Evolution T H E N A T U R A L E V O L U T I O N O F C O L L A G E N M E M B R A N E S. Heterologous mesenchymal tissue

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Evolution T H E N A T U R A L E V O L U T I O N O F C O L L A G E N M E M B R A N E S Heterologous mesenchymal tissue

A unique biotechnology TECNOSS : A UNIQUE PROCESS THAT ACCELERATES AND GUIDES NATURAL BONE REGENERATION Tecnoss developed and patented a unique biotechnology that prevents the ceramization phase of natural bone and preserves the tissue collagen, allowing an osteoclastic-type remodelling of the biomaterial similar to physiological bone turnover and delivering a product endowed with characteristics very similar to human mineral bone (1). The combination of these factors allows a consistent new bone formation and a close contact between neo-formed bone and biomaterial granules. COLLAGEN: A KEY FACTOR FOR BONE REGENERATION Collagen has a key role in bone regeneration process in that: a) it acts as a valid substrate for platelet activation and aggregation b) it serves to attract and differentiate the mesenchymal stem cells present in the bone marrow (2) c) it increases the proliferation rate of the osteoblasts up to 2/3 times (3) d) it stimulates the activation of the platelets, osteoblasts and osteoclasts in the tissue healing process Fig. A OSTEOBIOL : UNIQUE COLLAGENATED BIOMATERIALS Thanks to the innovative Tecnoss technology, the OsteoBiol line has the following important characteristics: 1) absence of a foreign body response (4) 2) gradual resorption over time (5,6) 3) stimulation/acceleration of physiological tissue healing process (2) 4) protection of the grafting site from infection (membranes) (7) 5) capability of carrying medication to the surgical site (8) The Tecnoss new generation of biomaterials, thanks to a revolutionary technology, goes beyond the simple role of aiding natural bone regrowth by stimulating and accelerating this vital physiological process. Fig. B Fig. A - SEM image of an OsteoBiol Evolution membrane. Courtesy of Prof. JL Calvo Guirado, Murcia, Spain Fig. B - OsteoBiol membrane collagenic structure. Courtesy of Nobil Bio Ricerche, Villafranca d Asti, (AT) Italy Fig. C - OsteoBiol Evolution membrane (1) Figueiredo M et al. J Biomed Mater Res B Appl Biomater, 2010 Feb; 92(2):409-419 (2) Brunelli G et al. Eur J Inflammat, 2011, Vol. 9, no. 3 (S), 103-107 (3) Hsu FY et al. Biomaterials, 1999, 20:1931-1936 (4) Crespi R et al. Int J Oral Maxillofac Implants, 2011 Jul - Aug; 26(4):866-72 (5) Nannmark U, Sennerby L. Clin Implant Dent Relat Res, 2008 Dec; 10(4):264-70 (6) Barone A et al. Clin Implant Dent Relat Res, 2012 Jun;14(3):373-9 (7) Barone A et al. Clin Oral Implants Res, 2013 Nov;24(11):1231-7 (8) Fischer K et al. Clin Oral Implants Res, 2015 Oct;26(10):1135-42. Epub 2014 Sep 15 Fig. C

The natural evolution of collagen membranes CHARACTERISTICS Obtained from mesenchymal tissue the Evolution membrane is gradually resorbable (5). Its structure is made of dense collagen fibers of high consistency and of extraordinary resistance. HANDLING The membrane can be shaped with sterile scissors until the desired size is reached; unless the grafting site is already bleending the membrane should be rehydrated with lukewarm physiological solution. Once it acquires the desired plasticity, it must be adapted to the grafting site. CLINICAL INDICATIONS OVERVIEW Experimental studies have shown histological evidence of the prolonged barrier effect of this membrane, which lasts at least eight weeks (5). The dense collagenic matrix of Evolution protects the graft from infection in case of accidental exposure: the membrane itself will also not be infected, allowing second intention healing (9,10). This property is particularly important in case of flapless regeneration of large posterior sockets (11) : in these cases, the standard model is recommended. In lateral access sinus lift Evolution membranes are indicated to cover antrostomy (standard model) (12,13,14) and to protect the sinus membrane from cutting risk due to graft pressure (fine model or OsteoBiol Special) (15). Evolution is also ideal to protect peri-implant regenerations (16) and periodontal grafts (17). Furthermore, Evolution fine has been successfully used in combination with OsteoBiol Gel 40 for the treatment of gingival recessions (18) and to protect Sp-Block in vertical augmentation with inlay technique (19). Tissue of origin Heterologous mesenchymal tissue Tissue collagen Preserved Physical form Dried membrane with one smooth side and one micro-rough side Thickness Fine: 0.3 mm (±0.1 mm) Standard: 0.5 mm (±0.1 mm) Estimated resorption time Fine: about 3 months Standard: about 4 months Packaging 20x20 mm, 30x30 mm, 25x35 mm (oval) GMDN code 38746 MAXILLARY SINUS FLOOR AUGMENTATION PERI-IMPLANT DEFECTS INTRABONY DEFECTS POST EXTRACTIVE SOCKETS (9) Barone A et al. Clin Oral Implants Res, 2013 Nov;24(11):1231-7. Epub 2012 Jul 12 (10) Barone A et al. Clin Oral Implants Res, 2015 Jul;26(7):806-13, Epub 2014 Mar 1 (11) Cardaropoli D et al. Int J Periodontics Restorative Dent, 2008 Oct; 28(5):469-77 (12) Ramirez Fernandez MP et al. Clin Oral Implants Res, 2013 May;24(5):523-30. Epub 2012 Jan 26 (13) Barone A et al. Clin Oral Implants Res, 2013 Jan;24(1):1-6. Epub 2011 Dec 12 (14) Scarano A et al. Clin Implant Dent Relat Res, 2011 Mar; 13(1):13-18 (15) Cassetta M et al. Int J Periodontics Restorative Dent, 2012 Dec;32(6):e182-8 (16) Covani U et al. J Oral Implantol, 2009; 35(4):189-95 (17) Esposito M et al. Eur J Oral Implantol, 2015;8(3):233-244 (18) Cardaropoli D et al. Int J Periodontics Restorative Dent, 2009 Feb; 29(1):59-67 (19) Felice P et al. Int J Periodontics Restorative Dent, 2013 Mar;33(2):159-66 TWO-WALL DEFECTS VERTICAL AUGMENTATION INLAY TECHNIQUE

Excellent clinical performances Fig. 1 Fig. 3 CASE REPORT Alveolar regeneration Fig. 2 Sex: Female Age: 53 Fig. 1 Pre-op x-ray Fig. 2 Tooth extraction Fig. 3 Socket filling with OsteoBiol mp3 Fig. 4 Graft protection with OsteoBiol Evolution membrane, left exposed to allow second intention healing Fig. 4 Fig. 5 Fig. 6 Fig. 5 Healing after 2 weeks Fig. 6 Healing after 5 weeks Fig. 7 Healing of the gum after 4 months Fig. 8 Bone width measurement Fig. 9 Implant insertion Fig. 10 Final x-ray Fig. 7 Fig. 8 Fig. 9 Fig. 10 Documentation provided by Prof Antonio Barone DDS, PhD, MSc University of Pisa, Italy e-mail: barosurg@gmail.com Bone substitute: OsteoBiol mp3 Membrane: OsteoBiol Evolution

Scientific publications BARONE A, CRESPI R, ALDINI NN, FINI M, GIARDINO R, COVANI U MAXILLARY SINUS AUGMENTATION: HISTOLOGIC AND HISTOMORPHOMETRIC ANALYSIS INT J ORAL MAXILLOFAC IMPLANTS, 2005 JUL-AUG; 20(4):519-25 BARONE A, AMERI S, COVANI U IMMEDIATE POSTEXTRACTION IMPLANTS: TREATMENT OF RESIDUAL PERI-IMPLANT DEFECTS. A RETROSPECTIVE ANALYSIS EUR J IMPLANT PROSTHODONTICS, 2006,2: 99-106 BARONE A, SANTINI S, SBORDONE L, CRESPI R, COVANI U A CLINICAL STUDY OF THE OUTCOMES AND COMPLICATIONS ASSOCIATED WITH MAXILLARY SINUS AUGMENTATION INT J ORAL MAXILLOFAC IMPLANTS, 2006 JAN-FEB; 21(1):81-5 COVANI U, BARONE A, CORNELINI R, CRESPI R CLINICAL OUTCOME OF IMPLANTS PLACED IMMEDIATELY AFTER IMPLANT REMOVAL J PERIODONTOL, 2006 APR;77(4):722-7 BARONE A, SANTINI S, MARCONCINI S, GIACOMELLI L, GHERLONE E, COVANI U OSTEOTOMY AND MEMBRANE ELEVATION DURING THE MAXILLARY SINUS AUGMENTATION PROCEDURE. A COMPARATIVE STUDY: PIEZOELECTRIC DEVICE VS. CONVENTIONAL ROTATIVE INSTRUMENTS CLIN ORAL IMPLANTS RES, 2008 MAY;19(5):511-5. EPUB 2008 MAR 26 BARONE A, CORNELINI R, CIAGLIA R, COVANI U IMPLANT PLACEMENT IN FRESH EXTRACTION SOCKETS AND SIMULTANEOUS OSTEOTOME SINUS FLOOR ELEVATION: A CASE SERIES INT J PERIODONTICS RESTORATIVE DENT, 2008 JUN; 28(3):283-9 BARONE A, ALDINI NN, FINI M, GIARDINO R, CALVO GUIRADO JL, COVANI U XENOGRAFT VERSUS EXTRACTION ALONE FOR RIDGE PRESERVATION AFTER TOOTH REMOVAL: A CLINICAL AND HISTOMORPHOMETRIC STUDY J PERIODONTOL, 2008 AUG;79(8):1370-7 COVANI U, CORNELINI R, BARONE A BUCCAL BONE AUGMENTATION AROUND IMMEDIATE IMPLANTS WITH AND WITHOUT FLAP ELEVATION: A MODIFIED APPROACH INT J ORAL MAXILLOFAC IMPLANTS, 2008 SEP-OCT; 23(5):841-6 CARDAROPOLI D, CARDAROPOLI G PRESERVATION OF THE POSTEXTRACTION ALVEOLAR RIDGE: A CLINICAL AND HISTOLOGIC STUDY INT J PERIODONTICS RESTORATIVE DENT, 2008 OCT; 28(5):469-77 NANNMARK U, SENNERBY L THE BONE TISSUE RESPONSES TO PREHYDRATED AND COLLAGENATED CORTICO-CANCELLOUS PORCINE BONE GRAFTS: A STUDY IN RABBIT MAXILLARY DEFECTS CLIN IMPLANT DENT RELAT RES, 2008 DEC;10(4):264-70. EPUB 2008 JAN 30 COVANI U, MARCONCINI S, CRESPI R, BARONE A IMMEDIATE IMPLANT PLACEMENT AFTER REMOVAL OF A FAILED IMPLANT: A CLINICAL AND HISTOLOGICAL CASE REPORT J ORAL IMPLANTOL, 2009; 35(4):189-95 CARDAROPOLI D, CARDAROPOLI G HEALING OF GINGIVAL RECESSIONS USING A COLLAGEN MEMBRANE WITH A DEMINERALIZED XENOGRAFT: A RANDOMIZED CONTROLLED CLINICAL TRIAL INT J PERIODONTICS RESTORATIVE DENT, 2009 FEB; 29(1):59-67 BARONE A, RICCI M, COVANI U, NANNMARK U, AZARMEHR I, CALVO GUIRADO JL MAXILLARY SINUS AUGMENTATION USING PREHYDRATED CORTICOCANCELLOUS PORCINE BONE: HYSTOMORPHOMETRIC EVALUATION AFTER 6 MONTHS CLIN IMPLANT DENT RELAT RES, 2012 JUN:14(3):373-9. EPUB 2010 MAY 11 SCARANO A, PIATTELLI A, ASSENZA B, QUARANTA A, PERROTTI V, PIATTELLI M, IEZZI G PORCINE BONE USED IN SINUS AUGMENTATION PROCEDURES: A 5-YEAR RETROSPECTIVE CLINICAL EVALUATION J ORAL MAXILLOFAC SURG, 2010 AUG; 68(8):1869-73. EPUB 2010 MAY 10 BARONE A, RICCI M, GRASSI RF, NANNMARK U, QUARANTA A, COVANI U A 6-MONTH HISTOLOGICAL ANALYSIS ON MAXILLARY SINUS AUGMENTATION WITH AND WITHOUT USE OF COLLAGEN MEMBRANES OVER THE OSTEOTOMY WINDOW: RANDOMIZED CLINICAL TRIAL CLIN ORAL IMPLANTS RES, 2013 JAN;24(1):1-6. EPUB 2011 DEC 12 RAMIREZ FERNANDEZ MP, CALVO GUIRADO JL, MATÉ SANCHEZ DE VAL JE, DELGADO RUIZ RA, NEGRI B, BARONA DORADO C ULTRASTRUCTURAL STUDY BY BACKSCATTERED ELECTRON IMAGING AND ELEMENTAL MICROANALYSIS OF BONE-TO-BIOMATERIAL INTERFACE AND MINERAL DEGRADATION OF PORCINE XENOGRAFTS USED IN MAXILLARY SINUS FLOOR ELEVATION CLIN ORAL IMPLANTS RES, 2013 MAY;24(5):523-30. EPUB 2012 JAN 26 BARONE A, ORLANDO B, CINGANO L, MARCONCINI S, DERCHI G, COVANI U A RANDOMIZED CLINICAL TRIAL TO EVALUATE AND COMPARE IMPLANTS PLACED IN AUGMENTED VS. NON-AUGMENTED EXTRACTION SOCKETS. A 3-YEAR EVALUATION J PERIODONTOL, 2012 JUL;83(7):836-46. EPUB 2011 DEC 5 ESPOSITO M, CANNIZZARO G, SOARDI E, PISTILLI R, PIATTELLI M, CORVINO V, FELICE P POSTERIOR ATROPHIC JAWS REHABILITATED WITH PROSTHESES SUPPORTED BY 6 MM-LONG, 4 MM-WIDE IMPLANTS OR BY LONGER IMPLANTS IN AUGMENTED BONE. PRELIMINARY RESULTS FROM A PILOT RANDOMISED CONTROLLED TRIAL EUR J ORAL IMPLANTOL, 2012 SPRING;5(1):19-33 FELICE P, PIANA L, CHECCHI L, PISTILLI R, PELLEGRINO G VERTICAL RIDGE AUGMENTATION OF THE ATROPHIC POSTERIOR MANDIBLE WITH A 2-STAGE INLAY TECHNIQUE: A CASE REPORT IMPLANT DENT, 2012 JUN;21(3):190-5 BARONE A, RICCI M, TONELLI P, SANTINI S, COVANI U TISSUE CHANGES OF EXTRACTION SOCKETS IN HUMANS: A COMPARISON OF SPONTANEOUS HEALING VS. RIDGE PRESERVATION WITH SECONDARY SOFT TISSUE HEALING CLIN ORAL IMPLANTS RES, 2013 NOV;24(11):1231-7. EPUB 2012 JUL 12 CASSETTA M, RICCI L, IEZZI G, CALASSO S, PIATTELLI A, PERROTTI V USE OF PIEZOSURGERY DURING MAXILLARY SINUS ELEVATION: CLINICAL RESULTS OF 40 CONSECUTIVE CASES INT J PERIODONTICS RESTORATIVE DENT, 2012 DEC;32(6):E182-8 FELICE P, PIANA L, CHECCHI L, CORVINO V, NANNMARK U, PIATTELLI M VERTICAL RIDGE AUGMENTATION OF ATROPHIC POSTERIOR MANDIBLE WITH AN INLAY TECHNIQUE AND CANCELLOUS EQUINE BONE BLOCK: A CASE REPORT INT J PERIODONTICS RESTORATIVE DENT, 2013 MAR-APR;33(2):159-66 WACHTEL H, FICKL S, HINZE M, BOLZ W, THALMAIR T THE BONE LAMINA TECHNIQUE: A NOVEL APPROACH FOR LATERAL RIDGE AUGMENTATION - A CASE SERIES INT J PERIODONTICS RESTORATIVE DENT, 2013 JUL-AUG;33(4):491-7 RODRIGUEZ JG, ELDIBANY RM VERTICAL SPLITTING OF THE MANDIBULAR BODY AS AN ALTERNATIVE TO INFERIOR ALVEOLAR NERVE LATERALIZATION INT J ORAL MAXILLOFAC SURG, 2013 SEP;42(9):1060-6. EPUB 2013 JUN 12 FELICE P, PISTILLI R, PIATTELLI M, SOARDI E, CORVINO V, ESPOSITO M POSTERIOR ATROPHIC JAWS REHABILITATED WITH PROSTHESES SUPPORTED BY 5 X 5 MM IMPLANTS WITH A NOVEL NANOSTRUCTURED CALCIUM-INCORPORATED TITANIUM SURFACE OR BY LONGER IMPLANTS IN AUGMENTED BONE. PRELIMINARY RESULTS FROM A RANDOMISED CONTROLLED TRIAL EUR J ORAL IMPLANTOL, 2012 SUMMER;5(2):149-61 PISTILLI R, FELICE P, PIATTELLI M, GESSAROLI M, SOARDI E, BARAUSSE C, BUTI J, CORVINO V, ESPOSITO M POSTERIOR ATROPHIC JAWS REHABILITATED WITH PROSTHESES SUPPORTED BY 5 X 5 MM IMPLANTS WITH A NOVEL NANOSTRUCTURED CALCIUM-INCORPORATED TITANIUM SURFACE OR BY LONGER IMPLANTS IN AUGMENTED BONE. 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MKT-EVO0915EN Evolution T H E N A T U R A L E V O L U T I O N O F C O L L A G E N M E M B R A N E S Heterologous mesenchymal tissue Tecnoss s.r.l. is an innovative, globally active company that develops, produces and documents premium-quality xenogenic biomaterials by the brands Tecnoss and OsteoBiol. Its 20 years of research led to its patent-protected production process that ensures neutralization of antigenic components in order to achieve biocompatibility, while preserving the natural collagen matrix inside the biomaterial. Tecnoss products comply with highest quality standards such as ISO 10993, ISO 13485 (notified body Kiwa Cermet) and 93/42/EEC (notified body CE 0373). Tecnoss Dental Via Torino, 23 10044 Pianezza (TO) Italy Tel +39 011 9682823 Fax +39 011 9787577 info@tecnoss-dental.com www.osteobiol.com International Sales & Marketing Authorized Distributor