The Joseph Stokes, Jr., Research Institute Project 1: Biocompatible heterograft biomaterials Robert Levy, PI Aims 1. Chemistry and crosslinking using triglycidyl amine ( to prepare bioprosthetic heart valves: Rapoport et al, Biomaterials. 2007;28(4):690-9 2. Biomechanical effects of TGA crosslinking: Sacks et al, Ann Thorac Surg. 2006;82(4):1369-77 3. Extracellular matrix interactions—TGF1 related calcification mechanisms: Clark-Greuel et al, Ann Thorac Surg. 2007;83(3):946-53
16
Embed
Project 1: Biocompatible heterograft biomaterials Robert Levy, PI
Project 1: Biocompatible heterograft biomaterials Robert Levy, PI. Aims Chemistry and crosslinking using triglycidyl amine (TGA) to prepare bioprosthetic heart valves: Rapoport et al, Biomaterials. 2007;28(4):690-9 2. Biomechanical effects of TGA crosslinking: - PowerPoint PPT Presentation
Welcome message from author
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
The Joseph Stokes, Jr., Research Institute
Project 1: Biocompatible heterograft biomaterials Robert Levy, PIAims
1. Chemistry and crosslinking using triglycidyl amine (TGA) to prepare bioprosthetic heart valves:
Rapoport et al, Biomaterials. 2007;28(4):690-9
2. Biomechanical effects of TGA crosslinking:
Sacks et al, Ann Thorac Surg. 2006;82(4):1369-77
3. Extracellular matrix interactions—TGF1 related calcification mechanisms:
Clark-Greuel et al, Ann Thorac Surg. 2007;83(3):946-53
The Joseph Stokes, Jr., Research Institute
Triglycidyl Amine (TGA)
O
CH2Cl
HO
Cl
N
Cl
OHHO
Cl
NH3
i-PrOH-water
O
NO
O
aq. NaOH, toluene-THF
-HCl
TGA
Epichlorohydrin
Project 1
•Reacts irreversibly with lysine, methionine, cystine, histidine
•Results in biomechanical properties superior to glutaraldehyde
•Biocompatibility—supports cellular growth of all cardiovascular cell types
The Joseph Stokes, Jr., Research Institute
Reaction of MABP with residual epoxy groups
MABP
Collagenfiber
O
X
OH
X
HSCH2 CH2 NH CH2 CH
PO3H2
PO3H2MABP
S
NH CH2 CH
PO3H2
PO3H2
X = residue of TGA
The Joseph Stokes, Jr., Research Institute
Ca-PO4-MABP Precipitation Experiment: Prepared and Precipitated at pH=7.4
0.00
20.00
40.00
60.00
80.00
100.00
120.00
Ca (
ug/m
l)
2 mM MABP, 10 mM TGA
10 mM TGA
Ca-PO4-MABP Precipitation Experiment: 2 mM MABP, 10 mM TGA
0.00
20.00
40.00
60.00
80.00
100.00
120.00
NoTreatment
2.5 mM Ca 2.5 mM Ca,2pM PO4
2.5 mM Ca,2nM PO4
2.5 mM Ca,2μM PO4
2.5 mM Ca,2mM PO4
2.5 mM Ca,20mM PO4
2.5 mM Ca,200mM PO4
Ca
(ug/
ml)
pH=7.4
pH=9.0
Ca-PO4-MABP Precipitation Experiment
0.00
20.00
40.00
60.00
80.00
100.00
120.00
Ca
(ug/
ml)
- 2 mM MABP
+ 2 mM MABP
MABP interactions with Ca/phosphates:
The TGA-MABP reaction product is an inhibitor of Ca-phosphate formation
The Joseph Stokes, Jr., Research Institute
Aim 3: Proposed model for 5-HT/Fenfluramine heart valve cell and/or
macrophage interactions
With resulting transcriptional effects on cytokines, proliferation, ECM