HYPRO­OSS & HYPRO­SORB

Innovative Bovine Biomaterials for Implantology,

Periodontology and Maxillofacial Surgery

bioimplon Biotech Innovation Pioneers

© bioimplon 2015
Letter from the General Manager
Dear clinical user,
Bioimplon's focus is to develop, manufacture and market unique native bovine products in the cutting edge field of
regenerative medicine. Our extensive product offerings cover the fields of bone and tissue regeneration, tissue engineering
and wound healing for dental, spinal, orthopaedic and dermatologic applications. They are used by oral and maxillofacial
surgeons, periodontists and dental implantologists as well as by orthopaedic and spinal surgeons.
Patient safety, ease of use, reliable and predictable treatment results are our first priorities. Our products have proven their
success in safety, efficacy, reliability and superior handling characteristics in clinical studies and documented cases as well
as in the daily clinical work with many hundred thousands of patients worldwide.
In addition to our Hypro-Sorb® membranes, matrices and cones as well as Hypro-Oss® bovine bone substitution and
regeneration material, the company has developed a future-oriented product pipeline. These products contain moldable bone
graft blocks an injectable gel forms that we will launch in the near future.
We thank our customers worldwide for positive feedback and invite you to share with us your experiences and suggestions for
improvements.

Dr. med. Sami Watad

General Manager
Bioimplon GmbH

© bioimplon 2015
Table of contents
Bioimplon – Bovine biomaterials for your needs 1
Hypro­Oss – Bovine bone substitute 2
Hypro­Sorb M Matrix – Guided tissue regeneration 6
Hypro­Sorb M and F Membranes – Guided tissue and bone regeneration 10
Hypro­Sorb R – Haemostatic sponges 14
Hypro­Sorb X and Z – Alveolar ridge preservation and haemostasis 16
Dental portfolio 18
About Atelo­Collagen 19
Safety Information 21
Certifications and Copyright 22

© bioimplon 2015
Bioimplon
Bovine biomaterials for your needs
Bioimplon GmbH is one of the leaders in the development, manufacture, and distribution of innovative regenerative
biomaterials for the medical and dental fields. Our product portfolio includes:
• Bone substitute material
• Membranes for guided bone and tissue regeneration (GBR / GTR)
• Collagen matrices for GBR / GTR and haemostasis
• Haemostatic sponges and cones
Our biomaterials are indicated for use in the following dental fields:

Maxillofacial
Implantology Periodontology
Surgery

We continuously invest in research and development and trust in our qualified and specialized employees.
All our products contain Atelo-Collagen of bovine origin. Our membranes, matrices, and sponges are made entirely of this
modified, non-immunogenic collagen.
HYPRO-OSS®: The patented bone graft innovation was developed by scientific teams of Bioimplon GmbH and Hypro s.r.o. It
is the first native bovine bone substitute material that is composed of about 30% Atelo-Collagen integrated within the
hydroxyapatite particles of each bone granule structure. The bone graft is manufactured using a lyophilization processing
technology, atelopeptidized, and biocompatible. It has been histologically proven that Hypro-Oss completes a high quality
new bone formation within a very short period of time.
HYPRO-SORB®: The range of our Atelo-Collagen-portfolio includes a large variety of shapes and sizes for a diverse field of
applications. All Hypro-Sorb products consist of 99.9% pure Atelo-Collagen type I – a biocompatible, non-immunogenic
collagen free of telopeptides. The source of the Atelo-Collagen is the bovine Achilles tendon. Atelo-Collagen is the most
effective haemostatic product with bacteriostatic effect. The Hypro-Sorb portfolio is the result of many years of experience
and an intensive research cooperation between Bioimplon and Hypro s.r.o.

1 © bioimplon 2015
 Hypro­Oss®
Hypro-Oss® is a natural bovine bone substitute material with incorporated Atelo-Collagen. It is used for the permanent filling
or reconstruction of antiseptic bone defects.

Hypro-Oss
Properties and advantages
Hypro-Oss is produced with our patented atelopeptidation and lyophilization technologies. These result in the following
important characteristics:
• Native bovine bone graft composite for enhanced new bone
formation
• Telopeptide-free collagen components; non-immunogenic peptide
• Acceleration of physiological tissue healing process
• Protects grafting site from infection (bacteriostatic effect of
Atelo-Collagen)
• Hydrophilic property: optimal cell adhesion and blood absorption
• Capability to carry medication to the surgical site
• Highest biocompatibility: absence of any foreign body response
• Natural structures of collagen and hydroxyapatite due to
lyophilization processing
• Osteopromotive Atelo-Collagen components and
osteoconductive hydroxyapatite components
• Native crystalline structure guarantees long-term dimensional
stability
• Powerful haemostatic effect of the Atelo-Collagen averts
haematoma formation after surgical procedures
• Consistent availability and safety
• Reliable clinical results
• No need for autograft harvesting
• Lyophilized bovine bone has a very similar composition to human
bone
These characteristics allow enhanced and consistent new bone formation, Hypro-Oss intraosseous implantation in beagle
and persistent integration between mature new formed bone and existing dogs – Histology after 14 weeks
bone materials.

© bioimplon 2015 2
Bovine bone substitute

Hypro-Oss grain size: 1.0 - 2.0 mm Hypro-Oss grain size: 0.5 - 1.0 mm

Hypro-Oss
Indications in implantology, periodontology and maxillofacial surgery:
• Sinus lift
• Vertical and horizontal augmentation
• Intraosseous defects
• Peri-implant defects
• Extraction sockets
• Furcation defects
• Filling of cysts
• Periodontal defects

Hypro-Oss used together with Hypro-Sorb F. Images courtesy of Dr. Amir Gazmawe DMD Prosthodontist

3 © bioimplon 2015
Hypro-Oss
Composition

Hypro-Oss is a natural bovine bone

graft. Each granule consists of
approximately 70% hydroxyapatite
and 30% Atelo-Collagen Type I. It is
sterile and safe.

Chemical composition: Human bone in comparison to lyophilized bovine bone

Hypro-Oss – Electron microscopy

© bioimplon 2015 4
 Hypro-Oss – X-ray diffraction Hypro-Oss – Energy dispersive spectoscropy (EDS)

Hypro-Oss
Available sizes and volumes

Storage conditions
Hypro-Oss must be stored in a dry place at room temperature. Hypro-Oss is not damaged by temperatures from 0°C to
+50°C. It needs to avoid sources of heat and direct sunlight.
Hypro-Oss is a sterile medical device class III, ISO and CE certified.

5 © bioimplon 2015
 Hypro­Sorb® M Matrix
Our multilayer Atelo-Collagen matrix for guided tissue regeneration in
periodontology and maxillofacial surgery

The Hypro-Sorb® M Matrix is a multilayer tissue matrix of pure,

crystalline Atelo-Collagen (telopeptide-free collagen) derived
from the bovine Achilles tendon. The Hypro-Sorb M Matrix
supports neovascularization and controlled soft tissue integration
and is a safe alternative to the patients’ own soft tissue grafting
material. In addition, it has an excellent barrier function due to
the solid collagen structure and long resorption time of six
months. The Hypro-Sorb M Matrix was conceived and
developed by researchers of Bioimplon GmbH and Hypro s.r.o.

multilayer, native, resorbable

Mechanism of regeneration and remodeling kinetics

After placement, the patient’s blood infiltrates the Hypro-Sorb M Matrix graft through the three-dimensional multilayer soft
tissue structure, bringing host cells to the soft tissue graft surface and starting the neovascularization process. Significant
neovascularization can begin after implantation depending on the patient’s health condition.
Regeneration is a heterogeneous process occurring at the interface of solid Atelo-Collagen and fluid (blood, wound exudate).
The kinetics of the heterogeneous processes depends primarily on the interface area and – as a consequence – on the
correlation with the internal surface area of the Atelo-Collagen Matrix. The internal surface area of the Hypro-Sorb M Matrix
exceeds 150,000 cm²/cm², which is one of the highest known values among similar products worldwide
The natural specific affinity of Atelo-Collagen to thrombocytes results in the release of agglutination factors and growth factors
such as IGF I, TGF-beta, PDGF, which in combination with blood plasma factors promote the regeneration of the soft tissue. In
addition, Atelo-Collagen inhibits the serine proteinase of exudate and promotes granulation and epithelisation.
Moreover, the implanted Hypro-Sorb M Matrix is absorbed within six months. Read more about the resorption process in
Resorption of Atelo-Collagen on page 19.

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Guided tissue regeneration

Hypro-Sorb M Matrix
Advantages
• Consistent availability and safety
• No need for autograft harvesting
• High patient acceptance
• Reliable clinical results
• Cost effective

Hypro-Sorb M Matrix – 20 x 25 x 2 mm

Hypro-Sorb M Matrix
Properties
• Biocompatible pure, crystalline Atelo-Collagen type I – free of
antigenic telopeptides (for more information on Atelo-Collagen, see
the chapter About Atelo-Collagen)
• Multilayer soft tissue structure
• Rapid neovascularization and integration
• Accelerates soft tissue replacement without the need for autograft
harvesting
Hypro-Sorb M Matrix – 25 x 25 x 2 mm
• Complete remodeling into patients’ own tissue
• Excellent barrier function
• Resorption time of approximately six months
• Easy handling, can be easily applied and fixed
• Can be cut to shape for specific procedures
• Sterile for five years, safe and resorbable

7 © bioimplon 2015
Hypro-Sorb M Matrix
Indications
• Maxillofacial and periodontal surgery
• Treatment of gingival recession
• Sinus lifting
• Segmental growing of the alveolar tissue
• Periimplantitis
• Furcation treatment
• Vertical and segmental augmentation
• Cleft lip and palate

Hypro-Sorb M Matrix – 25 x 50 x 2 mm

Hypro-Sorb M Matrix
Handling instructions
1. Trim the matrix to the size you need using scissors.
2. The matrix should overlap the walls of the defect by at least 2-3 mm in order to achieve complete coverage of the
bone and thus prevent lateral ingrowth of gingival tissue.
3. The defect cavity is then filled loosely with bone substitute material such as Hypro-Oss.
4. The matrix is applied over the defect with its smooth side turned towards the soft tissue and held in place with
moderate pressure. The saturation of the matrix with blood and exudate permits perfect adaptation to the bone
surface. Additional stabilization by pins may be indicated for complex defects.
5. The flaps are closely sutured over the matrix and should be free of tension. The wound should, whenever possible, be
completely closed.
6. During the healing phase, stress in the wound area from prosthetic pressure or palpation should be avoided. Intensive
mechanical oral hygiene should be replaced by antibacterial rinsing (e.g. with chlorhexidine) for the first three weeks.
Antibiotic therapy is prescribed at the discretion of the clinician.

Hypro-Sorb M Matrix
Available sizes

© bioimplon 2015 8
Composition
Natural pure (99.9%), crystalline, multilayer Atelo-Collagen tissue structure of bovine tendon.

Storage conditions
The Hypro-Sorb M Matrix must be stored in a dry place at room temperature. It is not damaged by temperatures between
-25°C to +50°C. It must be protected from direct sunlight and heat. The product is sterile for five years.
Hypro-Sorb M is a medical device class III, ISO and CE certified.

9 © bioimplon 2015
 Hypro­Sorb® M and F
Our natural Atelo-Collagen membranes for guided tissue and bone regeneration
in maxillofacial surgery and implantology

Hypro-Sorb® M membranes are biphasic, bilayer membranes of pure,

crystalline Atelo-Collagen of bovine origin. They come in three different
sizes and two convenient thicknesses.
The membranes differ with regards to their handling: The 0.8 mm thick
Hypro-Sorb M membrane is soft, whereas the 0.3 mm thick Hypro-Sorb
M membrane is medium rigid. Due to the special processing of the
collagen fibers it is not necessary to soak these membranes with saline
or the patient's blood before application.

biphasic, native, resorbable

Hypro-Sorb® F is a rigid, bilayer membrane of pure, crystalline Atelo-

Collagen derived from the bovine Achilles tendon. It is the most rigid
membrane in our portfolio and comes in three different sizes.
Hypro-Sorb F is 0.2 mm thick with high tensile and bending stength due
to densely packed collagen fibers. Therefore, it is recommended to
soak the membrane with saline or the patient's blood for at least 1
minute before application to facilitate handling.

bilayer, native, resorbable

The membranes are the result of many years of experience and an intensive research collaboration between scientific teams
of Hypro s.r.o. and Bioimplon GmbH.

© bioimplon 2015 10
Membranes
Guided tissue and bone regeneration
Hypro-Sorb M and F Membranes
Properties and advantages
As all our membranes consist of Atelo-Collagen and have been lyophilized, they share the following characteristics:
• Pure, crystalline Atelo-Collagen type I – free of telopeptides
• Highest degree of tissue biocompatibility with excellent wound healing characteristics
• Quick adaptation to the defect due to its potent hydrophilic properties
• Reduced risk of dehiscence formation due to the texture and mild bacteriostatic effect of Atelo-Collagen
• Can be attached with pins and suturing material
• Sufficiently long barrier function – membranes stay intact for the first six weeks
• Naturally resorbable within six months
• Long shelf life – safe and sterile for five years after production
• Consistent availability and safety
• Reliable clinical results
• Unmistakable rough and smooth sides

Rough side of Hypro-Sorb M

Hypro-Sorb M and F Membranes

Indications
All our membranes can be used for the following indications:
• Sinus Lifting
• Segmental growing of the alveolar tissue
• Periimplantitis
• Furcation treatment
• Vertical and segmental augmentation Smooth side of Hypro-Sorb M
• Cystectomy
• Maxillofacial and Periodontal surgery
• Cleft lip and palate
However, periodontists tend to prefer Hypro-Sorb M, whereas Hypro-Sorb F is often favoured by maxillofacial surgeons.

Application of Hypro-Sorb® M and Hypro-Oss® – Images courtesy of Dr. Labazanov Ashab, Maxillofacial Surgeon, Moscow, Russia

11 © bioimplon 2015
Hypro-Sorb M and F Membranes
Handling instructions
1. Trim the membrane to the size you need using scissors.
2. The membrane should overlap the walls of the defect by at least 2-3 mm
in order to achieve complete coverage of the bone and thus prevent
lateral ingrowth of gingival tissue.
3. The defect cavity is then filled loosely with bone substitute material such
as Hypro-Oss.
4. The membrane is applied over the defect with its smooth side turned
towards the soft tissue and held in place with moderate pressure. The Rough side of Hypro-Sorb F
saturation of the membrane with blood and exudate permits perfect
adaptation to the bone surface. Additional stabilization by pins may be
indicated for complex defects.
5. The flaps are closely sutured over the membrane and should be free of
tension. The wound should, whenever possible, be completely closed.
6. During the healing phase, stress in the wound area from prosthetic
pressure or palpation should be avoided. Intensive mechanical oral
hygiene should be replaced by antibacterial rinsing (e.g. with
chlorhexidine) for the first three weeks. Antibiotic therapy is prescribed
at the discretion of the clinician.

Smooth side of Hypro-Sorb F

Application of Hypro-Sorb® F and Hypro-Oss® – Images courtesy of Fahim Atamni, DDS, specialist for oral surgery

Postoperative care
In case of wound dehiscence with membrane exposure, the usual antimicrobial precautions are recommended. Removal of
the membrane is not necessary. The resorption time may be accelerated by external influences such as saliva, etc. The
properties of collagen may favour a rapid healing of the wound dehiscence.

© bioimplon 2015 12
Composition
Natural pure (99.9%), crystalline Atelo-Collagen tissue structure of bovine tendon.

Hypro-Sorb M: Electron microscope image Hypro-Sorb F: Electron microscope image

Hypro-Sorb M and F Membranes

Available sizes

Storage conditions
Hypro-Sorb M and F must be stored in a dry place at room temperature. They are not damaged by temperatures between
-25°C to +50°C. It must be protected from direct sunlight and heat. The product is sterile for five years.
Hypro-Sorb M and F are medical devices class III, ISO and CE certified.

13 © bioimplon 2015
 Hypro­Sorb® R
Our natural Atelo-Collagen sponge for an effective haemostasis and wound
regeneration

Hypro-Sorb R® is a range of bioabsorbable haemostatic

sponges of pure, crystalline Atelo-Collagen type I of bovine
origin (for more information on Atelo-Collagen in general and
how it induces haemostasis in particular, see the chapter
About Atelo-Collagen).

Hypro-Sorb R
Properties and advantages
• Haemostatic sponge of pure, crystalline Atelo-Collagen type I of bovine origin – free of antigenic telopeptides
• Highest degree of tissue biocompatibility and safety with excellent wound-healing characteristics
• Most effective haemostatic material with bacteriostatic effect
• Usable in infected wounds or with medically compromised patients
• Can be cut to size without loss of haemostatic properties
• Resorbs spontaneously within two to four
weeks
• Available in a large variety of shapes and
sizes
• Long shelf life – safe and sterile for five
years

Atelo-Collagen haemostatics are fastest in helping achieve haemostasis and reduce blood
loss substantially better than other haemostatic materials, when stopping parenchymatous
bleeding from surgically cut liver.

Hypro-Sorb R
Indications
Hypro-Sorb R is indicated for the control of capillary and parenchymatous bleeding in maxillofacial surgery. It can also be
used as resorbable cyst filling in surgery, stomatology and traumatology.

© bioimplon 2015 14
Haemostatic sponges
Hypro-Sorb R
Handling instructions
1. Hypro-Sorb R is applied usually with its smooth side onto the wound surface, softly pressed down and left on the
wound until the fibrin adhesion develops.
2. Bleeding usually stops in two to five minutes; it lasts longer in haemophiliacs.
3. Usually it is used in dry state but it may also be moistened with sterile saline solution.
4. It should be used in amounts which fully cover the wounded surface. It is recommended that the surgeon remove the
excess felt before closing the wound or leave only the minimum amount in the tissue because it slightly swells and it
could exert pressure on the vicinity of the wound.

Hypro-Sorb R
Available sizes

Hypro-Sorb R 20 x 25 x 4 mm Hypro-Sorb R 10 x 10 x 10 mm Hypro-Sorb R 50 x 50 x 4 mm

Composition
Natural pure (99.9%), crystalline Atelo-Collagen tissue structure of bovine tendon.

Storage conditions
Hypro-Sorb R must be stored in a dry place at room temperature. It is not damaged by temperatures between -25°C to
+50°C. It must be protected from direct sunlight and heat. The product is sterile for five years.
Hypro-Sorb R is a medical device class III, ISO and CE certified.

15 © bioimplon 2015
 Hypro­Sorb® X and Z
Our natural Atelo-Collagen cones for the preservation of the alveolar ridge and
an effective haemostasis

Hypro-Sorb® X and Z are root-shaped cones of pure,

crystalline, bovine Atelo-Collagen that are indicated to stop
the bleeding after tooth extraction and to help preserve the
alveolar ridge (for more information on Atelo-Collagen in
general and how it induces haemostasis in particular, see
the chapter About Atelo-Collagen).

Hypro-Sorb X and Z
Properties and advantages
• Haemostatic cones of pure, crystalline Atelo-Collagen type I of bovine
origin – free of antigenic telopeptides
• Highest degree of tissue biocompatibility and safety with excellent
wound-healing characteristics
• Usable in infected wounds or with medically compromised patients
• The special shape of the cones (Ø6mm x 20 mm x Ø10mm,
and Ø3mm x 15mm x Ø6mm respectively) is an excellent matrix for the
bone formation after tooth extraction
• Accelerated soft tissue healing
• Potent haemostatic effect Hypro-Sorb X
• Can be cut to size without loss of haemostatic property
• Resorbed within two to four weeks
• Long shelf-life, sterile and safe for five years after production

Hypro-Sorb X and Z
Indications
• Control of capillary and parenchymatous bleeding
• Haemostasis after tooth extraction in stomatology
• Closure of extraction sites
• Alveolar ridge preservation
• Control of bleeding in extraction sockets or biopsy
site

© bioimplon 2015 16
Alveolar ridge preservation and haemostasis
Hypro-Sorb X and Z
Handling instructions
1. Hypro-Sorb X and Z are applied usually with the smooth side onto the
wound surface, softly pressed down and left on the wound until the
fibrin adhesion develops.
2. Bleeding usually stops in two to five minutes; it lasts longer in
haemophiliacs.
3. Usually it is used in dry state but it may also be moistened with sterile
saline solution.
4. The cones should be used in amounts which fully cover the wounded
surface. It is recommended that the surgeon remove the excess felt
before closing the wound or leave only the minimum amount in the
tissue because it slightly swells and it could exert pressure on the Hypro-Sorb Z
vicinity of the wound.

Hypro-Sorb X and Z
Available sizes

Composition
Natural pure (99.9%), crystalline Atelo-Collagen tissue structure of bovine tendon.

Storage conditions
Hypro-Sorb X and Z must be stored in a dry place at room temperature. They are not damaged by temperatures between
-25°C to +50°C. They must be protected from direct sunlight and heat. The product is sterile for five years.
Hypro-Sorb X and Z are medical devices class III, ISO and CE certified.

17 © bioimplon 2015
Dental portfolio

© bioimplon 2015 18
About Atelo­Collagen
What is Atelo-Collagen?
Atelo-Collagen is a specifically modified type of collagen that has been
freed from immunogenic telopeptides during the process of
atelopetidation.

What is atelopeptidation?
Atelopeptidation is a term that describes the physicochemical deletion of
the immunogenic/antigenic terminal peptide sequence (telopeptide) in a
collagen molecule. The resulting modified collagen is called an Atelo-
Collagen, a safe non-immunogenic collagen that can be implanted in
patients without any adverse reactions. Our patented biological
technology (registered patent no. 276891) allows us to physicochemically
delete the antigenic peptide segment within the bone or membrane
compound, and therefore preserve the native collagen matrix structure Pure, crystalline Atelo-Collagen structure
inside the granules, membranes, sponges and cones, making them
biocompatible.
Moreover, thanks to the unique lyophilization processing technology implemented, the crystalline molecular structure of the
collagen is preserved without alteration. In our bone graft – Hypro-Oss® – the same is true for the molecular structure of the
natural hydroxyapatite.
In contrast to the manufacturing processes implemented by other manufacturers, heat (thermal processing) was not used in
processing Hypro-Oss. It is well known that heating bone materials negatively affects the natural crystalline micro-structure of
hydroxyapatite, causing bone ceramization, in addition to destroying collagen components.

What is lyophilization?
Lyophilization is a process of freeze-drying that removes water from the material by sublimation – i.e. by directly converting
ice to water vapor, without passing through the intermediary stage of a liquid. Freeze-dried materials become highly
absorbent and can be stored at room temperature.

Properties of Atelo-Collagen
• Highest degree of tissue biocompatibility and safety
• Very weak – if any – inflammatory response
• No support of microbial growth
• Excellent wound healing characteristics
• Strong hydrophilicity results in optimal cell adhesion and blood absorption
• Release of clotting and growth factors (IGF 1, TGF-beta, PDGF) by thrombocytes
• Inhibition of the collagenolytic activity of wound excretions
• Promotion of soft tissue healing and guided tissue regeneration through the supported granulation and epithelisation
• Powerful haemostatic effect of the Atelo-Collagen averts haematoma formation after surgical procedures
• Capability to induce differentiation of mesenchymal osteoprogenitor stem cells into osteoblasts
• Significantly enhanced proliferation rate of osteoblasts in association with a scaffold of natural hydroxyapatite

Resorption of Atelo-Collagen
The mechanism of absorption and biotransformation is initiated through the activity of specific enzymes – latent collagenases
– which are activated in the tissues during injuries and healing. Collagenases are also present in lysosomes, granulocytes
and other cell structures near the wound.
Preclinical tests have shown that the process is apyrogenic (without inflammatory reaction) and the presence of macrophages
(inflammation cells) is irrelevant to the resorption of the Atelo-Collagen. The absorption process results in slow hydrolysis of
the collagen protein to give soluble peptides and amino acids, which are metabolized by the tissue cells and so promote the
regeneration process and remodeling into the patients’ own tissue. The Atelo-Collagen is tolerated by human tissues without
any immune reaction and is metabolized through a mechanism similar to that of the tissue’s own collagen.

19 © bioimplon 2015
Haemostasis with Atelo-Collagen
Haemostasis is triggered by a protein called collagen,
which is present in the walls of the blood vessels. It is
normally isolated from direct contact with the blood by
the internal endothelium. However, if a blood vessel wall
is damaged by an injury or contusion, collagen comes
into contact with the blood, whereby haemostasis is
induced so as to minimize blood loss.
The activation of haemostasis by drying materials of
Atelo-Collagen occurs in a heterogeneous system
consisting of a liquid phase – blood – and a solid phase
– Atelo-Collagen. The rate, or reaction kinetics, of such
reactions is mainly determined by the interface area, i.e.,
the surface area of the solid phase which is in contact
with the liquid.
The larger this interface area is, the faster the process of
stopping the bleeding is activated. The interface area is
determined by what is called the internal area of the
solid phase and also by the moistening ability of the
liquid in contact with it. Thus, the porosity and
hydrophilic nature of the surface are very important, not
only pertaining to the drying process but also regarding
haemostasis.
Atelo-Collagen is a naturally hydrophilic peptide. The
enormously porous matrix of non-immunogenic collagen
in our products is achieved by lyophilization and is
highly hydrophilic. Thus, huge interstitial space as well
as the hydrophilicity of the collagen matrix provides a
big surface area for thrombocytes to adhere on,
followed by quick release of coagulation factors, which
explains the immense hemostatic effect of Hypro-Sorb
products.
During the initial phase of blood coagulation, fibrinogen
is hydrolyzed enzymatically and fibers of fibrin are
formed. The fibers form agglomerates under the effect of
the surface charge, forming soft coagulate. This is Atelo-Collagen activates a cascade of coagulation steps, as a result of which a
converted to hard coagulate by crosslinking under the blood clot is formed and bleeding is stopped. The picture was modified. Courtesy
effect of transglutaminase FXIIIa, which forms new Lars Faxälv, www.haemostasis.se.
amidic bonds. Serine proteinase, which catalyzes
fibrinogen hydrolysis, is called thrombin. It is released
from its precursor, prothrombin, on the action of another
proteinase whose activity is controlled by the factor FVIII complex.

© bioimplon 2015 20
Safety information
BSE prevention regulations
The safety of our products is of the utmost importance to us. This is why the manufacturer, Hypro s.r.o., only uses material of
cows/oxen from countries that have established strict regulations for the protection against BSE. E.g. the compulsory
notification of BSE, and that all slaughtered animals are subject to an obligatory examination based on the Notices of the
Department of Agriculture no. 286/1999, Coll. of Laws, DOA no. 399/2001, Coll. of Laws, and DOA no. 400/2001, Coll. of
Laws. The manufacturer monitors and reacts to current requirements or directives issued by the European Union, including
the OIE notice Terrestrial Animal Health Code.

Deactivation and removal of infectious agents

The method of collagen treatment includes several repeated extractions that are employed to remove non-collagen globular
proteins from the connective tissue, since prion (the infectious agent of BSE) belongs to the category of globular proteins. The
extraction process is an additional safeguarding procedure that results in reduced prion content, in case there is any in the
tissue.
Another technological process that is appropriate in view of deactivation of prions is the action of a saturated calcium
hydroxide solution with pH-value of 12.5. The prion protein (globular protein) contains an elongated conformation of the beta-
pleated sheet type that changes to a physiologically normal conformation (non-infectious) through the action of hydrotropic
substances (saturated calcium hydroxides with PH 12.5). The action of hydroxides is recommended in the WHO Document
CPMPaCVMP EMEA/410/01, Rev. 2 as an effective measure to reduce the risk of TSE transfer through medical devices.
These procedures induce structural changes such as decrystallization of prion protein (sensitive to proteolysis), which results
in irreversible, non-toxic conformation of the prion protein. Collagen treated this way is used in the production of Hypro-Oss
and Hypro-Sorb. It consists of prion-free tissues, which are fully safe as TSE is concerned.

Sterilization method
After being packed in a double blister packaging, our biomaterials undergo Gamma Irradiation as the final sterilization step.
Gamma irradiation sterilization is a process that effectively kills or eliminates almost all microorganisms like fungi, bacteria,
viruses and spore forms. Gamma irradiation is a physical means of decontamination, because it kills bacteria by breaking
down bacterial DNA, thus inhibiting bacterial division.

21 © bioimplon 2015
The products fulfill the following regulatory requirements:
• DIR 93/42/EEC: 2007 Council Directive concerning medical devices
• DIR 2003/32/EC Commission Directive on medical devices manufactured utilizing tissues of animal origin
• CSN EN ISO 14971:2009 Medical devices – Application of risk management on medical devices
• CSN EN ISO 22442:2008 Medical devices utilizing animal tissues and their derivatives
• CSN EN ISO 10993-1:2010 Biological evaluation of medical devices – Evaluation and testing
• CSN EN ISO 10993-5:2010 Biological evaluation of medical devices – Tests for in vitro cytotoxicity
• CSN EN ISO 10993-6:2009 Biological evaluation of medical devices – Tests for local effects after implantation
• CSN EN ISO 10993-10:2011 Biological evaluation of medical devices – Tests for irritation and skin sensitization
• CSN EN ISO 11137:2012 Sterilization of health care products – Sterilization by radiation

Hypro-Sorb & Hypro-Oss – CERTIFICATIONS

• EC Certificate No. 13 0049 QS/NB attesting that the products are manufactured under conditions meeting the
requirements of the quality system in accordance with Annex II, Sections 3.3.and 5, of the Directive 93/42/EEC,
Notified Body No.1023.
• EC Design-Examination Certificate No. 13 0050 CN/NB certifying that the products comply with the essential
requirements specified in Article 4 of Annex II to Council Directive 93/42/EEC, Notified Body No.1023.

© bioimplon 2015 22
copyrigt reserved: Bioimplon GmbH, February 2015.

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Bioimplon GmbH info@bioimplon.de
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