**2.1.3.2 Type II – BIO (Bending and Independent Opening)**

This type II device modified version is intended for use in ascending aorta substitution in absence of dissection. The two ends of the device can vary their reciprocal axis up to 90° to

New Approaches for Treatment and Prevention of Aortic Aneurysms 279

For this purpose, on one side, the wireframe consistency was decreased by variably reducing the gauge of nitinol wires and their respective position within wireframe and, on the other side, the external ligature was carried out with the thinnest possible prolene (5-0) encircling suture, transfixing full thickness the device and aortic wall at three equidistant points. The limit of the former was the ability to sustain the external ligature without wireframe deformation/collapse at pressure providing "airtight" seal; the limit of the later was the ability

The present versions of the devices with minimal consistence and great compliance minimize the risk of mechanical conflict and erosion with the confining tissue/organs; moreover wireframe consistency was settled in such a way that is minimal at the device end

Concerning the external ligature and its many possible ways of application, it may be useful to recall that vascular anastomosis must guarantee haemostatic sealing and stability of the coupling which, contrariwise to standard suture, rely on different mechanisms with this

Thus even though external devices surface is provided with short needles perpendicularly positioned around its circumference at 4-6 equidistant points, reduction of the wireframe

To optimize coupling stability in this lighter expandable wireframe we successfully tested 5- 0 prolene encircling suture, transfixing full thickness the device and aortic wall at three equidistant points (fig. 18). In this way in fact the minimal expandable wireframe consistence to sustain the external ligature can be further significantly reduced and stability increased, by splitting the external ligature circumference in three separate and equivalent segments. In this embodiment the expandable ring will be then really only a bit more

to provide stability of the aortic stump-expandable device coupling at stretch test.

consistency may probably decrease their reliability in keeping coupling stability.

To provide reliable coupling stability, instead of simple external ligature, 5-0 prolene encircling suture, transfixing full thickness the device and aortic wall at three equidistant points, was passed and tied as shown, in a sort of revival of the Carrel triangulation historical technique. Video at http://www.fondazionecarrel.org/tsb2/tsb2.html

dislocation on the expandable wireframe throughout the entire circumference.

This coupling stability was proved by a stretch test consisting in a sequence of manoeuvres carried out on the anastomosis that includes: **1)** complete compression of the anastomosis in orthogonal directions and then **2)** vigorous manual stretching of the anastomosis in the coaxial plane separately at four points of its circumference. The sequence was repeated three times and the anastomosis checked for any significant vascular stump backwards

where the possible conflict with aortic wall could be higher.

type of coupling (Fig. 8).

consistent of a common graft tube.

Fig. 18. Carrel's triangulation - back to the future.

better fit with the curvature of the ascending aorta; their aperture can be independently controlled in order to comply with possible differences in diameter of the proximal and distal stumps. In this way the ascending aorta substitution can be carried out very quickly by one single device.

Fig. 17. Device Type II – BIO.

This type II device version allows the bending up to a 90° degree angle of the axis of their ends, whose aperture can be independently controlled. This allows to fit curved anatomy of ascending aorta and possible variations in diameter of the vascular stumps. Video at: http://www.fondazionecarrel.org/tsb2/tsb2.html

In case of dissection however type III device previously connected with graft tube should be better used for distal anastomosis. Proximal anastomosis can be carried out with standard suture, time being not here a critical factor, or by a second type III device if dissection involves also the proximal anastomosis line.

This device version can also be used in isthmus rupture repair, having care of entering the aorta through or close to the laceration in order to preserve integrity of the vascular wall at site of device ends deployment.

#### **2.1.3.3 Recent refinements**

The extensive past experience provided full mechanical reliability of devices in all their versions and proved their easy applicability to aortic stump in all conditions. While the expandable device allows a much easier, quicker and more efficient ("airtight" seal) graftaortic stump coupling than standard suture (Nazari 2010), it implies however the permanence of endovascular tubular wireframe and external ligature that could, at least theoretically, mechanically conflict with aortic wall, particularly at device ends, and with confining tissues/organs.

Aorto-digestive fistula is an infrequent but well documented occurrence after aortic open (Geraci et al 2008; Luo et al, 2010) as well as after endovascular (Ruby & Cogbill, 2007; Marone et al, 2007; Chiesa et al, 2010) repair. While graft or/and suture line contamination/infection may occasionally be suspected as the primary etiological factor, pure mechanical erosion from systolic movements of graft and even from the suture line only (Tanaka et al, 2009) may probably represent the first triggering factor in a portion of cases difficult to quantify.

The pure mechanical effect of these movements on the confining tissue/organ is predictably higher the harder/less compliant is the prosthetic material as well as the more conflicting is its orientation in relation to the confining tissue/organ.

We then recently focused on optimal consistency of the expandable wireframe and on means to provide external fixation with the final aim of achieving mechanical forces of coupling as much as possible similar to those taking place in standard hand suture anastomosis.

better fit with the curvature of the ascending aorta; their aperture can be independently controlled in order to comply with possible differences in diameter of the proximal and distal stumps. In this way the ascending aorta substitution can be carried out very quickly

This type II device version allows the bending up to a 90° degree angle of the axis of their ends, whose aperture can be independently controlled. This allows to fit curved anatomy of

In case of dissection however type III device previously connected with graft tube should be better used for distal anastomosis. Proximal anastomosis can be carried out with standard suture, time being not here a critical factor, or by a second type III device if dissection

This device version can also be used in isthmus rupture repair, having care of entering the aorta through or close to the laceration in order to preserve integrity of the vascular wall at

The extensive past experience provided full mechanical reliability of devices in all their versions and proved their easy applicability to aortic stump in all conditions. While the expandable device allows a much easier, quicker and more efficient ("airtight" seal) graftaortic stump coupling than standard suture (Nazari 2010), it implies however the permanence of endovascular tubular wireframe and external ligature that could, at least theoretically, mechanically conflict with aortic wall, particularly at device ends, and with

Aorto-digestive fistula is an infrequent but well documented occurrence after aortic open (Geraci et al 2008; Luo et al, 2010) as well as after endovascular (Ruby & Cogbill, 2007; Marone et al, 2007; Chiesa et al, 2010) repair. While graft or/and suture line contamination/infection may occasionally be suspected as the primary etiological factor, pure mechanical erosion from systolic movements of graft and even from the suture line only (Tanaka et al, 2009) may

The pure mechanical effect of these movements on the confining tissue/organ is predictably higher the harder/less compliant is the prosthetic material as well as the more conflicting is

We then recently focused on optimal consistency of the expandable wireframe and on means to provide external fixation with the final aim of achieving mechanical forces of coupling as

probably represent the first triggering factor in a portion of cases difficult to quantify.

much as possible similar to those taking place in standard hand suture anastomosis.

its orientation in relation to the confining tissue/organ.

ascending aorta and possible variations in diameter of the vascular stumps.

Video at: http://www.fondazionecarrel.org/tsb2/tsb2.html

involves also the proximal anastomosis line.

by one single device.

Fig. 17. Device Type II – BIO.

site of device ends deployment. **2.1.3.3 Recent refinements** 

confining tissues/organs.

For this purpose, on one side, the wireframe consistency was decreased by variably reducing the gauge of nitinol wires and their respective position within wireframe and, on the other side, the external ligature was carried out with the thinnest possible prolene (5-0) encircling suture, transfixing full thickness the device and aortic wall at three equidistant points. The limit of the former was the ability to sustain the external ligature without wireframe deformation/collapse at pressure providing "airtight" seal; the limit of the later was the ability to provide stability of the aortic stump-expandable device coupling at stretch test.

The present versions of the devices with minimal consistence and great compliance minimize the risk of mechanical conflict and erosion with the confining tissue/organs; moreover wireframe consistency was settled in such a way that is minimal at the device end where the possible conflict with aortic wall could be higher.

Concerning the external ligature and its many possible ways of application, it may be useful to recall that vascular anastomosis must guarantee haemostatic sealing and stability of the coupling which, contrariwise to standard suture, rely on different mechanisms with this type of coupling (Fig. 8).

Thus even though external devices surface is provided with short needles perpendicularly positioned around its circumference at 4-6 equidistant points, reduction of the wireframe consistency may probably decrease their reliability in keeping coupling stability.

To optimize coupling stability in this lighter expandable wireframe we successfully tested 5- 0 prolene encircling suture, transfixing full thickness the device and aortic wall at three equidistant points (fig. 18). In this way in fact the minimal expandable wireframe consistence to sustain the external ligature can be further significantly reduced and stability increased, by splitting the external ligature circumference in three separate and equivalent segments. In this embodiment the expandable ring will be then really only a bit more consistent of a common graft tube.

Fig. 18. Carrel's triangulation - back to the future.

To provide reliable coupling stability, instead of simple external ligature, 5-0 prolene encircling suture, transfixing full thickness the device and aortic wall at three equidistant points, was passed and tied as shown, in a sort of revival of the Carrel triangulation historical technique. Video at http://www.fondazionecarrel.org/tsb2/tsb2.html

This coupling stability was proved by a stretch test consisting in a sequence of manoeuvres carried out on the anastomosis that includes: **1)** complete compression of the anastomosis in orthogonal directions and then **2)** vigorous manual stretching of the anastomosis in the coaxial plane separately at four points of its circumference. The sequence was repeated three times and the anastomosis checked for any significant vascular stump backwards dislocation on the expandable wireframe throughout the entire circumference.

New Approaches for Treatment and Prevention of Aortic Aneurysms 281

In synthesis this method ideally allows to change any vascular-graft anastomosis ≥ 6 mm in diameter from the current facing ends Carrel suture into a simpler, quicker and more efficient ("airtight" seal) telescoping anastomosis, sealed and fixed by single thread external ligature passed full thickness at three points (or more when appropriate), in a sort of ideal

The hypothesizable potential impact (table 1) may exceed that expected on complication rate of open prosthetic substitution of all aortic tracts and in particular in those higher risk conditions as acute dissection. In fact the technical simplification with increased reliability of anastomosis haemostasis and dissection layer approximation with false lumen permanent seal has the logical direct consequence, for example, of enabling also lesser expert cardiovascular surgeons to deal with these clinical cases very often requiring immediate surgical attention, thus increasing surgical team efficiency and hospital unit productivity.

Table 1. Potential impact of expandable device aortic anastomosis compared with current

hand suture technique

re-elaboration of the historical Carrel triangulation technique.

Fig. 19. Stretch test.

Stability coupling was validate by stretching test consisting in vigorous manual stretching of the anastomosis in the coaxial plane separately at four points of its circumference; the anastomosis was than checked for any significant vascular stump backwards dislocation on the expandable wireframe throughout the entire circumference. Video at: http://www.fondazionecarrel.org/tsb2/tsb2.html

Device type III stability was also increased by further buttressing the inner and outer Dacron wrapping by 4-0 prolene suture transfixing the circumference in 3-6 points (fig. 20), a manoeuvre that however can be predictably carried out after perfusion is resumed. While it's certainly easier and also a bit quicker to use expandable device wireframe strong enough to block the aortic stump between simple external ligature and outer surface of the device fixing needles, I think that it's much more technically appropriate and probably safer to realize a vascular/graft coupling where the forces applied are as much as possible similar to those involved in standard vascular suture, even though this can mean a minimal increase of ischemic time, required for placing the 3 full thickness stitches around the positioned device.

Fig. 20. Type III security fixation.

A simpler in and out 4-0 prolene buttressing in 4-6 points of the inner and outer device wireframe will greatly increase coupling stability.

Video at http://www.fondazionecarrel.org/tsb2/tsb2.html

Stability coupling was validate by stretching test consisting in vigorous manual stretching of the anastomosis in the coaxial plane separately at four points of its circumference; the anastomosis was than checked for any significant vascular stump backwards dislocation on

Device type III stability was also increased by further buttressing the inner and outer Dacron wrapping by 4-0 prolene suture transfixing the circumference in 3-6 points (fig. 20),

While it's certainly easier and also a bit quicker to use expandable device wireframe strong enough to block the aortic stump between simple external ligature and outer surface of the device fixing needles, I think that it's much more technically appropriate and probably safer to realize a vascular/graft coupling where the forces applied are as much as possible similar to those involved in standard vascular suture, even though this can mean a minimal increase of ischemic time, required for placing the 3 full thickness stitches around the positioned device.

a manoeuvre that however can be predictably carried out after perfusion is resumed.

A simpler in and out 4-0 prolene buttressing in 4-6 points of the inner and outer device

the expandable wireframe throughout the entire circumference. Video at: http://www.fondazionecarrel.org/tsb2/tsb2.html

Fig. 19. Stretch test.

Fig. 20. Type III security fixation.

wireframe will greatly increase coupling stability.

Video at http://www.fondazionecarrel.org/tsb2/tsb2.html

In synthesis this method ideally allows to change any vascular-graft anastomosis ≥ 6 mm in diameter from the current facing ends Carrel suture into a simpler, quicker and more efficient ("airtight" seal) telescoping anastomosis, sealed and fixed by single thread external ligature passed full thickness at three points (or more when appropriate), in a sort of ideal re-elaboration of the historical Carrel triangulation technique.

The hypothesizable potential impact (table 1) may exceed that expected on complication rate of open prosthetic substitution of all aortic tracts and in particular in those higher risk conditions as acute dissection. In fact the technical simplification with increased reliability of anastomosis haemostasis and dissection layer approximation with false lumen permanent seal has the logical direct consequence, for example, of enabling also lesser expert cardiovascular surgeons to deal with these clinical cases very often requiring immediate surgical attention, thus increasing surgical team efficiency and hospital unit productivity.

Table 1. Potential impact of expandable device aortic anastomosis compared with current hand suture technique

New Approaches for Treatment and Prevention of Aortic Aneurysms 283

Fig. 21. The Rational. The experimental hypothesis is based on the fact that the net prosthesis positioned and maintained in stable contact with the aortic walls (A) is spontaneously, gradually covered by the neo-intima (B), invaded by fibroblasts and thus stably associated to the aortic wall. If the net mesh is appropriately dimensioned, it may be expected that the blood

flow through the collateral branches is not affected (arrows) (from Nazari et al, 1996c)

*Left square.* After 6 weeks the net prosthesis, a braided polipropilene fitted with a co-axial thin stainless steel coil surgically positioned in swine upper descending aorta, was found to be covered by the new intima and well attached to the aortic wall. In the lower right side of the prosthesis segment the net is no longer visible and presumably, with little more time, this smooth, normal intimal surface would extend to completely cover the whole net prosthesis (metallic coil was removed). *Right square.* Histology shows the net prosthesis completely included into the intima layer and lying in contact with the media. The square area shows the magnified polypropylene mesh net pattern. (mod from Nazari et al 1996 c)

The fabric framework linked to the aortic wall would then condition its significant, regular and uniform mechanical strengthening that fractionates and absorbs the centrifuge systolic stress of the bloodstream. The significant mechanical strengthening achieved in this way was measurable by comparison of compliance (∆V/∆P) of the treated aortic tract with that

Fig. 22. Swine experimental model.

Video http://www.fondazionecarrel.org/tsb2/tsb2.html

of the immediately confining segment (fig 23)

#### **3. New endovascular "net" prosthesis for aortic wall strengthening without blocking aortic branches perfusion to early stop aneurysm progression or to prevent its formation in high risk patients**

#### **3.1 Background**

While endovascular procedures already proved lower mortality and complications rate than open surgery and as good long term results in infrarenal and upper descending aorta, in all other aortic tracts endovascular techniques are much more complex and long term results less predictable mainly due to the presence of significant collateral branches, that require additional maneuvers to avoid their obstruction by the endoprosthesis (i.e. hybrid procedure with open surgery for supraortic trunks de-branching).

Moreover endovascular procedures failed to protect from spinal chord ischemia and consequent paraplegia in extended descending aorta prosthetic substitution; it has been hypothesized that this could be due, at least in some case, to the fact that while endoprosthesis prevents intercostal branches to be physiologically perfused, cannot prevent, at least for a certain time in the initial phase, backwards blood flow into the space between endoprosthesis and aortic wall, thus generating conditions for a blood flow "steal" from perfusion of the spinal chord (Kawaharada et al, 2010).

On the other hand current data (Gopaldas et al, 2010) show that only less than 1/4 of ideal candidates to endovascular treatment (uncomplicated, non genetic, isolated, elective descending aortic aneurysms) underwent endovascular procedure, while the remaining 3/4 still underwent open surgical repair in US.

#### **3.2 The rational**

The relative slowness of aneurysm formation and progression to rupture indicates that the decrease in the strength of the arterial wall under the aneurysm formation threshold may be very gradual and limited. Consequently one can imagine that measures to increase, even moderately, the mechanical strength of the arterial wall, for example by means of a dacron fabric network, should be successful in preventing aneurysm formations and thus its complications (dissection and rupture), without requiring complete prosthetic substitution. Moreover the conclusive understanding that a destruction of the elastin fibrils network is at the basis of aneurysm formation [Gott et al, 1996], might acknowledge the re-establishment of a uniform and regular network strengthening of the vascular wall with a net prosthesis as a logic, direct correction of the primary defect. On the other hand this mechanical approach since long time is already in use in many other technology fields for prevention of deformation of elastic/floppy tubes or structures subject to inner high pressure, as for example gardening tubes, tires, rubber boat etc.

In previous animal experiments we showed that the endovascular positioning of polypropilen "net" prosthesis, if kept in contact with the inner vascular surface, is spontaneously covered by new intima and included in the aortic wall in few weeks (fig 21 and fig 22), still keeping perfusion of some intercostals vessels, even though the net meshes used in those experiments were certainly too tight to assure their long term patency.

The experimental hypothesis is based on the fact that the net prosthesis positioned and maintained in stable contact with the aortic walls (A) is spontaneously, gradually covered by the neo-intima (B), invaded by fibroblasts and thus stably associated to the aortic wall. If the net mesh is appropriately dimensioned, it may be expected that the blood flow through the collateral branches is not affected (arrows) (from Nazari et al, 1996c)

While endovascular procedures already proved lower mortality and complications rate than open surgery and as good long term results in infrarenal and upper descending aorta, in all other aortic tracts endovascular techniques are much more complex and long term results less predictable mainly due to the presence of significant collateral branches, that require additional maneuvers to avoid their obstruction by the endoprosthesis (i.e. hybrid

Moreover endovascular procedures failed to protect from spinal chord ischemia and consequent paraplegia in extended descending aorta prosthetic substitution; it has been hypothesized that this could be due, at least in some case, to the fact that while endoprosthesis prevents intercostal branches to be physiologically perfused, cannot prevent, at least for a certain time in the initial phase, backwards blood flow into the space between endoprosthesis and aortic wall, thus generating conditions for a blood flow "steal" from

On the other hand current data (Gopaldas et al, 2010) show that only less than 1/4 of ideal candidates to endovascular treatment (uncomplicated, non genetic, isolated, elective descending aortic aneurysms) underwent endovascular procedure, while the remaining 3/4

The relative slowness of aneurysm formation and progression to rupture indicates that the decrease in the strength of the arterial wall under the aneurysm formation threshold may be very gradual and limited. Consequently one can imagine that measures to increase, even moderately, the mechanical strength of the arterial wall, for example by means of a dacron fabric network, should be successful in preventing aneurysm formations and thus its complications (dissection and rupture), without requiring complete prosthetic substitution. Moreover the conclusive understanding that a destruction of the elastin fibrils network is at the basis of aneurysm formation [Gott et al, 1996], might acknowledge the re-establishment of a uniform and regular network strengthening of the vascular wall with a net prosthesis as a logic, direct correction of the primary defect. On the other hand this mechanical approach since long time is already in use in many other technology fields for prevention of deformation of elastic/floppy tubes or structures subject to inner high pressure, as for

In previous animal experiments we showed that the endovascular positioning of polypropilen "net" prosthesis, if kept in contact with the inner vascular surface, is spontaneously covered by new intima and included in the aortic wall in few weeks (fig 21 and fig 22), still keeping perfusion of some intercostals vessels, even though the net meshes used in those experiments

The experimental hypothesis is based on the fact that the net prosthesis positioned and maintained in stable contact with the aortic walls (A) is spontaneously, gradually covered by the neo-intima (B), invaded by fibroblasts and thus stably associated to the aortic wall. If the net mesh is appropriately dimensioned, it may be expected that the blood flow through

**3. New endovascular "net" prosthesis for aortic wall strengthening without blocking aortic branches perfusion to early stop aneurysm progression or to** 

**prevent its formation in high risk patients** 

procedure with open surgery for supraortic trunks de-branching).

perfusion of the spinal chord (Kawaharada et al, 2010).

still underwent open surgical repair in US.

example gardening tubes, tires, rubber boat etc.

were certainly too tight to assure their long term patency.

the collateral branches is not affected (arrows) (from Nazari et al, 1996c)

**3.1 Background** 

**3.2 The rational** 

Fig. 21. The Rational. The experimental hypothesis is based on the fact that the net prosthesis positioned and maintained in stable contact with the aortic walls (A) is spontaneously, gradually covered by the neo-intima (B), invaded by fibroblasts and thus stably associated to the aortic wall. If the net mesh is appropriately dimensioned, it may be expected that the blood flow through the collateral branches is not affected (arrows) (from Nazari et al, 1996c)

Fig. 22. Swine experimental model.

*Left square.* After 6 weeks the net prosthesis, a braided polipropilene fitted with a co-axial thin stainless steel coil surgically positioned in swine upper descending aorta, was found to be covered by the new intima and well attached to the aortic wall. In the lower right side of the prosthesis segment the net is no longer visible and presumably, with little more time, this smooth, normal intimal surface would extend to completely cover the whole net prosthesis (metallic coil was removed). *Right square.* Histology shows the net prosthesis completely included into the intima layer and lying in contact with the media. The square area shows the magnified polypropylene mesh net pattern. (mod from Nazari et al 1996 c) Video http://www.fondazionecarrel.org/tsb2/tsb2.html

The fabric framework linked to the aortic wall would then condition its significant, regular and uniform mechanical strengthening that fractionates and absorbs the centrifuge systolic stress of the bloodstream. The significant mechanical strengthening achieved in this way was measurable by comparison of compliance (∆V/∆P) of the treated aortic tract with that of the immediately confining segment (fig 23)

New Approaches for Treatment and Prevention of Aortic Aneurysms 285

The structural properties of the aortic wall associated to the intraluminal net prosthesis rely on three factors (fig 24): 1) the structural properties of the net prosthesis, 2) the structural properties of the aortic wall, 3) the strength of the bonds between the aortic wall and the net prosthesis, based substantially on fibroblastic invasion of the net fabric and its permanent integration with aortic wall. Given the structural adequacy of the net prosthesis (polypropylene net prosthesis squared mesh 5x5 mm with a thread diameter of 0.5 mm sustaining a pressure of 300 mmHg (0.04 Nmm2) is charged at 50% of its failure tension (Nazari at al, 1996b, 1996c) and the mechanical effect of fractioning the aortic wall in the small area of the net meshes (fig 24, lower part), the important point of this model is the strength of the links biologically established between the threads of the mesh and the aortic

It may be hypothesized that its strength relies mainly in the degree of integration of the net thread with the intimal layer mainly due to fibroblastic invasion and is then predictably

stronger with porous material (PTFE) or multifilament braided polyester (Dacron).

Fig. 25. Variation of the circumferential stress through the aortic wall thickness.

from Robicsek and Thubrikar 1994)

For a thick cylinder (thickness > 8% of the radius (R)) such as the aorta, the stress is not uniform throughout the wall; it is maximal on the inner wall, it decreases through the thickness of the wall and is minimal on the outer wall. This explains the pathogenic mechanism of dissection, where only stress to the inner part of the wall is strong enough to cause tear; moreover it adds arguments to the rationale of intraluminal positioning of the net prosthesis in order to achieve the structural strengthening just where this is most needed, i.e. where the circumferential stress is maximal. This allows for the required

strengthening with optimization of the amount of prosthetic material (thinner threads) (Mod

The latter is the crucial point of this model. In fact if this link is sufficiently strong and stable in the time, it can be hypothesized to be able to stabilize aortic wall and prevent dilatation even independently from the "net" prosthesis own diameter, which could not be further distended after that their meshes have been firmly integrated into the aortic wall (Redaelli & Fiore, 2011). The practical consequence is that the precise equivalence between diameter of the net prosthesis and aortic diameter is not necessary; the prosthesis in fact can be

wall tissues (point 3 in fig. 24) during the 4-6 weeks integration process.

Fig. 23. Aortic wall compliance (ΔV/ΔP).

To quantify aortic wall strengthening induced by the net prosthesis its compliance (ΔV/ΔP). was compared with that of the confining segments that was found significantly higher. (from Nazari et al 1996b) Video at http://www.fondazionecarrel.org/tsb2/tsb2.html

The structural properties of the aortic wall associated to the intraluminal net prosthesis rely on three factors: **1)** the structural properties of the net prosthesis, **2)** the structural properties of the aortic wall, **3)** the strength of the bonds between the aortic wall and the net prosthesis, based substantially on fibroblastic invasion of the net fabric and its permanent integration with aortic wall. The latter is the crucial point and can be viewed as the true "functional unit" of this model. In fact if this link is sufficiently strong and stable in the time it can be hypothesized to be able to stabilize aortic wall and prevent dilatation even independently from the "net" prosthesis own diameter, which could not be further distended after that their fabric threads have been integrated into the aortic wall. (mod. from Nazari et al 1996b)

To quantify aortic wall strengthening induced by the net prosthesis its compliance (ΔV/ΔP). was compared with that of the confining segments that was found significantly higher. (from Nazari et al 1996b) Video at http://www.fondazionecarrel.org/tsb2/tsb2.html

The structural properties of the aortic wall associated to the intraluminal net prosthesis rely on three factors: **1)** the structural properties of the net prosthesis, **2)** the structural properties of the aortic wall, **3)** the strength of the bonds between the aortic wall and the net prosthesis, based substantially on fibroblastic invasion of the net fabric and its permanent integration with aortic wall. The latter is the crucial point and can be viewed as the true "functional unit" of this model. In fact if this link is sufficiently strong and stable in the time it can be hypothesized to be able to stabilize aortic wall and prevent dilatation even independently from the "net" prosthesis own diameter, which could not be further distended after that their fabric threads have been integrated into the aortic

Fig. 23. Aortic wall compliance (ΔV/ΔP).

Fig. 24. Aortic wall strengthening factors.

wall. (mod. from Nazari et al 1996b)

The structural properties of the aortic wall associated to the intraluminal net prosthesis rely on three factors (fig 24): 1) the structural properties of the net prosthesis, 2) the structural properties of the aortic wall, 3) the strength of the bonds between the aortic wall and the net prosthesis, based substantially on fibroblastic invasion of the net fabric and its permanent integration with aortic wall. Given the structural adequacy of the net prosthesis (polypropylene net prosthesis squared mesh 5x5 mm with a thread diameter of 0.5 mm sustaining a pressure of 300 mmHg (0.04 Nmm2) is charged at 50% of its failure tension (Nazari at al, 1996b, 1996c) and the mechanical effect of fractioning the aortic wall in the small area of the net meshes (fig 24, lower part), the important point of this model is the strength of the links biologically established between the threads of the mesh and the aortic wall tissues (point 3 in fig. 24) during the 4-6 weeks integration process.

It may be hypothesized that its strength relies mainly in the degree of integration of the net thread with the intimal layer mainly due to fibroblastic invasion and is then predictably stronger with porous material (PTFE) or multifilament braided polyester (Dacron).

Fig. 25. Variation of the circumferential stress through the aortic wall thickness. For a thick cylinder (thickness > 8% of the radius (R)) such as the aorta, the stress is not uniform throughout the wall; it is maximal on the inner wall, it decreases through the thickness of the wall and is minimal on the outer wall. This explains the pathogenic mechanism of dissection, where only stress to the inner part of the wall is strong enough to cause tear; moreover it adds arguments to the rationale of intraluminal positioning of the net prosthesis in order to achieve the structural strengthening just where this is most needed, i.e. where the circumferential stress is maximal. This allows for the required strengthening with optimization of the amount of prosthetic material (thinner threads) (Mod from Robicsek and Thubrikar 1994)

The latter is the crucial point of this model. In fact if this link is sufficiently strong and stable in the time, it can be hypothesized to be able to stabilize aortic wall and prevent dilatation even independently from the "net" prosthesis own diameter, which could not be further distended after that their meshes have been firmly integrated into the aortic wall (Redaelli & Fiore, 2011). The practical consequence is that the precise equivalence between diameter of the net prosthesis and aortic diameter is not necessary; the prosthesis in fact can be

New Approaches for Treatment and Prevention of Aortic Aneurysms 287

Possible prototypes versions were realized by 5x5mm meshes of braided fabric embodied with very thin nitinol wider helicoidal wireframe (*left*:blu lines, red arrows, 12-15 mm). Ascending aorta and arch would require curved prosthesis (*right*), maybe bespoke to the

A more straight, ready, maybe oversimplified method, but still mechanically efficient, could consist in the simple substitution of the Dacron tube with a fabric net prosthesis in any of

The prototypes resulting from the above project phase will undergo "in vivo" animal experiments. Ideally these experiments should include long term (≥12 months) evaluation in an appropriate animal (sheep) models. These may consist in prototypes positioning in the thoraco-abdominal aorta (model 1) and in the aortic arch (model 2) surgically or, possibly, as endovascular procedure if the endovascular delivery system is realized and suitable with the animal model peripheral vascular diameter. Half surviving animals could be sacrificed

regular integration of the net prosthesis into the intimal layer, looking for site and

the real structural strengthening achieved by measuring the aortic wall compliance

The remaining animals could be followed indefinitely and examined in case late

Ideally during the experimental phase will be identified and monitored Marfan patients with still normal or initial dilatation of any tract of the aorta in order to select those to be offered/accepting the prophylactic endovascular aortic strengthening. Obviously associated risk factors, in particular familiar history of aneurism and rupture, as well as other inclusion and exclusion criteria indicated by the Marfan Associations and clinical Institution Marfan

Marfan diseases is a condition where pure prophylaxis of aortic aneurism would be in most cases "per se" appropriate, due to its very high incidence and rather early in the patient life; on the other hand prophylactic surgical aortic substitution is an already considered option

extension of possible areas on lacking integration with aortic wall

(∆V/∆P) compared to that of the confining aortic segment (Fig. 5) absence of complications such as migration, ulceration, perforation etc

Centers, will form the basis for planning the possible future clinical trial.

preserved perfusion of all collateral branches for the extent of the net prosthesis

Fig. 26. "Net" prosthesis prototypes.

patient aortic anatomy on CT scans.

the current endovascular devices.

at 12 months and examined to verify:

complication or death.

**3.3.3 Preparation of clinical trial** 

**3.3.2 Experimental protocol** 

significantly redundant in respect to the effective aortic diameter, thus allowing for its easier adaptability to geometrical irregularity of aneurysm wall without consequences on its efficiency in keeping stable aortic diameter. The final "functional unit" of this model for aortic wall strengthening is then the single mesh of the net integrated into the aortic wall, whose efficiency relies then on the bonds between net threads and aortic tissue.

Interestingly enough in this model the endovascular net prosthesis provides aortic wall mechanical support just where the mechanical stress is higher (Robicsek & Thubrikar, 1994) (fig. 25), and thus just where it's most needed both to prevent further dilatation, theoretically preventable also by external aortic wall wrapping (Pepper et al 2010), and to avoid partial (dissection) or total rupture, with optimization of the amount of prosthetic material. The reduced volume of the net prosthesis in comparison with current endoprosthesis (≤1/6th approximately) further greatly enhances its introduction through peripheral vessel often tortuous and restricted by atherosclerosis.

#### **3.3 Methodology**

The previous experimental work as well as structural mechanical theoretical considerations allow to predict applicability and reliability of the method in the clinical setting of preventing aneurysm formation or arresting its progression at an early stage.

The organizative plan for achieving this final goal however includes several further distinct steps.

#### **3.3.1 Ideal "net" prosthesis prototypes setup**

This part of the project includes


The nitinol wireframe adds to the net further structural strengthening then greatly exceeding that required; an accurate structural mechanics computation would theoretically allow the achievement of the necessary aortic wall structural strengthening to permanently fix aortic diameter with really a very thin and wide meshes net prosthesis.

Fig. 26. "Net" prosthesis prototypes.

286 Front Lines of Thoracic Surgery

significantly redundant in respect to the effective aortic diameter, thus allowing for its easier adaptability to geometrical irregularity of aneurysm wall without consequences on its efficiency in keeping stable aortic diameter. The final "functional unit" of this model for aortic wall strengthening is then the single mesh of the net integrated into the aortic wall,

Interestingly enough in this model the endovascular net prosthesis provides aortic wall mechanical support just where the mechanical stress is higher (Robicsek & Thubrikar, 1994) (fig. 25), and thus just where it's most needed both to prevent further dilatation, theoretically preventable also by external aortic wall wrapping (Pepper et al 2010), and to avoid partial (dissection) or total rupture, with optimization of the amount of prosthetic material. The reduced volume of the net prosthesis in comparison with current endoprosthesis (≤1/6th approximately) further greatly enhances its introduction through

The previous experimental work as well as structural mechanical theoretical considerations allow to predict applicability and reliability of the method in the clinical setting of

The organizative plan for achieving this final goal however includes several further distinct

the selection of the best fabric material (PTFE, multifilament polypropylene, etc) with

 identification of its appropriated dimensioning and mechanical features, including elasticity, to provide the best support to the stream pressure stress up to its extreme

 identification of the most appropriate net prosthesis embodiment able to maintain it in permanent contact with intimal surface, which is essential to its quick and spontaneous incorporation into the aortic wall. This may include a thin nitinol wireframe associated to the main net prosthesis; a prototype for descending aorta currently in study is illustrated at fig. 26. However fluid-dynamic shapes of the net threads will be also evaluated in mechanical models with the aim to verify if it is possible to achieve

 Ascending aorta and Arch require variably curved net prosthesis (fig 26, right); for these tracts however bespoke prosthesis on the individual TC scan, maybe with wider meshes for the supraortic trunks area, is an option to be considered for clinical use; bespoke prosthesis however have being already realized in a external ascending aorta

The nitinol wireframe adds to the net further structural strengthening then greatly exceeding that required; an accurate structural mechanics computation would theoretically allow the achievement of the necessary aortic wall structural strengthening to permanently

whose efficiency relies then on the bonds between net threads and aortic tissue.

peripheral vessel often tortuous and restricted by atherosclerosis.

the best chances of the strongest links with aortic wall

conduit inner wall contact by means of pure fluid stream

fix aortic diameter with really a very thin and wide meshes net prosthesis.

**3.3.1 Ideal "net" prosthesis prototypes setup** 

wrapping protocol (Pepper et al, 2010)). Endovascular delivery system is also to be realized

This part of the project includes

pathological limit (300 mm hg)

preventing aneurysm formation or arresting its progression at an early stage.

**3.3 Methodology** 

steps.

Possible prototypes versions were realized by 5x5mm meshes of braided fabric embodied with very thin nitinol wider helicoidal wireframe (*left*:blu lines, red arrows, 12-15 mm). Ascending aorta and arch would require curved prosthesis (*right*), maybe bespoke to the patient aortic anatomy on CT scans.

A more straight, ready, maybe oversimplified method, but still mechanically efficient, could consist in the simple substitution of the Dacron tube with a fabric net prosthesis in any of the current endovascular devices.
