Growth & development general concepts/endodontic courses

GENERAL CONCEPTS
www.indiandentalacademy.com

INTRODUCTION
 “GROWTH WAS CONCEIVED BY AN
ANATOMIST,BORN TO A
BIOLOGIST,DELIVERED BY A
PHYSICIAN,LEFT ON A CHEMIST’S
DOORSTEP,& ADOPTED BY A
PHYSIOLOGIST.AT AN EARLY AGE SHE
ELOPED WITH A STATISTICIAN,DIVORCED
HIM FOR A PSYCHOLOGIST AND IS NOW
BEING WOOED, ALTERNATELY &
CONCURRENTLY, BY AN
ENDOCRINOLOGIST, A PEDIATRICIAN, A
PHYSICAL ANTHROPOLOGIST, AN
EDUCATIONALIST, AN ORTHODONTIST, A
EUGENIST AND THE CHILDREN’S

CONTENTS
 Importance of Growth to orthodontists
 Growth & dvevlopment a comparisons
 Definitions of growth& development
 Factors affecting growth & development.
 Nature of skeletal growth.
 Bone formation
 Growth centers vs growth sites.
 Growth process: basic concepts
 Sites and types of growth in craniofacial complex.
 Theories of growth.
 Methods of studying growth.
 Growth: Pattern,Variability,Timing
 Growth rhythm.

IMPORTANCE OF GROWTH TO ORTHODONTISTS
As orthodontists we are interested in
understanding:
 how the face changes from its embryologic form
through childhood,adolescence & adulthood.?
 how and where growth occurs?
 how much growth is remaining and in which
direction and when will the gowth express
itself,what roles the genetic & environmental
factors play in influencing facial growth ?
 how we can influence these factors with our
treatment to achieve the optimal results in the
potential of each individual.?

GROWTH & DEVELOPMENT A COMPARISON
(PROFFIT PG27,MOYER’S PG8-9)
 Growth & development though closely related are not
synonymous. Growth is largely an anatomic
phenomenon, whereas development is physiologic and
behavioral.
 Growth usually refers to an increase in size or
number.(occasionally,however,the increase will be
neither in size or number,but in complexity).
 Growth is the result of biologic processes by means of
which living matter normally gets larger.
 It is quantitative aspect of biologic development and is
measured in units of increase per units of time,for
instance,inches per year or grams per day.
 It is change in quantity.
 It may result in increase or decrease in size(thymus
gland after puberty),change in form and proportion.

 Development is used to refer to an increase in
complexity.
 Development carries an overtone of increasing
specialization.
 It is unidirectional.
 ’Multifunctional unit’ emphasizes the elaboration
of multiple functions rather than multiple
cellularity.
 DEVELOPMENT = GROWTH +
DIFFERENTIATION + TRANSLOCATION

DEFINITIONS:

GROWTH
 “Self multiplication of living systems” (J.S.Huxley)
 “Increase in size, change in proportion and
progressive complexity” (Krogman)
 “An increase in size” (todd)
 “Entire series of sequential anatomic and physiologic
changes taking place from the beginning of prenatal
life to senility” (Meridith)
 “Quantitative aspect of biologic development per unit
of time” (Moyers)
 “Change in any morphological parameter which is
measurable” (Moss)

DEVELOPMENT
 “Progress towards maturity” Todd
 “Development refers to all the naturally
occurring unidirectional changes in the life of
an individual from its existence as a single
cell to its elaboration as a multifunctional unit
terminating in death.It encompasses the
normal sequential events between
fertilization and death” Moyers

DIFFERENTIATION
 Differentiation is the change from generalized
cells or tissues to more specialized kinds
during development.Development is change
in quality or kind.

TRANSLOCATION
 Translocation is change in position. The chin
point is translocated(moved) downward &
forward far more than any growth at the chin
itself. Indeed ,most of the growth is taking
place at the condyle & ramus while the entire
mandible is translocated ventrally (Moyers)

MATURATION
 Qualitative changes which occur with
ripening or aging. (Moyers)

FACTORS/VARIABLES AFFECTING/INFLUENCING
GROWTH AND DEVELOPMENT

A)HEREDITY(PROFFIT PG39-40)
 Genetic studies of physical growth makes use of twin &
family data. About two-thirds of the 25000 human
genes play a role in craniofacial development.
 There is GENETIC CONTROL of the size of parts to a
great extent, of the rate of growth, & of the onset of
growth events , for ex:- dental calcification, eruption of
teeth, ossification of bones, & start of adolescent
growth spurt.
 Genes play a major role in the overall growth of a
person.
 The actual outcome of growth depends on the
interaction between the genetic potential &
environmental influences.
 The hand-wrist ,dental,sexual,& other biologic ages of
identical twins are similar,whereas maturity indicators

Y CHROMOSOME’S DELAYING EFFECT ON
GROWTH. (BISHARA PG39)
 The marked advancement of girls over boys
in the rate of maturation is attributed to the
delaying action of Y CHROMOSOME in
males. By delaying growth, the Y
CHROMOSOME allows males to grow over
a longer period of time than females,
therefore making possible greater overall
growth.

MOLECULAR GENETICS
 Rapid advances in MOLECULAR GENETICS
are providing new information about growth &
its control. For ex:- the importance of
HOMEBOX GENES in the establishment of
body plan, pattern formation & morphogenesis
is well recognized. Whole family of
TRANSFORMING GROWTH FACTOR BETA
GENES now is known to be important in
regulating cell growth & organ development.

 There are a no. of genes determining
mandibular size.
 Genetic alterations in muscle development &
function translate into changes in the forces
on areas of bone where muscles attach,and
this leads to modification of skeletal areas
like the coronoid process & gonial angle area
of the mandible.

 An exciting prospect is the better understanding
of how patients with orthodontic problems that
are known to have a genetic component(classIII
malocclusion being the best example) will
respond to treatment.
 It is clear that there are multiple subtypes of
CLASS III, & a necessary first step is better
characterization of these phenotypes.(by
establishing distinct phenotypic markers,distinct
clinical characteristics).

 Genes at each level pass instructions down
the chain(control of hierarchy).
 After maternal genes have established an
anterior/posterior gradient in the embryo,
different types of embryonic genes are
activated in sequence, each reacting to the
activity of the level above(&probably other
levels)& specifying in increasing detail how
the cells within it’s domain should develop.
(Beardsley,enlow pg254)

 It is highly unlikely that any component of the
facial skeleton is inherited in the Mendelian
fashion.
 Rather,the evidence strongly supports
POLYGENIC INHERITANCE, greatly limiting
our ability to explain facial dimensions from the
study of parents.
 Even if the size of facial bones were inherited in
a Mendelian fashion, that inherited pattern is
altered by environmental influences , some
epigenetic & some general, to such an extent
that in the patient the underlying genetic
features can not be easily detected.(moyers
MENDELIAN VS POLYGENIC INHERITANCE

 There are local feedback & intercommunication
mechanisms between individual cells & tissues that
continue throughout the life of an organism.
 Three subdivisions. A) There are molecules that control
adhesion of specific cells to other cells (cell adhesion
molecules CAMs) & molecules that control adhesion of
specific cells to substrate (substrate adhesion molecules
SAMs). These adhesion controlling molecules are thought to
permit regulation of cell division, mobility &
shape(according to SLAVKIN 1988).
 B) There are general “humoral” chemicals synthesized by a
cell to regulate its own activity (Autocrine) & chemicals
secreted by cells to regulate the activity of adjacent cells
(Paracrine).
 C) Under local mechanisms,is the gap junction that allows
direct intercellular communication through which electric
signals & small molecules pass from one cell to
another.(enlow pg253-254)
LOCAL FEEDBACK & INTERCOMMUNICATION
MECHANISMS

FUTURE TRENDS
 It is likely that in future genetic screening of
blood or other tissue samples will be used to
identify patients with orthodontic problems
who are likely to respond well or poorly to
specific treatment modalities.

B) NEURAL CONTROL: (BISHARAPG40)
A growth center exists in the region of the
HYPOTHALAMUS, which keeps children on their
genetically determined growth growth curves.
Hypothalamus is situated above pituitary gland,& is thought
that the hypothalamus sends messages to the pituitary
gland through an elaborate feedback mechanism.
Peripheral nervous system plays a part in growth control.
Peripheral nerve fibres exert a nutritive or trophic effect on
the structures they innervate

C) HORMONAL CONTROL:(BISHARA PG40)
 Probably all the endocrine glands influence
growth.
 Timing & sequence of maturation is under
hormonal control.
 From birth to adolescent spurt : bone and
dental growth are under thyroid control.
 At adolescence, bone falls under increasing
influence of gonadal hormones.

GROWTH HORMONE(SOMATOTROPIN):
 Produced by the anterior lobe of pituitary &
the peak of daily secretion is in the early
stages of sleep.
 It is essential to growth from birth onwards.
 It is necessary for proliferation of cartilage
thus it has a great effect on bone growth &
consequently height growth.
 Its growth functions become ineffective when
the epiphyses close.
 Excess – Gigantism : Deficiency –
Dwarfism.

THYROTROPHIC HORMONE
 Secreted from anterior lobe of pituitary
 Affects growth by stimulating the thyroid
gland to secrete its hormones.
 Hormones of thyroid gland THYROXINE &
TRIIODOTHYRONINE, both stimulate
general metabolism and are important in
growth of bones, teeth, brain.
 Thyroid secretions decreases from birth to
adolescence & then increases for the
duration of adolescent growth spurt.

ANDROGENS & GONADAL HORMONES
 Major role during adolescent growth in both
the sexes.
 Androgens produced by supra-renal cortex
which is controlled by ACTH (produced by
pituitary gland).
 No change in ACTH during adolescence, so
inhibiting mechanism to androgen production
removed at adolescence to permit secretion
of androgens.

GONADOTROPHIC HORMONE
 Secreted from pituitary gland
 Stimulates production of testosterone in
males and progesterone in females.
 Testosterone & Adrenal Androgens both
stimulate growth of muscles,bone,blood red
cells & secondary sex characters in males.
 In females ovarian secretions have less
general effect on growth and Androgens
mainly responsible for growth at
adolescence.

PARATHYROID SECRETIONS: PARATHORMONE &
CALCITONIN
 Control the amount of calcium in blood & its
interchange with calcium in bone. They are
mutually antagonistic. Affect bone growth.

NUTRITION
 MALNUTRITION may affect size of parts, body
proportions, quality & texture of tissues & onset
of growth events. It includes deficiency in
calories & required food elements. It
accentuates the normal differential growth of the
body tissues.
 STARVATION alters the composition of the
body. Protein not accumulated but gets
consumed, so that cell mass of body is reduced.
Fat is consumed & depleted. Extracellular body
fluid increased.
 BALANCED DIET includes an adequate supply

 AMINO ACIDS: Nine amino acids are essential for
growth. Absence of any one results in disordered
growth.
 CALCIUM,PHOSPHORUS,MAGNESIUM,MANGANE
SE,FLUORIDES: Essential for proper bone & tooth
growth.
 IRON: Hemoglobin production
 VITAMIN A: Controls activity of both osteoblasts &
osteoclasts. Deficiency may cause defects in bone
growth.
 VITAMIN B2: Considerable influence on growth.
 VITAMIN C: For proper bone & connective tissue
growth.

E) SECULAR TREND
 Children today are growing faster than they
grew in the past.
 The trend is probably result of both more
food & better balanced diets.
 Although children are growing at a faster
rate, they are also stopping growth sooner.
Ex. Earlier in 20th century men reached their
final height at 25 years of age, now final
height is reached at about 20 years of age.
 Adolescent spurt is earlier now.

F) SEASON & CIRCADIAN RHYTHM
 GROWTH IN HEIGHT: faster in spring than
in autumn.
 GROWTH IN WEIGHT: faster in autumn than
in spring.
 GROWTH IN HEIGHT & ERUPTION OF
TEETH: greater in night than in daytime.
 Reason attributed to fluctuations in hormone
release.

G)DISEASE
 Effects of disease are similar to those of
malnutrition.
 Catch-up growth: after an illness, catch-up
growth period brings child back to
predetermined growth curve.Females
compensate better than males following illness.
 Diseases that slow growth probably reduce
production of growth hormone (as a result of
increased production of cortisone during
disease.).

H) PSYCHOLOGICAL FACTORS: (BISHARA PG42)
 Psychological factors have various effects on
growth.
 Children in an orphanage governed by a
harsh headmistress grew less in height &
weight than the children in other orphanage.

J) RACE
 Race does play a role in growth process. Ex.
In American blacks, calcification & eruption of
teeth occurs almost an year earlier than their
white counterparts.

K) NATURAL & DISRUPTIVE FACTORS(MOYERS PG51-53)
 i) NATURAL FACTORS: Genetics, Normal
function, General body growth,
Neurotropism
 ii) DISRUPTIVE FACTORS: Are those which
do not routinely contribute to normal variation
but when they appear in the individual may
be important.They may be
elective,environmental or congenital in origin.
Ex: Orthodontic force surgery,malnutrition,
Malfunction,gross cranio - facial deformities.

FUNCTION
 Normal function plays a role in skeletal
growth, for its absence, as in tmj
ankylosis,results in gross distortion of bony
morphology.
 The role of function as the primary factor in
control of craniofacial growth is the essence
of MOSS’ “FUNCTIONAL MATRIX
HYPOTHESIS”.

MALFUNCTION
 Function helps determine morphology during
normal growth & that altered function can
produce altered morphology.
 Role of naso-respiratory malfunction (mouth
breathing) may be an example.
 Malfunction causes compensatory abnormal
growth.

NATURE OF SKELETAL GROWTH: (PROFFIT PG40-43)

 At cellular level there are only 3 possibilities
of growth. (all these occur in skeletal growth)
 A: HYPERTROPHY: Increase in SIZE of
individual cells
 B: HYPERPLASIA: Increase in NUMBER of
cells.
 C: SECRETION OF EXTRACELLULAR
MATRIX: Thus contributing in size
independent of the number or size of cells
themselves.

 Hyperplasia is a prominent feature (more imp
than hypertrophy) of all forms of growth.
 Distinction between growth of the soft or
nonmineralised tissues of the body & the hard
or calcified tissues of the skeleton: the
extracellular matrix of the skeleton becomes
mineralized.
 Hard tissues: bones, teeth & sometimes
cartilage
 Cartilage , particulary the cartilage significantly
involved in the growth,behaves like soft tissue

GROWTH OF SOFT TISSUES:
 It occurs by a combination of hyperplasia &
hypertrophy, & occurs at all points within the
tissue (INTERSTITIAL GROWTH).
 Secretion of extracellular material can also
accompany interstitial growth.
 Interstitial growth is a characteristic of nearly
all soft tissues & of uncalcified cartilage
within the skeletal system.

GROWTH OF HARD TISSUES
 When mineralization takes place so that hard
tissue is formed, interstitial growth becomes
impossible.
 Hyperplasia, hypertrophy & secretion of
extracellular matrix all are still possible, but in
mineralized tissues , these processes can occur
only on the surface, not within the mineralized
mass.
 DIRECT OR SURFACE APPOSITION OF BONE
(direct addition of new bone) to the surface of
existing bone can & do occur through the activity
of the cells in the Periosteum(soft tissue

New cells formed in Periosteum
ECM secreted
It Mineralizes
New Bone formed

 A major portion of skeletal system is
originally modeled in CARTILAGE ,this
includes basal part of skull as well as the
trunk & limbs.

DEVELOPMENT & MATURATION OF CHONDRO-CRANIUM
AT 8 WEEKS OF IUL solid bar of cartilage extends fom nasal
capsule anteriorly to the occipital area posteriorly.

SKELETAL DEVELOPMENT AT 12 WEEKS IUL
Ossification centres have appeared in the midline cartilage structures & in
addition, intramembranous bone formation of the jaws & brain case has
begun.

At 4th month of IUL:
 In-Growth of blood vascular elements into into
various points of the chondrocranium.
 These areas become centers of ossification, at
which cartilage is transformed into bone & later island
of bone appears in sea of surrounding cartilage.
 The cartilage continues to grow rapidly but is
replaced by bone with equal rapidity. Eventually old
chondrocranium is represented only by small areas of
cartilage (SYNCHONDROSES) interposed between
large sections of bone.

LONG BONES OF EXTREMETIES:
EPIPHYSIS
DIAPHYSI
S
Areas of ossification appear in the center of the bones &
at the ends , ultimately producing DIAPHYSIS ( a central
shaft) & Epiphysis ( a bony cap on each end).

 EPIPHYSEAL PLATE: between the
epiphysis & diaphysis is a remaining area of
uncalcified cartilage.
 It is major GROWTH CENTER of long bones
responsible for almost all growth in length.

 As long as the rate at which cartilage cells
proliferate is equal to or greater than the rate at
which they mature , growth will continue.
 When the rate of maturation exceeds the rate
of proliferation(Toward the end of normal
growth period), the last of the cartilage is
replaced by bone & epiphyseal plate
disappears.
 At that point , the growth of the bone is
complete , except for the surface change in
thickness, which can be produced by the

DEVELOPMENT OF MANDIBLE: (PROFFIT PG42)
 Early in embryonic life, the mandible of higher animals
develops in the same area as the cartilage of the first
pharyngeal arch – MECKEL’S CARTILAGE. (primary
cartilage of mandible).
 Development of mandible begins as a condensation of
mesenchyme just lateral to meckel’s cartilage.
 Proceeds entirely as an intra-membranous bone
formation.
 Spreads posteriorly along it without any direct
replacement of the cartilage by the newly forming bone of
the mandible.
 Meckel’s cartilage disintegrates & largely disappears as
the bony mandible develops.
 Remnants of this cartilage are transformed into malleus
& incus ossicles of the middle ear & its perichondrium
persists as sphenomandibular ligament.

REPRESENTATION OF RELATION OF INITIAL BONE FORMATION IN
MANDIBLE TO MECKEL’S CARTILAGE & INFERIOR ALVEOLAR NERVE.

 Condylar cartilage develops initially as an
independent secondary cartilage, which is
separated by a considerable gap from the
body of mandible. It fuses with developing
mandibular ramus at 4 months of IUL.

DEVELOPMENT OF CRANIAL BASE:
 In contrast to cranial vault, the bones of the
base of the skull (cranial base) are formed
initially in cartilage & are later transformed by
endochondral ossification into bone .

SYNCHONDROSIS
(PROFFIT PG 44,BISHARA PG46,49)
 A synchondrosis is a cartilaginous joint
where the hyaline cartilage divides &
subsequently is converted into bone. As
ossification proceeds, bands of cartilage
called sunchondrosis remain between
centers of ossification.

 Histologically a synchondrosis looks like a two
sided epiphyseal plate. Immature proliferating
cells at the center, while bands of mature
cartilage cells extends in both directions away
from the center(which will eventually be
replaced by bone, by endochondral ossification)

GROWTH AT SYNCHONDROSES
GROWTH AT THE SYNCHONDROSES LENGTHENS THIS AREA OF THE
CRANIAL BASE.
INTER SPHENOID
SYNCHONDROSES

REPRESENTATION OF THE SYNCHONDROSES OF CRANIAL BASE

 The cranial base is thus like a single long
bone, except that there are multiple
epiphyseal plate like synchondrosis. The
changes in cranial base occur primarily as a
result of endochondral growth through a
system of synchondroses.

 Centres of ossification appear early in
embryonic life in chondrocranium, indiacting
eventual location of basioccipital, sphenoid,
& ethmoid bones, that form the cranial base.

VARIOUS SYNCHONDROSES OF CRANIAL BASE
 Spheno-occipital synchondrosis
 Inter-sphenoid synchondrosis
 Intra ethmoidal synchondrosis
 Intra occipital synchondrosis
 Sphenoethmoidal synchondrosis.

OSSIFICATION TIME OF VARIOUS SYNCHONDROSES OF THE
CRANIAL BASE
 Intra ethmoidal & intra sphenoidal
synchondrosis close before birth.
 Whereas the intraoccipital synchondrosis
closes before 5 years of age.
 Spheno-ethmoidal synchondrosis closes
around 6 years of age.
 Spheno-occipital synchondrosis closes by 13
to 15 years of age.

SUBSEQUENT CHANGES
 Any subsequent changes that occur in length
or the flexure of cranial base are result of
surface deposition or resorption.

BONE FORMATION: (EMBRYOGENESIS OF
CRANIOFACIAL SKELETAL TISSUES)
BISHARA PG 43-45, GRABER PG 39-40
 Craniofacial skeleton is derived from three
unique processes:-
 A: Chondrogenesis : Formation of cartilage
 B: Endochondral bone formation: Process of
converting cartilage into bone.
 C: Intramembranous bone formation: Process
of bone formation from undifferentiated
mesenchymal tissue. Secretion of bone matrix
directly within connective tissues, without
intermediary formation of cartilage. Ex cranial
vault & both the jaws.

 Bone can either form directly from
osteoblasts,(intramembranous ossification)
OR
 Have a cartilaginous precursor
(endochondral ossification).
 In the latter case Chondroblasts initially form
cartilage,which,in turn is calcified & invaded
by osteogenic tissue.

INTRAMEMBRANOUS BONE FORMATION

INTRA-MEMBRANOUS BONE FORMATION
Area of mesenchyme prior to mesenchymal
condensation.

At the site where membrane bpne is to be formed, the
mesenchymal cells become densely packed.
Region becomes highly vascular.

Some mesenchymal cells lay down bundle of collagen.

Some mesenchymal cells enlarge & acquire basophilic
cytoplasm to become OSTEOBLASTS.
Come to lie along the bundles of collagen fibres.

OSTEOBLASTS secrete a gelatinous matrix in which fibres
get embedded.
FIBRES SWELL UP.
This mass of swollen fibres & matrix is called OSTEOID.

Under the influence of OSTEOBLASTS calcium salts are
deposited in osteoid.
Now the layer of osteoid is called LAMELLUS OF BONE.

Another layer of osteoid layed down over the lamellus of
bone.
Osteoblasts then move away to line new layer of osteoid.
Some get trapped in the osteoid & become OSTEOCYTES.

In this way a number of lamellae are laid down one
over another.
These lamellae together form TRABECULUS OF
BONE.

THE ACTUAL ARRANGEMENT OF COLLAGEN BUNDLES IN A
MEMBRANE.

BONE FORMATION occuring along each of these bundles ,
also follows the same pattern.
In this way typical CANCELLOUS BONE is formed.
Cancellous bone is later converted into COMPACT BONE.

ENDOCHONDRAL BONE FORMATION

At the site where bone is to be formed the, mesenchymal cells
become closely packed to form a mesenchymal
condensation.

Chondrocytes(cartilage cells) differentiate from original
mesenchymal cells & form a rough model of future future
bone enclosed by perichondrial cells.(forming
perichondrium which contains osteoprogenitor cells).
Cartilage mass grows rapidly, both by interstitial &
appositional increments.

Primary bone forming center becomes evident.
Mature cartilage cells hypertrophy & matrix between
chondrocytes begins to calcify(under influence of
alkaline phosphatase secreted by cartilage cells).

Nutrition of cartilage cells cut off. They die. Leaving empty
spaces primary areolae.
Calcified cartilage
matrix

Blood vessles & UMC from perichondrium now invade the
changing cartilaginous matrix.
Mass of vessels & cells are called periosteal bud.
It eats away much of the calcified matrix forming the wall
of primary areolae, creating large cavitie called
SECONDARY AREOLAE (medullary spaces).

Walls of secondary areolae formed by thin layers of
calcified matrix.
Osteoblasts arrange on these bars or plates of calcified
matrix. They lay down osteoid (a layer of ossein fibrils
embedded in gelatinous ground substance).
Osteoid calcifies & lamellus of bone formed.

Then another layer osteoid laid down & so on. Bony
trabeculae formed.
Osteoblasts forming medullary type of bone in the mold
Perichondrium differentiates into periosteum and forms
intramembranous bone around the mold.

 Calcified matrix of cartilage provides only a
support for the developing trabeculae & is
not itself converted into bone. Process of
bone formation is same in both.

At present:
Zone 1: where bone has formed
Zone 2: calcified cartilaginous matrix surrounding dead & dying
cartilage cells.
Zone 3: hypertrophie cartilage cells in an uncalcified matrix.
Zone 4: normal cartilage.

Later:
Ossfication extended into zone 2
Matrix in zone 3 has been calcified.
Zone 5: more superficial cells that have hypertrophied.
IN THIS WAY FORMATION OF NEW CARTILAGE KEEPS PACE
WITH THE LOSS DUE TO REPLACEMENT BY BONE.
OSSIFYING CARTILAGE PROGRESSIVELY INCREASES IN
SIZE.

FIVE STEPS OF CHONDROGENESIS
 Chondroblasts produce matrix:the
intercellular matrix produced by cartilage
cells is hard but flexible and capable of
providing rigid support.

 Cells become encased in matrix: when the
chondroblasts become fully encased within
their secretory matrix material, the cartilage
cells become chondrocytes.
New chondroblasts are differentiated from
the surface membrane (perichondrium), &
this results in increased cartilage size (i.e
cartilage can increase in size by appositional
growth.)

 Chondrocytes enlarge, divide & produce
matrix: cells continue to grow & secrete
matrix, thereby increasing the cartilage mass
from within.Growth resulting from internal
expansion is called INTERSTITIAL
GROWTH.

Matrix remains uncalcified:
Cartilage matrix is rich in chondroitin sulfate
associated with non collagenous protein.
This combination has the special property of
marked Hydrophilia.
Nutrients & metabolic wastes diffuse directly
through the soft matrix to & from cells.
Hence blood vessles are not required in
cartilage.

Membrane covers the surface but is
not
essential:
Cartilage has an enclosing surface
membrane called perichondrium ., but
cartilage can also exist without one.
This property allows cartilage to grow &
adapt in sites involving pressure.(e.g joints).
Cartilage is pressure tolerant.

GROWTH CENTRES VS GROWTH SITES:

 GROWTH SITE: it is merely a location at
which growth occurs. (compensatory growth
mechanisms)
 GROWTH CENTER: It is a location at which
independent (genetically controlled) growth
occurs.
All centers of growth are also growth sites
but reverse is not true.

SUTURES
Earlier sutures between membranous bones
of the cranium & jaws were considered
growth centres, capable of generating
tissue separating forces..
If it had been true then growth at sutures
should occur largely independently of the
environment, & it would not be possible to
change the expression of growth at the
sutures very much.

BUT:
 A: when a suture between two facial bones is
transplanted to another location it does not
continue to grow.(lack of innate gowth potential in
sutures)
 B: growth at sutures responds to outside
influences, ex if cranial/facial bones are
mechanically pulled apart at sutures, new bone fills
in. if suture compressed, growth at that site will be
impeded.
 So sutures are not primary determinant of
craniofacial growth, & are areas that just react.
Thereby the sutures of maxilla are growth sites

CRANIAL BASE SYNCHONDROSIS
Develops from the primary cartilage, and
has growth directing capacity early in
life(spheno occipital synchondrosis. So it is a
GROWTH CENTER.

MANDIBULAR CONDYLES
 Once considered growth center with directive
capacity.
 Cartilage found at head of condyle is a secondary,
fibrous type of cartilage (differs from growth-plate
type cartilage which is under strong genetic control).
 It does not originate from a primary cartilage
precursor. It grows peripherally (appositionally) & is
highly responsive to mechanical stimulation.
 Compensatory growth of condylar cartilage occurs.
 Has some intrinsic growth but does not generate
tissue separating forces (as epiphyseal pates does).
 So, condylar cartilage is a GROWTH SITE.

NASAL SEPTUM
 Scott suggested that primary cartilage
present in the nasal septum is the primary
mechanism responsible for growth of
nasomaxillary complex.
 Experimentally when it was transplanted , it
continued to grow. (innate growth
potential).
 In general, nasal septum cartilage is
considerd as a GROWTH CENTER.

GROWTH PROCESS – BASIC CONCEPTS
(ENLOW PG 25-38)

CONCEPT 1
 FACIAL GROWTH & DEVELOPMENT IS A
MORPHOGENIC PROCESS WORKING
TOWARDS A COMPOSITE STATE OF
AGGREGATE STRUCTURAL & FUNCTIONAL
BALANCE AMONG ALL OF THE MULTIPLE ,
REGIONAL GROWING & CHANGING HARD &
SOFT TISSUE PARTS.
 THE SAME UNDERLYING PROCESS THEN
CONTINUES TO WORK IN ORDER TO
SUSTAIN ONGOING EQUILIBRIUM
THROUGHOUT ADULTHOOD & OLD AGE IN
RESPONSE TO EVER CHANGING INTERNAL

CONCEPT2
BONES GROW BY ADDING NEW BONE
TISSUE ON ONE SIDE OF A BONY CORTEX
& TAKING IT AWAY FROM THE OTHER SIDE.
 Surface facing toward the direction of
progressive growth receives new bone
deposition (+).
 The surface facing away undergoes resorption
(-).
 This composite process is termed as
CORTICAL DRIFT(a combination of bone
deposition & resorption resulting in growth
movement towards the depositing surface).
 It produces a direct growth movement of any

CONCEPT 3
 The outside & inside surfaces of a bone are
completely blanketed by a mosaic like pattern of
“GROWTH FIELDS”.
 Outside surface is not all depository. About half of
the periosteal (external ) surface of a whole bone has
characteristic arrangement of RESORPTIVE
FIELDS(darkly stippled areas), while DEPOSITORY
FIELDS covers the remainder (lightly stippled areas).
 If a given periosteal area has a resorptive field , the
opposite inside (endosteal) surface of that same area
has a depository field.
 These combinations produce the characteristic
GROWTH MOVEMENTS(drift) of all parts of an
entire bone.

CONCEPT 4
 Periosteal bone ( bone formed by covering
membrane) constitutes about half of all the
cortical bone tissue present, while endosteal
bone(bone formed by lining membrane)
forms the other half.

 Fig: cortex on right formed by periosteum &
cortex on left formed by endosteum, as both
shifted (drifted) in unison to the right.

CONCEPT 5
 The operation of growth fields is carried out
by OSTEOGENIC MEMBRANES & other
surrounding tissues rather than by hard part
of the bone.
 The bone does not “grow itself”;
 Growth is produced by the SOFT TISSUE
MATRIX that encloses each whole bone.
 The blueprint for design, construction, growth
of bone & the genetic & functionl
determinants of bone growth reside in the
composite of soft tissues.

CONCEPT 6
 All the resorptive & depository growth fields
throughtout a bone do not have same rate
of growth activity.
 During remodeling, extent of bone deposition
is usually more than resorption, so that the
regional parts of a bone gradually enlarge &
cortical plates thicken as they remodel.

Growth does not occur just at special growth sites. Entire
bone participates.
The entire ramus together with condyle participates actively
and directly (not just the condyle)

CONCEPT 7
 Remodeling is a basic part of the growth
process.
 As the whole bone enlarges, the drift moves
each part from one location to other.
 This progressive, sequential movement of
component parts as a bone enlarges is termed
RELOCATION.
 Ex: in Maxilla the palate grows downward(i.e
becomes relocated inferiorly) by periosteal
resorption on the nasal side & periosteal
deposition on oral side.

Growth remodeling has following functions:
 A: Progressively enlarge each whole bone
 B: Sequentially relocate each of the
component parts
 C: Shape the bone – to accommodate
various functions.
 D: Good fitting of all separate bones to each
other & to their contiguous growing
functioning soft tissues.

CONCEPT 8
PRIMARY
DISPLACEMENT/TRANSLATION:
 As bone enlarges, it is simultaneously
carried away from other bones in direct
contact with it,in the opposite direction.
 The bone gets displaced as a result of its
own growth.
 It is a physical movement of of a whole
bone & occurs while the bone grows &
remodels by resorption & deposition.

 Ex: The nasomaxillary complex is in contact with the floor
of the cranium. The whole maxillary region, in toto , is
displaced downward & forward from the cranium by the
expansive growth of the soft tissues in the midfacial region.

 This then triggers new bone growth at the various sutural
contact surfaces between the nasomaxillary composite &
the cranial floor.
 Displacement thus proceeds downward & forward as
growth by bone deposition simultaneously takes place in an
opposite upward & backward direction,(that is toward its
contact with the cranial floor)

CONCEPT 9
SECONDARY DISPLACEMENT:
 If the bone gets displaced as a result of
growth & enlargement of an adjacent bone.
The displacement effect is thereby secondary
type
 Ex: Increase in size of bones that form the
middle cranial fossa result in marked
displacement of the whole maxillary complex
anteriorly & inferiorly.
 This is quite independent of the growth &
enlargement of maxilla itself.

CONCEPT 10
 Facial growth is a process that requires
intimate morphogenic inter-relationship
among all of its component growing,
changing & functioning soft & hard tissue
parts.
 No part is developmentally independent or
self contained.

TWO BASIC TYPE OF GROWTH MOVEMENTS
THAT OCCUR:
 A: REMODELING: which produces change
in size, shape, proportion, relationship of
bone to adjacent structures.
 B: DISPLACEMENT: movement of whole
bones away from each other , creating the
space within which growth enlargement of
each of the separate bones takes place.

SITES & TYPES OF GROWTH IN THE
CRANIOFACIAL COMPLEX:

SITES & TYPES OF GROWTH IN THE CRANIOFACIAL COMPLEX:
To understand growth in any area of the
body it is necessary to understand:
 A: the sites or location of growth
 B: the type of growth occuring at that
location
 C: the determinant or controlling factors in
that growth.

CRANIOFACIAL COMPLEX IS DIVIDED INTO FOUR
AREA THAT GROW RATHER DIFFERENTLY:
 A: the cranial vault, the bones that cover
the upper & outer surface of the brain.
 B: the cranial base, the bony floor under the
brain, which is also the dividing line between
the cranium & face.
 C: the nasomaxillary complex, made up of
nose,maxilla, & associated small bones
 D: the mandible.

MAXILLA (NASO-MAXILLARY COMPLEX)
Maxilla develops post-natally entirely by
intramembranous ossification. There is no
replacement of cartilage.Growth occurs in three
ways:
 A: by apposition of bone at the sutures that
connect the maxilla to the cranium & cranial
base.
 B: by a push from behind created by cranial
base growth.
**Maxilla should move, through growth, a
considerable distance downward & forward
relative to the cranium & cranial base. This is
accomplished by above mentioned two ways.

 Lengthening of cranial base pushes maxilla
forward(as it is attached to anterior end on
cranial base).

 Uptill 6 yrs of age , displacement from
cranial base growth is an important part of
maxilla’s forward growth. Failure of it as in
achondroplasia creates midface deficiency.
 At age 7, cranial base growth stops, &
sutural growth only mechanism for bringing
the maxilla forward.

 Sutures attaching the maxilla posteriorly &
superiorly are ideally situated to allow its
downward & forward repositioning.

 As growth of surrounding soft tissues
translates maxilla downward & forward ,
opening of space occurs at its posterior &
superior sutural attachment, which is filled in
by proliferation & apposition of new bone on
both sides of the suture. Width of suture
remains same but various processes of

C: BY SURFACE REMODELING
 As the maxilla grows downward & forward,
its front surface are remodeled, the bone is
removed from most of the anterior surface.

 As maxilla is carried downward & forward. Its
anterior surface tends to resorb.
 Almost entire anterior surface of the maxilla is
an area of resorption, not apposition.(small area
of ANS is an exception).
 Bone is removed from the anterior surface,
although the anterior surface is growing
forward.
 The overall growth changes are the result of
both a downward & forward translation of the
maxilla & a simultaneous surface remodeling.

 Maxilla is like a platform on wheels, being
rolled forward, while at the same time its surface
, represented by the wall in the cartoon, is being
reduced on its anterior side & built up
posteriorly, moving in space opposite to
direction of overall growth.

 Remodeling changes may not always
oppose the direction of translation.
 Depending on specific location translation &
remodeling may produce additive effect or
oppose each other.

 Additive effect: on roof of mouth. This area
is carried downward & forward along with
rest of maxilla, but at the same time bone is
removed from nasal side and deposited on
oral side, thus creating an additional &
forward movement of the palate.

Opposing effect: on anterior surface , bone is
removed, partially cancelling the forward translation.

MANDIBLE:
 Both endochondral & periosteal activity are
important in growth of the mandible.
 Cartilage covering surface of mandibular
condyle: hypertrophy, hyperplasia,
endochondral replacement occurs.
 All other areas of mandible: grow by direct
surface apposition & remodeling.

GROWTH OF MANDIBLE
Fig A :-As viewed from perspective of stable cranial base:
Chin moves downward & forward

GROWTH OF MANDIBLE
Fig: B As viewed from the perspective of vital staining studies.
Minimal changes in the body & chin area.
While there is exceptional growth & remodeling of ramus,
moving it posteriorly.

The correct concept of mandibular growth is:
The mandible is translated downward &
forward & grows upward & backward in
response to this translation, maintaining
its contact with the skull

 Principal sites of growth are the posterior
surfaces of the ramus & the condylar &
coronoid process.
 Mandible body grows longer by apposition
of new bone on the posterior surface of
ramus, with resorption on anterior surface of
ramus.
 Ramus grows higher by endochondral
replacement at the condyle accompanied by
surface remodeling.

As mandible grows in length,
ramus is extensively
remodeled.
Bone at tip of condylar process
at an early age could be found
at the anterior surface of
ramus , some years later.

CRANIAL VAULT:
 Cranial vault is made of a number of flat
bones that are formed directly by
intramembranous ossification.
 Remodeling occurs at periosteum lined
cranial sutures. Majority of growth in the
cranial vault occurs at these sutures.
 Bone is also removed from the inner surface
of cranial vault , while at the same time, new
bone is added on exterior surface. This
allows changes in contour during growth.

THEORIES OF CRANIOFACIAL GROWTH

GENETIC THEORY
 The genetic theory simply said that genes determine all.
 All growth is controlled by genetic influence & is pre-
planned. Although considered a theory it was more
assumed than proven.(moyers pg 50)
 The assumption was made that the cartilages & facial
sutures were under genetic control & that the brain
determined the vault dimensions(which meant vault
sutures were passive while facial sutures were actively
forcing bones apart). The concept was one of an
invariant, predetermined pattern of craniofacial
growth.
 In 1940s two events reflected changing ideas about the
dominant genetic concepts:
 A: a marked increase in the use of animals in craniofacial
research
 B: the introduction of jaw & facial electromyography.

GENETIC THEORY

SICHER’S HYPOTHESIS ( SUTURAL DOMINANCE):
 SICHER deduced from the many studies using vital
dyes that the sutures were causing most of the
growth & that cranio-facial growth occurs at the
sutures.
 He said “ the primary event in sutural growth is the
proliferation of connective tissue between the two
bones. If sutural connective tissue proliferates it creates
the space for oppositional growth at the borders of the
two bones.”
 Replacement of the proliferating connective tissue was
necessary for the functional maintenance of bones.
 He felt that the connective tissue in sutures of both the
nasomaxillary complex & the vault produced forces
which separated the bones (just as synchondroses

 He viewed the cartilage of mandible
somewhat differently stating that it grew
interstitially,as epiphyseal plates,&
appositionally, as bone grew under
periosteum. It would seem he held sutures,
cartilage & periosteum all responsible for
facial growth & assumed all were under tight
genetic control.(moyers pg50)

SICHER’S THEORY

POINTS RAISED AGAINST THIS THEORY
 A: when an area of the suture between two facial
bones is transplanted to another location(to a pouch
in the abdomen,for ex), the tissue does not continue
to grow. This indicates a lack of innate growth
potential in the sutures.
 B: growth at sutures will respond to outside
influences under a number of circumstances. If
cranial or facial bones are mechanically pulled
apart at sutures, new bone will fill in & the bones
will become larger than they would have been
otherwise.If a suture is compressed, growth at that
site will be impeded.
 So sutures must be considered areas that react –
not primary determinant. The sutures of maxilla are
sites of growth but are not growth centres.

SCOTT’S HYPOTHESIS (NASAL SEPTUM) CARTILAGINOUS THEORY:
 It states that the determinant of craniofacial
growth is the growth of cartilage.
 If cartilaginous growth were the primary
influence, the cartilage at the condyle of the
mandible could be considered as the
PACEMAKER for growth of that bone, & the
remodeling of the ramus & other surface
changes could be viewed as secondary to
the primary cartilaginous growth.

SCOTT’S CARTILAGINOUS THEORY

MANDIBLE
 Imagining the mandible as the diaphysis of a
long bone, bent into a horseshoe with the
epiphyses removed, (leaving the epiphyseal
plates exposed) so that there is cartilage
representing “half an epiphyseal plate” at the
ends, which represent the mandibular
condyles.
 If this analogy was correct , of course, the
cartilage at the mandibular condyles should
behave like true growth cartilage.(as an
epiphyseal growth cartilage, growth center)
 Modern experiments indicate, although the
analogy is attractive, it is incorrect.

MAXILLA
 Although there is no cartilage in maxilla
itself, there is cartilage in the nasal septum,
& the nasomaxillary complex grows as a unit.
 Cartilaginous nasal septum serves as a
pacemaker for other aspects of maxillary
growth.
 Downward & forward translation of maxilla as
guided by the location of the nasal cartilage.
New bone formed at sutures as they are
pulled apart.

Possible role of cartilaginous nasal septum in
downward & forward growth of maxillary complex.

CARTILAGE AS A DETERMINANT OF CRANIOFACIAL GROWTH:
TWO KINDS OF EXPERIMENTS HAVE BEEN CARRIED
OUT TO TEST THE IDEA THAT CARTILAGE CAN SERVE
AS A TRUE GROWTH CENTER.
 A: an analysis of the results of transplanting
cartilage.
 B: an evaluation of the effect on growth of
removing cartilage at an early age.

TRANSPLANTING EXPERIMENTS
 Transplanting experiments demonstrate that not all
skeletal cartilages acts the same when transplanted.
 If a piece of the epiphyseal plate of a long bone is
transplanted, it will continue to grow in a new location
or in culture, indicating that these cartilages do have
“innate growth potential”.
 Nasal septal cartilage was found to grow nearly as
well in culture as eiphyseal plate cartilage.
 Little or no growth was observed when cartilage of
mandibular condyle was transplanted.
 From these experiments the, the other cartilages
appear capable of acting as growth centres, but the
mandibular condylar cartilage does not.

REMOVING CARTILAGE
 if removing a cartilaginous area stops or diminishes growth,
perhaps it really was an important center for growth.(proffit pg50-
52).
 In rodents, removing a segment of the cartilaginous nasal septum
causes a considerable deficit in the growth of midface.
 Entire effect on growth may not be attributed to the loss of
cartilage (surgery itself, interference with blood supply to that
area).
 One individual in whom the entire nasal septum was removed at
age 8 after an injury showed midface deficiency. (but cant be
solely attributed).
 Septal cartilage does have some innate growth potential, whose
loss makes a difference in maxillary growth.
 In experiments in children, after a fracture, all of the original bone
& cartilage resorb, & a new condyle regenerates directly fom the

 IT APPAERS THAT EPIPHYSEAL
CARTILAGES & THE CRANIAL BASE
SYNCHONDROSES CAN & DO ACT AS
INDEPENDENTLY GROWING CENTERS,
AS CAN THE NASAL SEPTUM (TO A
LESSER EXTENT.
 IT APPEARS THAT GROWTH AT THE
MANDIBULAR CONDYLES IS MUCH
MORE ANALOGUS TO GROWTH AT THE
SUTURES OF THE MAXILLA- ENTIRELY
REACTIVE- THAN TO GROWTH AT AN

FUNCTIONAL MATRIX HYPOTHESIS
 In 1960s MELVIN MOSS & SALENTIJN
reintroduced a concept regarding the controlling
influence of functional space development on
craniofacial growth. This concept came to be
known as FUNCTIONAL MATRIX CONCEPT.
 It explicitly claims that the origin,growth &
maintainence of all skeletal tissue & organs are
always secondary, compensatory & obligatory
responses to temporally & operationally prior
events for processes that occur in specifically
related non skeletal tissues, organs or
functioning spaces(functional matrices).(moyers
pg49)

 The functional matrix concept tries to
comprehend the relationship between form
and function.
 This theory also holds that neither cartilage of
the mandibular condyle nor the nasal septum
cartilage is a determinant of jaw growth. Instead
growth of face occurs as a response to
functional needs & neurotrophic influences
& is mediated by the soft tissue in which the
jaws are embedded.
 SOFT TISSUES GROW,& BONE &

 Growth of cranial vault is a direct response to
growth of the brain.
 Pressure exerted by the growing brain separates
the cranial bones at the sutures, & new bone
passively fills in at these sites so that braincase
fits brain.
 Size of eye and size of orbit: enlarged eye or
small eye will cause a corresponding change in
size of orbital cavity. Here eye is the
FUNCTIONAL MATRIX.

 MOSS & SALENTIJN suggested that the
head carries out several vital functions & that
the craniofacial structures respond to the
changing requirements for those functions.
According to this theory, craniofacial growth
is the result of both changes in the
CAPSULAR MATRICES, causing spatial
changes in the position of bones
(translation), & by the PERIOSTEAL
MATRICES, causing more local changes in
the size & shape of the
skeleton(remodelling). (bishara pg51)

 There are a number of functions carried out
by the head(cranio-facial region),& all require
the development & maintainance of spaces.
Ex: neural growth & integration is a critical
function & space is required for the brain as
well as the central & peripheral nervous
system expansion. (bishara pg52)
 Other functions include respiration,
olfaction,vision,hearing,balance,chewing
digestion,swallowing, speech & neural
integration.

FUNCTIONAL CRANIAL COMPONENT
 Each of these functions is carried out by a
FUNCTIONAL CRANIAL COMPONENT.(a
group of soft tissues which are supported &/or
protected by related skeletal elements). Each
FUNCTIONAL CRANIAL COMPONENT
consists of all the tissues,organs, spaces &
skeletal parts necessary to carry out a function.
 The FUNCTIONAL CRANIAL COMPONENT is
divided into:
 FUNCTIONAL MATRIX
 SKELETAL UNIT

SKELETAL UNIT
All skeletal tissues associated with a single
function(related to a specific functional matrix) are
called ‘the skeletal unit’. It may be comprised of
bone, cartilage, tendinous tissue.
Microskeletal units:
 When a bone is comprised of several contiguous
skeletal units . ex: maxilla & mandible are comprised
of a number of such microskeletal units. Maxilla :
orbital,pneumatic,palatal & basal micro-skeletal units.
Mandible: alveolar, angular, condylar, gonial, mental,
coronoid, & basal microskeletal units.
Macroskeletal unit:
 When adjoining portions of a number of neighbouring
bones are united to function as a single cranial
component. Ex: entire endocranial surface of the
calvarium is an example of macro-skeletal unit.

FUNCTIONAL MATRIX HYPOTHESIS

FUNCTIONAL MATRIX
It consists of muscles,glands, nerves,
vessels, fat, & functioning spaces.
 A: PERIOSTEAL MATRIX
 B: CAPSULAR MATRIX

PERIOSTEAL MATRIX
 The Periosteal matrices(such as muscles &
tendons) act directly & actively upon their
related skeletal units, via the periosteum, to
produce a secondary compensatory
transformation of the size & shape of their
skeletal units through bone apposition &
resorption.
 It includes muscles, blood vessels,nerves
glands etc. These tissues act directly on their
related skeletal units thereby bringing about a
transformation in their size & shape.
Transforming action brought about by bone

CAPSULAR MATRIX
 The capsular matrices act indirectly & passively on
their related skeletal units to produce a secondary
compensatory translation in space through
expansion of the oro-facial capsule within which the
facial bones arise, grow & are maintained.
 The facial SKELETAL UNITS are passively &
secondarily moved in space(translation) as their
enveloping capsule is expanded. This translative
growth not brought by deposition & resorption.
 Ex: of capsular matrices: Neuro-cranial capsule &
orofacial capsule. Orofacial capsule surrounds &
protects the oro-nasal-pharyngeal spaces which
constitute the oro-facial capsular matrix.
 Moss argues , The skeletal tissue grow only in
response to soft tissue growth.(moyers pg 50)

NEUROTROPHIC PROCESS IN ORO-FACIAL GROWTH

NEUROTROPHIC PROCESS IN ORO-FACIAL GROWTH
(GRABER PG 74,75)
 Neurotrophism: is a non-impulse
transmittive neurofunction, involving
axoplasmic transport, providing for the long
term interactions between neurons &
innervated tissues which hemostatically
regulate the morphological, compositional &
functional integrity of those tissues. The
nature of neurotrophic substances & the
processes of their introduction into the target
are unknown at present.

 Neurotrophic processes are involved in the
translation of functional stimuli at the skeletal
unit interface & in the regulation & control of
functional matrices.

TYPES OF NEUROTROPHIC MECHANISMS
(MOSS)
A: NEURO-VISCERAL TROPHISM:
The salivary glands are trophically regulated,
atleast partially.
Increase or decrease of salivary glad tissue is
under trophic control
Normal rate of growth, expresed in part as
regulation of cell number & size, is under
neurotrophic control.

NEURO MUSCULAR TROPHISM
 If periosteal(muscular) functional matrices
actually regulate the size & shape of
specifically regulated skeletal unit, it is
apparent that the genetic control of the
structural, chemical & functional attributes of
the same matrices can not reside solely in
the matrices themselves.
 They reflect constant neurotrophically
regulated,homeostatic control of genome.
(Moss)

NEURO EPITHELIAL TROPHISM
 Epithelial mitosis & synthesis are
neurotrophically controlled.
 The normal epithelial growth is controlled by
release of certain neurotrophic substances
by nerve synapses.
 If this neurotrophic process is lacking then
abnormal epithelial growth may occur.
 Ex: Epithelial mitosis,
maintenance,enzymatic synthesis, genomic
potential expression are all under afferent

VAN LIMBORGH’S THEORY

VAN LIMBORGH’S THEORY
(GRABER PG42-48)
 A multi factorial theory was put forward by
Van Limborgh in 1970.
 According to him the three theories of growth
were not satisfactory, yet contained elements
of sinificance that can not be denied.
 He synthesized his theory from parts of all
the three basic theories of
craniofacialgrowth.
 It represented a logical relationship but could
not answer all the questions.

FIVE FACTORS CONTROLLING GROWTH
 Intrinsic genetic factors: genetic control of the
skeletal units themselves.
 Local epigenetic factors: bone growth is
determined by genetic control originating from
adjacent structures.
 General epigenetic factors: they are genetic
factors determining growth from diatant
structures. Ex. Growth hormones.
 Local environmental factors: non genetic
factors from local external environment.
 General environmental factors: general
nongenetic influences ex nutrition.

ESSENTIAL ELEMENTS OF THREE HYPOTHESES AS
LISTED BY LIMBORGH (GRABER PG47)
 A: Growth of the synchondroses & the ensuing
endochondral ossification is almost exclusively controlled
by intrinsic genetic factors.
 B: The intrinsic factors controlling intramembranous
bone growth, i.e, the growth of the sutures & the
periosteum, are small in number & of a general nature.
 C: The cartilaginous skull parts must be seen as
growth centers.
 D: Extent of sutural growth is controlled by both the
cartilaginous growth & the growth of other head
structures.
 E: Extent of periosteal bone growth largely depends on
the growth of adjacent structures.
 F: The intramembranous processes of bone formation
can be additionally influenced by local environmental
factors, muscle forces inclusive.

Inter relationship of GENETIC, EPIGENETIC, & ENVIRONMENTAL
controls chondrocranium & desmocranium growth processes.(
based on six observations of Van Limborgh)
Influence of chondrocranium on desmocranium, yet chondrocranium
is under the influence of intrinsic genetic factors (primarily)

ENLOW’S COUNTERPART/GROWTH
EQUIVALENTS PRINCIPLE
 The counterpart principle of craniofacial
growth states that the growth at any given facial
or cranial part relates specifically to other
structural & geometric counterparts in the face
& cranium.
 If each regional part & its counterpart enlarge to
the same extent, balanced growth occurs.
 Imbalances in regional relationships are
produced by differences in
 a) amounts of growth between counterparts.
 B) direction of growth between counterparts.
 C) time of growth between them

 Component regions of skull: a)anterior cranial
base b) spheno-occipital complex c)naso-
maxillary complex d) mandible.

Elongation of anterior cranial fossa is related to
corresponding elongation of naso maxillary complex.
Arrows show that maxillary growth is dominantly posterior
but resultant displacement is anterior.

 Lengthening of spheno occipital region
(m)is a growth equivalent to corresponding
enlargement of underlying pharyngeal
region (p). & increasing length of ramus

 The composite vertical lengthening of the clivus
& mand ramus (b &d) is a growth equivalent to the
total vertical elongation of naso maxillary region
(c).

ENLOW’S EXPANDING ‘V’ PRINCIPLE
ENLOW PG85-89,39-41:GRABER PG 49,56,68
 Many facial & cranial bones or parts of bones
have ‘V’ shaped pattern of growth.
 The growth movement & enlargement of
these bones occur towards the wide end of
‘V’, as a differential deposition & selective
resorption of bone.
 It occurs in a number of regions such as
base of mandible, ends of long bones,
mandibular body, palate.

 Deposition occurs on the inner side of ‘V’ &
Resorption takes place on the outer surface

 The ‘V’ thereby moves from point A to point B &, at
the same time, increases in overall dimensions.
 Direction of movement is towards the wide end of ‘V’.

 Thus a simultaneous growth movement &
enlargement occurs by additions of bone on
the inside & removal from outside.

 The diameter at A is reduced because broad
part of bone is relocated to position B.
Periosteal resorption & Endosteal deposition
of bone carry this out.

TRANSVERSE HISTOLOGIC SECTION
Done at 4 points A,B,C,D

TRANSVERSE HISTOLOGIC SECTION
 At point A: Periosteal surface resorptive &
Endosteal surface is depository.
 At point B: New Endosteal bone added to the
inner surface of the cortex.

 At point C: Endosteal layer that was formed
during inward growth phase. This is covered by
periosteal layer of bone following outward
reversal, as this part of bone now increases in
diameter.

 At point D: The cortex is composed entirely
of periosteal bone. Outer surface is
depository & inner surface is resorptive.

METALLIC IMPLANT MARKER
METALLIC IMPLANT MARKERS INSERTED
AT POINTS X,Y,Z

METALLIC IMPLANT MARKER
 X released from bone because that part
removed by periosteal resorption. It will lie
free in surrounding soft tissue.

 Z is also released due to endosteal resorption. It
will lie free in the medullary cavity.
 Y was originally inserted into cortex on periosteal side
but gets TRANSLOCATED over to endosteal side of
cortex. New bone was added to the left & removed
from the right.

 The oral plate & floor of nasal cavity moves in a
downward direction as a result of bone
deposition on various inferior surfaces , with
resorption from contralateral superior surfaces.

 C & D illustrate the expanding ‘V’ principle, as
palate grows in an inferior direction by bone
deposition on its entire oral surface & resorptive
removal from opposite surface.
 Entire structure thereby moves in a direction toward
the wide end of ‘V’ & increases in overall size at the
same time.

VERTICAL SECTION THROUGH RAMUS &
CORONOID

 Periosteal deposition on lingual surface of
coronoid process & removal from buccal
surface.
 On basal part of ramus: periosteal deposition on
buccal side & contralateral resorption on lingual

 As coronoid processes become higher their termini
grow farther apart at their apices, by addition on
lingual surface.
 This remodelling mechanism illustrates expanding ‘V’
principle.

Functional
matrix
revisited

FUNCTIONAL MATRIX REVISITED
It includes following parts-
1. The role of mechanotransduction
2. The role of an osseous connected
cellular network
3. The genomic thesis
4. The epigenetic antithesis and the
resolving synthesis

1. THE ROLE OF MECHANOTRANSDUCTION
 Mechanotransduction
 All vital cells respond to alterations in their external
environment by Mechanosensing processes, which
include
 A. mechanoreception: transmits an extracellular
physical stimulus into a receptor cell.
 B. mechanotransduction: transduces or transforms
the stimulus's energetic and/or informational content
into an intracellular signal.

OSSEOUS MECHANOTRANSDUCTION
 Static and dynamic loadings are continuously
applied to bone tissues, tending to deform
both extracellular matrix and bone cells.
When stimulus exceeds threshold values, the
loaded tissue responds by, Osteoblasts that
directly regulate bone deposition and
indirectly regulate osteoclastic resorption.

OSSEOUS MECHANOTRANSDUCTION IS
UNIQUE IN FOUR WAYS:
 (1) Other mechanosensory cells are cytologically
specialized, but bone cells are not;
 (2) One bone-loading stimulus can evoke three
adaptational responses, whereas non-osseous
processes generally evoke one;
 (3) Osseous signal transmission is aneural,
whereas all other mechanosensational signals use
some afferent neural pathways,
 (4) The evoked bone adaptational responses are
confined within each "bone organ" independently,
e.g., within a femur, so there is no necessary
"interbone" or organismal involvement.

THERE ARE TWO, SKELETAL CELLULAR
MECHANOTRANSDUCTIVE PROCESSES.
 Ionic or electrical processes. This involves some
processes of ionic transport through the bone cell
(osteocytic) plasma membrane that, in turn, are the
operation of an osseous connected cellular network
(CCN).
 Stretch-activated channels. One of the types of
deformation involves the plasma membrane stretch-
activated (S-A) ion channels, a structure found in bone
cells. When activated in strained osteocytes, they permit
passage of a certain sized ion or set of ions, including K+,
Ca2+, Na+, and Cs+.Such ionic flow initiate intracellular
electrical events.

ELECTRICAL PROCESSES
 Electromechanical - the osteocytic plasma
membrane contains voltage-activated ion
channels, and transmembrane ion flow may be a
significant osseous mechanotransductive
process.
 Electrokinetic - Bound and unbound electric
charges exist in bone tissue, the bone fluid(s).
Streaming potential (SP) of ±2 mV can initiate
both osteogenesis and osteocytic action
potentials.
 Electric field strength - A significant parallel
exists between the parameters of these
exogenous electrical fields and the endogenous
fields produced by muscle activity. Bone
responds to exogenous electrical fields in an

MECHANICAL PROCESSES
 The mechanical properties of the
extracellular matrix influence cell behavior.
Loaded mineralized bone matrix tissue is
deformed or strained. a series of
extracellular macromolecular mechanical
levers exist, capable of transmitting
information from the strained matrix to the
bone cell nuclear membrane.

2. THE ROLE OF AN OSSEOUS CONNECTED
CELLULAR NETWORK
 All bone cells, except osteoclasts, are
interconnected to form an osseous CCN. It
connects upto 12 neighboring cells lying within
canaliculi.
 The small space between the cell process
plasma membrane and the canalicular wall is
filled with macromolecular complexes, permitting
the intercellular transmission of ions and small
molecules and fluorescent dye transmission.

A SKELETAL CCN DISPLAYS THE
FOLLOWING ATTRIBUTES:
 (1) Developmentally, it is an untrained self-organized,
self-adapting and epigenetically regulated system.
 (2) Operationally, it is a stable, dynamic system that
exhibits oscillatory behavior permitting feedback. It
operates in a noisy, nonstationary environment, and
probably uses useful and necessary inhibitory inputs.
 (3) Structurally, an osseous CCN is nonmodular, i.e., the
variations in its organization permit discrete processing of
differential signals. It is this attribute that permits the triad
of histologic responses to a unitary loading event.

REGULATION OF RESPONSES OF SKELETAL
UNITS BY IONIC MECHANOTRANSDUCTIVE
PROCESSES
(a) Normal muscle function strains the attached bone
tissue intermittently.
(c) The range of specific strain-frequency of muscle
dynamics are found to be osteoregulatory.
(d) Normal skeletal muscle activity produces
intraosseous electric fields.
(e) Bone cells may be stimulated by two
mechanisms-
directly by strain-activated plasma membrane
channels
indirectly by electrokinentic phenomena.
both the ionic membrane and the mechanical
transductive processes are combined with both

 The original FMH version offered only verbal
descriptions of periosteal matrix function and
skeletal unit response.
 The addition to the FMH of the concepts of
mechanotransduction and bone biology offers an
explanatory chain extending from the epigenetic
event of skeletal muscle contraction,
hierarchically downward, through the cellular and
molecular levels to the bone cell genome, and
then upward again, through histologic levels to
the event of gross bone form adaptational
changes.

3. THE GENOMIC THESIS
 The currently dominant scientific paradigm
suggests that genomic, instead of epigenetic
(functional) factors regulate growth.
 The whole plan of growth, the whole series
of operations to be carried out, the order
and site of synthesis and their co-ordination
are all written down in the nucleic acid
message.

THE GENOMIC THESIS
 The genomic thesis holds that the genome, from
the moment of fertilization, contains all the
information necessary to regulate (cause, control,
direct)
1. the intranuclear formation and transcription of
mRNA
2. all of the intracellular and intercellular
processes of subsequent, and structurally more
complex, cell, tissue, organ, and organismal
morphogenesis
All features are ultimately determined by the
DNA sequence of the genome.

THE GENOMIC THESIS IN OROFACIAL
BIOLOGY
 most genetic studies of cephalic or
cranial morphogenesis assume
genomic regulation of each
anatomical structure.

SPECIFIC ORTHODONTIC IMPLICATIONS OF
THE GENOMIC THESIS INCLUDE
 Poor coordination controls of form and size of
structures, or groups of structures (e.g., teeth and
jaws) by regulator genes, should explain the very
frequent mismatches found in malocclusions and
other dentofacial deformities.
 Single regulatory genes can control the
development of complex structures, indicating that
single gene can determine the morphology of at
least some complex structures, including how
characteristic noses or jaws are inherited from
generation to generation.

 It is claimed that regulatory molecules can
 Alter the manner in which genes coordinate
cell migration and subsequent cell
interactions that regulate growth.
.

4. THE EPIGENETIC ANTITHESIS AND THE
RESOLVING SYNTHESIS
 This article continues the
dialectical analysis of the roles of
genomic and epigenetic
processes and mechanisms in the
control of craniofacial growth and
development.

 Extrinsic musculoskeletal loading can
rapidly change
(1) both articular cartilage, intercellular
molecular syntheses and mineralization
(2) osteoblastic (skeletal unit) gene
expression.
Mechanical loads regulate skeletal muscle
(periosteal functional matrix) phenotype;
and chronic muscle stimulation can
change its phenotype.

 Both genomic and epigenetic processes
and mechanisms are necessary causes;
neither alone are sufficient causes; and only
their integrated activities provides the
necessary and sufficient causes of growth
and development.
 Genomic factors are considered as intrinsic
and prior causes; epigenetic factors are
considered as extrinsic and proximate
causes.

 Individually both are necessary causes, but
neither are sufficient causes alone. Together
they provide both the necessary and
sufficient causes for the control (regulation)
of morphogenesis. Nevertheless, epigenetic
processes and events are the immediately
proximate causes of development, and as
such they are the primary agencies.

CONCLUSIONS
 Integration of pertinent advances in biomedical and
bioengineering permitted an ongoing revision of the
functional matrix hypothesis.
 The first two articles in this series, by emphasizing
the roles of a number of biophysical and
biochemical factors in the regulation of
morphogenesis, implicitly argued for the
correctness of the fundamentally epigenetic thrust
of the FMH.
 However, because the conceptual tension between
hypotheses suggesting the regulatory primacy of
either genomic (genetic) or of epigenetic factors
continues unabated, it seemed useful to reevaluate
this nontrivial matter, using the dialectical method of
presenting a thesis, an antithesis, and a resolving
synthesis as illustrated in these two interrelated
articles.

PETROVIC SERVOSYSTEM THEORY
(CYBERNETICS)
To explain the servosystem theory petrovic was the first to
introduce the concept of cybernetics to account for the
physiologic phenomena involved in facial growth and the
method of operation of orthodontic and functional appliances.
Cybernetics is based on communication and information theory
particularly on feed back control systems.
Cybernetically organized system operates through signal that
transmit. It is similar to craniofacial growth as perception
transmission and storage of information.
Development of theory:-
Research has shown that Lateral Pterygoid Muscle plays a
regulating role in control of condylar cartilages growth
(Petrovic Stutzmann 1972)
Stutzman discovered that retrodiscal pad apparently has a
mediator role in efforts of Lateral Pterygoid muscle to control
condylar growth.

Based on research work in organ culture by Petrovic and
Stutzamann following dissimilarities concerning growth
of cartilage were identified.
Growth of 10 cartilage i.e. from differentiated chondroblasts
(epiphysis of long bone synchondroses and nasal septum)
appears to be subject to general extrinsic factors and more
specifically to Somatomedin (SMD), sex hormones, and
thyroxin. In this case ,effect of local biomechanic factors is
reduced to modulation of direction of growth with no effect
on amount of growth.
Growth of 20 cartilage results form cell division of
prechondroblasts (condylar coronoid and angular process of
the mandible) it is subject to local extrinsic factors. In this
case the amount of growth can also be modulated by
orthopedic appliances.

SERVO SYSTEM THEORY
According to this theory the influence of SMD on growth of
primary cartilage has a cybernetic form of constant command.
The influence of SMD on growth of secondary cartilage
combine direct and indirect effect on cell multiplication. The
indirect effects being the local factors involving primarily
neuromuscular mechanism affecting postural adjustment.
For examples: - The sagittal growth rates of the maxilla and
mandible are represented as a function of SMD testosterone
level with in the servo system limit.
Since maxillary growth is due to growth of 1 cartilage it grows
in proportion to levels of SMD and testosterone.
The condylar cartilage tries to adapt to maxillary growth by
increasing or decreasing LPM activity, which is the local
epigenetic factor.

METHODS OF STUDYING GROWTH

METHODS OF STUDYING GROWTH
 The evaluation of physical growth can be
done in 2 ways :-
1. Measurement approach.
2. Experimental approach.

MEASUREMENT APPROACHES
 It is based on the techniques for measuring
living animals (including humans), with the
implication that measurement itself does no
harm that the animal will be available for
additional measurements at another time.
 These include the following :-
1. Craniometry.
2. Anthropometry.
3. Cephalometric radiography.

CRANIOMETRY
It is based on the measurements of skull found
among human skeletal remains.
It has an advantage that these
measurements were made on dry skulls ;
its disadvantage is that all these growth data
must be cross-sectional .(same individual
can be measured only at one point of time).

ANTHROPOMETRY
In this technique, various landmarks established in
studies of dry skulls are measured using soft
tissue points overlying these bony landmarks.
These measurement can be done on both dried
skull or living individual, but the results would be
different because of the soft tissue thickness
overlying both landmarks.
Although the soft tissue introduces variation,
anthropometry does make it possible to follow
the growth of an individual directly, making the
same measurements repeatedly at different
times.

CEPHALOMETRIC RADIOLOGY
It is of considerable importance not only in the
study of growth but also in clinical evaluation in
orthodontic patients.
It allows a direct measurement of bony skeletal
dimensions, since the bone can be seen
through the soft tissue covering in a radiograph,
but it allows the same individual to be followed
over time.
Growth studies are done by superimposing a
tracing of a later cephalogram to a previous
one.

EXPERIMENTAL APPROACHES
 These include the following:-
1. Vital Staining.
2. Implant radiography.

VITAL STAINING
It is a technique in which growth is measured
by observing the pattern of stained
mineralized tissue after injection of the dyes
into the animal. Alizarin was found to be
active agent & it reacts strongly with calcium
at sites of active skeletal growth.(where
bone calcification is occuring).

IMPLANT RADIOGRAPHY
This method of study, was developed by
Prof. Arne Bjork & his co-workers.
In this technique, inert metal pins were
inserted anywhere in the skeleton including
face & jaws
Superimposing cephalometric radiographs
on the implants allow precise observation of
both changes in the position of one bone
relative to another & changes in external
contour of the individual bone.

GROWTH: PATTERN, VARIABILITY & TIMING

PATTERN
 Pattern reflects proportionality, usually a
comlex set of proportions.
 It includes both the spatial proportion of body
parts,as well as, changes in these spatial
proportions over time.
 Pattern has a string of predictability attached
to it.
 Thus we find:
a: Cephalo-caudal gradient of growth.
b: Scammon’s Curve

CEPHALO-CAUDAL GRADIENT OF GROWTH
 There is an axis of increased growth
extending from head towards the feet.
 It strongly affects proportions & leads to
changes in proportions with growth.
 There is more growth of lower limbs (parts
farther away from brain) during postnatal life.
 Mandible being farther away from brain,
tends to grow more & later than maxilla,
which is closer

Schematic representation of the changes in overall body proportions
during normal growth & development.
Proportion of total body size contributed by the head & face steadily
declines after 3rd month of IUL.

SCAMMON’S GROWTH CURVE
 Richard scammon reduced the growth curves of
the tisues of human body to four basic curves.
 All the tissues of the body do not grow at the
same rate.(muscular & skeletal elements grow
faster than brain & CNS.)
 Curves cover post natal period of 20 yrs.
 Four curves were proposed:
a: lymphoid
b: neural
c: general
d: genital

 LYMPHOID CURVE: includes thymus,
pharyngeal & tonsillar adenoids, lymph
nodes.
 Rise to nearly 200% between 10 to 15 yrs of
age.
 Reduction from 200% to 100% is mainly
achieved by involution of thymus.

 NEURAL CURVE: includes brain, spinal
cord, optic apparatus, vertebral column.
 Rises strongly during childhood.
 At age 8yrs brain is 95% of its adult size.
 Growth in size is accompanied by growth in
internal structures.

 GENERAL TISSUES: includes external
dimensions of the body, respiratory &
digestive organs, kidneya,musculature,
skeleton.
 S shape curve.
 Rapid growth upto 2-3 yrs,followed by slow
phase of growth between 3-10yrs.
 After 10th year a rapid phase of growth
occurs terminating by the 18-20 yr.

 GENITAL CURVE: includes primary sex
apparatus & all secondary sex traits.
 Small upturn in first year of life.
 Then quiescent till10 years of age
 Rapid upturn at the time of puberty, reaching
to maximum.

VARIABILITY
 Everyone is not alike in the way they grow.
 Its important to decide whether an individual
is merely at the extreme of normal variation
or falls outside the normal range.
 Rather than categorizing people as normal or
abnormal, it is more useful to think in terms
of deviation from the usual pattern & express
variability quantitatively.

One way to do this is to evaluate a given child
relative to peers on a Standard Growth Chart.
HELPFUL IN TWO WAYS:
 Firstly, location of an individual relative to the group
can be established.
 Secondly, they can be used to follow a child over
time to evaluate whether there is an unexpected
change in the growth pattern.

TIMING
 In different individuals events happen at
different times.
 Biological clock is set differently for different
individuals.
 Variation in timing arises because same
event happens for different individuals at
different times.
 Ex Onset of puberty in males & females, and
Variation in timing of growth spurts

Variations in growth & development due to timing are
evident in human adolescence.
Some mature early & some at a later stage

GROWTH SPURTS/ADOLESCENT SPURT
/PREPUBERTAL ACCELERATION
/CIRCUMPUBERTAL ACCELERATION
 Growth does not take place uniformly at all
times.
 These are periods of sudden acceleration of
growth.
 Some children grow rapidly, mature early
completing their growth quickly & thereby
appearing on high side of developmental
charts.

M F
First Peak 3 years 3years
Second Peak 7-9 years 6-7 years
(Mixed dentition spurts
Third Peak 14-16 11-13 years
(pubertal spurt)

 Timing of growth spurts:
It is different for boys & girls:
A: Just before birth
B: One year after birth
C: Mixed dentition growth spurt:
boys: 8-11 years
girls: 7-9 years
D: Pre-pubertal growth spurt:
boys: 14-16 yrs.
girls: 11-13 yrs.

GROWTH IN HEIGHT
 During spurt boys grow about 8inches in
height whereas girls grow about 6 inches.
 In girls menarche always follows peak
velocity of the adolescent spurt in height.
 The spurt in height begins at:
in girls: 10 ½ - 11 yrs
in boys: 12 ½ - 13 yrs
This spurt lasts for 2 yrs in both sexes.

GROWTH IN WEIGHT
 The velocity of weight growth decreases from
birth to about 2 yrs of age after which it
slowly accelerates untill the onset of the
adolescent spurt.
 Timing of adolescent weight spurt:
in girls: 12yrs
in boys: 14yrs
During spurt boys may add upto 35 pounds &
girls 35 pounds.

EFFECT OF GROWTH SPURT ON ORTHODONTIC
TREATMENT
 Growth modification by means of functional &
orthodontic appliances elicit better results
during growth spurts.
 Surgical correction involving maxilla &
mandible should be carried out only after
cessation of growth spurt.

RHYTHM OF GROWTH
 There is a great individual & a considerable
group variation in the inception, intensity &
duration of the various phases of the growth
rhythm.
 The maintenance of an adequate rate of
growth is more important than the actual
height or weight attained

 Hooton describes the “Rhythm of Growth”
as follows :-
 Human growth is not a steady & uniform
process of accretion in which all parts of
body enlarge at a same rate & the increment
of 1 year is equal to that of the preceding
year .
 The first & the most rapid movement of the
growth rhythm extends in both sexes from
birth to the fifth or sixth year .It is most
intense & rapid during the first 2 yrs.

 This follows a slower increase, terminating in
boys about the 10 to 12 yr & girls no later
than 10 yrs.
 After that both sexes enter upon another
period of accelerated growth which is
completed in girls between 14-16 yrs & in
boys from 16-18 yrs.
 But the final period of slow growth ends
between 18-20 yrs in female, but does not
terminate in boys until about the 25 yrs.

REFERENCES
1. Melvin L. Moss, The functional matrix hypothesis revisited. 1. The
role of mechanotransduction AJO-DO Volume 112(1) 1997 , pg 8
- 11
2. Melvin L. Moss, The functional matrix hypothesis revisited. 2. The
role of an osseous connected cellular network AJO-DO Volume
112(2)1997 , pg 221 - 226
3. Melvin L. Moss, DDS, PhD The functional matrix hypothesis
revisited. 3. The genomic thesis AJO-DO Volume112(3) 1997 , pg
338 - 342
4. Melvin L. Moss The functional matrix hypothesis revisited 4. The
epigenetic antithesis and the resolving synthesis, AJO-DO
Volume112(4) 1997, pg 410 - 417
 Contemporary orthodontics:4th edition William R Proffit.
 Orthodontics:- current principles & techniques: 3rd edition: Graber
TM
 Handbook of orthodontics:4th edition:Moyers
 Facial growth:3rd edition: Enlow
 Textbook of orthodontics:Samir E Bishara.
 Dentofacial orthopedics with functional appliances:2nd edition
Graber,Petrovic,Rakosi

Growth & development general concepts/endodontic courses

Recomendados

Recomendados

Mais conteúdo relacionado

Mais procurados

Mais procurados (20)

Semelhante a Growth & development general concepts/endodontic courses

Semelhante a Growth & development general concepts/endodontic courses (20)

Mais de Indian dental academy

Mais de Indian dental academy (20)

Último

Último (20)

Growth & development general concepts/endodontic courses