CLINICAL AND SCIENTIFIC LITERATUREABOUT NOBEL BIOCARE BIOMATERIALSCREOS™ REGENERATIVE PRODUCTS

creos™
xenogainTypecreos™ xenogain is a bovine bone mineral matrix for bone grafting inperiodontal, oral and maxillofacial surgery. This bone graft material
is a hydroxyapatite derived from bovine bone and it has a wide
application in bone regeneration. creos™ xenogain is a class III
medical device (Europe), it is CE marked and approved by GMED
notified body. creos™ xenogain is US class II cleared by the FDA
federal agency of the United States Department of Health andHuman Services. The material used for creos™ xenogain has been on
the market for more than 15 years.

Reference

Description

Extract (verbatim)

Maxillary sinus floor augmentation using
deproteinized bovine bone-derived bone
graft material (OCS-B). Clinical andhistologic findings in humans. Jun-BeomPark et al. The Journal of the Korean Dental
Association. 2007;45(8):491 – 499.

Clinical study with
10 patients. Up to 9months follow-up.
creos™ xenogain isnamed OCS-B in
the article.

“From the results, it is believedthat maxillary sinus augmentation
with OCS-B® can achieve excellent
level of bone mass gain before
implant insertion.”

Clinicalstudy

Periodontal Repair on Intrabony Defects
treated with Anorganic Bovine-derived
Xeonograft. Young-Taek Kim et al. J Korean
Acad Periodontol. 2007;37(3):489 – 496.

Clinical study with
10 patients, 6months follow-up.

“On the basis of these results,
anorganic bovine-derived
xenograft improves probing depth
and clinical attachment level inperiodontal defects.”

Clinicalstudy

A radiographical study on the changes inheight of grafting materials after sinus lift:
a comparison between two types of
xenogenic materials. Pham-Duong Hieu. J
Periodontal Implant Sci 2010;40:25-32

Clinical study with
21 patients, 4 years
follow-up. creos™
xenogain is named
OCS-B in thearticle.

“No significant difference in heightchange was observed between the
Bio-Oss® and the OCS-B® groups.”

Long-term results of new deproteinizedbovine bone material in a maxillary sinus
graft procedure. Seung-Yun Shin et al.
Periodontal Implant Sci 2014;44:259-264

Clinical study with
12 patients, 2-6
years follow-up.

“Our results show that the new
DBBM is useful for a maxillarysinus graft procedure. Goodhealing responses as well as
reliable results were obtained foran average follow-up period of
43.3 months.”

A multicenter clinical investigation
demonstrates bone regeneration in severe
horizontal defects in the posterior mandibleusing creos xenoprotect: Interim results[PR546]. Aleksic Z. et al. J Clin Periodontol
2018;45(S19):306.

Clinical study with46 patients, 8months follow-up.

“GBR led to robust boneregeneration after 8 months ofhealing.”

Clinicalstudy

Clinicalstudy

Clinicalstudy

Page 1 of 9

Clinical
study

Histomorphometric analysis of regenerated
bone in sinus lift by deproteinized bovinebone particles. De Santis D. et al. Clinical
Oral Implants Research 2018 Volume 29,
Issue S17.

Clinicalstudy

Peri-implantitis surgical treatment withxenograft and L-PRF. Orlando Martins &Sérgio M Matos. Clinical Oral Implants
Research Volume 29, Issue S17. November
2018

Clinicalstudy

Clinicalstudy

Alveolar Crestal Approach for Maxillary
Sinus Membrane Elevation with <4mm ofResidual Bone Height: A Case Report. Jae
Won Jang et al. International Journal of
Dentistry. Volume 2018, Article ID 1063459,
7 pages. Published 28 June 2018

Horizontal Ridge Augmentation andContextual Implant Placement with a
Resorbable Membrane and Particulated
Anorganic Bovine Bone-Derived Mineral
September. Ferdinando Attanasio et al.
Case Reports in Dentistry 2019(1):1-6 Follow
journal. DOI: 10.1155/2019/6710340

Histomorphometricanalysis ofregenerated bone
in sinus lift bydeproteinizedbovine bone
particles, 18months follow-up“The histologically observed
integration of deproteinizedbovine bone particles (creos
xenogain) and the good clinicalresults support bovine apatite as
valid bone substitute where sinus
floor elevation precedes implant
insertion. Bovine apatite acts asspacer and conducting structure
for the new bone formation.
Mesenchymal stem cells,
osteoblasts and capillaries areable to enter the macropores ofthe xenograft particles, promoting
the healing process.”

Peri-implantitis
surgical treatment,
6 months follow-up“PI treatment depends on defectconfiguration (Schwarz et a. 2010)
and the L-PRF/xenograft blockallows a higher biomaterial
stability and also their application
on more demanding peri-implant
defects.”

Clinical study with
10 patients, up to 3
years follow-up“The mean residual bone height
before implant placement was
3.41 ± 0.53 mm; no complications,
including membrane perforation,
severe postoperative pain, ordiscomfort, occurred either during
or after surgery.”Horizontal ridge
augmentation, 6months follow-up“Within the conﬁnes of this casereport, we can consider the GBR
technique to be successful in the
preprosthetic surgical treatmentof horizontally deﬁcient alveolar
ridges […]”

Table 1Page 2 of 9

Type

Reference

Description

Extract (verbatim)

In-vivo

A study on the safety and efficacy of bovinebone-derived bone graft material OCS-B.
Ho-Nam Park et al. J Korean Acad
Periodontol Vol. 35, No. 2, 2005

Histology in-vivoin rabbits andmouses. creos™
xenogain isnamed OCS-B in
the article.

“It is concluded that newly
developed inorganic bovine bonemineral (OCS-B) is a flourishingbone-forming material andbiocompatible material.”

In-vitro study.

“The apatite granules heattreated at 600°C showed muchbetter osteoconductivity
comparing to that heat-treatedat 1000°C.”

Bone reaction to human hydroxyapatite
grafted in the mandibular defects of beagle
dogs. Jun-Beom Park et al. Article in The
Journal of the Korean Academy of
Periodontology – January 2006. DOI:
10.5051/jkape.2006.36.1.39

In-vivo in dogs.

“New bovine hydroxyapatite wasproved to be an excellent
osteoconductive agent in graftedsites, which biologicallyincorporate with newly formed
osseous tissue.”

Evaluation on the bone regenerative
capacity of deproteinized bovine bonederived bone graft material (OCS-B). Park,
Jun-Beom et al.

In-vitro study.
creos™ xenogain
is named OCS-B
in the article.

“It is concluded that newly
developed deproteinized bovinebone (OCS-B) is biocompatible
material showing excellent
regenerative potential.”

The comparative study - the regenerative
effect depends on size of bone graft
material in bone loss site. Hong-kyun O etal. J Korean Acad Periodontol 2008;38:493502.

Investigation on
the regenerative
capacity in
rabbits.

“Small grafting material size has
great influence on boneregeneration.”

In-vitro

In-vivo

In-vitro

In-vivo

Effect of Heat-Treatment Temperature on
the Osteoconductivity of the Apatite
Derived from Bovine Bone. Sang-Hoon Rheeet al. Key Engineering Materials Vols. 309311 (2006) pp 41-44Online available since
2006/May/15 at www.scientific.net©
(2006) Trans Tech Publications, Switzerland
doi:10.4028/www.scientific.net/KEM.309311.41

Table 2

Page 3 of 9use in Guided Tissue Regeneration (GTR) and Guided Bonecreos™
Regeneration (GBR) procedures. In these procedures, creos™
can be used as a resorbable membrane for the
xenoprotect xenoprotect
containment of bone grafts in bone repair procedures duringcreos™ xenoprotect is a biodegradable barrier membrane fortreatment of periodontal bone defects (GTR) and for boneaugmentation procedures (GBR). creos™ xenoprotect is ahighly purified membrane produced from porcine collagenusing controlled and standardized manufacturing processes.
creos™ xenoprotect is a class III medical device (Europe), it is
CE marked and approved by ECM notified body. creos™
xenoprotect is US class II cleared by the FDA federal agency of
the United States Department of Health and Human Services.

Type

Clinicalstudy

Clinicalstudy

Clinical
study

Reference

Description

Extract (verbatim)

Horizontal ridge augmentation witha novel resorbable collagenmembrane: a retrospective analysis
of 36 consecutive patients. B.
Wessing et al. Int J Periodontics
Restorative Dent 2016;36(2):179–187.

Horizontal ridge
augmentation, 629 months followup“These early data demonstrate a low
dehiscence rate and excellent potential ofthis new noncross-linked collagen membrane
for use with horizontal ridge augmentation.”

Clinical study with
24 patients, 6months follow-up“The new resorbable non-cross-linked
collagen membrane facilitates bone gain to
support implant placement in expected
dehiscence defects. The observed trend
toward higher mean bone gain and lower
exposure rate with creos™ xenoprotect
compared to Bio-Gide should be further
investigated.”

24 patients, 6months follow-up.

“The new creos™ xenoprotect membrane
was statistically non-inferior to thereference Bio-Gide membrane with respect
to mean difference in bone defect height
between implant insertion and reentry
surgery (p <0.001). Moreover, there was nodifference in patient pain or quality of life
between the two treatment arms. However,there were trends in improved outcomes,
namely higher bone gain and lower
membrane exposure rates, when creos™
xenoprotect was used compared with BioGide, though not statistically significant.
Together, the study confirms that, evenusing a simultaneous surgical approach, thecreos xenoprotect collagen membrane
supports bone regeneration at dehisced
implant sites with few complications. This
demonstrates that new barrier membranematerials with improved properties, such as
creos™ xenoprotect, can provide clinicalbenefits to patients.”

A multicenter randomized controlled
clinical trial using a new resorbablenon-cross-linked collagen membrane
for guided bone regeneration at
dehisced single implant sites: interim
results of a bone augmentation
procedure. B. Wessing et al.
Clin. Oral Impl. Res. 28, 2017, e218–
e226 doi: 10.1111/clr.12995

Guided bone regeneration using
collagen membranes simultaneous to
implant placement at compromisedsites leads to reproducible results
and high success rates. B. Wessing etal. Musculoskelet Regen 2017; 3:e1537. doi: 10.14800/mr. 1537

Page 4 of 9

Clinical
study

Clinicalstudy

A multicenter randomized controlled
trial using a novel collagenmembrane for guided boneregeneration at dehisced single
implant sites: Outcome atprosthetic delivery and at 1-year
follow-up. I. Urban et al. Clin Oral
Implants Res. 2019 Jun;30(6):487497. doi: 10.1111/clr.13426.

24 patients, 1-year
follow-up.

“The use of creos™ xenoprotect and Bio-Gidefor simultaneous implant placement and
GBR at dehisced implant sites similarly
reduced defect height and improved
secondary measures, indicating noninferiority.”

A randomized controlled study
comparing guided bone regeneration
with connective tissue graft toreestablish buccal convexity at
implant sites: A 1-year volumetricanalysis. Thomas De Bruyckere at el.
PMID: 32686234 DOI:10.1111/cid.12934

21 patients, 1-year
follow-up“GBR as well as CTG are effective in
reducing horizontal alveolar defects foraesthetic purposes.”

Reference

Description

Extract (verbatim)

GBR with a mechanically stable
resorbable membrane as a potential
alternative to the use of autogenous
bone block grafts. B. Wessing et al.
October 2013. Clinical Oral Implants
Research 24(2):153. Conference:
European Association for
OsseointegrationAt: DublinVolume:22.

In-vitro formechanical tests.
creos™ xenoprotect
is named Remaix inthe article.

“The evaluation of the different membranes
in the first part of the study showed asignificantly higher mechanical stability of
the Remaix membrane than of all othermembranes tested, even the PTFE
membrane.”

Resorbable Collagen Membranes
Expansion In Vitro. Arrighi et al. J
Dent Res 93, 2014

In-vitro + clinicalcase“The clinical results achieved with the creos
xenoprotect membrane demonstrated easy
fixation, perfect containment of the graft
material and excellent wound healing. The
significantly lower surface expansion ofcreos xenoprotect provides for moreaccurate trimming of the membrane to thedefect dimensions in a dry stage. In
addition, the lower surface expansion
compared to Bio-Gide may potentiallyreduce strain on the primary woundclosure.”Differences in degradation behaviorof two non-cross-linked collagenbarrier membranes: an in vitro andin vivo study. Bozkurt A et al. Clin.
Oral Impl. Res.25, 2014, 1403–1411
doi: 10.1111/clr.12284

In-vitro + in-vivo inrats. creos™
xenoprotect isnamed Remaix inthe article.

“after 20 weeks, the thickness of Remaix
decreased only slightly, whereas Bio-Gideshowed a thickness loss of around 50% andstronger degradation than Remaix.”

Table 3Type

In-vitro

In-vitro

In-vivo

Page 5 of 9

In-vitro

In-vivo

In-vitro

In-vitro & clinical“• creos™ xenoprotect demonstrated thehighest force at break wet (21.2 N;interquartile range [IQR]: 13 –23.7).
• creos™ xenoprotect showed the highest
stress at break wet (14.2 N/mm2; IQR: 9.116.3).
• creos™ xenoprotect had the highest suture
retention wet (6.1 N; IQR: 5.9-6.5).
• In general, NXL membranes had a higher
force at break wet and a higher stress at
break wet in comparison to XL membranes.”

Tissue dynamics and regenerative
outcome in two resorbable noncross-linked collagen membranes for
guided bone regeneration: A
preclinical molecular and histologicalstudy in vivo. Omar O et al. Clin Oral
Implants Res 2018;29(1):7–19.

In-vivo in rats“[…] the creos™ xenoprotect groupdemonstrated significantly higher de novobone formation in the central portion of thedefect. This increase in bone formation wasreflected by triggered expression of potent
osteogenic growth factor, Bmp2, in thedefect. These findings suggest that thecreos™ xenoprotect membrane may have amore active role in regulating the bonehealing dynamics.”

Tensile Properties of Three Selected
Collagen Membranes. Perry Razet
al. BioMed Research International
2019(3):1-8

In-vitro, creos™
xenoprotect isnamed Remaix inthe article.

“Among the 3 tested membranes, Remaix
exhibited higher performance results in all
the mechanical tests.”

Mechanical stability of collagenmembranes: an in vitro study.
Gasser A et al. J Dent Res 2016;95(Spec Iss A):1683 (www.iadr.org)

Table 4

Page 6 of 9

creos™
syntoprotect

creos™ syntoprotect is a dense PTFE membrane that exists
in two version: non-titanium-reinforced and titaniumreinforced. Dense PTFE was designed to withstand exposurein the oral environment, which represents an improvement toearlier versions of expanded PTFE in applications such as
socket preservation where deliberate membrane exposure
offers several advantages. creos™ syntoprotect is CE
marked, cleared by the FDA federal agency of the UnitedStates Department of Health and Human Services.

creos™ syntoprotect has over 30 clinical publications available. Here are some of those:Type

Clinicalstudy

Clinicalstudy

Clinicalstudy

Clinical
study

Reference

Description

Extract (verbatim)

Alveolar Bone Preservation in
Extraction Sockets Using NonResorbable dPTFE Membranes: A
Retrospective Non-Randomized
Study. O. Hoffmann et al. j
Periodontol. 2008;79:1355-1369.

276 extraction
sockets in 276
patients,
measurements
taken 12 months
after surgery.

“a significant regeneration of the volume ofsockets could be noted by histologic
evaluation, indicating that the newly formed
tissue in extraction sites was mainly bone[…]. The use of dPTFE membranes
predictably led to the preservation of softand hard tissue in extraction sites.”

Soft tissue enhancement using nonexpanded PTFE membranes without
primary closure. Barboza EP et al.
Annual Meeting of the American
Academy of Periodontology (AAP) in
Seattle, WA, September 6-9, 2008.

15 lower posterior
extraction selected
to receive PTFE
membranes.

“Non-expanded PTFE membrane utilized
over extraction sockets, without primaryclosure, can be predictably used to promote
soft tissue enhancement.”

Comparison of Dermal Matrix and
Polytetrafluoroethylene Membrane
for Socket Bone Augmentation: A
Clinical and Histologic Study. Paul D.
Fotek et al. J Periodontol
2009;80:776-785.

Clinical study with
20 patients,
measurements
after 16 weeks ofhealing.

“All sites evaluated showed minimal ridge
alterations, with no statistical difference
between the two treatment modalities withrespect to bone composition and horizontal
and vertical bone loss, indicating that both
membranes are suitable for alveolar ridge
augmentation.”

Guided Bone Regeneration Using
Nonexpanded
Polytetrafluoroethylene Membranes
in Preparation for Dental Implant
Placements – A Reports of 420
Cases. E. Barboza et al. Implant
Dentistry Volume 19, Number 1, 2010

420 cases ofalveolar ridge
maintenance, ofsingle molars (286)and bicuspids (134),
using intentionally
exposed PTFE
membranes.

“Exposed nonexpanded PTFE membranes
positioned over fresh extraction sockets
associated or not with bone graft, provide
tissue both hard and soft formation suitablefor implant placement.”

Table 5

Page 7 of 9

during coverage procedures of localized gingival recessions and for
creos™
local soft tissue augmentation. creos™ mucogain is designed to
an off-the-shelf alternative to autogenous soft tissue
mucogain provide
grafts. The open, interconnecting porous structure of creos™
creos™ mucogain is a resorbable matrix intended to provide support

mucogain provides a matrix for the migration of proliferating cells
and vascular structures. As the healing process advances, creos™
mucogain is degraded whilst a new soft tissue matrix is regenerated
inside the creos™ mucogain structure. creos™ mucogain is composedof highly purified porcine collagen and elastin fibers. creos™
mucogain is a class III medical device (Europe), it is CE marked andapproved by ECM notified body.

Type

Reference

Clinicalstudy

Clinicalstudy

Clinicalstudy

ClinicalstudySoft tissue augmentation with a newregenerative collagen 3-d matrix
with oriented open pores as apotential alternative to autologous
connective tissue grafts [329].
Wessing B, Vasilic N.
Clin Oral Implants Res
2014;25(s10):342.

Soft tissue augmentation at
immediate implants using a novel
xenogeneic collagen matrix inconjunction with immediateprovisional restorations: A
prospective case series. Sanz-Martin
I. et al. Clin Implant Dent Relat Res.
2018;1–9.

Soft tissue augmentation with acollagen-based 3D matrix
with directed pore channels. B.
Wessing et al. Clinical Oral Implants
Research 30, 401-401. 2019

Treatment Of Multiple Gingival
Recessions With Tunnel Procedure
And A New Xenogeneic Collagen
Matrix. Gaudard M. et al. Clinical
Oral Implants Research 30, 401-401
and OBJECTIF PARO #50 September 2019

Description

Extract (verbatim)

Clinical study with
7 patients, 5months follow-up“The initial results obtained after clinicalapplication of the new 3-D collagen matrix inclosed-healing procedures are very
encouraging. All treatments with closed
healing procedures were able to reach asatisfying outcome, both for the surgeon
and the patient, without having to perform
any connective tissue harvesting.”

Clinical study, 1year follow-up“[…] this case series has shown that asurgical implant protocol consisting of
immediate implants in the anterior maxillary
region and premolar area, in conjunction
with hard and soft tissue grafting withxenogeneic substitutes, together withimmediate provisionalization, resulted inhigh aesthetic scores and patientsatisfaction […].”

Clinical study with
45 patients, 1.8 ±1.3 years follow-up“This retrospective analysis demonstrated
that creos mucogain promotes soft tissue
health and maintains adequate soft tissue
thickness when used simultaneously withimplant placement. The histological findings
demonstrate excellent biocompatibility ofcreos mucogain and indicate this matrix as avalid alternative to autologous grafts.”

Clinical study with
10 patients, 6months follow-up“The new creos mucogain matrix would leadto satisfactory clinical results and would
make it possible to have a large amount ofmaterial available without additional
surgical site. The operating time is reduced
for the practitioner as for the patient.”

Table 6

Page 8 of 9

TypeIn-vivo

Reference

Soft tissue volume augmentation in
the oral cavity with a collagen-based
3D matrix with orientated open pore
structure. Leon Olde Damink et al.
Current Directions in Biomedical
Engineering 2018;4(1) [conference
paper]

Description

Extract (verbatim)

In-vitro + in-vivo
with pigs“The in-vitro studies show that themechanical properties (e.g. suture retention,
volume recovery after cyclic compression)and the observed active cell migration into
the open porous structure of the matrix
fulfil essential design requirements. The invivo pig animal study shows that the matrix
is well integrated into the surrounding tissue
and replaced by newly formed autogenous
soft tissue without a significant loss intissue volume.”

Table 7

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Nobel Biocare, the Nobel Biocare logotype and all other trademarks are, if nothing else is stated or is evident from the context in a certain case, trademarksof Nobel Biocare. Please refer to nobelbiocare.com/trademarks for more information. Product images are not necessarily to scale. All product images are forillustration purposes only and may not be an exact representation of the product. Please contact the local Nobel Biocare sales office for current productassortment and availability.
Disclaimer: For prescription use only. Caution: Federal (United States) law or the law in your jurisdiction may restrict this device to sale by or on the order ofa licensed clinician, medical professional or physician. See Instructions For Use for full prescribing information, including indications, contraindications,warnings and precautions. Note: OCS-B Collagen (NIBEC Co., Ltd.) has been distributed as creos™ xenogain collagen since September 2016. creos™ xenogain
and creos™ xenogain collagen are manufactured by NIBEC Co., Ltd. creos™ xenoprotect and creos™ mucogain are manufactured by Matricel GmbH,
Kaiserstrasse 100, D-52134 Herzogenrath, Germany. creos™ xenogain, creos™ xenogain collagen, creos™ xenoprotect, creos™ mucogain are distributed byNobel Biocare Services AG. Cytoplast™ (Osteogenics Biomedical, Inc.) is distributed as creos™ syntoprotect since January 2021. Legal Manufacturer:
Osteogenics Biomedical, Inc., 4620 71st Street, Bldg 78-79, Lubbock, TX 79424, USA and distributed by Nobel Biocare Services AG.

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