SEALING I HEALING I REGENERATION

An introduction to Vivostat® products

Marko Rackovic
VP Sales and Marketing
Agenda

• Introduction to sealants

• The Vivostat system and the process

®

• What makes Vivostat® unique

• Vivostat Fibrin Sealant in different surgical

®

procedures
Introduction to sealants
What is fibrin sealant

• Fibrin is an essential component

in the coagulation process
• During bleeding fibrinogen, already
present in the blood, reacts with
thrombin and the coagulation starts
• Fibrin sealant made from pooled blood
has been used in surgical procedures
for many years for various indications
– Hemostasis (diffuse bleedings)
– Gluing (tissue)
– Sealing (lungs, anastomoses)
Mechanism of action for traditional
fibrin sealant

Fibrino- Fibrino-
peptide A peptide B

Soluble Soluble
Fibrinogen Fibrin II
fibrin I fibrin II

Ca++ Factor
Trombin XIIIa
Activation
Mechanism of action for Vivostat®
Fibrin Sealant

Fibrino- pH4 buffer pH10 Fibrino-

peptide A Ca++ buffer peptide B

Soluble Fibrin I
Fibrinogen Fibrin II
fibrin I solution

Batroxobin Faktor
XIIIa

Preparation process
Application process
The Vivostat® system and the process
 The Vivostat system

Processor Unit
Fibrin Set

Applicator Unit
Obsidian Set

PRF® set
 The Vivostat® system

Processor Unit

Applicator Unit
Can supply
multiple OR’s.
Fibrin Set
Placed in Placed outside
the OR the OR
SET consists of

Preparation Kit Application Kit

The process is simple and fully automated

Add citrate Draw blood Insert syringe

• For anti-coagulation • Venous, arterial blood or • The syringe contains

FFP the pH4 buffer
The preparation process

Steps of the preparation process

• Reference & Spin check
• Heating up to 36° Celsius
• Separation of plasma and RBC
• Transfer plasma
• Mixing Batroxobin and Plasma
• Polymerization
• Serum removal
• pH4 buffer addition
• Fibrin dissolving
• Surplus buffer dump
• Fibrin pick up
• Ready for use
Automatic preparation of Vivostat®
Fibrin Sealant

After approx. 24 min

a fibrin I solution is
ready
 Vivostat® offers a range of unique
application devices
Spraypen Kit1 Spraypen Kit - Concorde

Arthroscopic applicator

Endoscopic Kit – Straight2 Endoscopic Kit1

 Easy and accurate application

• In-flight mixing ensures intermittent application

and no blocking

• The Vivostat® solution polymerizes immediately

upon application

• The Vivostat® solution remains where it is applied,

even on inverted surfaces

• Choice between different spray-modes

Benefits of the Vivostat® application system

No blocking
• In-flight mixing ensures intermittent application, no blocking and good mixing of the fibrin sealant

Versatility
• A selection of various application devices and spray modes

Freedom and precision

• The Spraypen makes it easy to apply an even layer of fibrin sealant

Economical in use
• Up to four minutes of constant spraying
Application of Vivostat® Fibrin Sealant
in the OR

The Applicator
Unit is placed
outside the
sterile field
The surgeon can use
the Spraypen
intermittently
throughout the
entire procedure
Vivostat® Co-Delivery

• The option of co-delivering a substance (drugs, stem cells, skin cells etc.) together with the
Fibrin or PRF® solution.

• Examples of different applications:

Drug applications
– Antimicrobials (ex. gentamicin)
– Chemotherapeutic (ex. cisplatin)
– Pain medication

Stem cell applications

– Bone marrow derived
– Adipose tissue derived

Skin cell application

– Epidermal cells

• Up to 5,3 mL of substance may be co-delivered together with the Fibrin or PRF ® solution.

• In order to co-applicate Vivostat® you need a APL404 and a Foot Switch.

Vivostat® Co-Delivery
- How does it work

• To co-applicate Vivostat® you need an APL404 and a Foot Switch

Cross section of the Vivostat® co-delivery tube

Placement of the syringes in the syringe holder
Vivostat® Co-Delivery
- Benefits

Topical application
• Target affected/desired area
• Possible higher local dose
• Possible lower systemic dose
• Compliance

Fibrin/PRF® embedded
• ”Protection” of the substance
• Sustained release/impact of the substance

No thrombin is added to Vivostat® (unlike most other fibrin products)

• A high thrombin solution has been shown to have a negative effect on cell survival
What makes Vivostat® unique
Vivostat® benefits – Accuracy

The Vivostat® application system: A comparison with conventional fibrin sealant application systems
Dodd R A, Cornwell R et al. · Technology and Health Care 2002; 10: 401-411
Vivostat® benefits– Accuracy
 Vivostat® benefits - Spray Force

The Vivostat® application system: A comparison with conventional fibrin sealant application systems
Dodd R A, Cornwell R et al. · Technology and Health Care 2002; 10: 401-411
 Vivostat® benefits - Polymerisation

Comparative kinetics of polymerisation of three fibrin sealants and influence on timing of tissue adhesion
Kjaergard H K et al. · Thrombosis Research 2000; 98: 221-228
 Vivostat® benefits - Elasticity

Comparative kinetics of polymerisation of three fibrin sealants and influence on timing of tissue adhesion
Kjaergard H K et al. · Thrombosis Research 2000; 98: 221-228
Vivostat® benefits - Elasticity
 Vivostat® benefits – Adhesion

Comparative kinetics of polymerisation of three fibrin sealants and influence on timing of tissue adhesion
Kjaergard H K et al. · Thrombosis Research 2000; 98: 221-228
Vivostat® benefits – Adhesion
 Vivostat® Fibrin Sealant in
different surgical procedures
 Surgical applications

Maxillofacial
Abdominal
Thoracic
Cardiac

Neuro

Wound care
General

Urology
Vascular Plastic

Orthopaedic
Vivostat® Fibrin Sealant in cardiac surgery

Intended use: For all large and complicated cases

where
bleeding and for
Most common Vivostat® areas of use:
• Aortic dissections
• Bentall procedures
• Off pump procedures
• Minimally invasive cases
• Re-do procedures
• Heart transplants
there is a risk of severe
all cases with high risk patients
• (Double) valve procedures
• Sternal wound healing
• Elderly patients
• LVAD
• Congenital cases
Vivostat® Fibrin Sealant in
cardiac surgery

Sealing of proximal suture line Sealing of distal suture line

Vivostat® Fibrin Sealant in
cardiac surgery

Sealing of vascular anastomoses Sealing of aortic graft

and sealing of sternal marrow
Vivostat® Fibrin Sealant in thoracic surgery

Intended use:
For all procedures where there is a risk of air leakages, to
support of anastomotic lines and to reduce bleeding

Most common Vivostat® areas of use:

• Lobectomy
• Wedge resections
• Decortication of empyema
• Lung volume reduction surgery
• Bulla resection
• Broncho pleural fistula/bronchial stump insufficiency
Vivostat® Fibrin Sealant in thoracic surgery

Important Vivostat ® features:

• Autologous
• Adhesion
• Elasticity
• Easy and accurate application
• High volume of fibrin (5-6 ml) will cover a large surface
• Application devices (e.g. endoscopic for minimally invasive
surgery, Concorde spraypen and Endoscopic Kit – Straight for
bronchoscopy)
• No blocking and intermittent use (convenient for long
procedures, no need to change nozzle)
• The option of Co-Delivery
Vivostat® Fibrin Sealant in
thoracic surgery

Sealing of stapleline after

lung resection
Vivostat® Fibrin Sealant in neurosurgery

Intended use: For all procedures where there is a need

for a haemostat, a sealant or a glue e.g. to prevent
CSF leakages, support closure of the dura and fill dead space.

Most common Vivostat® areas of use:

• Open skull base procedures
• Re-operations
• Tumor/Hyphophysis (Transspenoidal procedures)
• Spinal surgery with dura opening
• Acusticus neurinoma
• Chiari
Vivostat® Fibrin Sealant in neurosurgery

Sealing of facial nerve anastomosis and sealing of

dural closure
Vivostat® Fibrin Sealant in neurosurgery
Vivostat® Fibrin Sealant in neurosurgery
Vivostat® Fibrin Sealant in vascular surgery

Intended use:
For large vascular procedures where it is necessary with a
haemostat, a sealant or a glue
Most common Vivostat® areas of use:
• Thoracic aorta
• Thoraco – abdominal aortic
• Abdominal aortic resection
• Aortobifemoral bypass
• Carotid resection
• Kidney transplantation
• Re-operations
Vivostat® Fibrin Sealant in abdominal
surgery

Intended use:
For all procedures where it is necessary with a haemostat, a sealant or a glue

Most common Vivostat® areas of use:

• Pancreatic resection • Radical mastectomy

• Liver resection (hepatectomy) • Gastric bleeding
• Esophageal reconstruction • Bariatric surgery
• Full / split liver transplant • Hernia mesh
Vivostat® Fibrin Sealant in
abdominal surgery
Vivostat® Fibrin Sealant in
abdominal surgery
Vivostat® Fibrin Sealant in
abdominal surgery

Fixation of hernia mesh

Vivostat® Fibrin Sealant in
abdominal surgery

Sealing of oesophagus anastomoses

(autolog oesophagus made of stomach)
Vivostat® Fibrin Sealant in urological
surgery

Intended use: For all procedures where it is necessary with a haemostat, a

sealant or a glue

Most common Vivostat® areas of use:

• Partial nephrectomy
• Radical prosthatectomy
• Cystectomy
• Mucosa of urinary bladder
• Pyelo-plastic operations
• Ureter anastomosis
Vivostat® Fibrin Sealant in
urological surgery

Nephrectomy with the da Vinci Surgical System

Vivostat® benefits for both the surgeon and
the patient

For the surgeon

• Application
– Versatile – spray in any direction For the Patient
– Accurate and controlled application
– No blocking due to in-flight mixing
– Easy to obtain an even layer of fibrin
• No exogenous thrombin (Thrombin can
• Intermittent use have a negative effect on cell survival)
– Up to 8 hours after preparation • No bovine or synthetic components
• Economical in use • No risk of viral cross infection
– Up to four minutes of non-stop spraying
• No risk of anaphylactic reaction
– Cover areas up to 200cm2
Contraindications, Cautions and Warnings

Contraindications
• Known hypersensitivity to batroxobin

Cautions and warnings

• Not for intravascular use
• Spray is achieved using pressurised air. Caution should
be used where there is a risk of air embolism
• Central nervous system: be aware of the possibility of
convulsions and be prepared to take appropriate
corrective action if they should occur
Combining fibrin and platelets
 The Vivostat system

Processor Unit

Applicator Unit
Placed
in or outside the
place of treatment
Placed next to
the patient PRF® set
The Vivostat PRF® biomatrix

Fibrin

Platelet

Scanning Electroscopic Microscope Image of PRF ®

 Platelet granules are preserved

Platelet

Granules
(containing several
growth factors)

Transmission Electroscopic Microscope Image of PRF ®

PRF® is the ideal combination of platelets and
fibrin

Cell stimulation is Vivostat PRF® promote

cell stimulation e.g. fibroblasts
fundamentally important in Cell stimulation
the process of regenerating proliferation and collagen
tissue synthesis

The fibrin matrix in Vivostat PRF®

The effect of a platelet acts not only as a haemostasis but
concentrate is dependant on Stability also as a delivery media that
the stability of the growth protects and slowly releases
factors in the tissue growth factors over time

Conventional platelet Due to instant polymerization

concentrates are Application of the fibrin, the Vivostat PRF®
difficult to apply solution remains where it is applied
PRF® is the ideal combination of
platelets and fibrin

Cell stimulation is Vivostat PRF® promote

fundamentally important in Cell stimulation cell stimulation e.g. fibroblasts
the process of regenerating proliferation and collagen
tissue synthesis

The effect of a platelet The fibrin matrix in Vivostat PRF®

concentrate is dependant on Stabilty acts as a delivery media that
the stability of the growth protects and slowly releases
factors in the wound growth factors over time

Conventional platelet Due to instant polymerization

concentrates are Application of the fibrin, the Vivostat PRF®
difficult to apply solution remains where it is applied
Stimulation of fibroblast proliferation

• R. Lundquist et al. Wound Rep Reg (2007) 1-8

Stimulation of fibroblast collagen synthesis

• R. Lundquist et al. Wound Rep Reg (2007) 1-8

PRF® is the ideal combination of platelets and
fibrin

Cell stimulation is Vivostat PRF® promotes cell

fundamentally important in Cell stimulation stimulation e.g. fibroblasts
the process of regenerating proliferation and collagen
tissue synthesis

The effect of a platelet The fibrin matrix in Vivostat PRF®

concentrate is dependant on Stabilty acts as a delivery media that
the stability of the growth protects and slowly releases
factors in the wound growth factors over time

Conventional platelet Due to instant polymerization

concentrates are Application of the fibrin, the Vivostat PRF®
difficult to apply solution remains where it is applied
Protection against proteolytic degradation

• R. Lundquist et al. Wound Rep Reg (2008) 1-8

Release of growth factors over time

Vivostat Technical Report No. 1005 – Data on file at Vivostat A/S

PRF® is the ideal combination of
platelets and fibrin

Cell stimulation is Vivostat PRF® promotes cell

fundamentally important in Cell stimulation stimulation e.g. fibroblasts
the process of regenerating proliferation and collagen
tissue synthesis

The effect of a platelet The fibrin matrix in Vivostat PRF®

concentrate is dependant on Stabilty acts as a delivery media that
the stability of the growth protects and slowly releases
factors in the wound growth factors over time

Conventional platelet Due to instant polymerization

concentrates are Application of the fibrin, the Vivostat PRF®
difficult to apply solution remains where it is applied
Easy and accurate application

• The Fibrin component polymerizes

immediately upon application

• The PRF® solution remains where it is

applied, even on inverted surfaces
High concentration of Fibrin

• The fibrin concentration in Vivostat PRF® is 18.1 mg/ml

• The fibrin component in Vivostat PRF® allows it also to be used for:
– Haemostasis
– Tissue gluing
– Tissue sealing

• Vivostat PRF® are two products combined into one product which can be used in
multiple settings and procedures
Multiple different growth factors

• Vivostat PRF® has an average 7 times increase in platelet concentration1

• These platelets contain a number of different growth factors that serve different purposes in the
complex process of tissue regeneration

• Growth factor increase compared to baseline in Vivostat PRF®2:

• BFGF: 75-fold
• TGF-β1: 5.1-fold
• PDGF-AB: 2.5-fold
• PDGF-BB: 1.6-fold
• VEGF: 1.2-fold

• Vivostat PRF® also includes growth factors such as EGF, IGF-1 and proteins such as cytokines and
chemokines

1: Bioactivity and stability of endogenous fibrogenic factors in platelet-rich fibrin · Lundquist R. et al. ·
Wound Repair and Regeneration 2008; 16(3): 356-365
2: Growth factor and proteinase profile of Vivostat platelet-rich fibrin linked to tissue repair · Ågren M. et
al. · International Society of Blood Transfusion 2013; DOI: 10.1111/vox.12120
Effect of growth factors in tissue regeneration
No Thrombin is added to Vivostat PRF®

As opposed to most other PRP products no thrombin is added to Vivostat PRF ®. Thrombin activates platelets and activated
platelets are less effective than non-activated platelets 1 (PRF®). Thrombin, furthermore, has a negative effect on cell survival 2.

Conclusion of article:
“Our results support the use of non-activated physiologic platelets for wound healing, to best activate fibroblast differentiation
and migration, promote angiogenesis, and ultimately stimulate healing.”

Another articles also concludes that thrombin negatively influences bone regeneration 3

The above findings show that Vivostat PRF ® out performs thrombin based PRP products when it comes to:
– Wound healing1
– Cell survival2
– Bone regeneration3

1 Nonactivated versus Thrombin-activated Platelets on Wound Healing and Fibroblast-to-Myofibroblast Differentiation In Vivo and In Vitro
2 High Thrombine concentrations in Fibrin Sealants induce apoposis in human keratinocyts
3 The Effect of Thrombin Activation of Platelet-Rich Plasma on Demineralized Bone Matrix Osteoinductivity
What is Vivostat PRF®
- Summing up

• Vivostat PRF® is a ”Delivery System” for autologous growth factors embedded in a

fibrin matrix
• Vivostat PRF® leads to increased and sustained cell growth
• Vivostat PRF® stimulates formation of collagen by skin fibroblasts
• Vivostat PRF® protects growth factors against proteolytic degradation
• Vivostat PRF® is also a sealant and haemostatic
• Vivostat PRF® contains a large number of different growth factors that all serve
different purposes in the complex process of tissue regeneration
• No Thrombin is added to Vivostat PRF®
Vivostat PRF® in
different surgical procedures

• Arthroscopic surgeries (cartilage, ACL, meniscus)

• Ligaments and tendons reconstructions
• Spinal surgery
• Grafts
• Soft tissue surgery
• Tumor and cysts removal (filling effects)
• Regenerative (surgery) medicine

• Cardiac surgery – sternal closure

• Chronic wounds and burns
 Obsidian ASG®
Endo
Anastomoses SafeGuard

Obsidian ASG®
Anastomoses SafeGuard
 Obsidian ASG® - indications
General surgery
Colorectal surgery

Pancreatic resection

Liver resection Fistula treatment

Oesophageal resection Stapleline reinforcement

Gastric resection

Bariatric surgery