Engineering of fibrin-specific biocompatible microgels for the use as hemostatic agents

• Applicant: Dr. Nicole Welsch
• Subject Area: Biological and Biomimetic Chemistry ; Biomaterials ; Polymer Materials ; Preparatory and Physical Chemistry of Polymers
• Term: from 2013 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 242801773

The proposed project aims at the development of fibrin-specific microgels which augment the natural clotting cascade in case of acute hemorrhage and help to keep blood loss to a minimum. The need of efficient hemostats to stem blood flow is clearly reflected by the high mortality rates due to trauma injury and exsanguination which is the major cause of death for people in the age range of 5-44. This highlights the fact that uncontrolled bleeding represents a significant clinical need in general surgery, trauma, and emergency medicine.The natural clotting cascade that is activated in response to vascular injury involves the formation of a temporary fibrin matrix at the site of the injured tissue. In this project, the major aim is to exploit the natural fibrin polymerization process towards the development of a bio-synthetic hybrid polymer system with superior provisional matrix properties. Colloidal microgels displaying fibrin-specific peptides will be designed that favorably interact with a developing fibrin mesh during injury. Due to their tunable swelling behavior and self-assembly characteristics, hydrogel microparticles are able to form interdigitated networks with an emerging biological matrix such as the fibrin clot. The microgels shall be prepared by using free radical polymerization techniques as well as controlled radical polymerization mechanisms. Conjugation of fibrin-specific humanized synthetic single chain variable fragment (scFv) antibodies to the biocompatible microgels shall induce specific binding of the microgel to fibrin in case of bleeding. Thus, upon contact with a deposited fibrin mesh, the functionalized microgels rapidly swell and form interdigitated networks with the biological matrix resulting in a concentration of clotting factors and application of compressive forces. The overall goal of this project is the design of a fibrin-specific microstructured material that will increase the polymerization rate and mechanical strength of fibrin networks to significantly reduce the clotting/bleeding time. Therefore, the suggested work includes systematic light scattering and rheological studies that analyze the influence of the microgels on the clotting time and clotting efficiency as well as on the viscoelastic properties of the formed fibrin matrix.

• DFG Programme: Research Fellowships
• International Connection: USA
• Participating Institution: Helmholtz-Zentrum Berlin für Materialien und Energie
• Host: Professor Dr. L. Andrew Lyon