Prevention of polyurethane valve cusp calcification with covalently attached bisphosphonate diethylamino moieties.
OBJECTIVE
Calcification of polyurethane prosthetic valve leaflets causes a major functional impairment. Previously we showed that polyurethane heart valves modified with covalently linked bisphosphonate groups were resistant to calcification in vivo. However, we also found that the highly polar anionic bisphosphonate groups on the polyurethane surface attracted sodium counter ion adsorption, and thereby increased the elastomer's water absorption to 20% of total weight. In this study we address the increased water absorption by investigating the hypothesis that covalently attaching cationic diethylamino groups to the bisphosphonate-modified polyurethane will reduce water absorption. Thus we evaluated the mechanical and in vivo anticalcification properties of heart-valve leaflets composed of this modified polymer.


METHODS
Diethylamino and bisphosphonate groups (DBP) were appended to the polyurethane Biospan's hard segment using previously published bromoalkylation methodology. Water absorption and biaxial mechanical and uniaxial failure testing were used to determine the mechanical properties of the DBP-modified polymer. Rat subdermal implants (60 days) and extended (150 days) single pulmonary leaflet replacements in juvenile sheep provided in vivo assessments of the bisphosphonate-modified polyurethane.


RESULTS
The water absorption properties of the DBP-modified polymers and unmodified polyurethanes were 1.86 and 2.3 %, respectively. Biaxial mechanical tests showed the DBP-modified polymer was more compliant than the unmodified control material, but all polymeric material had similar uniaxial failure properties. In both rat subdermal and sheep circulatory implants, the DBP-modified polyurethane resisted calcification, as assessed by scanning electron microscopy, with complete calcification inhibition in prosthetic sheep valve leaflet replacements.


CONCLUSIONS
DBP polyurethane possesses physical (water absorption) and biomechanical properties comparable to unmodified polyurethane and can resist intrinsic heart-valve leaflet calcification in blood-stream implants.
Alferiev
Ivan
I
Division of Cardiology, The Children's Hospital of Philadelphia, Abramson Research Bldg, 3516 Civic Center Blvd, Philadelphia, Pennsylvania 19104-4318, USA.
Stachelek
Stanley J
SJ
Lu
Zhibin
Z
Fu
Angela L
AL
Sellaro
Tiffany L
TL
Connolly
Jeanne M
JM
Bianco
Richard W
RW
Sacks
Michael S
MS
Levy
Robert J
RJ
D000818:Animals; D006350:Heart Valve Prosthesis; D008422:Materials Testing; D010710:Phosphates / Q000737:chemistry*; D011140:Polyurethanes / Q000737:chemistry*; D011664:Pulmonary Valve; D051381:Rats; D012756:Sheep; D014867:Water / Q000737:chemistry*
D010710:Phosphates; D011140:Polyurethanes; D014867:Water