Studying Thrombosis and Surface Roughness in the Penn State Pediatric Ventricular Assist Device

Open Access
Author:
Richardsen, Cecilia
Area of Honors:
Biomedical Engineering
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Dr. Keefe B Manning, Thesis Supervisor
  • Dr. Justin Lee Brown, Honors Advisor
Keywords:
  • thrombosis
  • heart
  • surface roughness
  • bridge to transplant
  • PVAD
  • artificial organ
  • polyurethane
  • platelets
  • fibrin
Abstract:
From 2010 to 2017, 439 children died while waiting for a donor heart among 4,731 children on the transplant list. (1) There is a clear shortage of hearts available for transplant and a need for a pediatric bridge-to-transplant device. To meet this need, the Division of Applied Biomedical Engineering at the Penn State College of Medicine has developed a pediatric ventricular assist device (PVAD). The Penn State PVAD is being tested currently in juvenile ovine models. While animal studies have been encouraging, thrombus formation is observed, which is a major problem in ventricular assist devices. One hypothesis is that roughness on the surface of the segmented poly-(ether polyurethane urea) (SPEEU) seamless blood sac can lead to the aggregation of platelets in a fibrin matrix. These deposits can block blood flow through the device or become detached and migrate to another location. This can lead to device failure, heart attack, or stroke. Explanted Penn State PVAD blood sacs from the ovine trials are examined to study surface irregularities in relation to the presence of platelet and fibrin deposits, which provides insight into why thrombosis occurs. Blood sacs are evaluated using immunofluorescent labeling and confocal microscopy. The samples are labeled with an indirect method using CAPP2A and Alexa Fluor 555 to label platelets and anti-fibrinogen and Alexa Fluor 488 to label fibrin. The sacs are viewed with confocal microscopy to determine if there are platelets or fibrin on the surface. The platelet and fibrin structures are confirmed by using environmental scanning electron microscopy (ESEM). The biological depositions are enzymatically degraded from the surface, and the sac surface roughness is studied with optical profilometry. The root mean squared (Rq), an average deviation from the roughness average center line, roughness average (Ra), an average of all values on the roughness profile, ten-point height (Rz), an average of the five highest peaks and the five lowest valleys, and Swedish height (H), a roughness average of the middle 90% of the data, are roughness parameters that are collected for each sample. Images taken from confocal, ESEM, and optical profilometry are correlated for each sample to determine the relationship between thrombus formation and surface topography. For Rq, Ra, and H, the macroscopic regions are significantly rougher than the microscopic regions and control. The microscopic regions are significantly rougher than the control. For Rz, the macroscopic regions are significantly rougher than the control and the microscopic regions are significantly rougher than the control. Regions with greater deposition are correlated with higher values of roughness. Areas of higher surface roughness on the SPEUU seamless blood sacs could promote deposition of platelets and fibrin.