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Functional Polymers for Biomedical Devices: Point-of-Care - - PowerPoint PPT Presentation
Functional Polymers for Biomedical Devices: Point-of-Care - - PowerPoint PPT Presentation
Functional Polymers for Biomedical Devices: Point-of-Care Diagnostics, and Surgical Sealants Peter Kofinas Associate Dean for Faculty Affairs and Graduate Programs Professor, Fischell Department of Bioengineering University of Maryland,
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Maryland Basketball Game 11/2009
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Thank you Bob!
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Enzyme Induced Stiffening of Nanoparticle-Hydrogel Composites with Structural Color
Enzyme Initial Red Hydrogel Collapsed Blue Hydrogel
Enzymatic cleavage of the peptide-polymer bonds alters the spacing between particles, changing the color of the hydrogel
Ayyub et al. ACS Nano 2015
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Fabrication of Nanocomposite
CYKC Peptide Silica Nanoparticles Polymerized Colloidal Array ℎ𝑤 4-Arm PEG Norbornene (PEG4NB) 1:4 PEG4NB to CYKC Ayyub et al. ACS Nano 2015
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Threshold Response Yields Logic Gates
- 70% of cross-links must be cleaved for response
- Incorporate two peptides specific to two different proteases
at 1:1 ratio as cross-links
- Degradation of both is needed for 70% threshold
Ayyub et al. ACS Nano 2015
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Breaking of Chemical Bonds Yields Color Change
- Nonspecific peptide was
introduced into the hydrogel
- Breaking 70% of
crosslinks induces blueshift
- Increased
concentration of non- cleavable peptide increases time to blueshift
Ayyub et al. ACS Nano 2015
10 20 30 40 50 60 70 50 60 70 80 90 100
Percent CYKC
Failure to Blueshift
Time to Blueshift (minutes)
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Concentration Dependent Response Time
𝑢$ =
'()* +,-(./0
Theoretical Time to Blueshift
Xc
Fraction of cross-links cleaved to initiate collapse
So
Peptide cross-link concentration
kcat
Turnover rate
E
Protease Concentration
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Metabolic Disorder Management
- Hyperammonemia: complication of urea-cycle disorder
- Occur in 1 out of 10,000 births
- Current analysis takes days – Hard to
diagnose
- Without treatment, patients suffer
irreversible brain damage, or even death
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Ammonia Sensor Design
Ayyub et al. Molecular Genetics and Metabolism, 2015
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Berthelot Specificity Toward Ammonia
Ammonia Arg Ala His Asn Ile Cys Leu Met Phe Ser Pro Lys Thr Val Trp Tyr Asp Glu Gln Gly Ammonia Arg Ala His Asn Ile Cys Leu Met Phe Ser Pro Lys Thr Val Trp Tyr Asp Glu Gln Gly
100 100 75 75 50 50 25 25 2 4 6 8
Larger response of ammonia versus amino acids present in blood
Ayyub et al. Molecular Genetics and Metabolism, 2015
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Ammonia Microfluidic Device
25µM 100µM 250µM 500µM
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Blood Ammonia Standard Curve
Linear detection of blood ammonia with microfluidic device using 40 μl blood Ayyub et al. Molecular Genetics and Metabolism, 2015
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Direct Deposition of Body Temperature Responsive Polymeric Medical Sealants
Conventional suturing and tissue stapling § Intestinal, vasculature, or airway anastomosis § Liver, lung, or kidney resections Current commercial sealants have drawbacks including cost, shelf stability, complex preparation, or difficult application
http://www.atlasofpelvicsurgery.com/ www.georgelianmd.com
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Solution Blow Spinning
Behrens et al. ACS Macro Lett. (3) 249-254 (2014)
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Differential Scanning Calorimetry
Behrens et al. Advanced Materials, 2015
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Fiber Mat Heating
- 10% PLGA 5% PEG fiber mat at 31 oC
Fiber Mat Film 31 oC
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Adhesion Testing
RT 37C
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
N/cm2
10% PLGA 0% PEG 10% PLGA 1% PEG 10% PLGA 3% PEG 10% PLGA 5% PEG
Blow Spun Polymer 1” X 1” Face
Large increase in adhesion at 37C
Behrens et al. Advanced Materials, 2015
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Cecal Intestinal Anastomosis Mouse Model
PLGA/PEG Deposition 4-Suture Anastomosis PLGA/PEG After 2 Minutes 24-Hour Burst Pressure
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1-Day Burst Pressure
PLGA/PEG Tisseel Coseal Control 20 40 60 80
˚ ˚
Burst Pressure (mmHg)
- >2X Greater Burst Pressure (n = 5)
- 7-day survival: 40% Improvement over control
4-Suture Control PLGA/PEG
Behrens et al. Advanced Materials, 2015
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2007 World Series
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