Experimental Non-Inferiority Trial of

Synthetic Small-calibre Biodegradable

vs. Stable Vascular Grafts
1

Beat H. WALPOTH, MD FAHA

Damiano Mugnai1, Sarra de Valence2, Wojciech Mrowczynski1, Jean-Christophe

Tille3, Xavier Montet4, Robert Gurny2, Michael Moeller2, Afksendiyos Kalangos1

Departments of 1Cardiovascular Surgery, 3Pathology and 4Radiology

University Hospital of Geneva;
2
Dept. of Pharmaceutics & Biopharmaceutics EPGL, University of Geneva; Switzerland.

OBJECTIVES: There is a big need for shelfready, synthetic, small calibre prostheses for
cardiovascular revascularisation procedures.
Biodegradable scaffolds resistant to
degradation-induced aneurysm formation in the
systemic arterial circulation have been
developed for :
in

vivo vascular tissue-engineering

Our aim is to assess the long-term results of

synthetic, biodegradable, electrospun, smallcalibre vascular grafts compared to ePTFE for
aortic replacement in the rat model.

Vascular Tissue Engineering:

Manufacturing of scaffolds
Biodegradable grafts
(polycaprolactone = PCL)
were produced by
random nano-fibre
electro-spinning
(porosity 80%)

Modern BARBAPAPA technique to

create novel vascular grafts

METHODS - I: 14 anaesthetised Sprague Dawley

rats (male, 275g), received an infrarenal aortic graft
(8 biodegradable; 6 ePTFE) replacement (end-to-end;
2mm ID; 20mm long) and 6 rats (same age) served
as sham (controls)

ePTFE
graft
PCL
graft

2 mm

Quality and patency

control after surgery
with transit time
flowmeter

METHODS - II:

After 15 months survival in vivo high

resolution ultra-sonography (Visualsonics) and
angiography were performed to assess patency, stenosis,
aneurysm formation, intimal hyperplasia and compliance.
After explantation micro CT calcification quantification,
histology, immuno-histology,
Rat 24
weeks after
scanning electron microscopy (SEM) 3operation
and morphometry were carried out.

Rat 24
3 weeks after
operation

RESULTS:
PCL vs. ePTFE grafts at 15 months

Patency (%)
Endothelialization (%)
Compliance (%)
Calcification (%)
Intimal Hyperplasia
(m)
Cellular Ingrowth (%)

PCL

ePTFE

P<

( n=8)

(n=6)

100
98
8.2
7.0
47.2

67
93
5.7
15.8
62.2

ns
ns
0.01
0.04
0.09

31.4

11.3

0.001

Angiography after 15 months implantation

A& B =
ePTFE
C = PCL
D = Native
Aorta

Vascular Compliance

HISTOLOGIC
ASSESSMENT
AFTER 15 MO
IMPLANTATION

PCL
Morphological analysis of PLC grafts. (A)
SEM image of the lumen of the PCL graft
after
explantation
showing
complete
endothelialization. (B) Longitudinal section of
the graft wall showing homogenous cellular
infiltration giant cells on the periphery
(arrows; HE staining, 100x magnification). (C)
Neo-intima with spindle shape cells above a
calcified area, indicated by the arrow. An
endothelium is present on the luminal side.
(HE staining, 200x magnification). (D)
Immunohistochemistry anti CD31 labeling
endothelial cells on the luminal side (200x
magnification) (E) Elastin deposition in the
neo-intimal layers is revealed in blue and
collagen deposition is revealed in green by a
Miller-Masson staining (200x magnification).
(F) Immunohistochemistry anti Smooth Mucle
Actin demonstrating positivity in spindle
shape cells forming the neo-intima (200x
magnification).

HISTOLOGIC
ASSESSMENT
AFTER 15 MO
IMPLANTATION

ePTFE
Morphological analysis of ePTFE grafts.
(A) Longitudinal section of the graft wall
with neointima formation, limited cellular
infiltration in the graft body and no giant
cell
reaction
(HE
staining,
100x
magnification). (B) Neointima formation
under the endothelium (indicated by an
arrow) with no signs of calcification (HE
staining, 200x magnification). (C) MillerMasson staining revealing elastin fibers in
bleu in the neointima and collagen
depositions in green in the inner part of the
graft (200x magnification). (D) Von Kossa
staining showing in black the calcifications
in the graft body (100x magnification). (E)
SEM image of the lumen of the graft
showing incomplete endothelialization (see
insert) and microthrombi.

SUMMARY
PCL vs. ePTFE grafts at 15 months :
100% patency vs. 67% for ePTFE
No aneurysms, no stenosis
Rapid and complete endothelialisation
Similar neo-intima formation to ePTFE
Better compliance than ePTFE, but
Worse compliance than native aorta
Less micro-calcifications than ePTFE (PET)
Better cellular ingrowth in PCL grafts
Vascular remodelling with live cells and ECM
formation (collagen and elastin) with PCL
degradation (65% MW reduction)

CONCLUSIONS
PCL vs. ePTFE grafts at 15 months :
Synthetic biodegradable small calibre
nano-fibre polycaprolactone grafts show
excellent results after 15 months of aortic
replacement and compare favourably with
the clinically used ePTFE grafts.
Thus, such novel in situ tissue engineered
grafts could become a future option for
clinical applications such as coronary artery
bypass grafting or endografting.