natural vascular scaffolding (nvs) · natural vascular scaffolding (nvs) to restore and maintain...

Natural Vascular Scaffolding (NVS)to Restore and Maintain Femoropopliteal Luminal

Patency in Peripheral Arterial Disease (PAD)

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Disclosure

Speaker name:

William A. Gray MD

I have the following potential conflicts of interest to report:

Consulting

Employment in industry

Stockholder of a healthcare company

Owner of a healthcare company

Other(s): Scientific Advisory Board member at Alucent Biomedical Inc.

I do not have any potential conflict of interest

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Components of NVS Therapy

Novel photoactivatable small molecule

Creates a Natural Vascular Scaffold through photoactivated linking of native structural proteins (i.e. collagen and elastin) in the vessel wall.

Light fiber Angioplasty balloon

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Photoactivated Linking of Extracellular Structural Proteins

+

Cross-links formed between amino acids

(covalent chemical bonds)

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NVS Therapy Targets Diseased Human Arteries Rich in Collagen

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Histological section of diseased human artery by

H&E staining

Trichrome staining showing that diseased human arteries are rich

in collagen

Fluorescent histological image of NVS

compound in diseased human artery

Untreated

Treated

ConclusionNVS increases the density of the treated vessel wall,

indicating crosslinking in the media.

NVS Effect on Extracellular Matrix

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100.0

200.0

300.0

400.0

Quantitation of Tissue Density Change

Untreated NVS Treated Positive Control -Glutaraldehyde

Recoil prevention is a clinically important effect.

Even a small difference in diameter carries physiological relevance, (Resistance = 1 / radius4.)

0%

5%

10%

15%

20%

25%

30%

35%

40%V

esse

l rec

oil

%

*p<0.05

*

POBA + NVSPOBA

Prevention of Recoil by NVS Therapy

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Lack of In Vivo Recoil Following 30% Overstretch of Normal Pig Arteries

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POBA

Control

NVS Treated

Both Arteries NVS

Treated

Retained Vascular Contractility of NVS Treated Human Arteries

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Contraction to Thromboxane Mimetic

Relaxation to Sodium Nitroprusside

Lack of Restenosis in Chronic Study Using Hypercholesterolemic Swine

Experimental design• Genetically engineered pigs kept on high

cholesterol diet for a 1 year to develop disease

• Initial angioplasty stretch injury (3 x 30%) to produce stenosis

• 3 arm treatment @14 day: NVS in comparison to Stent and POBA

• OCT imaging and histology @ 28day after treatment

0%

10%

20%

NVS PTA Stent

Are

a st

eno

sis

(%)

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OCT Image Analysis of Femoral Arteries

Conclusions

• The overall disease burden was low (compared to human PAD).

• Lumen size retained over 28days following NVS treatment

• NVS treatment does not cause restenotic injury like stents.

Is NVS Therapy Innovative?

POBA Stents NVS TherapyExpected benefit from NVS

therapy

Lumen Restoration Yes Yes YesMaintains the lumen for sustained

improvement of blood flow

Recoil Prevention No Yes YesMinimizes elastic recoil and helps the vessel recover from the insult of PTA

Vessel Elasticity Yes No YesRestored lumen retains more natural anatomic and physiologic properties

Avoids Implant Yes No Yes Eliminates stent-related complications

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