TISSUE ENGINEERING FOR ORTHODONTISTS

Biological Mechanisms of Tooth Eruption, Resorption and Movement

Edited by Davidovitch Z, Mah J and Suthanarak S, pages 385-410 © 2006
Harvard Society for the Advancement of Orthodontics, Boston, Massachusetts, USA

In vivo tissue engineering for

orthodontists: a modest first step ©

Neal C Murphy

Case Western Reserve University, School of Dental Medicine, Cleveland, Ohio, USA

Key Words: Tissue Engineering, Orthodontics, Periorthodontic, Orthopedic, Phenotype

Introduction to surgical dentoalveolar this evolution of literature, however, to our knowledge,

orthopedics no attempt was made to engineer a new regional
Twentieth Century orthodontists generally limited their phenotype by moving teeth through a healing bone graft
mission to the movement of teeth, allowing alveolar and redefining morphotype de novo prior to the seminal
bone to simply remodel naturally around the dental works of Wilcko and Wilcko. While Professor Johnston6
roots without specific concern for the form of alveolar has lamented the “death of theory” in orthodontics,
crest topography. However the destiny of Twenty-first this author, and others who enjoy the emerging clinical
Century orthodontists may lie within a greater vision. discipline of peri-orthodontics, certainly do not. We
Because the alveolar bone exists at the grace of the believe theory is alive and well in the young and eager
teeth, orthodontists may develop a method of mani- minds of thoughtful clinicians.
pulating or “morphing” bone, indeed even facial con- The aim of this paper is to review the dentofacial
tours, by employing a combination of surgical manipula- physiology that can be manipulated with a combination
tion and traditional biomechanical protocols. Specifically, of periodontal and orthodontic treatment. But in a larger
the alveolar bone, and perhaps even subjacent bone, sense, as a student of Professor Johnston it will hope-
can be reshaped by altering root positions in combination fully engender provocative ideas among basic science
with well-documented methods of elementary periodontal students and dentists to revive the hope of new theoretical
surgery and even modern regenerative techniques in horizons in facial orthopedics, unveiled by organized
some cases. collaboration.
A concept as old as the 1920’s,1 the movement of Bone morphing: the basic concept Based on the
teeth to alter alveolar osseous crest topography was tissue engineering literature, the physiology of alveolar
clinically popularized in the 1970’s.2, 3, 4 and reviewed bone itself can be altered with manifold collections
by Mihram and others in the late 1990’s.5 Throughout of clinical procedures that elicit what Frost7 called
Address Correspondence to: Dr. Neal C Murphy, 5400 Balboa Blvd., Encino, CA 91316, USA; Email: neal.murphy@case.edu

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“accelerating remodeling”. Collectively, they represent in the German literature of the 19th Century, have been
variable methods of what we denote as peri-orthodontic refined by numerous authors over the last 40 years,
surgery. Salient among these and the most evidence- since they were translated to English and published by
based is the unique combination of bone grafting and Kole in 1959.8 They have been scrutinized by the
therapeutic tensional stress application, known a rigorous scholarship of dental clinical investigators at
Periodontally Accelerated Osteogenic OrthodonticsTM, Loma Linda, St. Louis and Boston Universities since
or PAOOTM.* Other less sophisticated methods simply the 1990’s. In the evolution of this periorthodontic
induce a transient and reversible osteopenia through modality, special mention should be made about the
surgical perturbation of the alveolar cortex or adjacent pedagogical achievements of the WilckodonticsTM group
soft tissue. Depending on the treatment objectives, this of collaborators, especially the principals. The contri-
is done with or without endosseous implants, orthopedic butions they have made are difficult to overstate; history
force devices, or pharmaceutical agents. will no doubt see their work as an intellectual watershed
When this surgery is combined with a light (physio- in the specialty of orthodontics.
logic) force application to teeth, the result is (1) Some surgical protocols have proposed techniques
accelerated rates of tooth movement, as great as 400%, that attempt deep interproximal bony incisions connecting
(2) reduced appliance adjustment pain, (3) fewer side the buccal and lingual surfaces, sometimes with luxation
effects (e.g. root resorption), and (4) greater stability of the dentoalveolar unit. Most clinicians experienced
through the creation of a novel local osseous phenotype. in periorthodontic surgery do not endorse this method,
Another way to conceive the premises of this discussion because aggressive segmental osteotomies risk necrosis
is to view peri-orthodontic surgery as a bone-based of the dentoalveolar unit and of the dental pulp. Modern
equivalent of circumferential supracrestal fiberotomy. refinements of these rudimentary decortication techniques
The cellular and biochemical mechanisms, while now involve defined linear and/or punctuate decortication
somewhat enigmatic, are presumed to involve pharmaco- of the buccal and lingual alveolar cortex, 1-2 mm deep
logic stimulation of undifferentiated mesenchymal stem (Fig. 1). Although this illustration follows the Wilcko-
cells of the spongiosa. donticsTM protocol, the actual manipulation can be made
The pharmacology employs standard clinically- with a surgical blade, special hand instruments, or nearly
popular agents with or without carriers or biodegradable any kind of high or low speed rotary bur. The arma-
constructs. These agents include a host of growth factors mentaria are important, but should not be overemphasized
(GF) such as human bone morphogenetic protein (hBMP-2) as a short order recipe for success. Indeed, emphasizing
and human platelet derived growth factor, (PDGF) the instruments misses the central point of this paper
delivered in situ. Most familiar to periodontists and by a mile.
medical orthopedists is demineralized bone matrix The objective of selective alveolar decortication is
(DBM)** and other commonly produced tissue regene- to decalcify and reduce the mass of interproximal bone
rative materials. to a degree commensurate with an optimal amount of
By moving teeth through the healing surgical site applied force. The amount of reactive regional osteopenia
we postulate that new root positions provide an improved (mild osteoporosis) caused by this manipulation allows
spatial matrix for the bone and tensional stress on the the orthodontist to give patients an accelerated rate of
teeth act in a synergistic manner with GF, or specifically orthodontic tooth movement and when grafted, a new
DBM augmentation to redefine local bone mass and regional phenotype into which teeth can be moved. The
bone topography (morphotype). When combined with movement of the teeth seems to perpetuate the osteopenic
conventional orthodontic tooth-borne appliances, a kind state past the usual 4-6 months naturally induced by
of “distraction osteogenesis” occurs, which is neither decortication or even some adjacent soft tissue surgery.
7, 9
experimental, nor a totally new technique; it is a synthe- Decortication, however, does more than decalcify
sis or orchestration of prior data. Initial works, reported local bone to facilitate tooth movement. At its best, it
* aka : Accelerated Osteogenic OrthodonticsTM, or AOOTM trademarks of Wilckodontics, Inc.TM, Erie, PA USA
see: www.wilckodontics.com
**aka: demineralized freeze-dried bone allograft, (DFDBA)

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A B C

Fig. 1 Periodontally-accelerated osteogenic orthodontics (PAOOTM) refers to the combination of subperiosteal cortical scarification (“selective
alveolar decortication”) in a linear or punctuate pattern, and supplemented with a bone graft. The scarification is meant to elicit the regional
acceleratory phenomenon (RAP) of Frost and Jee. The bone graft provides lateral alveolar augmentation, to receive the “expanded” dental
arch successfully. A. is a schematic of the cortical scarification or decortication pattern, B. is the actual surgery. At this point the alveolar bone
will manifest Frost and Jee’s Regional Acceleratory Phenomenon, a therapeutically-induced, reversible, and localized osteopenia, through which
dental roots move about 400% faster than conventional orthodontics therapy would dictate. This also produces markedly less relapse and less
pain during appliance adjustments. Curiously, the teeth do not necessarily demonstrate more individual mobility. If sufficient labial bone is
present no graft is needed. C. demonstrates the supplemental admixture of demineralized freeze-dried bone allograft (DFDBA), also known as
demineralized bone matrix (DBM), and mineralized bovine-derived graft extender. This supplement is recommended where the surgeon notes
dehiscence or fenestration upon surgical flap reflection, or wishes to extend the labial buccal plate of alveolar bone.
From: Wilcko, WM and Ferguson, DJ et al, World J Orthod 4: 205, 2003, with permission. See also, Wilcko, WM, Wilcko MT, Bouquot JE,
and Ferguson DJ: Rapid orthodontics with alveolar reshaping: two case reports of decrowding. Int J. Periodontics Restorative Dent 21:
9119, 2001

liberates marrow stem cells, stimulates neovasculari-

zation, and exposes endogenous mesenchymal stem
cells to growth factors (e.g. hBMP-2).
The reconstitution of a stable convexity at the
mandibular symphysis (cephalometric A and B points),
regardless of the convexity apparent during grafting,
itself represents a kind of morphogenetic homeostasis
and therapeutic end-point marker, defined by a matrix of
root positions and newly engineered bone mass. (Fig. 2)
We denote this recurrent convexity at cephalometric A
and B points as the Wilcko Curve in homage to its
discoverer, Dr. William M. Wilcko, of Erie, Pennsyl-
vania, USA.
We speculate that the further development of recom-
binant growth factors will allow orthodontists to modulate A B
the shape of bone more discretely in the future. Helpful
in this regard is the consistently successful and popular Fig. 2 Despite the amount of grafted bone, a regional labial cortical
techniques of Wilcko and Wilcko* and especially the concavity appears at cephalometric B point. The radius of the curve
PAOOTM protocol, because they have been so widely is determined by the angle of the lower incisor to the mandibular
validated by prior students, independent collaborators plane, and we speculate the curve is centenary. For lack of a better
and numerous researchers at St. Louis and Boston Uni- term, we rely on the eponym “Wilcko Curve,” and speculate that it
represents a marker of regional morphogenetic homeostasis and a
* PAOOTM and Periodontally Accelerated Osteogenic OrthodonticsTM therapeutic endpoint. Note the stable increase in labio-lingual
are trademarks of Wilckodontics, Inc., Eire, Pennsylvania, USA
See: www.wilckodontics.com dimension of the alveolus.

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versities.* Although the protocol is trademarked for

the sake of intellectual integrity, no limitation on its
use in professional practice is invoked. The specific
technique developed by Drs. Wilcko, the addition of an
allograft to a refinement of prior work, constitutes an
ingenious and significant leap in the evolution of sur-
gically-facilitated tooth movement.
Theoretically, it is entirely consistent with the tradi-
tional concepts based on Moss’s Functional Matrix
Hypothesis10 and a logical next step for both modern
molecular biology and clinical genetics. In this regard
it is not dissimilar to surgical orthopedic protocols desig-
ned to treat talipes equinovarus. This approach freely
exploits the established techniques in conventional
periodontal regenerative surgery and demonstrates the Fig. 3 Demonstration of cytoskeleton which we believe is altered in
fruitful results of collegial interdisciplinary collaboration, bone cells during orthodontic therapy.
which is somewhat rare in our modern and sadly insular
private practices. In this regard the fact that the Drs. has defined modern periodontology, little is done in the
Wilcko worked alone, were not endowed or salaried specialty to enhance the function and esthetics of asso-
academics, and were entirely self-funded, makes their ciated teeth or alter periodontal architecture for the
professional contributions and personal sacrifices most orthodontic patient in health. The use of somatic cell
astounding. therapy in periodontics (bone grafting) is generally
It is important to realize that the surgery involved referred to as regenerative therapy, but when growth
here is not merely spatial restructuring, but rather the factors are used to alter genetic expression and mor-
purposeful alteration and modulation of the basic pro- photype by exploiting phenotypic plasticity, surgery
cesses of bone physiology that regulate remodeling: enters the realm of tissue engineering. It is speculated
osteoclastic resorption, ostecytic osteolysis, and osteo- by the author that mechanical tension is directly trans-
genesis. It exploits standard somatic cell therapy (gra- ferred to the nuclear cytoskeleton,12 perhaps by opening
fting) with gene therapy (growth factors) in an attempt nuclear pores to the effects of rhBMP-2 and other
to re-route the trajectory of regional morphogenesis to ligands; conformational change in the nuclear DNA,
a predetermined prescription. Because we think mesen- then produces novel genetic expressions, ultimately
chymal stem cells react synergistically in fields of defined by the functional tensional distortions and spatial
tensional stress when they are exposed to growth factors matrix of the dental roots. This hypothesis derives largely
(BMP-2), the techniques we review here speak not as an extension of the work by Ingber et al., and attempts,
merely to issues of standard biomechanics and regional on a molecular biologic basis, to explain how applied
osteogenesis within a fixed phenotype, but rather to force can alter intracellular activity through the altera-
more profound issues of surgically and pharmacologically tion of cytoskeleton tensegrity13 (Figs. 3, 4). An aphorism
modulated mechano-biology.11 which captures the essence of our hypothesis is the
Tissue Engineering for the Orthodontist Tissue basic syllogism:
engineering is the application of engineering and life
science principles using stem cells, growth factors, and Orthodontic force bends bone
mechanical stress, to replace, alter, enhance, or replicate Bending Bone bends DNA,12
human tissues and organs.** While the repair and re- Ergo, orthodontic force bends proteins responsible
generation of diseased or damaged periodontal structures for the genetic expression of DNA
* For a complete list of relevant research projects seeththe Appendix.
**Mao, J American Association of Orthodontists, 10 Annual Meeting, San Francisco, CA USA May 20-24, 2005. The regeneration of bone
with grafts is somatic cell therapy. When genetic potentials are upregulated the theoretical domain changes to gene therapy. Together in a clinical
setting they constitute the general field of tissue engineering in vivo.

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Fig. 4 Artist’s (Matt Pickett) rendition of tensegrity of the cytoskeleton, we hypothesize is altered by orthodontic force. Source: The laboratory
of Dr. Donald Ingber, Harvard University.

Or the mnemonic: All that is needed for producing intellectual synthesis

O→ B→D is visionary academic insight and the aggregate support
Implicit in this logic is the concept that clinical force of intrepid, academically oriented clinicians. That may
alters cytoskeletal shape and protein conformations already be a fait accompli, considering seminal articles
that account for intracellular biochemical behavior. Con- by Urist 17 Wilcko and Wilcko18 Fiorellini19 and Nevins,
sequently, cytoskeletal activity alters protein synthesis et al,20 and the original visions upon which these theses
of a new and stable regional phenotype. We suggest that have developed.
the operative signal transduction converting mechanical Most modern orthodontists rely upon standard forces
signal to these biochemical events is mediated by the delivered by conventional fixed appliances. While fixed
osteocyte-canalliculi syncytium,12, 14 in addition to the appliances have proven efficient in moving teeth, they
undeniable, but overly simplistic events described in the are problematic for a number of reasons. Chief among
classic periodontal “pressure-tension” model. these is a limited bony base, and infection. The former
Unfortunately, without retention, long term stability may ostensibly dictate the sacrifice of healthy teeth.
of conventional orthodontic mechanotherpay may be The latter can cause pathologic tissue hyperplasia or
lower than 30%.15 Thanks to modern tissue engineering exacerbation of incipient periodontitis even in teenage
principles, this exceedingly high incidence of unretained patients.21 We prefer herein to propose complementary
relapse may be routinely avoided with surgical recon- ideas which overcome theses limits through the entire
stitution of the bony alveolar base. Tissue engineering gamut of enhanced tooth movement surgery, collectively
integrates dental specialties in a context that expands referred to as periorthodontic surgery. These novel
the horizons of each, and portends a future filled with clinical protocols can minimize problems inherent in
collaborative enterprises defined by common experience, traditional care by making orthodontic care less socially
need, and expertise. obtrusive, safer, and faster, and PAOOTM is especially
This development, of course, represents a significant noteworthy, because of its ability to obviate any need
alteration of conventional thinking to the average ortho- for bicuspid extraction in some cases through bony
dontist. Technically, however, these concepts are aug- base extension.
mentations and refinements, not contradictions or invita- Thus, the orthodontist can use these techniques to
tions to abandon convention; they simply incorporate reach a vast untreated cohort of underserved patients
basic periodontal concepts to his or her standard ortho- who are not willing to take the time of conventional
pedic sensibilities. Nonetheless, old habits die hard, fixed appliance therapy, disdain extractions or simple
especially fundamental habits of thinking. Although orthognathic surgery, or are simply compromised by
altering paradigms is indeed a daunting pursuit,16 it periodontal disease. Periodontists can also expand their
remains, nonetheless, a categorical imperative for the sphere of responsibilities by collaborating with ortho-
dental educator, and the manifest destiny of the 21st dontists or simply use tissue engineering principles and
Century dental specialist. That destiny has already been tooth movement to enhance traditional periodontal
cast in modern biology and clinical genetics. The therapeutic objectives.
specialties are each ready and so is the basic science. The concept of optimal response The holy grail
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of clinical orthodontics has been the elusive and highly

individual optimal force.22 This is roughly defined as
an applied force, which moves teeth as fast as possible,
with as little morbidity as necessary. The protocol ex-
plained herein may render the quixotic search for optimal
force rather moot, because it proffers a surgically orche-
strated optimal response, defined as an engineered res-
ponse of affected bone, to move teeth as fast as possible,
with as little morbidity as necessary. Systemic alteration
of the bony supporting tissue has been addressed pre-
viously in orthodontic literature by researchers on ani-
mals,23, 24 but not on a regional basis. Previous reports
of accelerated tooth movement by “distraction osteo-
genesis of the periodontal ligament” 25, 26 come close to Fig. 5 Generalized bony dehiscence of labial alveolar bone upon
the concept we describe, but no genetic mechanism is flap reflection. Generally, when palpated clinically, this pattern of
engaged. What is important is not merely the surgical root prominence (“wash-board” topography in clinical orthodontic
manipulation of soft tissue and bone, but rather an parlance) serves as an indication for bicuspid extraction if the alveolar
appreciation of the underlying physiology and the cellular bone is presumed to be immutable. Extraction, however, may be
dynamics of epigenetic expression. undesirable by the patient, and may in some cases lead to a flattening
The techniques we describe in this paper attempt to or “dished-in” appearance of the lower face in the third or fourth
modulate natural healing events. Moving teeth during decade after orthodontic therapy. The universal immutability of
surgical healing simply perpetuates a reactive osteopenic alveolar bone is the axiom which we reject for the purposes of
state similar to the delayed healing of long bones when scientific arguments in this paper.
fractured but incompletely stabilized. Both produce a
kind of “mal-union”. Thus, in effect, the peri-ortho-
dontic approach recruits and perpetuates, as a therapeutic or linear removal of the facial and lingual cortical plate
adjunct, what have traditionally been considered pathoses after reflecting a mucoperiosteal surgical flap (Fig. 5).
(osteoporosis, osteopenia, malunion, delayed callus Demineralized bone matrix may be used to augment
maturation) in clinical medicine. The difference between “basal bone” when fenestrations or dehiscence are noted
pathosis and therapy is the ability to control the process. upon flap reflection, or when the orthodontist needs a
Practically speaking, the only concern is the need for larger bony base to avoid extraction of healthy bicuspid
weekly or biweekly adjustments. teeth. Otherwise, it is not necessary where labial bone
Without applied stress (tension, compression and is surfeit (Figs. 6, 7). Addition of GF directly or through
shear forces) on teeth, the bone “heals” itself by rever- DBM sanctifies the surgery as genetic manipulation
ting to its former homeostatic and highly calcified “steady (gene therapy). In contrast, grafting that only intends
state”. Morphology is then determined by gravity, to regenerative bone lost in an unstressed and fixed
muscle pull and dental forces. When this occurs following phenotype is referred to as somatic cell therapy. As any
peri-orthodontic surgery and prior to the completion of experienced periodontists will attest, this is not sufficient
orthodontic objectives, a site-specific surgical revision to “grow bone on a flat surface”. Thus simple lateral
may be needed in some cases. In the author’s experience, augmentation of the alveolus is impossible where grafting
most patients accept this minor inconvenience as an is done without the benefit of a field of orthodontic
acceptable trade-off for enhanced clinical efficiency, and tensional stress.
the merits of non-extraction treatment. What takes two Any number of methods may be employed to
years to achieve with conventional care may then be stimulate regional osteopenia, but the specific technique
accomplished in as little as six months. that has received most of the research is the procedure
The clinical techniques: a summary The desired described by Suya,27 and investigated thoroughly at
therapeutic state of bone to achieve optimal response is Loma Linda University. This is what has been refined
induced by selective alveolar decortication, viz. punctuate and developed into a regenerative procedure named the
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Fig. 6 Computerized tomography rendering of bony dehiscence Fig. 7 Computerized tomography of new bone formation around
prior to orthodontic therapy by the PAOOTM protocol. the teeth after PAOOTM therapy.

Periodontally-Accelerated Osteogenic OrthodonticsTM

technique or PAOOTM. The exact procedure of the latter
produces consistent outcomes that have been demon-
strated in numerous studies by Wilcko, Ferguson, et al28
While variations on the central theme of peri-orthodontic
surgical manipulation have yet to receive extensive do-
cumentation, the PAOOTM has been subjected to signifi-
cant formal scientific scrutiny and presents the most
dramatic example of concepts developed here. If not an
archetype for periodontal-orthodontic collaboration, it
certainly commands utmost respect; the reader is strongly
encouraged to secure formal education at the Wilcko-
donticsTM teaching facility in Erie, PA USA prior to
commencing any of their formal protocols.
The actual techniques range from mild scarification Fig. 8 Osteopenia (mild osteoporosis) is exemplified in these
to widespread regional decortication, with or without renderings from Image Source: www.nucleusinc.com
allograft supplementation, to produce varying degrees
of regional osteopenia (Fig. 8). The more the bone is The actual dose of BMP-2 added and the amount of
decorticated, the more it is rendered osteopenic, and subperiosteal scarification cannot be accurately stan-
the more proliferative granulation tissue will be elicited dardized for every procedure, because the degree of
at the surgical site. Moreover, greater numbers of undif- optimal response depends on the type of surgery, dosage
31
ferentiated mesenchymal cells are exposed to applied and natural biologic diversity of individual patient’s
growth factors when larger areas of bone are stimulated bone physiology. Prescribing an exact dose for what is
to produce neovascularization. This fact is important, often an individual- and site-specific response is proble-
because bone morphogenetic proteins in allografts may matic at best, and perhaps better consigned to the inviola-
further increase the osteogenic potential 29 as it binds to ble realm of individual clinical art in the hands of each
heparin sulfate, heparin and the type IV collagen in the surgeon. For example, the concentration of BMP within
endothelial basement membrane.30 an effective demineralized bone matrix (DBM)* is
* aka DFDBA, demineralized freeze-dried allograft. Musculoskeletatal Transplant foundation, (MTF) Edison, NJ 08837 & Regeneration Technologies
Inc. (RTI), Alachua, FL USA

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measured in picograms, while the amount of recom- selected laboratory rats. Concentrations of growth factor
binant human bone morphogenetic protein in absorbable can be altered by adding recombinant growth factor
collagen sponge often used for spinal fusion (rhBMP-2/ (rhBmp-2) directly into the grafted bone, with absorbable
ABS)* may be as high as 1.5 mg/cc.** The exact con- collagen sponges.33, 34 Xenografts and synthetic material
centration is an area of research that needs further work. may be “osteo-conductive,” but it may not be adequate
Unfortunately, no explanation is available to account just to establish a scaffold for bone growth. It seems
for the effective-dose disparity between the spinal fusion that osteo-induction must occur, and many synthetics
surgery and PAOOTM. Such information should inspire or xenografts are devoid of GF necessary for induction.
more research in both animals and humans, because it Therefore, they should be avoided, since they do not
would directly benefit medicine, as well as dentistry, appear to possess significant osteogenic potential.
with its basic science discoveries. Reportedly, the PAOOTM uses bovine derived mate-
Some patients demonstrate an immediate response rial, but only as a graft extender, not as an operative
to force, within hours, with a rate of tooth movement component for osteogenesis. Interestingly, recombinant
of about 1-2 mm per week. Others demonstrate a latent growth factor per se may even prove to be superior to
period of approximately 3-4 weeks, in which no move- autografts, if the quality of the graft is more important
ment is evident, and then suddenly display the same than merely the volumetric displacement of alveolar
kind of acceleration seen directly after surgery by others. periosteum. For example, Kawamoto et al. reported that
This author agrees with others in emphasizing the point in a dog study, rhBMP-2 regenerated more bone than
that absolutely no luxation of the dentoalveolar unit an autograft of tibial spongiosa.35
is involved with these surgical methods. Also, the unfor- While the best evidence suggests an important role
tunate use of the term corticotomy is often associated for GF, we cannot categorically rule out the possibility
with this kind of clinical project, but is eschewed here that volumetric distension of the periosteum itself is an
because of its indiscriminant use in a wide variety of important factor in achieving clinical results. It too is a
desirable and undesirable surgical protocols. functional matrix of bone.36-41
When systemic corticosteroids are given around Once the bone graft is secured under a replaced
the time of the surgery (parenteral or per os), a more mucoperiosteal flap, the orthodontic appliance can be
prolific osteopenic environment is produced for grafting, activated every 7-14 days. However, pharmaceutical
and the patients’ postoperative course is more benign. anti-inflammatory agents should not be used beyond
Caveat: this should be done prudently; package insert the immediate post-operative period. The protracted use
injunctions should be heeded seriously, because of of non-steroidal anti-inflammatory medications (NSAID’
systemic effects for which this drug is renowned. Auto- s) purportedly inhibits prostaglandin release, and thus
genous bone can be secured from intraoral sites, the retards inflammation-dependent movement of teeth if
anterior iliac crest, or the proximal tibial metaphysis. the analgesic is taken for an inordinate period of time.
Allografts, however, are effective and convenient. Yet, Although pharmacologic or surgical techniques may
they must be carefully selected, because commercial be learned by practice and good scholarship, what is
sources often deliver a wide variety of BMP-2 concen- critically important to understand is the underlying
trations. It is also important to understand if the sources concept of orchestrated bone physiology and modern
of donor allografts are intramembranous or endochondral, molecular biology. This knowledge helps enhance the
since the two sources may not provide equal osteogenic conceptualization of these new protocols, many of which
potential in situ.32 are frankly counterintuitive to the neophyte orthodontic
It is preferred to secure allografts from laboratories clinician. In this regard, a helpful analogue may be
that test the BMP-2 concentration in each bone product found in the lexicon of infectious disease management:
lot. It is important to know if the donor was old or host modulation. This is a commonly used term in
young, but regardless of the source the gold standard is engineering, and certainly modulation is occurring in
the “Urist Test”, viz. ectopic calcification in specially- the tissue as variable degrees of surgical manipulation
* aka Accelerated Osteogenic Orthodontics? or AAO?
**Medtronic Sofamor Danek, Memphis, TN USA

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Fig. 9 Minimal decortication, where minimal RAP is preferred. Fig. 10 Deep decortication, where significant RAP is desired

are engaged. In engineering theory, the patient is to be directs the trajectories and qualitative nature of new
considered as a biological system receiving exogenous woven bone to a predetermined morphotype prescription.
stimuli (input) in a second order cybernetic.* That Some experienced clinicians begin appliance activation
evokes variable individual feedback responses (output), (mechanobiologic stimulation) two weeks after surgery,
46
which are noted for “fine tuning”. Thus, the analogy is while this author and others apply force immediately
clearly fitting. In fact, some orthodontists already have upon flap closure. The relative benefit of each approach
a firm intuitive grasp of the epigenetic** potential of is not clearly defined, but since medical DO is often
the host modulation concept as a clinical indication in delayed until after an appropriate “latency”, waiting
the mixed dentition, to extract or hemisect deciduous may be more advisable.47
teeth.42 The difference may depend on the degree of inflam-
Regional osteopenia can result from simply elevation mation elicited in each individual patient, or on whether
a mucoperiosteal flap,9 but a more profound and regu- the tissue is inflamed prior to the surgical entry. In any
lated decalcification through variable degrees of decor- event, other authorities have demonstrated that after 4
tication are preferred. (Figs. 9, 10). This surgical weeks of healing, most bone grafts have integrated to
manipulation provides the orthodontist with a relatively the point where tooth movement into the grafted site
“force-friendly” environment to stimulate normal bone can proceed with impunity.48 Healthy bone remodeling
repair, but it does more. Decorticating the alveolus also is then coordinated by controlled therapeutic stress on
stimulates local angiogenesis. This effect is important the healing bone-graft-growth factor complex. In some
because mesenchymal stem cells are also present in cases this surgical manipulation can obviate the need
artery walls, smaller vessels and may even enter the for more extensive orthognathic surgery. Controlled
general circulation. 43-45 clinical studies by Ferguson et al49 have demonstrated
Whether through autografts, allografts, or collagen that this classic technique and its growth factor
sponges, the placement of BMP-2 directly in the surgical refinement also can minimize side effects of conventional
site may be immaterial, as long as it is delivered in orthodontic care, such as relapse, root resorption, and
purported threshold concentration for the particular adjustment pain, while still achieving an overall clinical
patient. It appears to interact with signal transduction outcome superior to conventional therapy.50
of the osteocyte-canalliculi syncytium, the principal agent Limited-objective orthodontic therapy to produce
converting mechanical stress to biochemical events. physiologic interradicular distance or upright abutments
Although the graft and growth factor seem critical, can employ this protocol as an embellishment to con-
they cannot augment alveolar bone alone in a fixed ventional pre-prosthetic surgery. However, patients with
phenotype; it is the modulated orthodontic force which severe orthognathic or arch-length-tooth size discrepancies
* See: Reference 20 in Suggested Reading
** epigenesis, (def) – the theory that specialized tissue develops through interaction of genotype and environmental perturbation.

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and compromised alveolar bone should secure an ortho- patients realize that the efficacy of the procedure is
dontist to plan a comprehensive mechano-therapeutic well documented, the clinical outcome lasts for decades,
protocol in collaboration with a periodontist and/or and that reduction in oral sepsis is easier, many patients
maxillofacial surgeon. become so enamored with their own progress that they
Acceleration of Orthodontic Tooth Movement proselytize coworkers and family members who have
Although most clinical orthodontists generally work with malocclusion. Patient testimonials are available on the
tooth movement rates of about 1mm per month, we World Wide Web and in video format.*
have been able to obtain physiologic tooth movement at It is fortunate that expediting orthodontic therapy
the rate of about 1-2 mm per week; others have reported and facilitating dentofacial orthopedic development has
rates as fast as 0.8 mm/day under similar conditions.51 met with enthusiastic acceptance by patients. From a
Since much clinic time is dedicated to managing ancho- professional perspective, efficient tooth movement is
rage, peri-orthodontic techniques can be used effectively also important, because the accumulation of bacterial
with mini-screw and implant orthodontic anchors. The damage is time related. This means that a prolonged
recent advent of implant-supported (absolute or perfect) time in fixed appliances necessarily exposes the gingival
anchorage52, 53 can free the orthodontist from vexing tissues to elevated bacterial loads, and allows a qualitative
concerns about anchorage, as long as the surgery is not microbial shift to more virulent gram-negative anaerobic
performed closer than 1 cm to the implant. The osteo- species, which are particularly destructive to the perio-
penia or regional acceleratory phenomenon, RAP, seems dontal attachment.
to extend no further than a 4-5 mm radius, but this is Treating adults always risks an exacerbation of
conjectural data. Researchers are presently investigating coincident periodontitis. So, intuitively, one may suspect
this issue. If PAOOTM or other peri-orthodontic methods that moving teeth quickly would increase the risk of
are employed with implant-secured devices; absolute periodontal attachment loss, but paradoxically just
anchorage is effectively amplified relative to peri- the opposite is true. If sound judgment is implemented,
orthodontically treated sites. and the alveolar bone calcium tissue perfusion is ade-
quately modulated, then accelerated tooth movement
Real Patients, Private Practice: the can be achieved with reasonable impunity. Thus, faster
Psychosocial and Periodontal Dimension treatment with peri-orthodontic surgeries is a safe treat-
This paper emphasizes theory but it is the “real world” ment modality. However, it is important to realize that
of private practice that literally defines both the needs well orchestrated orthodontic tooth movement resulting
of patients and the destiny of the profession. Fortunately, in a net displacement of teeth in space is qualitatively
in the author’s experience and from the testimonials different from the more destructive oscillating or “jig-
of other clinicians we have noted an almost universal gling” force seen in traumatogenic occlusion and
appreciation if not enthusiasm for accelerated tooth bruxism. Complicating occlusal factors should be avoided
movement therapies. It is speculated that many patients, or treated as they occur. All the parameters of good
especially adults, have latent desires for improved facial quality care cannot be abandoned with these new
appearance without reducing tooth structure that techniques. Otherwise, one sacrifices classic verities
accompanies prosthodontic preparation. Yet they are on the alter of innovation. If the orthodontist cannot
caught in a dilemma between desire for self-actualization, equilibrate his final case to a mutually protected occlusion
and fears of social stigmata, or internally perceived after settling, and properly eliminate occlusal pre-
vanity. Therefore, it is imperative that patients under- maturities during therapy as the need arises, these
stand that well aligned teeth do indeed produce a healthier techniques should await further fundamental dental
environment than a crowded dentition, and that the education. This is advanced orthodontics, not an
surgical procedures are outpatient, with mucosal penetra- alternative to traditional treatment methods.
tion not greater than the thickness 2-3 mm, or about As a rule, there is nothing in the description of the
the thickness of two dimes. fundamental physiology of wound healing that would
In the experience of this author and colleagues, once suggest infection is more probable with these peri-
* See: www. wilckodontics.com

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 TISSUE ENGINEERING FOR ORTHODONTISTS

orthodontic techniques, or that surgery may exacerbate stability. Wilcko, Ferguson et al, took a classic surgical
an underlying infection. Untreated systemic pathoses procedure from the realm of mechanical tissue mani-
(e.g. diabetes mellitus) and local untreated endodontic pulation, through regenerative somatic cell therapy
lesions, of course, are the exception to the rule. Some (allografts), to gene therapy, a strategy that recruits
experienced clinicians prefer to operate in infection endogenous stem cells for stimulation by allograft growth
free surgical fields54 by reconstructing an infected perio- factors in fields of altered cytoskeletal tensegrity (See:
dontium as a separate surgical appointment prior to the Ingber Lab in Suggested Reading). In the opinion of
commencement of the tooth-movement facilitating this author, an altered bone cell tensegrity (root words:
surgery. tension, integrity) is probably the most significant con-
Since conventional periodontal surgery eliminates ceptual development to impact dentofacial orthopedics
most infection efficiently, it seems reasonable that in the last decade, and will be around for awhile. It
simultaneous periodontal regeneration in infected tissue explains too much tissue behavior to disappear soon.
may accompany the periorthodontic surgery integrated In peri-orthodontic surgery these benign biologic
into one surgical procedure in the same appointment events are simply orchestrated concomitant natural pheno-
according to the experience of this author. Certainly mena, which the orthodontist may wish to employ for a
separating elective regenerative treatment from peri- select subset of patients. Therefore as legitimate, scieti-
orthodontic procedures is not mandated by science; fic, evidence-based, and perhaps even superior alterna-
the difference is merely stylistic. However, orthodontic tives to conventional care, they not only meet the contem-
complications are a function of time in therapy. There- porary standard of care but indeed, we respectfully
fore, anything that can prevent a delay in fixed-appliance submit, should be part of every orthodontic informed
therapy is salutary and in one sense meaningfully consent of every prudent practitioner, just like ortho-
prophylactic. gnathic surgical options or restorative alternatives.
There is a well recognized subset of the potential
An Historical Perspective and orthodontic patient population cohort who has no desire
Contemporary Standards of Care for bicuspid extraction, mild orthognathic surgery, or
The history of peri-orthodontic surgical techniques and even protracted fixed-appliance therapy. These patients
accelerated tooth movement antedates the Twentieth are invisible to most orthodontists because they never
Century and its development can be analyzed by five request an initial consultation. But many general practi-
distinct stages. First, published accounts lay untouched tioners can identify them easily. And the periodontist
in the German literature until the introduction of the who cannot place a suture through crowded lower incisor
procedures into America in the late 1950’s marked its teeth not only recognizes the need, but is often under a
second evolutionary incarnation. Stage III was defined professional obligation to refer patients for orthodontic
by controlled (evidence-based) studies conducted at consultation. That is the reality of contemporary den-
Loma Linda University in the 1980-90s, which establi- tistry.
shed its efficacy and safety. Stage IV was defined by The ethical imperative is particularly acute when
the analyses of Ferguson, et al studying the Wilcko’s skeletal dyplasia distorts jaw relationships sufficient to
meticulous data base at Saint Louis and Boston Uni- consider orthognathic surgery. Operating on an outpatient
versities. The present discussion of tissue engineering basis, incising little more than 2-3 mm deep to the
perspectives represents Stage V. mucosa, usually produces side effects no worse than
Reiterating: prior investigations have demonstrated temporary post-operative edema. Discomfort is easily
convincingly that successful surgical acceleration of managed with standard narcotic analgesics as in most
tooth movement is possible and sometimes superior to periodontal surgery. The factor that renders this surgery
conventional modalities. This research documented the safer and less morbid than say, impacted third molar
stability of surgically-facilitated tooth movement and extraction, is its superficiality, and the fact that no
implicitly suggests that if allografts stimulate bone growth exposed tissue is left to heal by secondary intention,
into more physiologic matrices as they are being ortho- except the bone cortex, which is covered by a replaced
dontically defined, then surgical dentoalveolar surgery mucoperiosteal flap. This situation clearly appears to
may minimize complications and enhances long term be preferable to the risks and morbidity of hospitaliza-
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tion for orthognathic surgery. Also, as an out-patient event cannot last for less than the natural period of
procedure, the risk of nosocomial infection is minimized. time of that remodeling system. Designated previously
Where less morbid surgery can replace more complicated as sigma, and an accurately measurable property of
procedures, the clinician is not only free to elect this bone dynamics, this minimum period approximates
procedure, but indeed bound to present it as a reasonable four months in healthy adult man and tree months in a
option in the patient’s complete informed consent (See: 10-year old7 (emphasis added).
Keeton WP in Suggested Readings). However well the Frost-Jee paradigm elucidates these
physiologic phenomena, many questions still remain,
An Orthopedic Analogue that must be answered by the basic scientist, hence the
The theory of peri-orthodontic surgery and the pioneering need for widespread dissemination of these data by
efforts of Drs. Wilcko, Ferguson et al, pay conceptual orthodontists, periodontists, and dental educators. The
homage to the regional acceleratory phenomenon (RAP) intellectual progeny of such collaborations, if history is
described in the Utah Paradigm of Bone by Frost and indeed prologue, are only limited by time, clinical
Jee.55, 56 This paradigm eloquently explains empirically materiel and scientific imagination.
observed events in bone healing, and provides a histo-
logical apologia for the periorthodontic approach to “Basal bone” and the bane of
dentofacial orthopedics as a kind of dentoalveolar DO. bicuspid extraction
As linear decortications are made, for example, mesial The clinical evidence that grafting BMP-2 to decor-
and distal to a canine, the movement of the canine into ticated spongiosa can permanently alter local osseous
a first premolar extraction site produces a DO at the phenotype and extend basal bone, is demonstrated by
mesial interproximal incision. the Wilcko Curve defined above. This fact is important,
Thus, conceptual extrapolations from medical because of a major schism about the need to extract
orthopedic DO and the surgical orthopedic principles teeth, and the behavior of bone remodeling, a polemic
used to correct talipes equinovarus are appropriate that has accompanied the evolution of orthodontics for
analogues to clinical dentofacial orthopedics. This 100 years. Succinctly described as “non-extractionists”,
protocol merely adds the dimensions of a minor surgical one school disdains the indiscriminate extraction of
technique and guiding precepts of contemporary tissue bicuspid teeth because of pernicious side effects on
engineering to a subset of existing data, dentofacial facial profile convexity, often not apparent until the 3rd
orthopedics, which has been a part of the orthodontic and 4th decades of life.57 (Figs. 11, 12) This school
specialty from its inception. of thought believes that dental roots are the functional
The biologic diversity noted by all experienced clini- matrix of alveolar bone,36-41 which is generated around
cians also defines the variable temporal patterns witnessed teeth regardless of their altered position. Thus, to some
with the RAP. Frost claims it is directly related to the extent where teeth are moved, bone will follow.
normal individual remodeling rate necessary for com- An opposing construct contends that the bony
plete return to a dynamic steady state evoked by a basic phenotype is fixed; any movement of teeth beyond their
multicellular unit (BMU) unique to each individual. It original position risks developing bony dehiscence and
lasts about three to four months, and since it is related ultimately gingival recession, a contention increasingly
to degrees of minor cortical perturbation, any surgical disputed by clinical studies.58 Yet gingival recession,
revisions or “boosters” should conceivably prolong the thought to be more likely at sites of bony dehiscence,
state indefinitely. Frost States: Thus, to some extent is no idle concern, because historically there has been
accelerating remodeling can counteract the effects on some compelling evidence for this argument in both the
tissue adaptability of the age related normal decrease in orthodontic and periodontal literature.59-63 To be fair to
remodeling, tissue injuries (whether the consequence those who endorse mid-arch tooth extraction, it is pro-
of an accident or of an intentional surgical procedure bably true that bicuspid extraction as a practical option
and whether of osseous or soft tissues) will increase or even as treatment imperatives will probably never be
regional bone and soft tissue remodeling by factors eliminated from the orthodontists armamentarium. The
ranging from two-fold to twenty-fold. This increase will efficiency is too well inculcated in the specialties culture,
persist until the underlying cause has healed, but in any and provides an acceptable course of therapy for many
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 TISSUE ENGINEERING FOR ORTHODONTISTS

Fig. 11 demonstrates a lack of labial support and flattened or “dished-in” lower facial contour in these examples of late life facial development.
Note how profile or ¾ poses accentuate the compromised facial esthetics. Compare to Fig. 12

Fig. 12 These photos contrast Figure 11 with a more protrusive, “fuller”, lower facial appearance where bone pathosis has created grossly
excessive alveolar bone. Where a lack of alveolar bone at cephalometric A or B point seemingly limits the treatment options to extraction but
facial esthetics require non-extraction options, PAOOTM may provide an alternative less morbid than traditional orthognathic alternatives.

patients; here we are only referring to those patients who right. The rub may be that the wrong authorities are
manifestly desire or need to avoid the treatment for being consulted with the wrong questions. The right
esthetic or emotional reasons. question we submit is,” What does the patient prefer?”
Nonetheless, haunting questions about the propriety Any treatment plan is rarely categorically incorrect when
of routine extractions remain. Those who support bicus- it is based on a compelling scientific rationale, falls
pid extraction as a matter of course may contend that within a reasonable range of accepted procedures, and
extraction of bicuspid teeth is justified, despite the occa- is based on a fully-informed doctor-patient meeting of
sionally unfortunate side effects. The bicuspid extrac- minds. Doctors always have a right to withhold “bad”
tion treatment is defended as meritorious because it choices and respectfully decline to treat within the range
is efficient and the sacrifice of dental units is necessary of reason. Nonetheless, in Modern America it seems
to accommodate the rest of the dentition onto an “immu- that the patient is the final arbiter of treatment choice
table” bony foundation (basal bone). Proponents claim and appropriate care. At the very least, the non-extrac-
that any incidence of “dished-in” or flattened contour tionist may rejoin, where accurate prediction of facial
in lower facial profiles is exaggerated or at least a side growth, tissue response, or patient remorse are impos-
effect that may not be necessarily dysmorphic. Even if sible, providing the chance for additional bone with
it is, one may claim that the occurrence is rarely perceptible PAOOTM defers extraction as a “fall-back” decision
by the uninitiated lay public or, even in worst cases, consistent with both common sense and Pascal’s Wager.
can be reversed with dental implants and standard The protocols discussed herein philosophically
periodontal reconstructive surgery. subsume this prudent choice in a very real and meaningful
Which philosophy is “right”; who is the iconoclast? way. Given that the roots are the functional matrix for
In a pluralistic culture with internet-educated dental development of the alveolar bone, inappropriate extraction
“consumers” demanding participatory care and a sensi- in a developing arch forecloses all options for further
tive regard for individual belief values, both may be development, be it ultimately unaesthetic or acceptable
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to the patient’s self image and cultural standards. At that growth factors in fields of force interact with altered
the very least, patients must have a choice. cannalicular ionic flux and distorted intracellular
tensegrity to elicit SMAD and alternate pathways to
Surgical wound healing recapitulates ultimately alter regional phenotype manifested by virtue
regional ontogeny of natural phenotypic plasticity.
The surgical alteration of alveolar dimensions may render
“the bane of bicuspid extraction” a rather moot issue, A Call for Consilience
and for some, a treatment planning anachronism. In a Based on the discoveries in other areas of tissue engi-
significant subset of the orthodontic patient population, neering, we hypothesize that the aforementioned
teeth can be moved within an “engineered” alveolus with histogenetic interactions take place between the GF
impunity, and the assurance of scientifically proven activated medullary mesenchymal stem cells in fields
superior results. Therefore, any purported categorical of therapeutically induced microstrain. If microstrain
indication for bicuspid extraction may need to be ree- can be limited to 1,500 - 3,000 units, most bones will
valuated in light of this novel peri-orthodontic alternative. respond by increasing bony mass.66 The techniques
In the technical terms of genetic expression and develop- elaborated herein simply embellish this naturally occur-
mental biology, events in the engineered dentoalveolar ring phenomenon along more clearly defined therapeutic
complex elicited by these surgical procedures redirect lines. How this is actually accomplished on a molecular
epigenetic determinants64, 65 of bony phenotype as sur- biological basis is not yet clearly defined, hence the
gical wound healing recapitulates regional ontogeny. need for a renewed commitment to consilience, the
In other words, a given undifferentiated mesenchymal synthesis of knowledge among disparate paradigms,67
stem cell in the healing wound does not “know” if it is that Professor E.O. Wilson has been advocating for
in a fetus, a nine-year old mixed dentition, or a 60-year decades in the academic community.
old edentulous ridge. All it “knows” is that it responds Others have been explicit in expressing this need
to local stimuli to differentiate. Thus, orthodontists are for synthesis in the discipline of craniofacial develop-
now empowered to marshal tissue engineering techniques ment, and even gone as far as recommending a “bottom-
necessary to perfect the growing face and dentoalveolar up” approach to research strategy, the study of the
milieu. If the regional ontogeny is indeed recapitulated contributions which cell growth and differentiation make
by wound healing, then extraction may even emerge as to organ dimensions through the nascent discipline of
a clinical “ablation demonstration,” similar to those mechanobiology. In contrast, in most dental school
taught in embryology classes. From a theoretical view- curricula the initial subject begins with changes in gross
point, one may argue that when a bicuspid is removed anatomy, that engages reductionist thinking “top-down”
from a developing alveolus all the future surrounding to biochemistry.11, 68
bone that would have developed at that functional matrix, On an empirical clinical level, the techniques of
never appears in later decades of life because its architec- Williams69 and Damon70 may also have captured the
tural template or functional matrix, e.g. the root, has bottom-up perspective of optimal response. Although
never “stimulated” it to develop. their terminology, such as “physiologically adaptive
force” and the objective of “creating adult smiles children
The Periorthodontic hypothesis can grow into” seem disparate, the thinking methods
Given: wound healing recapitulates regional ontogeny, and respect for bony response is the same. Close scrutiny
we therefore suggest that a novel bony phenotype of what these “front line” clinicians are saying suggests
engineered around a tooth in a new therapeutically- that the open-minded basic scientist should take a closer
determined position will relapse less than cases treated look at their results. The clinical outcomes cannot be
with simply orthodontic manipulation. This justifies contested, but that is not the important point. What is
investigations into the practical clinical application of missing is an explanation of mechanisms not yet fully
a new mechanobiologic paradigm in orthodontics. explicated from a filed of clinical observations, and
(See Suggested Readings: van der Meulen, et al 2002, consensus built on anecdotal data. The rationale of tissue
Wang JH-C and Thampatty BP, 2006) engineering may have a role for these styles of practice
Specifically, the PeriOrthodontic Hypothesis suggests if it is found that the force modules delivered to the
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alveolus are indeed within the physiologic range of

microstrain that maximizes steaming potentials necessary
for physiologic bone growth. If cone volumetric com-
puterized tomography indeed validates their speculations
that labial alveolar bone accommodates to their putative
“physiologic force,” then the bone stimulation and the
efficient tooth movements which they demonstrate may
have sound merit in the area of mechanobiology.
Clearly, peri-orthodontic perturbation of the spon-
giosa and PAOOTM surgery within the force fields has
produced clinical results which conventional theory
cannot explain. Perhaps the unique appliances of Damon
and Williams, designed by pure intuition and serendipity
on the part of a scientifically good-thinking clinician
may produce even more dramatic clinical results in the Fig. 13 Waddington’s Epigenetic Landscape: a visual metaphor
future, if combined with surgical facilitation. For peri- to aid the conceptualization of the interactions between genetic
orthodontic surgery and innovations such as these private potentials (round ball) and ultimate phenotype (lower valley
practitioners have developed, intellectual prejudice and endpoints).The trajectory of the ball (genetic expression) is influenced
disbelief should be temporarily suspended, at least until by environmental perturbations. We suggest that premature
the consilience of basic science can give us important deciduous canine loss and subsequent linguoversion of the lower
answers. Science and clinical findings should com- incisors in some cases represent a pathologic example of such
plement and synthesize, not contradict. an environmental perturbation. The stability of PAOOTM cases can
It may be reasonably proposed that grafting during be explained with this classic metaphor, because it overcomes
tooth movement creates an altered spatial and functional the “buffering” (height of ridges) that tends to stabilize any given
matrices into which alveolar bone develops, and that trajectory (canalization).
therapeutic orthodontic stress finally induces the threshold See: Siegal ML and Bergman A Waddington’s canalization revisited:
microstrain necessary for optimal signal transduction.71 developmental stability and evolution Proc Natl Acad Sci
Defining exactly what that microstrain is in precise 6;99(16):10528-10532 and The Strategy of the Genes Waddington,
mathematical terms is still elusive, but could easily be CH. Geo Allen & Unwin, London, 1957.
achieved with in vivo strain gauges, often used in
orthopedic research. This author has successfully used bation, which can overcome buffers that “protect” any
them in vitro for arch wire force analysis, and they given developmental trajectory from change. The canali-
have proven exquisitely precise and practical. As zation buffers must be overcome by environmental pertur-
mentioned above, Frost wrote that long bone threshold bations analogous to the “energy peaks and wells” that
for mass development is 1,500-3,000 microstrain,72 are used to explain protein conformational change and
but sutural cells in the human head appear to respond “energy of activation” in standard chemistry. For example,
to 500 microstrain.73 simple surgical wounds that heal to the original form
The phenomena discussed above also suggest that would not qualify as profound enough to overcome
peri-orthodontic therapy may reestablish the original canalization buffering. However, other more drastic
regional phenotype by overcoming the classical descrip- forms may indeed “allow” alternative epigenetic trajec-
tion of “buffered canalization” which Professor Wad- tories to manifest themselves. In therapy, we suggest it
dington dramatized with his metaphoric epigenetic land- is the combination of biochemical events induced by
scape (Figs. 13).74, 75 This visual metaphor illustrates surgical grafting in a milieu of tensional stress. Another
the observation ,independently suggested by Schmalhau- environmental (epigenetic) perturbation may be repre-
sen76 seven years after Waddington,77 that developmental sented by the premature and untreated loss of deciduous
systems which control morphology are pleomorphic in canines.78 Thus, by this reasoning, any given phenotype,
their potential; alternate forms of genetic expression pathologic, normal, or physiologic, is merely one of many
become manifest only by a unique environmental pertur- potential steady states of genetic expression that emerged
399
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Fig. 14 The amount of stable bone created with the PAOOTM is not insignificant. Certainly this 4 mm thickness of labial cortex can withstand
expansion and still maintain its structural integrity without dehiscence or fenestration. The stability of the some orthodontic clinical treatment
outcomes may be related in part to alveolar cortical bone thickness.* Therefore, it is important to distinguish the qualitative uniqueness of
alveolar bone from it’s underlying mandibular or maxillary base when discussing the effects of orthodontic therapy.
* (See: Chaison JB, Rothe LE, and Bollen A-M, Orthodontic relapse and mandibular cortical thickness- a case-control study, Paper # 1287, IADR/
AADR/CADR 82nd General Session, Honolulu, HA March 11, 2004)

Fig. 15 Before and after radiographs of a skeletal open bite treated with PAOOTM instead of orthognathic surgery. Note greater vertical height
of the alveolus in the post-treatment radiograph. Specific parts of the bone were not sectioned and rearranged in a new spatial pattern.
Through a combination of orthodontic tensional stress and periodontal flap surgery with bone grafting techniques unique to the PAOOTM
protocol the bone was “morphed” into a novel and therapeutically more desirable phenotype. Strict adherence to the protocol is critical to
a successful result.

as byproducts of complex interactions of environmental case that treats a collapsed Class II deep bite with bloc-
conditions interacting with multiple predisposing genetic ked out permanent cupids can be seen as reestablishing
proclivities. Certainly, this is evident as a common sense what would have originally occurred if intervening
explanation for excessive scar formation when wounds “perturbations” (e.g. premature extraction of deciduous
get infected, keloid formation in some individuals, and canines) did not occur. What is even more interesting
even the variability of gingival hyperplasia in pediatric is the speculation that the PAOOTM protocol as, reviewed
orthodontic patients. in this paper, has the potential to create a morphotype
The manifestly stable results of peri-orthodontic sur- which is not necessarily a return to original develop-
gery described above seems to fit Waddington metaphor mental ”intent,” but rather one which is created de
well. The clinical outcome of a peri-orthodontic surgical novo. In such a case, one would employ PAOOTM to
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 TISSUE ENGINEERING FOR ORTHODONTISTS

Fig. 16 These photos demonstrate the application of direct electric current to the bone surrounding the moved tooth. Incorporation of electric
current can accelerate tooth movement from about 36-68%. Removable intraoral appliance designed to deliver 20 ?a, 1.5 v for about 4 hours
per night. Bone forms next to the cathode and bone resorption occurs next to the anode. If this is combined with peri-orthodontic protocols during
surgical wound healing we believe that even more startling clinical outcomes will result. The use of bioelectric stimulus in joints and bone to
facilitate non-healing fractures has appeared in the medical orthopedics literature for many years
Left Photo: Note the greater movement of “experimental” canine on patient’s right compared to the “control” on patient’s left. Right Photo: Note
the unobtrusive power pack base apical to the bracket
(Photos compliments of Dr. Ze’ev Davidovitch) See: Park YG, Park SJ, Lee YJ et al: Effects of electrical stimulation by a miniature device on
tooth movement and tissue remodeling in cats. In: Biological Mechanisms of Tooth Movement and Craniofacial Adaptation.
Davidovitch Z, Mah J, editors. Harvard Soc Adv Orthod, Boston, MA, 2003. pp 337-350.

establish an entirely novel phenotype beyond that origi- very important to remember that strict adherence to the
nally “intended” (destined) during early arch develop- Wilcko protocol is necessary for consistently improved
ment. Thus, as the surgeon resurrects the normal and clinical outcomes. The “orchestration” and timing of
original phenotype in the cleft palate patient,79 the PAOOTM treatment procedures are as critical as the
periodontist and orthodontist together may help reesta- structural elements which they manipulate.
blish original alveolar phenotype through coordinated
orthodontic stress and induced bone growth. One can Denouement
reasonably conjecture that facial contours through serial Although profound scientific discoveries may emerge
PAOOTM procedures may even supplant some plastic or from the most curious and serendipitous origins, one
orthognathic surgical alternatives that are contraindi- should always anticipate novel methods of future research
cated by professional parameters, clinical parameters, which can help clinicians incorporate new kinds of
or foreclosed by patient preference (Figs.14, 15). orthopedics into practice. For example, an epilogue may
The periodontist, orthodontist and general practitioner rediscover how intraoral low amperage (<50 µa)80
now have a conceptual framework in bio-orthodontic electrical appliances can deliver exogenous electrical
principles which liberates them from a century of con- potentials to the healing periodontal environment and
tention about basal bone, to reach patients who decline amplify regional osteogenesis (Fig. 16), while mecha-
tooth extraction, orthognathic surgery, and long term nisms which orchestrate all the factors responsible for
fixed appliance therapy, as viable treatment options. bone remodeling remain enigmatic. Only a meaningful
The exact nature must await further studies in molecular dialogue among astute clinicians and scientific disciplines
biology, cellular genetics, and developmental biology. can reveal the best path to reconcile conflicting hypot-
In any event, peri-orthodontic manipulation represents heses and theories of cellular dynamics.
an exciting new dimension for the clinician who is This paper has presented a scientific theory, evidence-
enamored with dentofacial orthopedics as much as this based protocols, clinical examples, and reviewed con-
author. Whether tissue engineering would be elected clusions from a plethora of scientific studies, to hypothe-
through the use of GF or specifically in PAOOTM, it is size mechanisms of dentofacial orthopedic care based
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 MURPHY, NEAL C

Computer Generated Fractal Compare Fractal Simulation with

Pattern, “Barnsley Fern” Source: Natural Fern Leaf above
www.architecture.auckland.ac.nz/.../ 09.htm

Source: Math.bu.edu/people/ bob/papers.html Source: sci.agr.ca/crda/ indust/microscope_e.htm

A Sierpinski curve Julia set Nucleus of Crocus sativus (saffron)

for the function z2 -1 / 16 z2 Scale=2? Size=145 KB
Fig. 17 A comparison of computer generated fractal patterns (left) with natural structures (right) suggests that tissue dynamical systems
appear to be a choreographed by physical force or chemical gradients yet they are not strictly determinate and not merely random. It seems
that proliferating tissue elements responding to local stimuli, will after thousands of iterations through nutrient or morphogenetic gradients define
patterns similar to steady emergent states of cellular automata and the iterations of Julia and Barnsley set functions in fractal geometry. The
secrets of morphogenesis may emerge more profoundly from the realms of mathematic heuristics* than the dogma of reductionist
methodologies or even the universal musings of traditional biologic determinists.

on modern molecular biology. The dynamic systems ment in a manner similar to the iteractions of Julia and
appear to be a choreographed osteogenesis, yet they Barnsley formulae in fractal geometry84 (Fig. 17). On
are not strictly determined. It seems that proliferating this theoretical basis, the physics of tissue behavior
tissue elements, as any cellular automata81 respond only may be as important as the chemistry for osteogenesis
locally82 and only after thousands of iteractions through in a field of force. The nature of cellular dynamics,
nutrient or morphogenetic gradients,83 do they redefine similar to fluid or particle dynamics in the formation of
the epigenetic course of regional dentoalveolar develop- fractal patterns are influenced by growth factors gra-
* (See: Do N-N, Wagle N, Yu JC and Borke JL, Increa­sed fractal dimension following tooth movement may involve “micro­distraction
osteogenesis, Paper #128 IADR/AADR/CADR 82nd General Session, Honolulu, HA March 11, 2004)

402
 TISSUE ENGINEERING FOR ORTHODONTISTS

Fig. 18 Trans-Mucosal Perturbation (TMP): These photos demonstrate “trans-mucosal perturbation” of the subjacent alveolar cortices to elicit
a regional acceleratory phenomenon (RAP) with minimal surgical morbidity. This can be employed where isolate areas of bone physiology are
needed but a flap reflection to place grafts of growth factor is unnecessary.

dients, but seem to follow a stochastic course; it is other disciplines pregnant with 21st Century science.
clearly not entirely random but not exclusively deter- The peri-orthodontic perspective has demonstrated
ministic. The precise cellular dynamics of osteogenesis clinical results not explained by the classic orthodontic
in tensional stress for facial tissue and the alveolus is concepts of Schwartz, Reitan and Tweed, et al. Perhaps,
still shrouded by ignorance, but reason and extrapolation in his adamant condemnation of extraction therapy,
from sister sciences and biomathematics would suggest Edward Angle realized just how the malleable tooth-
that it most probably has something to do with the alveolus complex (organ) can actually be. It is ironic
actions of numerous determinate (strange) attractors, that the startling demonstrations of Drs. Wilcko and
operating in a progression of nonlinear complexity. other 21st Century peri-orthodontic pioneers, originating
Thus, the secrets of morphogenesis may emerge more outside the limits of traditional orthodontic dogma, may
profoundly from the realms of mathematic heuristics have brought us clinical orthodontists full circle, and
than the dogma of reductionist methodologies or even the vindicated Dr. Angle after all. But the emergence of
universal musings of traditional biologic determinists.85, 86 fresh ideas from outside a given scientific discipline is
No logical reason exists to exclude human den- not historically unknown. In fact it is common, as
toalveolar ontogeny from the basic principles of self- Professor Kuhn16 has so eloquently taught us. The
organizing biologic systems,87, 88 which produce the ramifications of this new paradigm in the practice of
novel emergent steady states. Clearly then, this perspec- clinical orthodontics are profound indeed, but only time
tive argues, empirically and deductively, that the critical will tell exactly how prescient this hypotheses really
anatomical unit (or more correctly the organ*) we work are. One can, nonetheless, claim this perspective has
with, the dentoalveolar complex of root, cementum, been soundly articulated and candidly held out for review,
periodontal ligament and the entire alveolus, should critique and modification. We who support it are secure
define the orthodontic and dentofacial orthopedic func- in the belief that constantly evolving, revising and embelli-
tional unit. A narrow focus on the crown and root, or shing hypotheses, ultimately leads to workable theories
on pressure-tension models, can only eclipse from our for everyone. Yet, in a world where the word “theory”
professional vision more illuminating concepts from connotes intellectual constructs temporarily designed
403
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to explain or predict natural phenomena, all scientific Acknowledgments

truth is tentative and the truth of orthodontic stability The author gratefully acknowledges all colleagues
may be established with a mere “transmucosal pertur- in dentistry who have helped us develop a scientific
bation” of the alveolus (Fig. 18). approach to clinical practice, particularly the indispen-
The emerging stochastic “truths” of cellular dynamics sable assistance of Drs M. Thomas and William M.
certainly seem as elusive as Platonic forms, and often Wilcko of Eire, Pennsylvania. Dr. Ze’ev Davidovitch
slip our minds when we are an hour behind in our clini- must be admired by all for his indefatigable and faithful
cal schedules. They are, nonetheless, real and abiding dedication to the welfare of our patients and our pro-
companions to the curious mind sustained, in the spirit fession, and we must not forget how Drs. Mao, Pavlin,
of free inquiry. When we remember the fundamentals Mah, Rabie and others integrating basic science into
of science and mathematics, those last bastions of truth the orthodontic curriculum are extending that legacy.
in an overspun politically correct world, they serve us For the conceptual insights upon which we have
well as a refreshing balm for the existential angst of based these syntheses of tissue engineering and facial
Professor Johnston6 and others, whose apocalyptic orthopedics, we extend our gratitude to Melvin L. Moss,
visions of clinical orthodontics sans scientific theory Professor Emeritus, Columbia University, for his helpful
at times haunts us all. Truth is there for those who advice and inspiration.
choose to look, and it will always guide the hands of Special thanks go to Dr. Nabil Bissada, Professor
those who choose to embrace it. “Truth” in orthodontics and Chairman of Periodontics, Case Western Reserve
about one hundred years ago was “ extractions should University, for all his teaching and research in perio-
be avoided because it restricted growth of the face.” dontology, through which the scientific concepts in this
Then, about 50 years ago, “truth” suggested that “one paper were fundamentally expressed. Dr. Bissada teaches
cannot move teeth outside of the alveolar housing his students not only facts relevant to successful surgery,
without risking permanent damage.” In a humorous but also the ethical and intellectual cognitive processes
vein, there is an old joke among American dental that liberate the clinician from perfunctory tissue
students who use old tests as study guides. The senior manipulation, to higher realms of intellectual discovery
student speaks for science in general when he advises and scholastic integrity.
the freshman to be careful because, “ although the “If I have seen further it is by standing on the
professors’questions never vary from year to year, the shoulders of Giants.”
answers always do.” — Sir Isaac Newton (1643-1727)
The explication of truth demands the constant revision
of popular notions, and the liberation of thought from References
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LG, Rodan GA, editors. Academic Press, San editor. Wiley-Liss, New York, 1993.
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in orthopedic applications. Expert Opin Biol Ther where computers meet biology. First Vintage Books,
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sponge device for local alveolar ridge preservation review of cell mechanobiology. Biomechan Model
or augmentation. Int J Periodont Rest Dent 17: Mechanobiol 5: 1-16, 2006.
125-139, 1997.
7. Frost HM: The Utah Paradigm of Skeletal Physio- Appendix
logy. International Society of Musculoskeletal and Below are referenced the studies at St. Louis and Boston
Neuronal Interactions, Vol. I & II, Pueblo, CO, University under the aegis of Professor Donald J.
2002. Ferguson who has investigated the meticulous Wilcko
8. Roux W: Der Kampf der Teile im Organismus. data in the greatest depth and with the most rigorous
Engelmann, Leipzig, 1881. scholastic standards. The author finds no contradiction
9. Snustad DP, Simmons MJ: Principles of Genetics, between the clinical application of the Wilckodontics
2nd edition. John Wiley and Sons, New York, methods he has employed and the findings of these
2000. excellent research papers. Indeed it is the scholarship
10. Orthopedic Tissue Engineering: Basic Science and contained herein that has inspired more investigation
Practice. Goldberg VM, Caplan AI, editors. Marcel into this clinical phenomenon.
Dekker, Inc., New York, 2004. Source: www.wilckodontics.com.
11. Human Molecular Biology. Epstein RJ, editor.
Cambridge University Press, Cambridge, 2003. Papers published in Various Journals Throughout the
12. Garant PR: Oral Cells and Tissues. Quintessence World
Publishing Co., Inc., Chicago, 2003. 1. Wilcko WM, Ferguson DJ Bouquot, JE, Wilcko
13. Bone Tissue Engineering. Hollinger JO, Einhorn MT: Rapid orthodontic decrowding with alveolar
TA, Doll BA, Sfeir C, editors. CRC Press, Boca augmentation: case report, with alveolar augmenta-
Raton, 2005. tion: case report. World J Ortho 4: 197-205,
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