PB0299 - Surface modification of lung assist device for neonates by dual-modification with antithrombin-heparin (ATH) and tissue plasminogen activator (t-PA)

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Siyuan Li, MSc

PhD Candidate
School of Biomedical Engineering
Hamilton, Ontario, Canada

Co-Author(s)

NS

Neda Saraei

M.A.Sc.
Department of Mechanical Engineering, McMaster University, Hamilton, Canada
Hamilton, Ontario, Canada
HA

Helen M. Atkinson

Research Assistant
Department of Pediatrics, McMaster University, Hamilton, Canada
Hamilton, Ontario, Canada
CF

Christoph Fusch

Neonatologist
Paracelsus Medical University, Department of Pediatrics, University Hospital Nuremberg, Nuremberg, Germany
Nuremberg, Bayern, Germany
NR

Niels Rochow

Neonatologist
Paracelsus Medical University, Department of Pediatrics, University Hospital Nuremberg, Nuremberg, Germany
Nuremberg, Bayern, Germany
GF

Gerhard Fusch

Senior Research Associate
Department of Pediatrics, McMaster University, Hamilton, Canada
Hamilton, Ontario, Canada
PS

P. Ravi Selvaganapathy

Professor
Department of Mechanical Engineering, McMaster University, Hamilton, Canada
Hamilton, Ontario, Canada
JB

John L. Brash

Professor Emeritus
Department of Chemical Engineering, McMaster University, Hamilton, Canada
Hamilton, Ontario, Canada
Anthony KC. Chan, MBBS

Professor
McMaster University, McMaster Children’s Hospital, Hamilton, Canada
Hamilton, Ontario, Canada
KS

Kyla N. Sask

Assistant Professor
Department of Materials Science & Engineering, McMaster University, Hamilton, Canada
Hamilton, Ontario, Canada

Background: Blood oxygenators, using microfabrication technologies, are being developed as lung assist devices to treat neonates with respiratory distress. Blood compatibility of polydimethylsiloxane (PDMS) in these devices must be improved to reduce thrombus formation.

Aims: To achieve long-term antithrombogenicity, dual-modification with an antithrombin-heparin (ATH) complex and tissue plasminogen activator (t-PA) was used to modify a PDMS surface, using polydopamine (PDA) as a “bio-glue”.

Methods: PDMS discs were incubated in PDA for 24 h to form a PDA surface coating. ATH and t-PA were then immobilized on the surface, both sequentially and simultaneously. I-125 radiolabeling was used to determine density of proteins on disc surfaces; overnight plasma incubation and sodium dodecyl sulfate (SDS) elution were carried out to evaluate protein density and stability. Anti-Xa and S-2288 assays were used to determine heparin and t-PA activities, respectively. PDMS microfluidic oxygenators were similarly modified with ATH and t-PA. Recalcified citrated plasma was circulated through the oxygenators and pressure monitored over time to evaluate clot formation.

Results: PDMS-PDA-tPA-ATH surfaces demonstrated high levels of t-PA surface density which was stable in plasma and SDS (Figure 1). Similarly, PDMS-PDA-ATH-tPA surfaces exhibited high density and stability of ATH. ATH and t-PA activities on dual-modified samples were similar to those of singly-modified samples. Upon flowing plasma through PDMS, PDMS-PDA and PDMS-PDA-tPA coated oxygenators, pressure increased within 15 min indicating clot formation; however, clot lysis occurred in the PDMS-PDA-tPA oxygenator after 17 min (Figure 2). Oxygenators modified with ATH alone or with both proteins showed no clot formation within 45 mins.

Conclusion(s): PDMS discs modified sequentially demonstrate the advantages of dual-modification with ATH and t-PA via PDA due to their stability in plasma and bioactivity. The ability of the dual-modification method to prevent clotting in oxygenators demonstrates its potential to provide antithrombotic surfaces in lung assist devices, central venous catheters, and other devices.