Read RegenPRP ­ Kit (platelet-rich plasma) text version

RegenLab Mollens-VD C.H.

RegenPRP-Kit

Medical Device IIa

CE1250

Platelet-Rich Plasma of RegenLab

· Autologous preparation which increases the rate of healing process · Clinically proved reduction of wound pain · Efficiency proved in fields of : - surgery - dermatology - treatment of burns - dentistry · Efficiency proved in the autologous transplantation of cells and tissues · Preparation « point of care » (pre- or perioperative) simple, rapid, economic · Significant cost reduction of the treatment

RegenLab SA ­ 5, rue de l'Eglise ­ C.H.-1146 Mollens-VD ­ Tel. +41 (0)21 864 38 00 ­ Fax +41 (0)21 864 38 01 ­ E-Mail : [email protected]

RegenPRP-Kit

-2-

Table of Contents

In brief : the RegenPRP-Kit (platelet-rich plasma) of RegenLab ...........................................................................3 Physiology of healing ..................................................................................................................................................4 Can we increase the rate of healing process? ..........................................................................................................7 The System "RegenPRP-Kit'': .....................................................................................................................................8 Laboratory studies of RegenPRP .............................................................................................................................10 Clinical studies : applications of RegenPRP ...........................................................................................................13

Illustrations on the cover page: top: down: thrombocytes in their inactive disc form in the circulating blood activated thrombocytes forming pseudopodia in the blood clot

RegenLab SA ­ 5, rue de l'Eglise ­ C.H.-1146 Mollens-VD ­ Tel. +41 (0)21 864 38 00 ­ Fax +41 (0)21 864 38 01 ­ E-Mail : [email protected]

-3-

RegenPRP-Kit

In brief : the RegenPRP-Kit (platelet-rich plasma) of RegenLab

· · · Increase of the wound repair rate by local application of an autologous solution of plasma enriched with thrombocytes, derived from the blood's patient. Its efficiency is proved in the domain of surgery, for treatment of severe burns and for the transplantation of cells and tissues. The preparation « point of care » pre- or perioperative of the PRP is simple, rapid and advantageous.

Increase the tissue regeneration phase, by releasing various growth factors from activated thrombocytes, which have been deposited in high concentration onto the wound. Increase of the migration and mitosis rates of the stem cells for the regeneration of the damaged tissues. At the same time, growth factors of the plasma preparation locally stimulate the angiogenesis process, i.e. formation of the new blood vessels. Increase of the final phase of wound healing process, consisting in the tissue restructuring:re-epithelization, development of the local blood and lymphatic vessels, formation of the bone matrix and its mineralisation.

Increase of the hemostatic barrier formation, the initial phase of the wound healing process, by locally increasing the rate and the amount of blood clothing formation. RegenPRP acts like an autologous biological glue. It stops the bleeding and closes the wound and then prevents the contamination of the wound by pathogenic agents (fungus, bacteria etc.) Increase the rate of the inflammatory phase by the impregnation of the wound with the autologous signal proteins retrieved in the plasma preparation and leukocytes. Chemoattraction of the micro- and the macrophages required for the destruction of the pathogenic agents that may infiltrate the wound, and for the elimination of dead and damaged cells.

Field of applications of the RegenPRP (platelet-rich plasma), increase of the rate of healing and tissue restructuring

DERMATOLOGY INTERNAL MEDICINE GERONTOLOGY

cutaneous reconstruction and transplantation ulcer and chronic wound therapy (e.g. after radio therapy) re-implantation of autologous cells, extemporaneous or cultivated in-vitro

SURGERY

DENTAL MEDICINE

RESEARCH & DEVELOPMENT

cardio-vascular surgery

dental extraction dental implantation

cell separation

abdominal surgery

autologous culture cell autologous stem cells culture cell differential

maxillo-facial surgery

orthopedic surgery plastic and reconstructive surgery treatment of severe burns

tissue regeneration

healing remodelling

RegenLab SA ­ 5, rue de l'Eglise ­ C.H.-1146 Mollens-VD ­ Tel. +41 (0)21 864 38 00 ­ Fax +41 (0)21 864 38 01 ­ E-Mail : [email protected]

RegenPRP-Kit

-4-

Physiology of the healing process

Closing of the wound

Tissue restructuring Tissue regeneration Inflammation

Healing process in presence of whole blood

Hemostasis physiological process (time)

Fig. 1

An injury resulting from an accident or a surgical intervention damages destroys several tissues (epithelium, conjunctive, fat, muscular, nervous, bone or cartilage tissues) and also the blood and lymphatic vessels. Following such a trauma, the body reacts by a series of repairing steps called « healing cascade » (fig 1). Hemostatic phase The blood leaking from the damage blood vessels crosses the wound and forms a clot in few minutes. As the result of clot formation, the bleeding is stopped and the wound is isolated from the outside environment. The thrombocytes and the blood plasma play an essential role in the clot formation. The thrombocytes present in the blood circulation looks like a disk having a smooth surface. When the endothelial cells are destroyed, the collagen threads made of fine fibers, located just under the endothelium, came in direct contact with the circulating blood. The thrombocytes which remains attached to the lining of the injured blood vessels,

immediately change their appearance by forming pseudopodia. In the cell membrane of the pseudopodia, various receptors are activated such as glycoproteins GPIIb and GPIIa. Some receptors bind to fibrinogen solubilized in the plasma, others bind to a specific plasma proteins (von Willebrand Factor, vWF), which have an affinity to naked subendothelial collagen. This initiates the platelet aggregation in the wound: formation of local small platelet aggregats and their adhesion to the naked subendothelial collagen (fig. 2). The activated thrombocytes release the thrombin, which will transform fibrinogen found in the plasma in two peptide chains and a fibrin . Monomers of fibrin newly formed, will bind together to form a tridimensional network of fibrin fibers into which the platelets, the leukocytes and the erythrocytes will be encaged. This process of clot formation prevents the blood to leak out from the injured blood vessels and also, to avoid the xenobiotic or pathogenic agents to enter in the blood circulation (fig. 3).

Fig. 2

RegenLab SA ­ 5, rue de l'Eglise ­ C.H.-1146 Mollens-VD ­ Tel. +41 (0)21 864 38 00 ­ Fax +41 (0)21 864 38 01 ­ E-Mail : [email protected]

-5-

RegenPRP-Kit

Conversion monomers

of

plasmatic

fibrinogen

into

fibrin

Formation of a tridimensional network by the binding of the fibrin monomers Encagement of erythrocytes, leukocytes and the thrombocytes in the fibrin mesh allowing the clot formation

Fig. 3 : The biology of the wound : formation of the fibrin network

Inflammatory phase The leukocytes and the activated platelets, enclosed in the clot, begin to release the signalisation proteins (Chemiokines). This stimulates the leukocytes present in the blood vessels around the wound, and promotes the migration of the macrophages from the conjunctive tissue. The function of the macrophages is to clean the wound from dead cells, damaged extracellular structures and also, from the pathogenic agents which could have invaded the wound. This clean up is required for the following phase, the tissue regeneration. Tissue regeneration The alpha granules of the activated thrombocytes, embedded in the clot, release more and more growth factors. They induce the migration and the proliferation of the non-differentiated mesenchymal cells.

Afterwards these stem cells become functional cellswith specific functions. The leukocytes release also a growth factor (VEGF), which induces the creation of the blood vessels (angiogenesis). Adhesion molecules, polypeptides, enzymes, vitamins as well as oligo elements retrieved in the plasma, show a crucial role on the recruitment and the differentiation of the stem cells. These molecules are necessary to support the high level of metabolism associated with these activated cells. However, erythrocytes entrapped in large numbers in the blood clot, do not seem to have a important role to play in this process. They are eliminated by phagocytosis. All the important growth factors involved in the healing process are shown in table 1.

RegenLab SA ­ 5, rue de l'Eglise ­ C.H.-1146 Mollens-VD ­ Tel. +41 (0)21 864 38 00 ­ Fax +41 (0)21 864 38 01 ­ E-Mail : [email protected]

RegenPRP-Kit

-6-

Formation of tridimensional fibrin network

Release of chemo-attractors and growth factors by the thrombocytes and leukocytes present in the blood clot

Migration of leukocytes, tissue macrophages and the stem cells originated from the wound

Stem cells proliferation

Stem cells differentiation

Fig. 4 : The biology of the wound : the proliferative matrix

factor PDGF aa PDGF bb PDGF ab TGF-alpha TGF-beta

name platelet-derived growth factors transforming growth factors

principal source Activated thrombocytes

effects Mitogenes of the mesenchymal stem cells, promote the synthesis of the extracellular matrix

Stimulation of DNA synthesis, proliferation and differentiation of various types of cells. Favorise the synthesis of collagen. Activated thrombocytes Stimulates the proliferation and differentiation of IGF-I insulin-like growth factors IGF-II osteoblasts. Activated thrombocytes Stimulates the proliferation and differentiation of EGF epidermal growth factor the epidermic cells, co-stimulating angiogenesis. VEGF vascular endothelial growth leukocytes Stimulate angiogenesis, chemo-attractor of factor endothelial cells osteoblasts In addition, the activated thrombocytes have onto their surface a multitude of signalisation molecules like e.g. CD9, CD-W17, CD31, CD41, CD42a-d, CD51, CD-W60, CD61, CD62P, CD63 Table 1 : The growth factors acting on the healing cascade

Activated thrombocytes

RegenLab SA ­ 5, rue de l'Eglise ­ C.H.-1146 Mollens-VD ­ Tel. +41 (0)21 864 38 00 ­ Fax +41 (0)21 864 38 01 ­ E-Mail : [email protected]

-7-

RegenPRP-Kit

Can we increase the rate of healing process?

The healing cascade shows that there are specific components of blood plasma such as thrombocytes and leukocytes, which are playing an important role in all phase of tissue's regeneration. Consequently, any attempt to increase the rate of the healing process must take in consideration these blood elements. The signalisation molecules (e.g. the chemoattractors), the growth factors (e.g. PDGF, plateletderived growth factor) and the other substances acting on the wound (e.g. vitamins, essential elements) can be purified by biotechnological processes from a plasma pool, manufactured by genetic engineering or by chemical synthesis. They can be applied onto the wound separately or in form of a mixture. However, these products cannot be considered as physiological by definition. The organic molecules isolated from a plasma pool or manufactured by genetic engineering are by definition heterologous and are not specific to an individu. Their precise dosage on an isolated wound is almost impossible. Also, several growth factors synergically interact together. At any given time, the synergic effect depends not only of the concentration of these growth molecules but also, of the concentration range of other molecules and ions (e.g. essential elements). Contrary to the abovementionned products, an autologous plasma, extracted pre- or perioperative from the patient himself, enriched in thrombocytes and also containing leukocytes, replies to the requirements necessary for a product that intended to increase the rate of healing process.

· · · · ·

Leukocytes and thrombocytes, imbedded in the fibrin mesh, synthesize and release all molecules necessary for the healing process following a specific time sequence. The higher concentration of thrombocytes retrieved in the PRP, results in an increase of the amount of growth factors released. The healing process is then faster. The blood plasma of the patient contains all the supplementary factors (vitamins, essential elements etc.) for an optimal healing process. Because all constituents retrieved in the PRP are from autologous origin, the risk of a local immunological reaction is ruled out. The preparation of the RegenPRP required for a treatment, is simple, rapid and advantageous.

Healing with a native clot, rich in erythrocytes

Closing of the wound

Tissue restructuring Tissue regeneration Inflammation Hemostasis physiological process (time)

Healing with plasma without erythrocytes and rich in thrombocytes (RegenPRP)

Closing of the wound

Due to the concentration of the specific proteins and the growth factors, the time of healing can be reduced in a significant manner physiological process (time)

Fig. 5 : Reduction of the time frame of the « healing cascade » observed when the RegenPRP is used

RegenLab SA ­ 5, rue de l'Eglise ­ C.H.-1146 Mollens-VD ­ Tel. +41 (0)21 864 38 00 ­ Fax +41 (0)21 864 38 01 ­ E-Mail : [email protected]

RegenPRP-Kit

-8-

The System "RegenPRP-Kit'':

During all steps of the development of the RegenPRP-Kit, the following objectives were pursuited: · · · Kit for an easy preparation and « point of care » of an autologous plasma solution enriched in thrombocytes and leukocytes, having a minimal amount of erythrocytes, in order to obtain a « white clot » in the wound bed. Significant enrichment in locally acting growth factors and signal molecules to increase the rate of the healing process. Staunching (mechanical barrier) of the wound bed to prevent the infiltration of harmful agents (e.g. pathogenic agents). Production of a quantity of PRP to covert the size of the wound.

·

REGEN THT (CE1250)

A Vacutainer RegenTHT® empty B Vacutainer RegenTHT® after blood withdrawal C Vacutainer RegenTHT® after centrifugation at 1 500 g for 8 minutes.

A

B

C

Fig. 6 : Separation of the constituents of the blood with the Vacutainer RegenTHT®

RegenLab SA ­ 5, rue de l'Eglise ­ C.H.-1146 Mollens-VD ­ Tel. +41 (0)21 864 38 00 ­ Fax +41 (0)21 864 38 01 ­ E-Mail : [email protected]

-9-

RegenPRP-Kit

Constituents

Native blood Spontaneous clot

Clot with RegenPRP

erythrocytes

hematocrit of 35 ­ 50%

hematocrit of < 1%

thrombocytes

140 ­ 440 x 109/L

2 to 6 times more concentrated 2 to 6 times more concentrated

growth factors

native concentration

fibrin

native concentration

native concentration

leukocytes

native concentration

2 to 6 times more concentrated

Tableau 2 : native clot (red) in comparison to the « white » clot produced with the RegenPRP

PRP from the RegenPRP-Kit < 1% hematocrit (« white clot »)

PRP from kit of another source > 15% hematocrit (« red clot »)

Fig. 7 : Comparison of RegenPRP with a PRP from another source on a healthy skin left: Application of 2ml of RegenPRP on healthy skin of the arm right: Application of 2ml of a PRP from another source

Vacutainer RegenTHT® (Thrombocyte Harvesting Tube) compared to other conventional tubes intended for in vitro diagnosis (IVD)

Vacutainer RegenTHT®:

· · developed for therapeutic application anticoagulant ACD-A for an optimal preservation of the structural and functional integrities of leukocytes and thrombocytes the separator gel in the Vacutainer RegenTHT® allows an excellent cell separation (optimal yield of the thrombocytes) ISO 10993 tested for its good tolerance and absence of allergic and mutagenic effects

Conventional tubes for IVD

· · the IVD tubes are prohibited for therapeutic application the anticoagulant EDTA damages the structure and function of cells, specially thrombocytes the separator gel acts differently than the Vacutainer RegenTHT® can contain traces of clotting activator and allergenic substances

·

·

·

·

RegenLab SA ­ 5, rue de l'Eglise ­ C.H.-1146 Mollens-VD ­ Tel. +41 (0)21 864 38 00 ­ Fax +41 (0)21 864 38 01 ­ E-Mail : [email protected]

RegenPRP-Kit

- 10 -

Laboratory studies of RegenPRP

Separation and enrichment of thrombocytes with the RegenPRP-Kit

700 600

A B C

Whole blood Plasma before centrifugation PRP (plasma rich in thrombocytes) after the 2nd centrifugation PPP (Plasma poor in thrombocytes), supernatant after the 2nd centrifugation

Thrombocytes x 10 /L

500 400 300 200 100 0 A B C D

9

D

Fig. 8 The RegenPRP prepared according to the standard protocol (see page Error! Bookmark not defined.) shows a significant increase in the concentration of thrombocytes

Separation and enrichment in leukocytes, separation and reduction of the number of erythrocytes with the RegenPRP-Kit

16 14 12 10 8

A B C

Whole blood Plasma before centrifugation PRP (plasma rich in thrombocytes) after the 2nd centrifugation PPP (Plasma poor in thrombocytes), supernatant after the 2nd centrifugation

Leukocytes x 10 /L 12 Erythrocytes x 10 /L

D

6 4 2 0 A B C D

9

Fig. 9 : The RegenPRP prepared according to the standard protocol (see page Error! Bookmark not defined.) shows an important increase in the number of leukocytes (in blue) and a significant reduction in the number of erythrocytes (in red).

RegenLab SA ­ 5, rue de l'Eglise ­ C.H.-1146 Mollens-VD ­ Tel. +41 (0)21 864 38 00 ­ Fax +41 (0)21 864 38 01 ­ E-Mail : [email protected]

- 11 -

RegenPRP-Kit

Stability of growth factors and specific plasma proteins retrieved into the RegenPRP

The preparation of the RegenPRP (platelet-rich plasma) with the RegenPRP-Kit is simple and rapid. Often, for organisational or technical reasons, it is necessary to prepare the quantity of the PRP required for the patient's therapy the day before the operation. This is possible, because the growth factors and the plasma proteins, retrieved into the RegenPRP, retain their biological activities for at least 20 hours, as long as PRP tubes are conserved at 4°C. Before used, the PRP and the activator are simply warmed for 10 minutes at 37°C. The results of stability tests are shown in figures 11 to 15.

PDGF aa 3500 3000 2500 2000 1500 1000 500 0

O O O 22 22 22 O 4T 1T 2T 1T 2T 3T 3T 4T 22

Concentration of PDGF aa (platelet derived growth factor) at 0 hour and after 22 hours at 4°C. Preparation of the RegenPRP the day before the operation. (Kit ELISA R&D)

concentration pg/ml

samples PRP 1 - 4

Fig. 10

TGF-beta 1 3500 3000 2500 2000 1500 1000 500 0 1TO 1T22 2TO 2T22 3TO 3T22 4TO 4T22 samples PRP 1 - 4

Fig. 11

concentration pg/ml

Concentration of TGF-beta 1 (transforming growth factor) at 0 hour and after 22 hours at 4°C. Preparation of the RegenPRP the day before the operation. (Kit ELISA R&D)

EGF 3500 concentration pg/ml

Concentration of EGF (epidermal growth factor) at 0 hour and after 22 hours at 4°C. Preparation of the RegenPRP the day before the operation. (Kit ELISA R&D)

3000 2500 2000 1500 1000 500 0 1TO 1T22 2TO 2T22 3TO 3T22 4TO 4T22 samples PRP 1 - 4

Fig. 12

RegenLab SA ­ 5, rue de l'Eglise ­ C.H.-1146 Mollens-VD ­ Tel. +41 (0)21 864 38 00 ­ Fax +41 (0)21 864 38 01 ­ E-Mail : [email protected]

RegenPRP-Kit

- 12 -

VEGF 3500 concentration pg/ml 3000 2500 2000 1500 1000 500 0 1TO 1T22 2TO 2T22 3TO 3T22 4TO 4T22 samples PRP 1 - 4

Fig. 13

Concentration of VEGF (vascular endothelial growth factor) at 0 hour and after 22 hours at 4°C. Preparation of the RegenPRP the day before the operation. (Kit ELISA R&D)

FIBRONECTINE 1000 concentration pg/ml 800 600 400 200 0 1TO 1T22 2TO 2T22 3TO 3T22 4TO 4T22 samples PRP 1- 4

Fig. 14

Concentration of the adhesion protein Fibronectin at 0 hour and after 22 hours at 4°C. Preparation of the RegenPRP the day before the operation. (Kit ELISA R&D)

2500

concentration ng/ml

2000 1500 1000 500 0 01 02 03 04 05 06 07 08 09 10

D-dimers in the whole blood D-dimers in the PRP

subjects: 01 - 05 : healthy subjects 06 - 10 : diabetic subjects

The preparation of the RegenPRP and the materials used do not change the concentration of D-dimers.

subjects

Fig. 15 : Concentration of the coagulation markers, D-dimers, in whole blood and in the PRP samples of 10 adult subjects

Labo-medical evaluation of PRP prepared with the RegenPRP-Kit

· · · Effective separation and enrichment of the cells necessary for healing (thrombocytes and leukocytes), The stability of the growth factors for at least 20 hours is observed when PRP is stored at 4°C, The efficacity of coagulation factors is preserved.

Prof. Dr. med. D. Hayoz, Divison of Hypertension and Vascular medicine, CHUV, Lausanne.

RegenLab SA ­ 5, rue de l'Eglise ­ C.H.-1146 Mollens-VD ­ Tel. +41 (0)21 864 38 00 ­ Fax +41 (0)21 864 38 01 ­ E-Mail : [email protected]

- 13 -

RegenPRP-Kit

Clinical studies : applications of RegenPRP

Plastic surgery

.

Deep burn of the inferior limb, required debridment and a thin skin graft.

A

B

A : site of graft sample B : site of the application of the graft Treatment of the two sites with RegenPRP to increase the healing rate. The graft was fixed uniquely with the PRP acting as a biologic glue. Result : Rapid and complete healing of two sites. Severe burn of 85% of the body surface

A

B

Use of RegenPRP as autologous biological glue to fix the skin graft and autologous keratinocytes cultivated in vitro and also to increase the rate of healing, A : site of graft sample and the keratinocytes B : site of application Result : Rapid healing of the sample site and the site of application. PD, Dr. W. Raffoul. Plastic and Reconstructive surgery, Centre Hospitalier Universitaire Vaudois (CHUV), CH-1011 Lausanne

Orthopedic surgery

Fracture on a plasmacytoma which has been massively irradiated. Indication: surgical retaking of the delay of consolidation

Result :

after 2 months, there iwas evidence of consolidation.

PD Dr. F. Chevalley, Orthopedic surgery, Centre Hospitalier Universitaire Vaudois (CHUV), CH-1011 Lausanne

RegenLab SA ­ 5, rue de l'Eglise ­ C.H.-1146 Mollens-VD ­ Tel. +41 (0)21 864 38 00 ­ Fax +41 (0)21 864 38 01 ­ E-Mail : [email protected]

RegenPRP-Kit

- 14 -

Plastic surgery

Randomised study of the transplantation of keratinocytes (in progress)

Sites of graft sample treated with a suspension of keratinocytes in the RegenPRP :

A

B

A: B:

Wound treated with RegenPRP. Healing was completed in 5 days. Photo at 20 days Test : wound non treated. Photo at 30 days Macroscopic observation shows a particularly positive evolution on the site treated with RegenPRP.

Result :

PD Dr. W. Raffoul (1), Prof. Dr. D. Hayoz (2), Dr. M. Benathan (3) (1) Plastic and reconstructive surgery, (2) Division of Hypertension and Vascular Medicine, (3) Dermatology laboratory, Centre Hospitalier Universitaire Vaudois (CHUV), CH-1011 Lausanne

RegenLab SA ­ 5, rue de l'Eglise ­ C.H.-1146 Mollens-VD ­ Tel. +41 (0)21 864 38 00 ­ Fax +41 (0)21 864 38 01 ­ E-Mail : [email protected]

- 15 -

RegenPRP-Kit

Dermatology

Voluminous ulcer secondary to a vascularitis, exposing the tendons . Status after vasculitis in an 83 year old patient, hospitalized for 3 months. Slow recovery after conventional treatment.

A

B

A : Presentation of the wound on the first day of the application of the RegenPRP (day 1) B : Presentation of the wound 20 days following a single application of the RegenPRP. C : Presentation of the wound 33 days following 2 applications of the RegenPRP Result :

C

Spectacular increase in the granular tissue covering tendons after 20 days. Rapid epidermization of the upper part of the ulcer. Due to this evolution, the 83 years old patient who was hospitalized for 3 months, can return home.

Post phlebitic ulcer Post phlebitic ulcer on the ankle cleaned in the budding phase in a 89 years old patient, hospitalised for 8 months. Difficult initiation of epidermization obtained after 4 years of dermatological treatment

A

B

C

A : Presentation of the ulcer on the first day of the application of RegenPRP B : Presentation of the wound 20 days following a single application of RegenPRP C : Presentation of the wound 33 days following 2 applications of RegenPRP Result : Epidermization on the periphery of the wound and fast progression of epidermization of the islets. The patient can return home.

Dr. S. Cairey-Remonnay (Head of the clinic) and Dr. F. Aubin, Department of Dermatology, Centre Hospitalier Universitaire, Besançon (France)

Chronic Radiodermitisis Chronic Radiodermitisis after a superficial irradiation on an epidermoidal carcinoma of the skin, stationary for 18 months after conventional treatment.

A

B

A : Presentation of the wound the day after the first application of RegenPRP. B : Evolution of the wound after 3 months of treatment and 5 applications of RegenPRP Result: 50% reduction of the wound surface

PD Dr. J. Bernier, Division of Radiotherapy and Nuclear Medicine, Ospedale San Giovanni, CH-6500 Bellinzona

RegenLab SA ­ 5, rue de l'Eglise ­ C.H.-1146 Mollens-VD ­ Tel. +41 (0)21 864 38 00 ­ Fax +41 (0)21 864 38 01 ­ E-Mail : [email protected]

RegenPRP-Kit

- 16 -

RegenLab SA ­ 5, rue de l'Eglise ­ C.H.-1146 Mollens-VD ­ Tel. +41 (0)21 864 38 00 ­ Fax +41 (0)21 864 38 01 ­ E-Mail : [email protected]

Information

RegenPRP ­ Kit (platelet-rich plasma)

16 pages

Find more like this

Report File (DMCA)

Our content is added by our users. We aim to remove reported files within 1 working day. Please use this link to notify us:

Report this file as copyright or inappropriate

904619