Regeneración de tejidos orales en

pacientes comprometidos
Pedro Aravena DDS, PhD
2018

paravena@uach.cl www.drpedroaravena.cl
1. Regeneración de tejidos orales

2. Regeneración de tejidos en pacientes con Enfermedades

crónicas y adultos mayores

3. Presentar biomateriales y biotecnología en regeneración de

tejidos
 Herida

Daño tisular

Inflamación
 response with successful alveolar bone healing. In conclusion, based on the set of resu

Vieira AE, et al. PLoS ONE . 2015; 10(5): e0128021.

Fig 7. Graphic representation of inflammatory and healing events in the bone healing process after tooth extraction. Briefly, the healing p
 Regeneración de
tejidos
En pacientes medicamente comprometidos
SOSPECHA DE HIPERTENSIÓN ARTERIAL (HTA)

Sospecha de HTA total país y según sexo.

ENS 2003, 2009-10 y 2016-17

27,6% nacional 80%

70%

60%

50%

40%

30%

20% 36,7%
33,7% 30,8%
26,5% 27,6% 28,1% 27,5% 25,0% 27,7%
10%

0%
Total país Hombres Mujeres

2003 2009-10 2016-17

Elaborado por Departamento de Epidemiología

Se entiende por “sospecha de HTA”, a personas con autoreporte y/o tratamiento médico HTA o con presión elevada mayor 140/90 (promedio con 3 tomas de presión arterial). En el
año 2003 se realizaron 2 tomas de presión arterial.
No se observan diferencias estadísticamente significativas entre las dos últimas mediciones en total país y sexo (IC 95%).
SOSPECHA DE DIABETES MELLITUS

Sospecha de Diabetes Mellitus total país y según sexo.

ENS 2003,2009-10 y 2016-17

12,3% nacional 40%

30%

20%

10%
12,3% 14,0%
9,0% 10,6% 9,7%
4,8% 8,3%
4,2% 3,8%
0%
Total país Hombres Mujeres
2003 2009-10 2016-17

Elaborado por Departamento de Epidemiología

Se entiende por “sospecha de Diabetes Mellitus” a la medición de glicemia en ayuno con resultados mayores o iguales a 126mg/dl.
No se observan diferencias estadísticamente significativas entre las mediciones (IC 95%).
 REVIEW F O C U S O N VA S C U L A R D I S E A S E
F O C U S O N VA S C U L A R D I S E A S E

Under pressure: the search for the

essential mechanisms of hypertension
Thomas M Coffman1,2

ure: the search for the

High blood pressure, or hypertension, is a very common disorder with a substantial impact on public health

Under pressure:
chanisms of hypertension the search for the
because of its associated complications. Despite the high prevalence of essential hypertension and years of
research, the basic causes remain obscure. Here I review recent advances in understanding the pathophysiology
of hypertension. I present a general overview of the field and, by necessity, use broad strokes to portray recent

- essential mechanisms of hypertension

progress and place it in context. For this purpose, I use illustrative examples from the large number of important
Excreción de sodio por los riñones.
developments in hypertension research over the last five years. The intent of this review is to provide a sense of
where the field is progressing, with an emphasis on work that sheds light on pathogenic mechanisms and that is
on, is a very common disorder with a substantial impact on public health
tions. Despite thetherefore likely toofinform
high prevalence new
essential translational
hypertension
1,2 andadvances.
years of
Thomas M Coffman
Contracción del árbol vascular.
obscure. Here I review recent advances in understanding the pathophysiology
-
l overview of the Hypertension is one of the
field and, by necessity, usemost
broad common
strokeschronic
to portray diseases
recentin the In the simplest sense, determinants of blood pressure are approxi-
or this purpose, I human
useHigh bloodexamples
population,
illustrative pressure,
affectingfrom moreor
the hypertension,
than 1 billion
large number people is a very. common
worldwide
of important 1 mated by Ohm’sdisorder with for
law modified a substantial impact= on
fluid dynamics (pressure flowpublic
× health
arch over the lastItsfive complications, including stroke, heart is failure and kidney disease, resistance). Blood flow depends on cardiac output and blood volume,
because
years. The ofintent
its associated
of this review complications.
to provide a sense Despite
of the high prevalence of essential hypertension and years of
lational advances.
- are
sure
Actividad del SNC y SN Simpático.
major sources
in individuals
of morbidity and
an emphasis on work that sheds light on pathogenic mechanisms and that is
research, thewith basic
mortality.
causesprevents
hypertension remain
Reducing blood
obscure.these
or attenuates
pres- whereas resistance is primarily determined by the contractile state of
Heresmall I review
arteries recent advances
and arterioles throughout intheunderstanding
body. These componentsthe pathophysiology
2. However, despite the high prevalence of hypertension of blood pressure
complications
of hypertension. I present a general overview of the field and,arebysubject to a range of
necessity, regulatory
use broadinfluences.
strokesThus,to portray recent
and increasing public awareness of this disorder and its risks, control unraveling the root causes of hypertension requires consideration of
on chronic diseases inprogress and placesense,it
and in context. For thisofarepurpose,
the In the simplest determinants of blood pressure approxi- I use illustrative examples from the large number of important
-
billion people worldwide
with
failure and kidney disease,
Vías de respuesta inmune e inflamatoria
rates 1remain
. mated
developments
hypertension
unsatisfactory,
by Ohm’s law modified
resistance).underBloodinflow
treatment
a substantial
hypertension
depends doonnot
proportion
for fluid dynamics
research
achieve
cardiac output
(pressure
theand over
target
blood
= flow × the many systems contributing to blood pressure homeostasis, includ-
people
levelsthe ing
volume, lastthefive years.theThe
vasculature, intent
central of this review
and sympathetic is to provide
nervous systems and a sense of
of blood pressure control recommended by current guidelines 3. The the kidney, along with their various hormonal regulators. Although
ality. Reducing blood pres- whereas resistance is primarily determined by the contractile state of
where
events or attenuatesreasons
these for
the
these
small
field
poorand
arteries
is
outcomes
progressing,
arteriolesare
with
complex.theHealth
throughout
an emphasis
service
body. These components
on work that sheds light on pathogenic mechanisms and that is
issues the interactions of these systems in the regulation of blood pressure
-
prevalence of hypertension
sorder and its risks, control
Microambientes cutáneos en control de sodio y volumen
therefore
regarding bloodlikely
ofaccess
unraveling
to care,to
pressure
the
are
root
inform
diagnosis
subject
causes of
toand new
a range
hypertension
oftranslational
optimal implementation
regulatory
requires
influences. advances.
consideration
of have been intensely scrutinized for decades, their specific roles in
Thus,
existing therapies have a role. However, persistent gaps in under- ofhypertension have not been resolved, and this remains an area of
people the
ntial proportion of standing themany systems contributing
pathogenesis of hypertensionto bloodaspressure
well ashomeostasis,
the availability includ-vigorous debate among hypertension researchers.
Hypertension
ot achieve the targetoflevels
only a relatively is one
ing the vasculature,
small ofcentral
the
repertoire theof most common
and sympathetic
antihypertensive chronic
nervous
therapiessystemsdiseases
alsoand Studies in the In the causality
of hypertension simplestare sense, determinants
particularly challengingof blood
in pressure are approxi-

The
extracelular
by current guidelines3. The the kidney, along with their various hormonal regulators. Although
humantopopulation,
contribute
etiology
disappointingaffecting
Itsofcomplications, of elevated blood
including
more than 1 billion people worldwide
clinical results.
plex. Health service issues the interactions of these systems in the regulation of blood pressure
pressure
stroke, cannot be
hearttheir determined
failure androlesin
kidney
1.
clinical settings,
and where
mated
primary
by Ohm’s law
where opportunities
pathophysiological
for modified
mechanisms
forare
invasive study
may
fluid
be
dynamics (pressure = flow ×
limited
masked
disease, resistance). Blood flow depends on cardiac output and blood volume,
optimal implementation have been intensely scrutinized for decades, specific in
the vast majority of individuals with ‘essential’ hypertension. Thus, it by compensatory pathways and the confounding effects of diet and
are major
persistent gaps in under- sources
hypertension haveofnotmorbidity
been resolved, andand mortality.
this remains Reducing
an area ofblood pres- whereas resistance is primarily determined by the contractile state of
has proved
n as well as the availability difficult
vigorous to develop
debate among precise profiles
hypertension for individual patients medications. To facilitate mechanistic studies, several widely used
researchers.
hypertensive therapiesforsure in Studies
the purposes
also individuals
of of
identifying with
hypertension hypertension
optimal therapies
causality and prevents
predicting
are particularly orprog-
attenuates
challenging models ofsmall
ingeneticthese arteriesinand
hypertension rats arterioles throughout
have been generated the body. These components
through
2 of for
blood
s. complications
nosis. clinical settings,
Consequently, .choices
However,
where despite the
of opportunities
antihypertensive forhigh prevalence
invasive
therapy study of hypertension
are limited
are typically selective breeding the pressure are subject
traits of increased to apressure,
blood range ofsalt
regulatory influences. Thus,
e cannot be determined and
empirical and
andwhere
in increasing primary
are based on pathophysiological
public awareness
broad mechanisms
of this
epidemiological disorder mayand
categories be masked
such its
as risks, control
sensitivity unraveling
or both. Hypertension thecan
root causes
also of hypertension
be induced in animals by requires consideration of
ntial’ hypertension. Thus, it
age,rates by
race and compensatory
the presence pathways
of and
coexisting the confounding
disorders such effects
as of
diabetes dietor and pharmacological or transgenic modulation of key neurohormonal
remain unsatisfactory, and a substantial
studies, severalproportion
widely used of people the many systems contributing to blood pressure homeostasis, includ-
files for individual patients medications.
heart disease. Accordingly,
with hypertension
rapies and predicting prog-
To facilitate mechanistic
genetic models of under
developing a more
treatment
hypertension in rats have
precise understand-
dobeennotgenerated
achievethrough Coffman TM. Nat Med. 2011;17:1402-1409
regulators. Although these models do not fully recapitulate all of the
the target levels ing the vasculature, the central and sympathetic nervous systems and
ing of theselective
ensive therapy are typically
molecular pathogenesis
breeding for the
of hypertension
traits of increased
remains
blood
apressure,
pressingsalt features of human hypertension, they have nevertheless provided
3. The
of blood
priority for bothpressure
basic and control recommended
translational researchers by current
in the field. guidelines useful insights the have
that kidney,
provedalong withtotheir
relevant variousdisorder.
the human hormonal regulators. Although
Curr Rev Musculoskelet Med (2009) 2:56–64
DOI 10.1007/s12178-009-9046-7

Curr Rev Musculoskelet Med (2009) 2:56–64

DOI 10.1007/s12178-009-9046-7

RANK, RANKL and osteoprotegerin in bone biology and disease

RANK,
H. L. WrightRANKL and Æosteoprotegerin
Æ H. S. McCarthy J. Middleton Æ in bone biology and disease
M. J. Marshall
H. L. Wright Æ H. S. McCarthy Æ J. Middleton Æ
58 Curr Rev Musculoskelet Med (2009) 2:56–64
M. J. Marshall

perhaps allowing systemic resorption. sRANKL can also TNFα RANKL IL-1

be formed by shedding, a process in which RANKL is OPG

cleaved from the cell surface membrane by sheddases such
TNFR RANK IL-1R
as matrix metalloproteinase 14 (MMP-14) [22].
Published online: 10 March 2009
! The Author(s) 2009. This article is published with open access at Springerlink.com
Published online: 10 March 2009 Cell membrane
OPG
! The Author(s) 2009. This article is published with open access at Springerlink.com
Abstract Upon the discovery of RANK, RANKL and Introduction
OPG in the Upon
late 1990s,OPG was
their first identified
importance by sequence homology to the
Abstract the discovery of RANK,in RANKL the maintenance
and Introduction TRAF-2 TRAF-5 TRAF-6
ofOPGtheinskeletal TNFR
structure family during a rat intestine cDNA sequencing
the late 1990s, theirand their dramatic
importance role in bone
in the maintenance Bone is a specialised tissue with a complex composite
disease were largely
of the skeletal project [23].
structure unexpected. They
and their dramatic named
In recent the
role in years protein becauseis aofspecialised
bone theBone structure its that
pro- enables Caspase-8
tissue it toa perform
with complex multiple
compositemechanical
disease were of
understanding largelytective
these effects
unexpected.
proteins, in recent
bone years
inInparticular (Latin:
their the os bone,
regula- structure
andprotegere
that to itfunctions.
enables
metabolic to perform In multiple
ordermechanical
to maintain these Src
NF- B, JNK
understanding protect).
of these proteins,OPG is a soluble
in particular glycoprotein
theirtoregula- secreted by various
tion, has greatly increased. This review aims bring theand metabolic
functions functions.
within the Inbody, orderbone
to maintain these state of
is in a constant
tion, has greatly mesenchymally derived tocells such as osteoblastswithin [24] and
interested reader increased.
up to dateThis withreview aims news
the latest bringandtheviewsfunctions
remodelling. the During
body, bone thisis process,
Apoptosis
in a constant
also state
knownof as bone
interested reader up to bonedatemarrow
with the stromal
latest newscellsand [25].
views remodelling. During this process, also knownOsteoclast as bone Osteoclast
on the mechanisms controlling bone resorption in normal turnover, osteoclasts demineralise and resorb formationold bone and activation
on the mechanisms controllingUnlike bone RANK resorption
and RANKL,in normalOPGturnover,does not osteoclasts
have ademineralise and resorb old bone and
and pathological conditions.
and pathological conditions.
osteoblasts depositbone newto bone to maintain a bone mass
transmembrane domain or cytoplasmicosteoblasts domain [2]. deposit
Com-new Fig. maintainrepresentation
2 Schematic a bone mass of RANK-RANKL binding signal-
appropriate
appropriate to the stresses placed on the skeleton. Any
posed of 401 aa, human and murine OPG consisttoofthe four stresseslingplaced on indicating
pathways, the skeleton. Any of RANK-RANKL
the inhibition binding by
Keywords Review
Keywords Review cysteine ! Osteoprotegerin
! Osteoprotegerin (OPG)
(OPG) ! ! alteration in the process of bone turnover may alter bone
rich pseudo repeats located in alteration in the process
the N-terminal, two of
OPG bone turnover may alter bone
Receptor-activator
Receptor-activator ofofdeathnuclearfactor
nuclear factor kappa
kappa betabeta
(RANK) (RANK)! !mineral
mineral
density density (BMD), bone strength
and bone and microbone micro
domains, a heparin binding site located in (BMD),
the bone strength
Receptor-activator
Receptor-activator ofofnuclear
nuclearfactor
factor kappa
kappa betabeta
ligand architecture.
ligand architecture. This most Thiscommonly
most commonly
occurs when occurs
therewhen
is an there is an
C-terminal and a 21 aa signal peptide [2] (Fig. 1c). The
(RANKL) !! Disease
(RANKL) Disease! !Structure
Structure increase in osteoclast
increase in osteoclast osteoclast
activity, differentiation
leading
activity, toleading
increased to and
bonethe expression
increased bone of the osteo-
four cysteine rich pseudo repeats form an elongated
resorption, resulting
resorption, in diminished
resulting clastin markerboneTRAP
diminished density
bone (osteo-
(tartrate
density resistant acid phosphatase)
(osteo-
structure and binds to one of the grooves Wright
of
penia).penia).the HL,
active
Osteopenia et al. Curr
may[28]. also Rev
occurMusculoskelet
due to lack Med. 2009;2(1):56-64.
ofto lack of
RANKL trimer [20] therefore preventing RANKL/RANK Osteopenia may also occur due
vitamin D (rickets and osteomalacia) or an excess of
Clin Oral Invest
DOI 10.1007/s00784-014-1369-0

ORIGINAL ARTICLE

Hypertension modifies OPG, RANK, and RANKL expression

during the dental socket bone healing process in spontaneously
hypertensive rats
Natalia Manrique & Cassiano Costa Silva Pereira & Eloá Rodrigues Luvizuto &
Maria Del Pilar Rodriguez Sánchez & Tetuo Okamoto & Roberta Okamoto &
Doris H. Sumida & Cristina Antoniali

Received: 13 April 2014 / Accepted: 13 November 2014

Objetivo:
# Describir
Springer-Verlag la expresión
Berlin Heidelberg genética
de Osteoprotegerina (OPS) receptor activador del
2015
factor nuclear (RANK) y su ligando (RANKL) en cicatrización de alveolos en ratas
Abstract
hipertensas post exodoncia Conclusion The results of this study show that RANK,
Objective The aim of this study was to evaluate the dental RANKL, and OPG immunolabeling was altered in SHRs,
Método:
socket bone 25 ratas
healing hipertensas
process vs 25 ratas
by histomorphometric andno-hipertensas
im- con exodoncia
and these results are associatedincisivo
with bonesuperior
healing delay and
derecho. Análisis
munohistochemical inmunohistoquímico
analysis a los
of osteoprotegerin (OPG), 7, 14,decreased
recep- 21, 28 trabecular
o 42 días thickness in SHRs.
tor activator of nuclear factor-κβ (RANK), and receptor acti- Clinical relevance Hypertension alters the expression of
vator of nuclear factor-κβ ligand (RANKL) proteins in spon- RANK, RANKL, and OPG and delays the socket bone
taneously hypertensive rats (SHR). healing process. These alterations could influence some dental
Materials and methods Under general anesthesia, 25 Wistar procedures such as orthodontic treatment and implant
rats and 25 SHRs underwent upper right incisor extraction. placement.
Rats were euthanized after 7, 14, 21, 28, or 42 days of dental Manrique N, et al. Clin Oral Investig. 2015;19(6):1319-27.
extractions. Histomorphometric and immunohistochemical Keywords Extraction socket healing . Histomorphometry .
 Clin Oral Invest

Fig. 2 Representative
histological sections stained with
hematoxylin and eosin (original
×16) of the middle third of Wistar
and SHR alveoli at postoperative
time periods (7, 14, 28, and
42 days)

the interaction between RANKL and RANK, which modu- alteration in socket bone tissues of SHRs, which can be
lates osteoclast formation and activation, induces both physi- explained by a decrease in bone formation percentage and
ological and pathological bone resorption, with noticeable trabecular thickness in the later periods studied.
Figura: Representación histológica de secciones elides con (original ×16) en el tercio medio de alveolo de ratas Wistar y
Ratas hipertensas (SHR) a los 7, 14, 28 y 42 días postoperatorios.
Manrique N, et al. Clin Oral Investig. 2015;19(6):1319-27.
 Antihypertensive Medications and the Survival
Rate of Osseointegrated Dental Implants: A
Cohort Study
Xixi Wu, DDS, MSc, PhD;* Khadijeh Al-Abedalla, DDS, MSc;* Hazem Eimar, DDS, MSc, PhD;*
Sreenath Arekunnath Madathil, PhD;* Samer Abi-Nader, BSc, DMD, MSc, FRCD(C);*
Nach G. Daniel, BSc, MSc, FRCD(C);† Belinda Nicolau, DDS, MSc, PhD;*
Faleh Tamimi, DDS, MSc, PhD*
Clinical Implant Dentistry and Related Research Volume 00, Number 00, 2016
Cohorte retrospectiva. Análisis 1,499 implantes dentales en 728 pacientes
ABSTRACT
Purpose: Antihypertensive drugs in general are beneficial for bone formation and remodeling, and are associated with
lower risk of bone fractures. As osseointegration is influenced by bone metabolism, this study aimed to investigate the
association between antihypertensive drugs and the survival rate of osseointegrated implants.
Materials and Methods: This retrospective cohort study included a total of 1,499 dental implants in 728 patients (327
implants in 142 antihypertensive-drugs-users and 1,172 in 586 nonusers). Multilevel mixed effects parametric survival
analyses were used to test the association between antihypertensive drugs use and implant failure adjusting for potential
confounders.
Results: Only 0.6% of the implants failed in patients using antihypertensive drugs while 4.1% failed in nonusers. A
higher survival rate of dental implants was observed among users of antihypertensive drugs [HR (95% CI): 0.12 (0.03–
0.49)] compared to nonusers.
Conclusions: Our findings suggest that treatment with antihypertensive drugs may be associated with an increased
survival rate of osseointegrated implants. To our knowledge, this could be the first study showing that the systemic use
of a medication could be associated with higher survival rate of dental implants.
KEY WORDS: antihypertensive drugs, epidemiology, hypertension, medical devices, multilevel, osseointegrated
implants

re 2 Kaplan–Meier survival curves for dental implant failure in terms

Wu X,et of:Implant
al. Clin (A) Antihypertensive drugs usage (D: Usage; !:
Dent Relat Res.2016;18(6):1171-1182.
usage); (B) Hypertension (D: Yes; !: No); (C) Smoking habits (D: Smoker; !: Nonsmoker).
INTRODUCTION tensive medications, such as beta-blockers, thiazide
Diabetes mellitus
tipo 2
AGE: Advanced Glication Ending products

Abiko Y, Selimovic D.. Bosn J Basic Med Sci. 2010 Aug;10(3):186-91.

 BON-10764; No. of pages: 8; 4C:
Bone xxx (2015) xxx–xxx

Contents lists available at ScienceDirect

Bone

journal homepage: www.elsevier.com/locate/bone

Original Full Length Article

Bone defect regeneration and cortical bone parameters of type 2 diabetic

rats are improved by insulin therapy☆
A.-K. Picke a, I. Gordaliza Alaguero a, G.M. Campbell b, C.-C. Glüer b, J. Salbach-Hirsch a, M. Rauner a,
L.C. Hofbauer a,c, C. Hofbauer d,⁎
a
Division of Endocrinology, Diabetes, and Metabolic Bone Diseases, Department of Medicine III, Technische Universität Dresden, Germany
b
Section Biomedical Imaging, MOIN CC, Department of Radiology and Neuroradiology, Christian-Albrechts-Universität zu Kiel, Germany
c
DFG Research Center and Cluster of Excellence for Regenerative Therapies, Technische Universität Dresden, Germany
d
Department of Orthopedics, Technische Universität Dresden, Germany

a r t i c l e i n f o a b s t r a c t

Article history: Zucker Diabetic Fatty (ZDF) rats represent an established model of type 2 diabetes mellitus (T2DM) and dis-
Received 27 February 2015 play several features of human diabetic bone disease, including impaired osteoblast function, decreased
Revised 27 May 2015 bone strength, and delayed bone healing. Here, we determined whether glycemic control by insulin treat-
Accepted 2 June 2015
ment prevents skeletal complications associated with diabetes. Subcritical femur defects were created in
Available online xxxx
diabetic (fa/fa) and non-diabetic (+/+) ZDF rats. Diabetic rats were treated once daily with long-lasting in-
Keywords:
Picke AK, et al. Bone. 2016;82:108-15
sulin glargin for 12 weeks for glycemic control. Insulin treatment successfully maintained serum levels of
Type 2 diabetes mellitus glycated hemoglobin, while untreated diabetic rats showed a 2-fold increase. Trabecular and cortical
y more effect. Additionally, these data could suggest that bolic effect on the endocortical bone compartment. In con
of osteoblasts on the bone surface was increased by insulin mittent administration of PTH only had bone anabolic eff
ut the T2DM-caused osteoblastic defect was still evident. trabecular but not on the cortical bone in T2DM ZDF rats [1

Volume ratio (BV/TV) μCT-based analysis of bone

defect filling after 12 weeks. Data represent the mean ±
SD (n = 8–10/group). Statistical analysis was performed
by one-way ANOVA: P* b 0.05 vs. non-diabetic control
(+/+); P# b 0.05 vs. untreated diabetic control (fa/fa).

nsulin on bone defect regeneration. Effects of insulin treatment on bone defect regeneration in diabetic rats. After fixation with a four-hole plate, subcritical f
Picke
enerated. Diabetic ZDF (fa/fa) rats were treated with insulin (up to 13 IU/d) for 12 weeks. (A) Representative AK, and
images et al.
(B)Bone. 2016;82:108-15
quantitative μCT-based analysis
ts of insulin
weeks. treatment
Data represent on bone
the mean ± SDdefect regeneration
(n = 8–10/group). in diabetic
Statistical rats.
analysis wasAfter fixation
performed with a four-hole
by one-way ANOVA: P* bplate, subcritical
0.05 vs. femoral
non-diabetic controldefec
(+/+
 Newcastle–Ottawa scale (NOS) of duplicates and title/abstract screening, the full-text doc-
were compared and a consensus
Acta Diabetologica ument of 23 studies was obtained and assessed. Thirteen
https://doi.org/10.1007/s00592-018-1120-4 studies matched the inclusion criteria, comprising 49,262
participants, including 3197 diagnosed with diabetes and/
REVIEW ARTICLE
ysis or metabolic syndrome with a diabetes component (Fig. 1).
Main reasons for study exclusion after full-text assessment
formed in Stata 14.2 (StataCorp, are shown in Appendix 1. Data for inclusion in meta-analy-
Fixed- Does diabetesmod-
and random-effects increase sis werethe risk
available of periodontitis?
only for six studies. A systematic review
obtain a combined relative risk Follow-up mean was approximately 4.8 years, ranging
and meta-regression
significant or considerable het-
analysis of longitudinal prospective
from 8 months to 20 years, and five studies presented follow-
studies
hi-square P value < 0.05) [22], 1
up shorter than 1
4 years [25–29]. Two 2,3,4
studies [30, 31] were 1 1
Gustavo G. Nascimento
was preferred since it considers · Fábio R. M. Leite  · Peter Vestergaard  · Flemming Scheutz  · Rodrigo López
thin-study variability. Estimates
were converted
Received: 8 into relative
January risk
2018 / Accepted: 12 February 2018
© Springer-Verlag Italia S.r.l., part of Springer Nature 2018
the absence of RR or OR meas-
ented the necessary data or the
Abstract
fter contact, RR estimates were
used Even
s were Aim though the
for analyzing crude association between diabetes and periodontitis is taken for granted, results on this association are
conflicting
ly the pooled modelwithin the literature. This systematic review assessed whether poorly controlled diabetes was associated with
of adjusted
periodontitis
ed. Studies with both onset or progression.
estimates
els. Methods Electronic searches were performed in PubMed, Scopus and Embase databases. Hand search was carried out
in the reference list of all articles included. Gray literature was investigated with a Google Scholar search. Prospective
ng subgroup analyses were per-
longitudinal studies on the association between diabetes and periodontitis were considered for this review. Studies should
ntial sources of between-study
have presented at least two measurements of periodontal conditions over time. Data on study design, crude and adjusted
he characteristics of the studies
estimates were collected. We used meta-analysis to estimate the pooled effect of hyperglycemia in people with diabetes on
y: socioeconomic status of the
periodontitis onset or progression. Meta-regression and subgroup analyses were employed to investigate potential sources
was conducted (high-income/
of heterogeneity between studies.
geographic
Resultslocation
Thirteen(Americas/
studiesAnálisis
matched 1the
Fig. de inclusion
Flowchart
49,262 criteria,
diagram
personasof comprising
studies
y 3,197 49,262
selection
con forindividuals, including
the systematic
diagnóstico de 3197 diagnosed with
diabetes.
mple size (< 500/≥ 500
diabetes. people);
Meta-analyses reviewestimates showed that diabetes increased the risk of incidence or progression of peri-
of adjusted
odontitis by 86% (RR 1.86 [95% CI 1.3–2.8]). However, there is scarce information on the association between diabetes and
periodontal destruction.
Nascimento GG. et al. Acta Diabetol. 2018. 1 Mar3 3. doi: 10.1007/s00592-018-1120-4.
Conclusions This study provides evidence that diabetes is associated with increased risk of periodontitis onset and progres-
 Acta Diabetologica

Fig. 2 Pooled effect of inadequately controlled diabetes mellitus on periodontitis. Data are presented as relative risk (RR) for each study (boxes),
95% CIs (horizontal lines) and summary as RR with 95% CI (diamond)
Riesgo de incidencia o progresión de periodontitis: 86% (RR 1.86 [IC 95% 1.3-2.8]).
cytokines, periodontal tissues healing is compromised [52]. vital structures, the cell membrane, and cause cell necrosis
At the same time, inadequately controlled diabetes mellitus or apoptosis in both connective and bone tissues [52, 53].
Nascimento
is known by the high formation of reactive oxygenGG. et al. Acta
species Diabetol.
This 2018. Mar phenotype
hyper-responsive 3. doi: 10.1007/s00592-018-1120-4.
of diabetic inflammatory
(ROS), even in unstimulated cells, which may directly injure cells can be reversed with pharmacological AGE receptor
3656 REVIEW

Table 3. Summary of the Different Type of Polymers Used in

Commonly Used Dressings

Natural Carboxymethylcellulose69–7

3656 REVIEW Bacterial cellulose44,72–74

Silk fibroin75–77
Pectin78,79
Table 3. Summary of the Different Type of Polymers Used80–82in
Carrageenan
Commonly Used Dressings
Synthetic Poly(ethylene oxide)80–83
Natural Poly(vinyl alcohol)84–87
Carboxymethylcellulose 69–71

Poly-L-lactic acid88–90
Bacterial 44,72–74
celluloseglycol)
Poly(ethylene 61,91,92
Silk fibroin 75–77
Polyurethane 60,93,94
Pectin 78,79
Bioactive Collagen95,96
80–82
Carrageenan 97,98
Gelatin 80–83
Synthetic Poly(ethylene oxide)53,54,99,100
Hyaluronic
Poly(vinyl acid
alcohol) 84–87
Chitosan 101–104
Poly- L-lactic acid88–90
Sodium alginate 105–108
Poly(ethylene glycol)61,91,92
Polyurethane60,93,94
Bioactive Collagen95,96
Gelatin97,98
materials in wound healing, the reader is referred to the recen
53,54,99,100
Hyaluronic acid
review article by Mogosanu et al.43Chitosan101–104
Sodium alginate105–108
Natural Inert Polymers
Figure 1. (a) Arterial ulcer at the cross malleolus of the leg with Natural polymers can be obtained from plant, bacterial, fun
sharp margins and a punched out appearance. (b) Venous stasis ulcer gal, or animal
materials sources
in wound and the
healing, arereader
commonly used because
is referred of thei
to the recent
with irregular border and shallow base. (c) Diabetic foot ulcer with biocompatibility
review article by Mogosanu et al. 43
and biodegradability. Bacterial cellulose is
surrounding callus, severe ulcer caused by diabetic neuropathy and pure natural exopolysaccharide produced by specific microbia
Natural Inert Polymers
bony deformity. (d) Pressure ulcer in a paraplegic (impairment of mo- genera. The good biocompatibility, hemocompatibility, mechan
tor or sensory function in the lower extremities) patient, causing full-
Figure 1. (a) Arterial ulcer at the cross malleolus of the legBOATENG
35 with permission with ical &strength,
Natural CATANZANO.
polymers canJbe
Pharm
microporosity,
obtainedSci from
and 104:3653–3680,
biodegradability 2015
make
plant, bacterial, fun-thi
thickness skin loss. Adapted from Fonder et al. from
sharp margins and a punched out appearance. (b) Venous stasis ulcer material
gal, or animal
one sources
of the and
mostaretrending
commonly used because
natural of their
polymeric mate
Elsevier Inc.
with irregular border and shallow base. (c) Diabetic foot ulcer with biocompatibility and biodegradability. Bacterial cellulose is a
44
NTO
divia
ivia elDE
ivia yy el LAS
ÚLCERAS DEL PIE DIABÉTICO Y OTRAS
Instituto
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cal for the extent of contraction in the x/y plane and expansion in the z axis. SEM images of the aerogels are

% Heri
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60
RÓNICAS DE INTERÉS PARA GARANTÍAS GES (AUGE).
shown in Fig. 5. The materials are composed of microsheets and microfibers presenting a smooth surface.

%
Ministerio de

40
40
Assays of measuring the porosity of the aerogels in a pycnometer failed, since the low volume displaced
Salud

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of the equipment.
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ra Vidal , Ignacio Moreno , Sandra20 Orellana

20 2, Felipe
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abrera1, Alfonso Sánchez3, Claudia López3, Isabel Aburto4, Marcos Ruminot5, Miguel Concha1.
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PARA EL
ología & Patología e 3Instituto de Cirugía, Facultad de Medicina; 2Instituto de Química, Facultad de
Gobierno de Chile

TRATAMIENTO DE LAS ÚLCERAS

Días
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PIE DIABÉTICO 4Y OTRAS
ón de Proyectos Institucionales. Universidad Austral Chile, Casilla 567, Valdivia, CHILE. Fundación
ABETIC FOOT ULCERS AND 
HERIDAS CRÓNICAS DE INTERÉS PARA GARANTÍAS GES (AUGE).
s, Rancagua 509, Providencia, Santiago, CHILE.
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en
Marcela Cabrera1, Ariana Cabrera1, Alfonso Sánchez3, Claudia López3, Isabel Aburto4, Marcos Ruminot5, Miguel Concha1.
ntroducción
1, Annesi Giacaman2, Alejandra  lado
lado contralateral
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efectuó operación
operación sham shamb2
sin
sin matriz
matriz (a(a corresponde
corresponde al al dí
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Figura 3. Estudio in vivo del heridas
cierreexcisionales. En a) yen
de la herida b) la herida se mediante
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modelo de y en el
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heridas excisionales. En a)b,ydía b)7.lac)herida
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Figura
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formulaciones del Concha
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diabético.
diabético.
(*) por a)
Adultos mayores
CHILE 2016
1996
2006

Fuente: PopulationPyramid.net
 CHILE Y SUS MAYORES
10 años de la encuesta Calidad de Vida en la Vejez
UC – Caja los andes

http://estudiosdevejez.uc.cl/images/documentos/Libro%20CHILE%20Y%20SUS%20MAYORES.pdf
 DOI: 10.4067/S0719-01072017000100009

LETTER TO THE EDITOR

Gerodontology: effects of ageing on the oral mucosa

César Rivera1, María Jesús Arenas-Márquez2
1. César Rivera. Department of Basic Biomedical Mr. Editor.
Sciences, Faculty of Health Sciences, University of
Talca (UTALCA), Talca, Chile. Ageing (biological) is characterized by a progressive loss of physiological integrity,
Email: contacto@cesarrivera.cl leading to functional changes and an increased vulnerability to death1. These progressive
changes can be observed in the oral mucosa. The aim of this letter - dedicated to geriatric
- Hipofunción de las glándulas salivales
2. María Jesús Arenas-Márquez. Gerontology
Program, Faculty of Medical Sciences, University dentistry and specialists in oral medicine- is to summarize the effects of aging in soft oral
of Campinas (UNICAMP), Campinas, São Paulo, tissues. The oral mucosa of elderly persons may not be distinguishable from that in young
Brazil. Email: arenasmarquez@gmail.com patients. Nevertheless, the continuing trauma (e.g., cheek biting), mucosal manifestations of
autoimmune skin diseases, habits (e.g., smoking) and hypofunction of the salivary glands can
Correspondencia a: arenasmarquez@gmail.com alter the appearance and character of the oral tissues in elderly persons2.
- Epitelio: crestas epiteliales menos prominentes, atrofia epitelial, reducción
Trabajo recibido el 20/10/2016. Aprobado para su In the epithelium, the major changes recorded are the presence of less prominent
epithelial ridges, epithelial atrophy and a reduction of the cellular density and mitotic activity3.
publicación el 08/02/2017
Along with this, there is a loss of elastin and adipose tissue in the submucosa and an increase
de la densidad celular y la actividad mitótica
in fibrous connective tissue with a degenerative change in the collagen. All this can result in
the slowing of tissue regeneration, which should be taken into consideration when installing
dental implants.
Normal ageing causes a loss of sense of taste due to changes in the membranes of the
gustatory cells, which alter the function of ionic canals and receptors4.
- Superficies mucosas orales lisas y delgadas, con una pérdida de
Clinically, the histological changes may be accompanied by dry thin smooth oral mucosal
surfaces, with a loss of elasticity and a characteristic stippling. These changes could
elasticidad y de tejido adiposo submucosa predispose the oral territories to trauma and infection, particularly when the patients are
using dental prosthesis or are afflicted by disturbances in salivary function (e.g., chronic
hyposialia)5. Ectopic sebaceous glands (Fordyce spots) in the lips and cheeks can also
increase with advancing age. Dorsum of the tongue shows a decrease in the filiform papillae,
which gives it a smooth and shiny appearance6. This appearance could be exacerbated by
the deficit of iron or B complex vitamins. The ventral zone of the tongue develops sublingual
- Pérdida del gusto, perdida de papilas gustativas y cambio en membrana
varicosities, which are considered variations from normal7.
Recently we carried out a systematic review of literature to identify major lesions of the
celular oral mucosa in older persons. The data received from thirteen countries showed that some
of the more relevant diagnosis in elderly persons are denture-related stomatitis, epulis
fissuratum, traumatic ulcers, irritation fibroma, recurring aphthous stomatitis, fissured tongue,
hemangioma, melanin pigmentations and oral lichen planus8.
The changes in the oral mucosa which occur frequently during the ageing process are
related to the subtle changes in the lining of the buccal structures. The knowledge of these
changes and to know what to look for in the mouth of the elderly persons is the first step
to guaranteeing oral health during the ageing process and providing good services in the
context of geriatric dentistry.

Rivera C & Arenas MJ Rev. Clin. Periodoncia Implantol. Rehabil. Oral Vol. 10(1); 09, 2017
ETHICAL DISCLOSURES
Protection of human and animal subjects. The authors declare that no experiments were
performed on humans or animals for this study.
 ORIGINAL ARTICLE Oral Health Impact Profile in elderly Chileans in southern Chile.

Matías Yobánolo-Hoffmann1. 387 AM (71.8±7.5

Abstract: Aim: Toaños; 53%
evaluate theMujeres)
impact ofportador de prótesis
oral health de of life
on the quality
Javiera Valentin-Hoyos1. ofCESFAM Valdivia,
elderly patients año
(EP) 2015
in the public health system of Valdivia, Chile in 2015.
Pedro Christian Aravena1,2. Methods: A descriptive study was conducted using the “Oral Health Impact
Profile Spanish version” (OHIP-14Sp), in a population of 387 EP (71.8±7.5
1. Bad breath.
2. Difficulty biting/chewing food.
3. Tooth sensitivity.
4. Toothache.
5. Unhappiness.
Item OHIP-14Sp

6. Appearance (unhappy with).

7. Difficulty biting/chewing food .
8. Difficulty to speak .
9. Trouble pronouncing words.
10. Being irritable with others.
11. Being less tolerant.
12. Problems at work.
13. Functional disability.
14. Totally unable to function.
0 25 50 75 100
Percentage of Elderly Adults (n=387)
Always Frequently Sometimes Almost never Never

Yobánolo-Hoffmann M, et al. J Oral Res 2015; 4(6): 365-370

Alopástico Xenoinjerto Aloinjerto Autoinjerto
 6 meses 11 años

DPBB: Desprotein Bovine Bone

Mordenfeld A, et al. Clin Oral Implants Res. 2010;21(9):961-70

injerto injerto

Mordenfeld A, et al. Clin Oral Implants Res. 2010;21(9):961-70

 tion.
es in theIPluselectrophoretic mobility of the
possibly some y-carboxyglutamic acidthree
residues compo-
and one hy- bone matrix gelatin by digestion with gelatinase, separated
DISCUSSION
with Mrs in the range
droxyproline of 17,000-18,000 Proc.
residue. were noted
Natl. be-USA
Acad. Sci. from Duethe to thedigest by packed
coprecipitation
bone matrix with calcium
structure, the phosphate
rela-
Vol. 81, pp. 371-375, January1984 densely
nd after mercaptoethanol reduction. Nevertheless,
Biochemistry (14), andsmall
tively proven to be
quantity a noncollagenous
compared protein in nature.
with other noncollagenous
ctivityThewas 18,000 ? 500
Mrdestroyed byputative BMP had a blocked
mercaptoethanol reduction. NH2-ter- However, proteins, and it was not untilto it
an inclination formwashydrophobic
quantitatively extracted
aggregates,
minus. ? 500 component was pres- BMP is difficult
matrixtoby isolate andof The first evidence
solventthat
ssay. When the Mr 18,500 Purification of
dif-
from
bovine bone
bone means purify.
a CaC12/urea mixture
of
mplantsferencesprotein
Reduction. No
fractions isolated significant
Mercaptoethanol by
measurable
hydroxyapatite and isolation
the was morphogenetic
hydrophobic
came when
possible low molecular protein
BMP was
weight byproteins were
released from
in the electrophoretic mobility of the three bone matrix gelatin by digestion with gelatinase, separated
compo- chromatography
atography induced bone formation in hydroxyapatite
the mouse
nents with Mrs in the range of 17,000-18,000 were noted be-
hind- solubilized
from the digest and disassociated from each other in 4 M
with calcium
by coprecipitation phosphate
r muscles (Fig. 3 Left and Right) and (cell
produced regen- Gdn-HCI
differentiation/osteogenesis/development) that BMP was isolated in for
fore and after mercaptoethanol reduction. Nevertheless, (14), and proven to be a noncollagenous protein inquantities
significant nature.
in trephine defects
BMP activity rat and by
wasindestroyed skulls
dogmercaptoethanol
M. R. (Fig.
URIST*, Im-
4).reduction.
Y. K. Huo*, detailed
A.However,
G. BROWNELL*, it wasW.
analysis (4,
not
M. 15).itThe
5,until
HOHL*, was combination
quantitatively
J. BUYSKE*, of procedures
extracted
A. LIETZE*, P. TEMPSTt,
Bioassay. When the Mr 18,500 ? 500 M.component
HUNKAPILLERt, was pres- J. from
AND R.reported DELANGEtbonehere demonstrate:
matrix by means of (i) three separate
a CaC12/urea solvent proteins with
mixture
ent, implants of protein fractions isolated byBone
hydroxyapatite andofofthe hydrophobic low
andmolecular weight
threeproteins wereof high-
bone formation
*UCLA
in the mouse hind- Mrs
ResearchLaboratory,Department 18,500,
Surgery 17,500,
and Division 17,000;
of Orthopedics (ii)
and Physiological proteins
Universityof California,
Chemistry, Los Angel
chromatography induced CA 90024; and tDepartment of Biology, solubilized
CaliforniaInstituteof and disassociated
Technology, Pasadena, CA 91125from each other in 4 M
and produced er Mr (34,000, 24,000, and 22,000); and (iii) one or more pro-
quarter muscles (Fig. 3 Left and Right)Communicated regen- Gdn-HCI
by C. H. Sawyer, September 26, 1983 that BMP was isolated in significant quantities for
eration inoftrephine
Purification defects
Bovine Bone dog skulls
in rat and Protein
Morphogenetic
teins
(Fig. 4). Im- Chromatography
by Hydroxyapatite
of lower Mr (14,000). One procedural
detailed analysis (4, 5, 15). The combination of procedures improvement
Author(s): M. R. Urist, Y. K. Huo, A. G. Brownell, W. M. Hohl,
ABSTRACT J. Buyske,
Bovine reported most
A. Lietze, P.protein
separates
bone morphogenetic of a Mr 34,000
demonstrate:
here (bBMP) protein,
(i) three
ble bone matrixseparate
osteonectin
proteins (16) (rep-
with describedpr
Tempst, M. Hunkapiller, R. J. DeLange gelatin (step 3) by previously
Source: Proceedings of the National Academy and
inducesdifferentiationof mesenchymal-type
of Sciences of the resenting
Mrs of about
cells into half
cartilage
18,500, 17,500, of the
and total
cedures
17,000; (10). three
noncollagenous
Ten
(ii) kilograms of of
proteins proteins),
high-
whole wet byproduc
bone
bone. bBMP hasUnited States
an apparent MrofofAmerica,
er Mr
virtue 18,500 ? 500
its solubility
of(34,000, and in
and =1.4
0.2% kg of freeze-dried
and
Triton X-100;
22,000); (iii) insoluble
one bone
BMP is pro-
or more matrix
insoluble T
gelatin.
Vol. 81, No. 2, [Part 1: Biological Sciences] (Jan. 15, 1984), pp. 371-375 24,000,
Published by: National Academy of Sciences
represents<0.001% of the wet weight of bone tissue.
teins of lower extrac-
A Mr
One procedural BMPwas extracted fromthe insolublebone matrixgelatin
34,000 protein resemblingosteonectinis separatedby Mr (14,000).
an inorganic/organic improvement
solvent mixtureof 0.5 M CaC12in 6
Stable URL: http://www.jstor.org/stable/22684 tion with TritonX-100. A Mr24,000separatesandmost
about of
halfa Mr
of 34,000 protein, osteonectin (16) (rep-N-ethylmaleim
protein urea at 28?C for 24 hr containing 10 mM
Accessed: 24/02/2009 08:33 a Mr22,000 proteinare disassociatedfrom bBMP
resenting about half of the(NEM)
by precipi- total noncollagenous
to protect BMP against
proteins), by degradativee
endogenous
tationin 1.5 M guanidinehydrochloride. virtue Aggregates of bBMP in 0.2%
of its solubility zymes. Triton X-100; BMP is insoluble
and a Mr 14,000 proteinare insolublein aqueousmedia; the The undissolved matrix and other substances were r
Your use of the JSTOR archive indicates your acceptance of JSTOR's Terms and Conditions of Use, available at
bBMPbecomessolublewhenthe Mr 14,000proteinis disasso- moved by filtration through cheesecloth. The supernat
http://www.jstor.org/page/info/about/policies/terms.jsp. JSTOR's Terms and Conditions of Use provides, in part, that unless
ciatedin 6 M urea and removedfrom the solutionby ultrafil- solution was decanted, dialyzed against 23 vol of deioniz
you have obtained prior permission, you may not download an entire issue of a journal or multiple copies of articles, and you
tration. Three separatemolecularspecies with apparentMrs water at 4?C, and allowed to stand overnight in the co
may use content in the JSTOR archive only for your personal, non-commercial use.
18,500, 17,500, and 17,000 are elutedat 0.10, 0.15, and 0.20 while a precipitateformed. The precipitatewas collected b
M phosphate ion concentrations, respectively, from a hy- centrifugation(Sorvall RC-5B refrigeratedsuperspeed)
Please contact the publisher regarding any further use of this work. Publisher contact information may be obtained at
droxy-apatite column. The Mr 18,500 protein has the amino 40,000 x g for 20 min, washed in cold deionized water, l
http://www.jstor.org/action/showPublisher?publisherCode=nas.
acid compositionof acidicpolypeptideand includesfour half- ophilized, and weighed (Table 1, step 4).
the is 4.9-5.1. The
pIthat appears on theMr 22,000component is
athe sameresidues;
Each copy of any part of a JSTOR transmission must contain cystine copyright notice screen or printed Sixty grams of the fraction obtained by step 4 (Table
3 page
(Left) Roentgenogram
of such transmission. of a deposit of bone (arrow)chromoprotein 3
resembling ferritin.The NH2-terminal amino was redissolved in the original0.5 M CaCl2/6 M urea sol
acid sequence of the Mr 17,500 protein simulates histone H2B.
after implantationof 5 mg of a Mr 18,500 +The 500 bovine BMP
Mr 17,000 protein may possess calmodulinactivity. Ag-
tion and dialyzed against 11 vol of 0.25 M citrate buffer(p
JSTOR is a not-for-profit organization founded in 1995 to build trustedin
P) (isolated FIG.by 3 hydroxyapatite
(Left) Roentgenogramchromatography)
of a deposit
gregates ofof a mouse
digital
bone
the archives for scholarship.FIG.
Mr (arrow)
18,500 and We work
3 otherproteins 5.induce
with the
Roentgenogram
formation of at
3.1)
lected
4?C.After 24 hr,of
large deposits
a grayish-white
at
bone (arrows)
x
precipitate
1
by centrifugation 40,000 g for hr. The preci
over- was co
scholarly community to preserve their work and the materialsof they rely upon, and to build a common research platform that
uscle. The
weeks contralateral
after implantationthighof 5 mg of
(control) a was
Mr +
implanted
18,500large 500
deposits with 5BMP
of bone;
bovine the Mr18,500
flowing the
protein
promotes the discovery and use of these resources. For more information about JSTOR, please contact support@jstor.org.
limbs
alone of the
is rapidly mouse
tate thigh
was in response
extensively washed,to an implant
defatted of two
in chloroform/me
absorbed
a crossand
ofother induces
section formationof small
mouse
in a of FIG. Noneof the seven
5. Roentgenogram
deposits.
of of large of 22,000
boneto(arrows)
ofevaporated over-and
5). one
ovine albumin. (Right)by
(bBMP) (isolated hydroxyapatitechromatography)
Photomicrograph proteins induces bone parts
formation. 18,500 protein, anol deposits
parts
(1:1), and Mr protein,
dryness (step
thighmuscle. The contralateral (control) was implanted
marrow. with 5 flowing the limbs of the mouse in
thigh aresponse
total to
of of an
the implant
3 mg, 21
fraction of two
obtained after
step 5 (T
posit shown on the Left. N, new thigh
bone; R, bone of a cross section of part of Mr14,000proteinweighing
of seven
Twenty-two
ble wasof
grams
redissolved
onlyin 4 M and daysby
one
mg of bovine albumin.and (Right)
azure II Photomicrograph the parts 18,500 protein, parts Mr 22,000 protein,guanidine hydrochlori
1)
hematoxylin/eosin stains.)
the deposit shown on the Left. N, new perivascular
Under
bone; R,
the influence
bone of bone
marrow. operation.
morphogenetic
part of Mrprotein
14,000 (BMP),
proteinweighinga total
(Gdn.HCl) andof
diluted
onlyto3 mg,
1.5 M days after
21Gdn-HCl by dialysis at 28
mesenchymal-type cells (pericytes) differenti- for 12 hr or until formation of a precipitate. The 1.5
(x100; hematoxylin/eosinand azure II stains.) ate into cartilageand woven bone. BMP the operation.
is an acidicpolypep- GdnHCl-solublefraction was dialyzed against water for 2
tide (1, 2) embedded in a complex assortmentof intra-and hr, until precipitation was complete. The water-insolu
extracellular protein aggregates derived from dentin (3), precipitatewas centrifuged,extensively washed in cold w
bone (4, 5), and osteosarcomatissues (6-9). We reporthere
on the purificationof BMP by means Urist MR, et al.Proc
of a combination of Natl Acad Sciand
ter, lyophilized,
Gdn-HCl-insoluble Uweighed
S A. 1984;81(2):371-5.
(step 6, Table 1). The 1.5
fractionwas centrifugedat 50,000 x g f
differentialprecipitation,ultrafiltration,and hydroxyapatite 1 hr, washed in cold water, lyophilized, and weighed (ste
chromatography. 7). The fractionobtained 7 was redissolved
B Bone

M Morphogenic

P-2 Protein type 2

Figura 7. Preparo do material, injetando agua destilada no frasco de
e
rhBMP-2 liofilizada, A propor~ao rhBMP-2 e liquido determinada pelo
fabricante, de acordo com 0 tamanho do kit de regenera~ao ossea que
sera utilizado, fundamental para que se obtenha a concentra~ao cor-
reta do material. Como ja foi dito, se houver uma concentra~ao menor
podera haver comprometimento da regenera~ao os sea, Figura 8. A adi~ao da rhBMP-2 na ACS e aguardam-se alguns minutos
para que haja a sua embebi~ao.

rh recombinant human

Figura 9. Apos a penetra~ao da rhBMP-2 na esponja, ela e

recortada
em varios peda~os para uma melhor adapta~ao ao espa~o que sera
Figura 10. Coloca~ao do enxerto de Bone Ceramic (Straumann, Sui~aJ
preenchido,
no seio maxilar direito e a ACS embebida em rhBMP-2 (Medtronics,
EUAJ abaixo do arcabou~o criado pela placa de titanio no pilar canino,
2 OSTEOGENIC CYTOKINES IN OSSEOUS REGENERATION AND REPAIR

FIGURE 4. A, Facial view of patient preoperatively. B, Radiograph showing m

surgical defect. E, Immediate postoperative radiograph. F, Exposure of the ridge a
Postoperative radiograph showing implants in place in a completely regenerated
Herford and Boyne. Osteogenic Cytokines in Osseous Regeneration and Rep

Herford & Boyne. J Oral Maxillofac Surg 66:616-624, 2008

 Fig. 1. Clinical photographs show sham-surgery control ø 4.0 ! 10 mm implants following
placement and wound closure, and healing at weeks 4 and 8. The implant platforms (cover
screws) can be visualized through the mucosa at weeks 4 and 8 when one implant becomes
exposed. Radiographs show limited new bone formation. The photomicrographs show limited
bone formation confined to the lingual aspect of the implants, whereas the buccal aspect
shows loss of crestal bone. Green arrows delineate the 5-mm notch placed level with the
resident alveolar bone.

Bone formation at rhBMP-2-coated implants 1003

placed into osteotomies prepared into

the reduced alveolar process when pla-
cement into extraction sites was not
possible. Five millimetres of the implant
was placed within the surgically reduced
alveolar ridge to the level of the refer-
ence notch, creating 5-mm, critical-size,
supra-alveolar, peri-implant defects. Six
animals received implants coated with
rhBMP-2 at 0.75 or 1.5 mg/ml in contra-
lateral jaw quadrants, and six animals
received implants coated with rhBMP-2
at 3.0 mg/ml or uncoated controls using
the same split-mouth design. Treatments
were randomized between left and right
jaw quadrants (Table 1). The periostea
of the mucogingival flaps were fene-
strated at the base of the flaps to allow
tension-free flap apposition and wound
closure. The flaps were advanced
3–4 mm coronal to the implants and
the flap margins adapted and sutured
(GORE-TEXt Suture CV5, W. L. Gore
Fig. 1. Clinical photographs show sham-surgery control ø 4.0 ! 10 mm implants followingFig.& 2. Associates Inc., Flagstaff,
Clinical photographs show øAZ, USA).
4.0 ! 10 mm implants coated with recombinant human
Photographic registrations were obtai-
placement and wound closure, and healing at weeks 4 and 8. The implant platforms (coverbone morphogenetic protein-2 (rhBMP-2) at 0.75 mg/ml following placement and wound
ned and
screws) can be visualized through the mucosa at weeks 4 and 8 when one implant becomesclosure, following
healing atimplant placement
weeks 4 and and platforms (cover screws) can be visualized
8. The implant
wound
exposed. Radiographs show limited new bone formation. The photomicrographs show limitedthrough closure.at weeks 4 and 8 when one implant becomes exposed. Radiographs show
the mucosa
bone formation confined to the lingual aspect of the implants, whereas the buccal aspectbone formation reachingfirst,
The maxillary the implant
secondplatform
and thirdat weeks 4 and 8. The photomicrographs show
shows loss of crestal bone. Green arrows delineate the 5-mm notch placed level with thebonepremolar
formationteeth
with were
an established cortex
surgically reaching or exceeding the implant platform. Green
extracted
resident alveolar bone. arrows
and the maxillary fourth premolarswith the resident alveolar bone.
delineate the 5-mm notch placed level
reduced
r 2008 in height and exposed pulpal
The Authors
tissues
Journal compilation 2008 s
sealed r(Cavit , ESPE,Munksgaard
Blackwell Seefeld/
Oberbayern, Germany) in order to
Wikesjö
alleviateUME et trauma
potential al ,J Clin
from Periodontol
the max- 2008; 35: 1001–1010
illary teeth to the experimental mandib-
(initiated after prosthesis insertion and lasting 24
months; Fig 1). The institutional review board at each
participating investigative center or the central insti-
tutional review board approved the study protocol.
SURGICAL PROCEDURE
The surgical procedure and postoperative medica-
tions were standardized across the participating cen-
ters. The lateral surface of the maxilla was to be
exposed by raising a mucoperiosteal flap by making
FIGURE 2. Clinical photographs of A, osteotomy site ready to receive augmentation material and B, rhBMP-2/ACS placed in maxillary
sinus.
Triplett et al. rhBMP-2/ACS Versus Bone Graft for Maxillary Sinus Floor Augmentation. J Oral Maxillofac Surg 2009.
with other bone grafting materials. A maximum of
two 7.5 ! 10-cm rhBMP-2-soaked sponges could be
used per sinus (24 mg rhBMP-2 maximum).
EFFICACY EVALUATION
Bone Induction
Bone induction was quantified by 3 independent
radiologists unaware of the treatment groups compar-
ing the CT scans 6 weeks before (baseline) and 6
months after graft implantation at the sites the dental
implants were to be placed. Bone height measure-
ments were taken from the level of the alveolar crest
to the floor of the maxillary sinus. A vertical line was
drawn from the alveolar crest to the floor of the
maxillary sinus parallel through the plane of the en- TriplettlinearRG, et al. Jformula.
FIGURE
dosseous dental1.implant
Study design schematic
site. The subject’sof bone
subject’s clinical
encoding the human BMP-2 sequence was cloned
using recombinant DNA techniques and expressed in
mammalian cells to yield large quantities of highly
purified rhBMP-2 at Wyeth Research (Cambridge,
MA).7 The carrier component, the ACS, is derived
from highly purified bovine tendon type-I collagen
and provided the matrix for the delivery of rhBMP-2,
in addition to serving as a space filler at the wound
site. The sinus antral was to be filled using approxi-
mately the same volume of material as routinely used
implants were placed) and in an adjacent area of
native bone. The dental implant location was identi-
fied from the CT scans taken after dental implant
placement. The density of the treatment area was
measured by identifying 2 rectangular areas of interest
(AOIs), which excluded cortical bone. The native
bone density was measured by identifying 2 AOI
boxes within the adjacent native bone, also excluding
cortical bone. All AOIs were at least 2 mm away from
the dental implant. Three densities of the standard
density block were measured from 3 axial slices at the
same level as the AOI and recorded in Hounsfield
units. The values were converted from Hounsfield
units to milligrams per cubic centimeters using a
regression Oral Maxillofac
The densitySurg
of the67:1947-1960,
newly 2009
inducedcourse from
bone was baseline
assessed to 24 to 36
by evaluation months.
of the mean
 Those in the rhBMP-2/ACS treatment group had a influx of fluid and cells into the treatment area relate
significantly greater amount of facial edema than to the chemotaxis and neovascularization at the site
those in the bone graft treatment group (P ! .048). Other than facial edema, none of the events reporte

FIGURE 6. Newly induced bone density. At 6 months postoperatively, mean bone density of bone graft group was significantly greater tha
that in rhBMP-2/ACS group (P " .0001). At 6 months after dental implant placement, bone density in rhBMP-2/ACS group was significant
greater than in bone graft group (P " .0001).
Triplett et al. rhBMP-2/ACS Versus Bone Graft for Maxillary Sinus Floor Augmentation. J Oral Maxillofac Surg 2009.
Triplett RG, et al. J Oral Maxillofac Surg 67:1947-1960, 2009
 Discussion
This pivotal trial was designed to compare rhB
2/ACS with bone graft treatment for use in maxil
sinus floor augmentation. Previous studies us
rhBMP-2/ACS have shown the feasibility of usin
and helped establish the appropriate dose concen
tion of 1.5 mg/mL to produce a satisfactory quan
and quality of bone augmentation. The purpose of
procedure was to grow or transplant an adequ
quality and quantity of bone to support functio
dental implant borne restoration for 6 months, w
follow-up after the loading date to 24 months
functional loading. The advantage of using rhBM
ACS is that it avoids harvesting autogenous bone
the associated morbidity, cost, and increased surg
time.
The bone formation in the 2 groups was excell
All patients grew bone in both treatment grou
except for 1 patient in the rhBMP-2/ACS treatm
group. Both groups were well matched, with no
nificant
FIGURE differences
7. Representative between
histologic findings the
from2subjects
groups in base
treated
with bone
bone graft or 1.50The
height. mg/mL rhBMP-2/ACS.
6-month Few marked differ-
postoperative mean b
ences were found in histologic parameters evaluated for rhBMP-2/
ACSheight
and bonefor the specimens,
grafted bone graft withgroup was
trabecular 14.98
bone mm
forming in and
eachthe
group consisting primarily
rhBMP-2/ACS of lamellar
group wasbone with small
13.27 mm, amount
both m
of woven bone (Goldner’s trichrome stain, magnification 1!).
than enough bone to place dental implants. This
Triplett et al. rhBMP-2/ACS Versus Bone Graft for Maxillary Sinus
FIGURE 7. Representative histologic findings from subjects treated Floorlows a clinician
Augmentation. to Maxillofac
J Oral restore the Surgpatient’s
2009. dentition w
with bone graft or 1.50 mg/mL rhBMP-2/ACS. Few marked differ- a variety of implant lengths. The patients were
Triplett RG,
ences were found in histologic parameters evaluated for rhBMP-2/ et al. JtoOral
quired haveMaxillofac
at least Surg
1 site67:1947-1960,
with less 20096 mm
than
ACS and bone grafted specimens, with trabecular bone forming in
 Xenoinjerto Aloinjerto Autologo
Biológico

Alloderm®,
Puros dermis®

Bioguide®
MucoGraft®
Molecular
Biomateriales

Dynamatrix®
Emdogain®
Celular

PRF

Duran YJC et al. Rev. Clin. Periodoncia Implantol. Rehabil. Oral Vol. 5(3); 144-151, 2012.
WBCs. Conversely, the fibrin clot captures blood cells, especially platelets and WB

Figure 7. Scheme of migration of major blood components during centrifu

essentially depending on their size. However, if aggregated, platelets would sp

To release possibly contaminating platelets and WBCs and determine their co

to the upper surface by buoyant force. These reactions are synchronized to form

2017;5(1).cou
into the RBC fractions, as demonstrated in previous studies [14,15]. WBCs and

Watanabe
we did mince the red thrombus using scissors; T, et al.the
however, J (Basel). platelet
resulting
Dent
O
Letters to the Editor Octob
Choukroun’s PRF is a solid biomaterial (A) with a specific 3-dimensional architecture and cell distribution. The ma
material is acellular and built with thick fibrin strands (B, hemalaun-eosin, magnification !52), and leukocytes and
gates are concentrated in some areas (C, hemalaun-eosin, magnification !52). PRF can be used as a clot (A,
nsed cylinder (A, middle), or a dense membrane (A, bottom). Gassling et al. claimed to have introduced 1.5mL
each 1mL culture well. What means ""1.5mL## of PRF? How Gassling et al. were able to introduce 1.5mL of
bulk into a 1mL culture well where cultivated cells were supposed to live?
 Platelet-rich fibrin (PRF): A second-generation platelet concentrate.
Part V: Histologic evaluations of PRF effects on bone allograft
maturation in sinus lift
Joseph Choukroun, MD,a Antoine Diss, DDS, MS,b Alain Simonpieri, DDS,c Marie-Odile Girard, DDS,c
Christian Schoeffler, DDS,c Steve L. Dohan,d Anthony J. J. Dohan,e Jaafar Mouhyi, DDS, PhD,f and
David M. Dohan, DDS, MS,g Nice and Paris, France, Los Angeles, Calif, and Göteborg, Sweden
NICE UNIVERSITY, UNIVERSITY OF PARIS V, UNIVERSITY OF PARIS VI, UNIVERSITY OF SOUTHERN
Fig. 1. Preliminary analyses highlight mineralized trabecular bone rich in osteocytes which appear green (A and B) or blue (C and
CALIFORNIA, AND GÖTEBORG UNIVERSITY
D) according to the staining. Osteoı̈d borders are stained in red (B and D) and are in contact with dense cellular osteoblast fronts.
The richness of osteoı̈d
Objective. tissue
Platelet-rich is evidence
fibrin of important
(PRF) belongs turnover inof both
to a new generation types
platelet of sampleswith
concentrates, (test and control).
simplified processing and without
biochemical blood handling. The use of platelet gel to improve bone regeneration is a recent technique in implantology.
However, the biologic properties and real effects of such products remain controversial. In this article, we therefore attempt to
evaluate the potential of PRF in combination with freeze-dried bone allograft (FDBA) (Phœnix; TBF, France) to enhance bone
regeneration in sinus floor elevation.
Study design. Nine sinus floor augmentations were performed. In 6 sites, PRF was added to FDBA particles (test group), and in
3 sites FDBA without PRF was used (control group). Four months later for the test group and 8 months later for the control group,
bone specimens were harvested from the augmented region during the implant insertion procedure. These specimens were
treated for histologic analysis.
Results. Histologic evaluations reveal the presence of residual bone surrounded by newly formed bone and connective tissue.
After 4 months of healing time, histologic maturation of the test group appears to be identical to that of the control group after a
period of 8 months. Moreover, the quantities of newly formed bone were equivalent between the 2 protocols.
Conclusions. Sinus floor augmentation with FDBA and PRF leads to a reduction of healing time prior to implant placement.
From a histologic point of view, this healing time could be reduced to 4 months, but large-scale studies are still necessary to
Fig. validate
2. Meanthesehistomorphometric
first results. analysis of bone samples Fig. 3. Mean histomorphometric analysis of bone samples
from(Oral
3 sinus floor
Surg Oralaugmentations after
Med Oral Pathol a healing
Oral period2006;101:299-303)
Radiol Endod of 8 from 6 sinus floor augmentation after a healing period of
months (control group: FDBA alone). 4 months (test group: FDBA1PRF).

Elevation of the sinus floor to increase the alveolar bone

transplanted bone to be integrated and substituted by os-
histomorphometric evaluations were performed by 3
needed to place implants is considered to be a highly
Nevertheless, trabecular bone areas are less massive,
teoconduction (creeping substitution). Alternatively,
different laboratories.
predictable and effective treatment option.1-3 Many more spaced
autogenous boneandtransplants
surrounded canby
beadipose
replacedtissue.
by boneThese
observations especially
Choukroun
techniques have been described J et al. Oral
to achieve Surg Oral
vertical Med Oraleg,Pathol
substitutes, Oral6concern
freeze-driedRadiol apical parts
Endod
bone allograft of thetosam-
2006;101:299-303
(FDBA),
RESULTS
augmentation of the maxillary sinus mucosa. When con- ples. donor
avoid This phenomenon
site morbidity. isMaturation
explainable by the
of these difficulty
materials
 1177

sites prepared. B, Rabbit cranium with surgical sites grafted.

FIGURE 5. Histologic evaluation of all grafted materials at 1, 2, and 4 months. Magnification, #4.
Aghaloo T et al. J Oral Maxillofac Surg 60:1176-1181, 2002
 A B C D

Effect of L-PRF in Bone Regeneration 5

1 semana
A B C D

Effect of L-PRF in Bone Regeneration 3

E F G H
A B C

6 Clinical Implant Dentistry and Related Research, Volume *, Number *, 2013

E F G H
5 semanas
A B C D

D E
Figure 3 The same scale was used for A, B, C, D and E, F, G, H, respectively. SEM pictures at the 5-week time point:
(A) empty hemisphere, the white arrow shows the bone growing against the wall; (B) L-PRF hemisphere; (C) BHA hemisphere;
(D) BHA + L-PRF hemisphere. Methylene blue/basic fushine pictures: (E) empty hemisphere, the white arrow indicates a massive
F blood clot; (F) L-PRF hemisphere; (G) BHA hemisphere, the white arrow indicates the titan wall; (H) BHA + L-PRF hemisphere,
the white arrow indicates the titan wall. BHA = bovine hydroxyapatite; L-PRF = leukocyte- and platelet-rich fibrin; SEM = scanning
electron microscopy.

Figure 2 The same scale was used for A, B, C, D and E, F, G, H, respectively. SEM pictures at 1 week of: (A) empty hemisphere;
(B) L-PRF hemisphere; (C) BHA hemisphere; (D) BHA + L-PRF hemisphere. Methylene blue/basic fushine pictures: (E) empty
hemisphere, the black arrow indicates the groove of the osteotomy; (F) L-PRF hemisphere, the black arrows indicate the split
between L-PRF and the connective tissues; (G) BHA hemisphere, black arrow showing red blood cells; (H) BHA + L-PRF
E
12 semanas
hemisphere, F
the black arrow indicates
SEM = scanning electron microscopy.
G
the L-PRF. BHA = bovine hydroxyapatite; L-PRF = leukocyte- andHplatelet-rich fibrin;

A B C D

amount
Figure 1 (A) L-PRF preparation, the red cell clot is removed; (B) the partial osteotomies; (C) of inmineralized
L-PRF placed the hemisphere; bone.The amount of BHA guided bone regeneration in a standardized model alone
(D) the hemispheres inserted in the partial osteotomies; (E) periosteal closure; (F) wound closure. L-PRF = leukocyte- and
platelet-rich fibrin. particles was not significantly different from 1 week or in combination with BHA. The main studied para-
to 12 weeks, remaining approximately 30%. After apply- meter was the bone quantity.
ing two-way ANOVA to the bone quantity data with The results displayed the presence of adequate
s.c., 12 hourly). Rabbits received premedication with i.v. 200 mg/kg after premedication with thalamonal
thalamonal (fentanyl/droperidol) i.m. 0.22 mL/kg. time
(fentanyl/droperidol) i.m.and
0.22conditions,
mL/kg. Samples no were
significant interaction effects osteogenesis in the four groups and no significant dif-
Anesthesia was induced by medetomidine (Domitor, collected and soakedbetween
Figure the
3 The
in fixative (10%two
same were found
scale was
formol). for=A,
used(p .7050).
B, C, DThe
and different ference SEM
E, F, G, H, respectively. was observed
pictures atat
theany timepoint
5-week in terms of regen-
time point:
Orion Corporation, Espoo, Finland) i.m. 0.25 mg/kg (A) empty hemisphere, the white arrow shows
conditions had no relevant effect on the quantity of the bone growing against the wall; (B) L-PRF hemisphere; (C)
erated bone quantity (p = .3623). These resultsBHA hemisphere;
might be
Histological Analyses(D)
E BHA + L-PRF hemisphere. Methylene
F blue/basic fushine pictures:
G (E) empty hemisphere, the whiteHarrow indicates a massive
and a second injection of ketamine (Imalgène, Virbac, bone
blood(p = .3623;
clot; (F) L-PRF Figure 5), while
hemisphere; (G)the time
BHA effect wasthe
hemisphere, sig- surprising
white arrow according
indicates the titan to the(H)
wall; multiple in vitro
BHA + L-PRF studies that
hemisphere,
Carros, France) i.m. 25 mg/kg. Surgical interventions The samples were treated for nondecalcified histology BHA = bovine
the white(p
nificant < .0001)
arrow indicates the titan
(Table wall.two-way
1). The ANOVA hydroxyapatite;
was show an =increase
L-PRF leukocyte- in and platelet-rich
osteoblast = scanning
fibrin; SEMdifferentia-
proliferation,
were performed under strict sterile conditions. The sur- using polymethacrylate (PMMA)
electron resin. Dehydration
microscopy.
also usedconcentrations
to analyze the quantity of bone hydroxyapatite tion, and protein production22–25 when cultured in pres-
gical area was shaved and disinfected with iodine. A
median cutaneous incision was performed on the cal- for 24 hours (1 × 70°,
Knapen M, et al. Clin Implant Dent Relat Res. 2015;17 Suppl 1:e143-52 2002
was performed in ascending
loaded in the
1 × 80°, BHA3 ×and
2 × 95°,
of ethanol
100°) and + LPRF groups. The time
BHA ence of L-PRF. However, in an in vivo model, the lack
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