Medical Design and Outsourcing

  • Home
  • Medical Device Business
    • Mergers & Acquisitions
    • Financial
    • Regulatory
  • Applications
    • Cardiovascular
    • Devices
    • Imaging
    • Implantables
    • Medical Equipment
    • Orthopedic
    • Surgical
  • Technologies
    • Contract Manufacturing
    • Components
    • Electronics
    • Extrusions
    • Materials
    • Motion Control
    • Prototyping
    • Pumps
    • Tubing
  • Med Tech Resources
    • DeviceTalks Tuesdays
    • Digital Editions
    • eBooks
    • Manufacturer Search
    • Medical Device Handbook
    • MedTech 100 Index
    • Podcasts
    • Print Subscription
    • The Big 100
    • Webinars / Digital Events
    • Whitepapers
    • Video
  • 2022 Leadership in MedTech
    • 2022 Leadership Voting!
    • 2021 Winners
    • 2020 Winners
  • Women in Medtech

New Study Reveals Ways to Better Inhibit Blood Clots

May 19, 2010 By Georgia Tech Institute of Technology

Fibrin, the primary ingredient of blood clots, creates a fibrous network that stems the loss of blood at an injury site. But beyond this essential work, fibrin can also cause heart attack, stroke and tissue damage by forming clots that block blood vessels.

Fibrin forms when an enzyme removes parts of a blood protein called fibrinogen, exposing “knobs” that fit into “holes” located on both ends of fibrinogen molecules. Uncovering these knobs allows the fibrinogen molecules to attach to one another, forming a fibrin network. To inhibit unwanted fibrin formation, researchers have developed synthetic knobs to fill the holes, but the best amino acid sequence and structure for these knobs have not been well investigated.

A new study published online in the journal Blood reveals factors that could improve the binding of synthetic fibrin knobs to holes and the structures of these knobs in solution. The study also identifies a novel synthetic knob that displays a 10-fold higher affinity for fibrinogen holes than current synthetic knobs. This research was supported by the National Institutes of Health and the Wallace H. Coulter Foundation.

“Understanding the fundamentals of this knob-hole interaction will lead to a more thorough knowledge of fibrin assembly mechanisms and allow us to establish criteria for designing superior anticoagulants with high hole affinity that can inhibit fibrin assembly,” said Thomas Barker, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

Barker, postdoctoral fellow Sarah Stabenfeldt and School of Computational Engineering graduate student Jared Gossett investigated the interactions between holes and short synthetic peptides modeled after real fibrin knob sequences. They focused specifically on modeling the binding interaction and characterizing the structure of the peptides in solution.

Using a technique called surface plasmon resonance, the research team explored the role of structural and electrostatic properties in regulating the binding of knobs to holes. The structural properties of knob peptides in an aqueous environment had not been examined previously because the small peptides could not be crystallized for structural X-ray studies.

“Researchers previously measured how knob molecules bound to holes in a saturated solution,” explained Barker, “but we wanted to know how fast the knobs were binding to the holes and the length of time the knob and hole interacted to determine if we could optimize these parameters to inhibit fibrin formation.”

The researchers measured the hole binding characteristics of six different knob sequences — each seven or eight amino acids in length — to evaluate the impact of additional backbone stabilization and/or different charge distributions. They found that the binding rates improved significantly by adding two amino acids, called proline and phenylalanine, for stabilization and having charged configurations in the sixth and seventh positions in the sequences.

“Investigating these binding events under dynamic conditions provided critical information, but the results didnt really surprise us,” noted Barker. “Small peptides in aqueous solutions ‘wiggle a lot, so the more stable the molecules are in their active structural state, the better chance they have of establishing a good knob-hole interaction because theyre not changing their shape as much.”

Analyzing the structural dynamics of the peptides through simulation indicated that the orientation of the arginine amino acid side chain and backbone stability contributed significantly to functional binding of the knobs and holes.

During their investigation, the researchers also identified a novel knob peptide mimic (GPRPFPAC) that exhibited a binding rate to holes one order of magnitude higher than previously published knob sequences — even surpassing the binding activity of the gold standard mimic (GPRPAAC). Future studies will involve modifying this novel peptide further to enhance its ability to inhibit fibrin formation for applications when blood clotting is undesirable.

The surface plasmon resonance and modeling techniques used in this study enable peptide sequences to be modified and optimized to control the typical wound healing matrix.

“An additional goal for this technology is to develop a viable delivery strategy for synthetically engineered fibrin glue so that we can guide and control the bodys response to an injury,” added Barker.

Shuming Nie, the Wallace H. Coulter Distinguished Faculty Chair in Biomedical Engineering, and Steve Harvey, a professor in Georgia Techs School of Biology, also contributed to this research.

This project is supported by the National Institutes of Health (NIH) (Award Nos. 1R21EB008463 and K12GM0007680). The content is solely the responsibility of the principal investigator and does not necessarily represent the official view of the NIH.

Research News & Publications Office

Georgia Institute of Technology

75 Fifth Street, N.W., Suite 314

Atlanta, Georgia 30308 USA Abby Vogel (avogel@gatech.edu; 404-385-3364) or John Toon (jtoon@gatech.edu; 404-894-6986)

Media Relations Contacts:

Writer: Abby Vogel

SOURCE

Related Articles Read More >

Johnson & Johnson Office of Digital Innovation Leader Peter Schulam
Imagining the future of cloud-connected medical devices with Johnson & Johnson leaders
Withings Body Scan
Withings plans launch for Body Scan smart scale platform
BinaxNow COVID-19 Ag Card
Time recognizes Abbott offerings among this year’s 100 best inventions
Koya Medical’s Dayspring device
Koya Medical reports positive early results in Dayspring lymphedema trial

DeviceTalks Weekly.

May 13, 2022
Our Pre-Post-DeviceTalks Boston episode, also MedtronicTalks replay with Gastro CMO Austin Chiang
See More >

MDO Digital Edition

Digital Edition

Subscribe to Medical Design & Outsourcing. Bookmark, share and interact with the leading medical design engineering magazine today.

MEDTECH 100 INDEX

Medtech 100 logo
Market Summary > Current Price
The MedTech 100 is a financial index calculated using the BIG100 companies covered in Medical Design and Outsourcing.
DeviceTalks

DeviceTalks is a conversation among medical technology leaders. It's events, podcasts, webinars and one-on-one exchanges of ideas & insights.

DeviceTalks

New MedTech Resource

Medical Tubing

Enewsletter Subscriptions

Enewsletter Subscriptions

MassDevice

Mass Device

The Medical Device Business Journal. MassDevice is the leading medical device news business journal telling the stories of the devices that save lives.

Visit Website
MDO ad
Medical Design and Outsourcing
  • MassDevice
  • DeviceTalks
  • MedTech 100 Index
  • Medical Tubing + Extrusion
  • Drug Delivery Business News
  • Drug Discovery & Development
  • Pharmaceutical Processing World
  • R&D World
  • About Us/Contact
  • Advertise With Us
  • Subscribe to Print Magazine
  • Subscribe to E-newsletter
  • Attend our Monthly Webinars
  • Listen to our Weekly Podcasts
  • Join our DeviceTalks Tuesdays Discussion

Copyright © 2022 WTWH Media, LLC. All Rights Reserved. Site Map | Privacy Policy | RSS

Search Medical Design & Outsourcing

  • Home
  • Medical Device Business
    • Mergers & Acquisitions
    • Financial
    • Regulatory
  • Applications
    • Cardiovascular
    • Devices
    • Imaging
    • Implantables
    • Medical Equipment
    • Orthopedic
    • Surgical
  • Technologies
    • Contract Manufacturing
    • Components
    • Electronics
    • Extrusions
    • Materials
    • Motion Control
    • Prototyping
    • Pumps
    • Tubing
  • Med Tech Resources
    • DeviceTalks Tuesdays
    • Digital Editions
    • eBooks
    • Manufacturer Search
    • Medical Device Handbook
    • MedTech 100 Index
    • Podcasts
    • Print Subscription
    • The Big 100
    • Webinars / Digital Events
    • Whitepapers
    • Video
  • 2022 Leadership in MedTech
    • 2022 Leadership Voting!
    • 2021 Winners
    • 2020 Winners
  • Women in Medtech