can be easily applied to fixed and removable prosthetic appliances for radiographic indexing.  Once applied, Radiosil sets at room temperature within about 20 minutes after exposure to air. Increasing the temperature of an object treated with Radiosil can decrease the time required for it to set. Specifically, at a temperature of about 150°F, Radiosil sets in about 10 minutes.  Moreover, the inventors have developed a product which greatly enhances the radiopacity of objects that are not naturally radiopaque.

 

 

Figure 1. Exemplary radiographic images of plastic teeth with and without treatment with Radiosil. A) Pre-operative buccal-lingual images of plastic teeth without B) and with Radiosil; C) Pre-operative mesial-distal images of plastic teeth without and D) with Radiosil; E) Working film without and F) with Radiosil.

 

 

Features and Benefits:

•       Significantly enhances radiopacity of non-radiopaque objects

•       Easily removed from object

•       Allows for better quality radiographs and reduces X-ray exposure time

 

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Mon, 05 Feb 2018 11:35:42 GMTmdossant@utk.eduhttp://utrf.technologypublisher.com/technology/2707317153-05Tue, 16 Oct 2018 07:33:16 GMTMaddieSingerDirector of AnaplastologyProsthondonticsJosanneO'dellAssistant ProfessorEndodonticsTimothyHottelProfessorProsthondonticsFranklinGarcia-GodoyExecutive Dean of ResearchBioscience ResearchRussellWicksProfessor and ChairProsthodonticsDental product, Dentistry, LakitaCavinLicensing Associatelcavin@uthsc.edu901.44837825False
Selective Antibacterials Agent for Multidrug-Resistant Acinetobacter Baumanniihttp://utrf.technologypublisher.com/technology/26980The Problem:

Multidrug-resistant (MDR) Acinetobacter baumannii is one of the most difficult Gram-negative bacteria to treat and eradicate. It cause a variety of diseases, ranging from pneumonia to serious blood infections, and affects people with compromised immune systems.

A. baumannii infections are commonly implicated in hospital-acquired infections, and represent a costly challenge for ICUs in many hospitals.

Mortality rates from A. baumannii septicemia are 34.0−43.4% in the ICU and 16.3% outside the ICU, which is largely attributed to the rise in MDR strains, limiting the treatment options significantly. Currently used agents have broad spectrum activity and are potent inducers of multidrug resistance in bacteria.

Therefore core requirements for a new agent are selectivity for A. Baumannii and activity against MDR strains.

 

The Solution:

The novel class of pleuromutilin derived antibacterials we developed showed significant synergistic effects with doxycycline against A. baumannii. A combination treatment with doxycycline proofed to be very effective in an in vivo lethal infection model.

Combinations of the current lead 1 and Dox at a series of concentrations exhibit bactericidal activity against drug-sensitive and drug–resistant A. baumannii. A combination treatment of 1-Dox = 35/1 delivered a MIC = 1.56−6.25 μg/mL  with an ED50 value of <2 mg/kg (a single dose). The in vivo efficacy of 1-Dox 35/1 was demonstrated via a mouse septicemia model using the infected C57BL/6 mice with A. baumannii. The in vitro bactericidal activity of 1-Dox 35/1 against A. baumannii is superior to that of clinically utilized drugs such as tobramycin, tigecycline, and colistin.

Early pharmacological data included good in vitro half-life (t1/2 > 60 min) in rat microsomes, low in vitro cytotoxicity against mammalian Vero cells (IC50 = 45.3 μg/mL), good permeability across Caco-2 epithelial monolayers with moderate levels of efflux, and a PPB of 76.9%.

The positive activity and pharmacological data we obtained suggest a lower development risk and higher chance to identify a successful candidate to move forward.

 

Benefits:

  • The combination of the lead structure with doxycycline is very effective in vivo even at a single dose.
  • Good metabolic stability and early in-vitro PK and toxicity properties. No cytotoxicity against mammalian cell lines at 40 µg/mL concentrations (IC50 50-100 µg/mL).
  • Straightforward scalable synthesis and derivatization.

 

Publications:

  • J. Med. Chem., 2017, 60 (7), pp 2869–2878

 

Patents:

  • Provisional patent application filed February 2017.

 

 

 

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Mon, 29 Jan 2018 15:03:36 GMTmdossant@utk.eduhttp://utrf.technologypublisher.com/technology/2698016102-05Mon, 29 Jan 2018 15:12:18 GMTMichioKurosuAssociate ProfessorPharmaceutical SciencesKatsuhikoMitachiPostdoctoral FellowPharmaceutical SciencesAnti-bacterial, Drug Discovery, Infectious Diseases, StefanSchweizerLicensing Associatesschwei1@uthsc.edu901-448-1146Human HealthFalse
Dynamic Attribution Platform for Predicting and Preventing Criminal or Fraudulent Activityhttp://utrf.technologypublisher.com/technology/26773The Problem:

Data security breaches and fraud are becoming more and more frequent, and increasingly sophisticated methods are being used to steal data or cause targeted damage, hindering efforts to prevent attacks.

The Solution:

Researchers at the University of Tennessee have developed a novel method for predicting undesirable events using similarity-based information retrieval software. This method uses multivariate statistical analysis and principal component analysis for indexing object attributes. The software can predict if an event is likely to occur and identify who/where the fraudulent activity is coming from, thereby enabling precautionary measures to be taken to avert the attack.

Advantages:

  • Can be easily tailored for any industry
  • Minimizes financial losses
  • Improves decision making
  • Mitigates risk
  • Enhances privacy
  • Increases customer confidence

Applications:

  • Predict, detect, and prevent criminal/fraudulent activity in
    • Finance
    • Health care
    • Law enforcement, etc.
  • Regulatory compliance
  • Risk management

Patents:

  • U.S. 8,375,032
  • U.S. 8,392,418
  • U.S. 8,396,870
  • U.S. 8,713,019
  • U.S. 8,762,379
  • U.S. 8,775,427
  • U.S. 8,775,428

The Inventors:

Dr. David Icove is a UL Professor of Practice in the Department of Electrical Engineering and Computer Science at UT. His research focuses on forensic engineering and high-performance computer modeling of fires and explosions; and cyberterrorism, intrusion detection, and computer security.

Dr. Doug Birdwell is a Professor Emeritus in the Department of Electrical and Computer Engineering at UT. His research expertise includes control systems, information processing, high-performance databases, data mining, and bioinformatics.