Download Biology and bioresorbable materials in cardiac surgery: why could

International Cardiovascular Forum Journal 2 (2015)
DOI: 10.17987/icfj.v3i0.114
2 | Editorial
Biology and bioresorbable materials in
cardiac surgery: why could they be important
in the current era of innovations and
technology?
Cristiano Spadaccio1, Francesco Nappi2
1 Department of Cardiothoracic Surgery, Golden Jubilee National Hospital, Clydebank, Glasgow, United Kingdom
2 Cardiac Surgery Centre Cardiologique du Nord de Saint-Denis, Paris, France
Key words:
bioresorbable materials; pediatric cardiac surgery; biology
Citation:
Spadaccio, C. & Nappi, F. Biology and bioresorbable materials in cardiac surgery: why could they be important in the current
era of innovations and technology?
International Cardiovascular Forum Journal. 2015;3:2-4. http://dx.doi.org/10.17987/icfj.v3i0.114
Abstract
In the era of implantable vascular devices and minimally invasive
technologies, several aspects of the biological response of
cardiovascular structures to surgical procedures and materials
seem to be neglected. However, especially in pediatric cardiac
surgery, the main mechanisms underlying the most frequently
encountered complications are to be found in an inadequate
biological adaptation of the heart vascular structures to the
conduits and surgical materials used. In particular, inability of
the grafts used to follow somatic growth, exuberant scar tissue
formation, presence of non-viable tissue at the anastomosis
site or impaired tissue viability of the conduits are claimed
to be the most significant factors. Biocompatible materials
might constitute a useful adjunct in this context as providing
at the same time a valid tissue surrogate and a biological
support to orientate and improve the physiologically occurring
biological processes imposed by surgical corrections or
vascular replacements. We explored the use of bioresorbable
materials in an experimental model of the Ross procedure
and of neopulmonary trunk reconstruction with encouraging
results. Reinforcement of a pulmonary autograft with a
polydioxanone mesh prevented graft dilation and induced a
structural remodeling leading to the formation of a neo-vessel
comparable to the native aorta. A similar approach applied to
the reconstruction of the pulmonary trunk with pericardium
during arterial switch operations, prevented occurrence of
subvalvular pulmonary stenosis and warranted the formation of
an hemodynamically effective neo-conduit.
Understanding, ameliorating or just exploiting naturally occurring
processes through ad hoc designed biocompatible materials
might constitute a keystone in several pathological conditions.
Modern cardiac surgery is currently going through a period of
profound change due to the introduction of novel technologies
and devices with the progressive abandonment of previously
established procedures. In the field of congenital cardiac
surgery, the recent literature is pointing at the underuse of the
* Corresponding author. E-mail: [email protected]
Ross procedure1, while in the pediatric field limitations of the
materials and conduits currently used in reconstructive surgery
of right ventricular outflow tract (RVOT) and pulmonary artery
(PA) are increasingly reported2.
For the Ross procedure, is clear that technical difficulties
and risks of the procedure, especially if not performed by
experienced hands, have conspired against the widespread
use of this life-saving operation. Additionally, the advancing
technologies of bioprosthesis manufacturing, the reports on their
prolonged life together with the increasingly available option
of percutaneous valve-in-valve implantation, discouraged the
majority of the surgeons to embark in technically challenging
operation carrying augmented surgical risk and potential burden
on their track records and on the economic management of
cardiac units. We think that a parallel miscomprehension of the
intrinsic value of this procedure played a role in this situation. As
pointed out by Yacoub3 and by the its inventor4 the real keystone
of this procedure is represented by the possibility to maintain
the viability of the aortic valve and preserve the biological
activity of the valve leaflets which, as demonstrated recently,
warrant an adequate coagulative balance and a favorable tissue
homeostasis5. When compared to the glutaraldehyde fixed
bioprostheses, the active function of a living leaflet would be
reflected in prevention of calcific degeneration and avoidance
of anticoagulation5, but more importantly, when applied to
the pediatric or young adult clinical scenario, the advantage
of Ross procedure would result in the possibility to provide
an aortic root substitute that harmoniously integrates in the
vascular system accompanying the progressive somatic growth
of the aortic structures. Unfortunately, long-term neoroot
dilation with need for re-operation is well described after Ross
procedure and represents another major deterrent especially
in the surgical management of young patients6. This is mainly
due to the anatomical and histological features of the native
pulmonary artery (PA), which is normally subjected to pulmonary
pressures and behaves as a venous conduit. A progressive
structural remodeling triggered by the arterial hemodynamic load
generally occurs after the early phases of implantation, but if it
ISSN: 2410-2636 © Barcaray Publishing
International Cardiovascular Forum Journal 2 (2015)
DOI: 10.17987/icfj.v3i0.114
is unsuccessful or inadequate, conduit dilation might happen.
Attempts to reinforce the PA using synthetic materials as Dacron
or PTFE have been performed but, albeit effective in preventing
dilation, the poor elastomechanical properties and the artificial
nature of the materials limit the effectiveness of this approach7.
The potent foreign body reaction associated with their use
impairs PA viability, preventing any arterialization or vascular
remodeling process and eventually resulting in a constraint effect
on the growing aorta and in a fibrous degeneration of its wall.
Impoverishment of vascular compliance and loss of windkessel
effect has been shown to produce in turn detrimental effects on
the aorta and the valve leading to regurgitation8.
Considering the biological cascade of events triggered by
the transposition of the PA in aortic position leading to wall
modification and aiming at respecting graft viability and
biological features, we explored the possibility to guide and
boost the remodeling process through the use of resorbable
external reinforcement7. The hypothesis at the basis of
this strategy relies in the possibility to provide a temporary
mechanical support to the PA while guiding and optimizing the
process of vascular remodeling through the biological interaction
between the resorbable material and the native vessel.
A biocompatible device designed to minimize radial tension
and based on the combination of a single-layer polyglactin
(PG) (early resorbability material) strengthened by an interlaced
polydioxanone (PDS) (late resorbability material) was used in
an experimental model of Ross procedure in growing lambs
as reinforcement of the PA7. The device, embracing PA outer
aspect, prevented aneurysmal dilation of the neo-aorta
while allowed a harmonic growth of the PA. Surprisingly, the
resorbable materials triggered a process of histoarchitectural
rearrangement at the medial and adventitial side of the vessel
in absence of a strong inflammatory infiltrates. Over time new
matrix deposition was observed and a shift towards an elastic
remodeling of the PA7. In a separate set of experimental studies
biologically reinforced PA showed 6 months after implantation
a medial thickening with highly organized fibromuscular cells
mixed to abundant neo-formed connectival tissue could be
detected. Interestingly, MMP-9 was found to be overexpressed
in this group, indicating an ongoing matrix remodeling process.
Specific analysis of extracellular matrix revealed the presence of
high amount of elastic fibers, reliably deposited by fibromuscular
cells, and absent in the control group, while collagen appeared
to be more organized and dense with a compact distribution in
the “elastic zone” of the vessel9, 10.
We might reliably speculate that the temporary interaction
between the bioresorbable reinforcement and the PA might
have orchestrated a complex process of vascular remodeling
based on a balance between inflammation and extracellular
matrix production. After biomaterial resorption, a “neovessel”
exhibiting characteristics similar to those of the aorta but still
biologically alive and capable of growth was obtained. This
system would therefore facilitate the creation in vivo of a PA
with morphostructural features enabling it to both face the
hemodynamic load of the arterial system and guarantee an
harmonious increase in size during the somatic growth11. Even
if in need of more confirmatory results, the possibility to guide
and improve the physiologically occurring processes of graft
biological remodeling and reaction to foreign materials through
the use of biocompatible external reinforcements which respect
tissue growth, might constitute a innovative avenue to solve
some of the drawbacks of Ross procedure.
Editorial | 3
Similarly, in pediatric surgery, the disadvantages inherent in
currently available valve conduits concerning low durability,
inability to match the somatic growth and early valve
dysfunction12, demand alternative materials to allow efficient
cardiac structures reconstruction. Additionally, biological
conduits cannot be applied during reconstruction of RVTO in
neonates with simple transposition of the great arteries (sTGA)
undergoing arterial switch operation (ASO). In these conditions
autologous pericardium to reconstruct the neopulmonary trunk
(NPT) is generally considered the best option even if harnessed
by long-term drawbacks, especially concerning supravalvular
pulmonary stenosis (SPS). Also in the case of SPS, the main
mechanisms underlying this complication need to be found
in the inadequate biological adaptation of the heart vascular
structures to the conduits and surgical materials used. Scar
tissue formation and the presence of non-viable tissue at the
anastomosis site13, impaired tissue viability of NPT and its
inability to follow somatic growth are claimed to be the most
significant factors14. Applying similar concepts, we thought to
augment the biological properties of the autologous pericardium
used to reconstruct NPT through the use of biocompatible
materials able to confer increased resistance to dilation but also
promoting its harmonious integration with cardiac structures and
preventing progression to SPS. In a model of NPT reconstruction
in growing lambs a bioresorbable mesh composed by PDS
was wrapped around the pericardium neopulmonary artery.
The mesh did not impair the viability and physiological somatic
growth of the neopulmonary artery as testified by formation of
an intact endothelial lining on the inner surface of the graft and
by the consensual increase in diameter over time. While animals
treated with non-reinforced NPT underwent SPS during time,
animals treated with PDS reinforcement showed at the end of
the resorption period of the bioprosthesis a phenomenon of
histoarchitectural remodeling within the neopulmonary wall,
leading to the formation of a trilaminar structure, similar to
native vessels. This process was accompanied by a minimal
inflammatory reaction and avoided formation of fibrotic tissue,
which is considered among the determinants of SPS as causing
neointimal hyperplasia and hemodynamic abnormalities.
In conclusion, there is an increasingly emerging need to
reconsider biological adaptive mechanisms and the response of
cardiovascular structures to surgical procedures. Understanding,
ameliorating or just exploiting naturally occurring processes
through ad hoc designed biocompatible materials might
constitute a keystone in several pathological conditions.
Statement of ethical publishing: The authors state that they
adhere to the statement of ethical publishing of the International
Cardiovascular Forum Journal15.
Disclosures:
Authors declare no conflicts of interest
Address for correspondence:
Francesco Nappi, MD
Cardiac Surgery Centre Cardiologique du Nord de Saint-Denis
36 Rue des Moulins Gémeaux, 93200 Saint-Denis, France
E-mail: [email protected]
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al. 20 years of arterial switch operation for simple TGA. Acta Chir Belg.
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4 | Editorial
3. Yacoub MH, El-Hamamsy I, Sievers HH, Carabello BA, Bonow RO, Stelzer
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biomedical journals. International Cardiovascular Forum Journal 2015;2:2
DOI: 10.17987/icfj.v2i1.4
International Cardiovascular Forum Journal 2 (2015)
DOI: 10.17987/icfj.v3i0.114