CRANIOMAXILLOFACIAL DEFORMITIES/COSMETIC SURGERY

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Italy.

Hydroxyapatite/Collagen Composite Isa Reliable Material for Malar

AugmentationAntonio D’Agostino, MD,* Lorenzo Trevisiol, MD,y Vittorio Favero, MD,z

Michael J. Gunson, DDS, MD,x Federica Pedica, MD,k Pier Francesco Nocini, MD, DDS,{and G. William Arnett, DDS#

Purpose: To evaluate the long-term results of cheekbone augmentation using porous hydroxyapatite

granules mixed with microfibrillar collagen in a large group of patients.

Materials andMethods: Four hundred thirty patients who underwent zygomatic augmentation and in-

termaxillary osteotomy were evaluated clinically, radiologically, and histologically.

Results: Complicationswere found in 13 patients (1.56%). Therewere no relevant radiologic differences

in prosthesis volume after 1 month (T1) or after 24 months (T2) in any patient; there were no clinically

relevant differences in 110 patients after 36 months. At T1, the prosthesis had a granular structure and

the granules had not migrated; at T2, the prosthesis was staunchly adhering to the underlying bone.

Over time, the radiopacity of the material increased. Histologic results of 19 biopsy specimens obtained

from 8 patients 2 years after the procedure showed prominent ossification with low inflammation, con-firming new bone formation over time. According to the visual analog scale, the patients were generally

satisfied with the aspects that were considered.

Conclusion: Hydroxyapatite and collagen composite used during malarplasty produced a successful

outcome. Its main drawback is a learning curve that is longer than for more frequently used implantable

biomaterials.

� 2016 American Association of Oral and Maxillofacial Surgeons

J Oral Maxillofac Surg -:1.e1-1.e15, 2016

Functional and esthetic facial rehabilitation has become

an important sector of maxillofacial surgery. Harmonic

facial features and natural proportions favor self-

confidence and psychological health. Facial defects orasymmetries can result from soft tissue asymmetry or

bony framework alterations. Intermaxillary osteotomy

corrects skeletalmalocclusions, aligns the upper incisor

ociate Professor, Department of Surgery, Unit of Maxillofacial

y and Dentistry, University of Verona, Verona, Italy.

sociate Professor, Department of Surgery, Unit of Maxillofacial

y and Dentistry, University of Verona, Verona, Italy.

nical Assistant, Department of Surgery, Unit of Maxillofacial

y and Dentistry, University of Verona, Verona, Italy.

vate Practice, Arnett and Gunson Facial Reconstruction, Santa

a, CA.

nical Assistant, Department of Pathology and Diagnostics,

sity of Verona, Verona, Italy.

ofessor and Chief, Department of Surgery, Unit of

facial Surgery and Dentistry, University of Verona, Verona,

1.e1

sagittal and vertical planes, and improves the esthetics

of the lower third of the face, including the paralatero-

nasal area, the upper and lower lips, and the chin.While

the osteotomy procedure is being carried out, somepatients also might require contouring of the malar

soft tissue complex or other facial areas to improvemid-

face definition and to obtain greater facial harmony.

#Private Practice, Arnett and Gunson Facial Reconstruction,

Santa Barbara, CA and Assistant Professor, Department of Oral and

Maxillofacial Surgery, Loma Linda University, Loma Linda, CA.

G.William Arnett is the assignee of U.S. patent 6506217 B1 (mold-

able postimplantation bone filler and method).

Address correspondence and reprint requests to Dr Favero:

Department of Surgery, Unit of Maxillofacial Surgery and Dentistry,

University of Verona, Ple LA Scuro, 10, Verona 37134, Italy; e-mail:

Vittorio_favero@yahoo.it

Received December 9 2015

Accepted January 28 2016

� 2016 American Association of Oral and Maxillofacial Surgeons

0278-2391/16/00144-0

http://dx.doi.org/10.1016/j.joms.2016.01.052

1.e2 HYDROXYAPATITE FOR MALAR AUGMENTATION

The first facial reconstruction techniques date to the

1970s, when silicone prostheses were commonly

used.1-3 Since then, other techniques using

autogenous or alloplastic materials have been used

by plastic surgeons for this type of esthetic surgery.

Autologous bone grafts to optimize facial harmony

were considered the gold standard for facial

reconstruction for many years,4 but lost popularitybecause they were encumbered with donor-site

morbidity, were not easily molded, and were charac-

terized by unforeseeable resorption results over

time.5 Osteotomy procedures (Le Fort II and III) pro-

posedbyvarious investigators, includingTessier,6 begin-

ning in the 1980s were later abandoned because of

high surgical invasiveness, technical difficulties in actu-

ating the procedures, unpredictability, and the frequentnecessity of using ‘‘low’’ osteotomies (Le Fort I) to

optimize the occlusal plane.6-9 Currently, implantable

biomaterials play a predominant role in these

procedures. Silastic has long been used in plastic and

esthetic surgery; it is easily positioned, does not need

stabilization, and has led to satisfying results in

facial contouring. However, it is associated with a

relatively large percentage of complications, includinginfections, dislocations, formation of fibrous capsules,

lack of integration, and in some cases resorption of

native bone.10-12

Other alloplastic materials derived from polymers

and ceramics have been described in the literature.

Porous polyethylene (Medpor, Porex Corporation,

Newman, GA) is a widely used plastic allogenic mate-

rial to contour the face and in trauma medicine. It ispreshaped, easily positioned, and fixed with screws.

However, according to some surgeons, it is character-

ized by decreased malleability and adaptability at the

recipient site. Although the risks associated with the

use of this material are lower with regard to percent-

ages, the risks include malposition, a remarkable inci-

dence of early- and late-onset infections, formation of

pseudocapsules, and osseous integration failure.13-15

Another implant material, Gore-Tex, which is pre-

shaped and easy to position, is characterized by

long-term complications and results that are not

entirely satisfying; cases of bone graft extrusion,

seroma, and lack of integration over time have been

reported.16

Coral-derived porous hydroxyapatite (HA; Interpore

200, Interpore Orthopaedics, Inc., Irvine, CA), whichis available in granule and block forms, is another ma-

terial frequently used in maxillofacial procedures to

augment the splanchnocranium. According to the

literature, porous HA granules are stable over time

and are osteoconductive.17,18 Nevertheless, the

prosthesis requires hypercorrection, and in some

cases there might be problems linked to

irregularities in facial symmetry; it also seems to be

structurally incapable of withstanding functional

load.19 Because porous HA granules are not preshaped

or prepackaged for prosthetic use, it is used less

frequently than the materials described earlier.

All biomaterials have short- and long-term advan-

tages and disadvantages depending on the point of

view. The aim of this study was to evaluate clinically,

radiologically, and histologically the long-term resultsof porous HA granules used to contour the facial skel-

eton in a large group of patients.

Materials and Methods

The present study followed the Declaration of Hel-

sinki on medical protocol. This study was approved

by the institutional review board of the Verona Hospi-

tal (Verona, Italy) and all participants signed an

informed consent agreement. Over a 7-year period

(2005 through 2012), 430 patients (270 women and

160 men; mean age, 28 yr; range, 18 to 45 yr) under-went procedures using porous HA granules to

augment the zygomatic region (total, 860 prosthesis)

and optimize facial esthetics during orthognathic sur-

gery. All procedures were carried out in the Arnett-

Gunson Center for Corrective Jaw Surgery (Santa Bar-

bara, CA) or the Unit of Dentistry and the Maxillofacial

Surgery Unit of the University of Verona Medical Cen-

ter (Verona, Italy). The treatment plan, which aimed toachieve functional and esthetic improvement, was to

enhance the zygomatic region of patients with inade-

quate cheekbone projection or facial asymmetry of

the zygomatic arch.

All procedures were carried out using general anes-

thesia after prophylactic antibiotic administration

(ampicillin and sulbactam 1.5 g intravenously 1 hour

before surgery). In accordance with the patent of G.William Arnett (U.S. patent 6506217), the prostheses,

which were handmade, were prepared by mixing HA

granules 5 mL (Pro-Osteon 200, Interpore Cross Inter-

national, Irvine CA), microfibrillar collagen hemostat

flour 1 g (Avitene, Davol Inc., Warwick, RI), and sterile

saline solution 5 mL (Fig 1A,B).

The mixture is shaped using sterile instruments and

according to the desired result in relation to the pa-tient’s features. Initially, the material is very malleable.

After it has been shaped, it is warmed for at least

150 minutes under a 150-W heating lamp and allowed

to stiffen. Shaping is carried out at the end of an

orthognathic procedure (Le Fort I), because the

same upper vestibular incision is used after debriding

the area between the infraorbital nerve medially and

the zygomatic arch laterally, creating pockets (whosesizes should match those of the prostheses) within

the zygomatic bones (Fig 2A,B); this is a very impor-

tant detail that will prevent prosthesis displacement.

Careful hemostatic control of the recipient site is

FIGURE 1. A, B, Preparing the prosthesis.

D’Agostino et al. Hydroxyapatite for Malar Augmentation. J Oral Maxillofac Surg 2016.

D’AGOSTINO ET AL 1.e3

extremely important. If the prosthesis is positionedmore laterally, then the more the inter-zygomatic

diameter will be augmented. Likewise, if the pros-

thesis is positioned more medially, then the sagittal

projection will be improved. No internal fixation is

needed to stabilize the prostheses; instead, extraoral

compressive dressings are applied to stabilize

the implants.

All patients included in the study underwent a clin-ical assessment and participated in at least a 3-year

follow-up (mean follow-up, 6 yr; range, 3 to 10 yr).

Clinical evaluations consisted of quantifying short-

and long-term complications linked to inflammatory

or infectious problems or the need for other proce-

dures, implant stability (absence or presence of

clinically appreciable signs of resorption), and photo-

graphic records taken 1 to 3 years after surgery.Seventy-six of the 430 patients agreed to complete

the visual analog scale (VAS), a psychometric response

scale that measures a continuum of values on a scale of

0 to 100. In this study, patients were asked to judge the

naturalness of the facial contour of the zygomatic arch:

they were instructed to give a grade of 0 if they judged

the prosthesis appeared unnatural and to give a grade

of 100 if they were completely satisfied with their newprofile. They also were asked about symmetry: they

were asked to give a grade of 0 if one side seemed

different from the other and a grade of 100 if the 2

sides were exactly the same. The third parameter

was the implant’s natural feel: they were asked to

give a grade of 0 if the prosthesis seemed foreign to

their body and a grade of 100 if it seemed part of their

body. The patients were asked to define their satisfac-tion with the implant as a grade of 0 if they were

entirely dissatisfied and 100 if they were

completely satisfied.

All patients underwent imaging after 1 month (T1)

and after 24 months (T2). One hundred ten of the

430 patients also agreed to undergo cone-beamcomputed tomography (CBCT; NewTom 3G device;

QR srl, Verona, Italy) at least 36 months after surgery

(T3). Signs of resorption of native bone and variations

in the structure and radiopacity of the implanted pros-

thetic material were evaluated by a blinded observer

(the radiologist who analyzed the CBCT); these phe-

nomena were evaluated over a long period

($36 months) in 110 of the patients studied.Biopsy samples were obtained from implants in 8

patients who required removal of fixation screws

from the upper jaw 2 years after surgery. Once the pa-

tients gave informed consent, biopsy samples were

taken using trephine burs (inner diameter, 2 mm;

outer diameter, 3 mm) and 19 samples of prosthetic

material were collected. Each sample was taken so

that a portion of the prosthesis in the entirety of itswidth from the periosteum to the native bone could

be collected, and the periosteum side was marked

with a pen. The material collected was fixed in form-

aldehyde buffered with 4% phosphate and washed in

the buffer. After decalcification with Osteodec (Bio-

Optica Milano Spa, Milan, Italy), the sample was dehy-

drated using increasing concentrations of alcohol and

xylene and then embedded in paraffin. Morphologicand immunohistochemical analyses of bone samples

were performed to evaluate remodeling and eventual

osteogenesis. Four-micrometer-thick sections were

stained with hematoxylin and eosin, and immunohis-

tochemistry was performed on subsequent sections

using 2 monoclonal antibodies specific for cathepsin

K (clone CK4, Novocastra, Newcastle, UK; clone

3F9, Abcam, Cambridge, UK) to stain osteoclastsand for CD56 (clone 123C3.D5, 1:100; Thermo Scien-

tific, Grand Island, NY) to stain osteoblasts, as previ-

ously described.20 Cathepsin K is fundamental for

the degradation of type I collagen in bone resorption

mediated by osteoclasts21 and CD56 stains resting and

FIGURE 2. A, Placement of the implants in the subperiosteal pockets. B, Cone-beam computed tomogram showing final position of the pros-thesis in the malar area. Prostheses differ in shape and size owing to the asymmetric nature of the defect to recontour.

D’Agostino et al. Hydroxyapatite for Malar Augmentation. J Oral Maxillofac Surg 2016.

1.e4 HYDROXYAPATITE FOR MALAR AUGMENTATION

activated osteoblasts.22 Vital areas were identified

by checking the section stained with hematoxylin

and eosin under an optical microscope and

looking for nucleated osteocytes. Then, applying

immunohistochemical analysis, the presence of osteo-

clasts was evaluated by staining of cathepsin K

D’AGOSTINO ET AL 1.e5

antibody23 and osteoblasts reactive to CD56.22 Per-

centage of new bone formation, percentage of fibrous

tissue, and presence of the biomaterial also were

investigated.

Results

CLINICAL EVALUATION

Clinical evaluation (Table 1) of patients showed that

prosthesis malposition, which was noted in 6 cases,

was probably due to excessively large subperiosteal

pockets in which the prostheses were positioned.The inappropriate dimension led to a caudal rather

than contralateral slippage of the prosthesis. Five cases

of partial resorption were noted; all were linked to

inadequate hemostasis of the recipient site or in

some cases to massive bleeding at the patient’s awak-

ening. There were 2 cases of early infection

(<30 days) requiring removal of the prosthesis. There

were no cases of late-onset infection, dehiscence, fis-tula, or thinning or alteration of overlying soft tissues.

Comparison of photographs taken 1 and 3 years later

confirmed the registered clinical data (Figs 3-6).

Some patients reported bilateral edema and pain in

the zygomatic region during the first month after

surgery. Thirteen patients (1.56%) had some kind of

complication; 2 (0.2%) had infectious complications.

The VAS was completed by 76 of the 430 patients(Table 2). The patients substantially agreed on their

perception of the primary parameters characterizing

the result. On a scale of 0 to 100%, the average judg-

ment about the natural contour of the zygomatic pro-

file was 85.83 � 22.22 of 100 (median, 95.19). The

average judgment about symmetry was 85.68 �23.00 (median, 96.44). The average judgment about

the implant’s natural feeling was 80.30 � 26.28 of100 (median, 92.10). The patients’ average general

Table 1. CLINICAL COMPLICATIONS

Complications

Prostheses

(N = 860), n (%)

Malposition requiring

secondary correction

6 (0.72)

Partial or total resorption

requiring secondary

correction

5 (0.64)

Dehiscence 0

Fistula 0

Infection 2 (0.2)

Thinning of overlying soft tissue 0

Total 13 (1.56)

D’Agostino et al. Hydroxyapatite for Malar Augmentation. J Oral

Maxillofac Surg 2016.

satisfaction with the result was 84.41 � 23.96 of 100

(median, 96.72).

RADIOLOGIC EVALUATION

Except for the cases of partial or complete resorp-

tion (n = 5; 0.64%), the imaging data collected at T1showed that the prosthesis maintained its granular

structure and that the granules had not migrated to

the surrounding soft tissues (Fig 7). The structure

of the prosthesis was radiotransparent compared

with the compact portion of the zygomatic bone. At

T2, the prosthesis seemed to adhere staunchly to the

underlying zygomatic bone in all patients. The gran-

ular structure was still distinguishable, although itwas less evident, and the partial radiotransparency

had evolved to a radiopacity similar to that in the

compact part of the native bone, making it impossible

to distinguish the interface between the prosthesis

and bone (Fig 8). That tendency continued, according

to the imaging data available at T3, toward progressive

loss of definition of the granular architecture and an

almost complete radiopacity and apparent corticaliza-tion of the bone in contact with the prosthesis. The

interface between the prosthesis and bone at T3

appeared indistinguishable (Fig 9).

HISTOLOGIC EVALUATION

The persistence of porous HA and of macrophages,although without inflammatory infiltrate, was found in

all samples (Table 3). Fibrous stromawas found in 50%,

and the presence of new osteogenesis and mature

bone was found in 70% of cases. According to biopsy

findings, the presence of mature bone was found

only at the periosteal side (marked with a pen), and

the presence of new formation of immature bone

was found entirely on the deep side of the nativebone with a bone maturation gradient proceeding

from the periosteal to the deep side (Fig 10). Immuno-

histochemical investigations uncovered some

cathepsin K protease contained in the cytoplasm of

the macrophages, thus indicating the presence of oste-

oclast activity localized around the HA residues (Fig

11). The anti-CD56 antibodies indicated greater new

osteogenesis activity at the side of the biopsy sampleadjacent to the native bone (deep), confirming the re-

sults of histomorphometric analyses (Fig 12).

Discussion

Arem et al2 and Moos et al3 were among the first to

describe pioneering experiences with Proplast to

enhance the lower third of the face at the end of the1970s. These procedures were followed by autologous

onlay bone grafts that were initially collected from the

rib and iliac crest and later from the calvarial bone.

Although those grafts that were positioned for esthetic

FIGURE 3. Patient 1 at preoperative assessment. A-C, Class III dentoskeletal malocclusion, vertical excess, and mild malar deficiency in pro-jection and contour treated with multisegment Le Fort I osteotomy, bilateral sagittal split osteotomy, and bilateral malarplasty with porous hy-droxyapatite prosthesis.

D’Agostino et al. Hydroxyapatite for Malar Augmentation. J Oral Maxillofac Surg 2016.

1.e6 HYDROXYAPATITE FOR MALAR AUGMENTATION

FIGURE 4. Patient 1. A-C, Postoperative assessment 24 months after the procedure.

D’Agostino et al. Hydroxyapatite for Malar Augmentation. J Oral Maxillofac Surg 2016.

D’AGOSTINO ET AL 1.e7

FIGURE 5. Patient 2 at preoperative assessment. A-C, Class I dentoskeletal malocclusion with vertical excess, mandibular left deviation, andasymmetry in soft tissues and hard tissues of the right zygomatic region treated with multisegment Le Fort I osteotomy, bilateral sagittal split os-teotomy, and bilateral asymmetrical malarplasty with porous hydroxyapatite prosthesis.

D’Agostino et al. Hydroxyapatite for Malar Augmentation. J Oral Maxillofac Surg 2016.

1.e8 HYDROXYAPATITE FOR MALAR AUGMENTATION

FIGURE 6. Patient 2. A-C, Postoperative assessment after 24 months.

D’Agostino et al. Hydroxyapatite for Malar Augmentation. J Oral Maxillofac Surg 2016.

D’AGOSTINO ET AL 1.e9

Table 2. VISUAL ANALOG SCALE OUTCOMES

Patients, n Natural Contour Symmetry Natural Feel Satisfaction

76 85.83 � 22.22;

95.19 (88.19, 99.91)

85.68 � 23.00;

96.44 (87.14, 100)

80.30 � 26.28;

92.10 (70.86, 99.39)

84.41 � 23.96;

96.72 (79.77, 100)

Note: Data are presented as mean � standard deviation; median (quartiles 1, 3).

D’Agostino et al. Hydroxyapatite for Malar Augmentation. J Oral Maxillofac Surg 2016.

1.e10 HYDROXYAPATITE FOR MALAR AUGMENTATION

purposes were considered the gold standard in the

1980s, they have since been abandoned because of

donor site morbidity, the difficulty in modeling non-

adaptable graft materials, and, in particular, the unpre-

dictable results of graft volumetric maintenance.5,24-27

Brusati et al7 and Denny and Rosenberg8 who pro-

posed using Le Fort III osteotomies to obtain esthetic

results initially followed the method described by Tess-

ier6 to harmonize facial disharmonies and his sugges-

tions on modifying and simplifying those

procedures. Those methods foresaw midfacial

FIGURE 7. Cone-beam tomogram, coro

D’Agostino et al. Hydroxyapatite for Malar Augmentation. J Oral Maxill

advancement, at times in conjunction with bone graft-

ing and stabilization. Given the high surgical invasive-

ness of these procedures, the need for an extraoral

(coronal sub-palpebral) approach, the technical diffi-

culty in carrying them out, and controlling occlusalproblems, they are no longer used in traditional or-

thognathic surgery and currently are used only in

cases of malformations in pediatric patients. The low

zygomatic maxillary osteotomy proposed by Bell

et al28 in 1988 is a technique that corrects defects in

a transverse direction of the zygomatic region,

nal slice, at 1 month after surgery.

ofac Surg 2016.

FIGURE 8. Cone-beam tomogram, coronal slice, at 24 months after surgery.

D’Agostino et al. Hydroxyapatite for Malar Augmentation. J Oral Maxillofac Surg 2016.

D’AGOSTINO ET AL 1.e11

requiring an augmentation of the bizygomatic diam-eter, but also necessitating9 grafts composed of onlay

bone grafting material (eg, HA granules) if an increase

in the sagittal projection of the malar bone is clinically

necessary. Traditional orthognathic and plastic sur-

geries have moved in the direction of using allogeneic

material, or rather so-called implantable biomaterials.

The ideal material should be biocompatible and osteo-

conductive and show a high degree of reabsorptionthat is predictable over time.17 More specifically,

biocompatibility presupposes an inert chemical state,

an absence of toxicity, an inability to induce hypersen-

sitivity responses, and a low rate of infections.

Gore-Tex (polytetrafluoroethylene), a widely used

prosthetic bone graft material, presents a sufficient de-

gree of volumetric stability over time. Because it is pre-

shaped, it is easily positioned and can guaranteesatisfying esthetic results. However, it needs to be sta-

bilized with screws, it is difficult to adapt it to the

recipient site, and it is characterized by a relevant

rate of infectious complications. Moreover, Gore-Tex

implants remain slippery because there is no host

tissue ingrowth and they carry an increased risk ofinfections, seroma formation, and extrusion.16,29-31

Although rigid screw fixation is a very effective and

efficient method of fixing malar implants, there are

complications, such as the pneumatocele described

by Garner and Jordan.30 The low biocompatibility of

the material probably plays a part in this type of

complication.

Silicone derivatives likewise present a series of ad-vantages and disadvantages. They are available in pre-

shaped forms, are easily positioned, and do not need

to be stabilized with screws, characteristics that

explain their wide use. According to many investiga-

tors, such as Metzinger et al11 and Mommaerts et al,9

the percentage of residual malposition asymmetry

varies from 15 to 35%. Nevertheless, silicone im-

plants lack the potential for vascularized healing, pro-mote thick capsule formation, cause resorption of the

underlying bone, and display a tendency of shifting

or extruding over long periods.10,32 In the present

study, the complications were probably linked to

the limited osteoconductive properties of the

FIGURE 9. Cone-beam tomogram, coronal slice, at 36 months after surgery.

D’Agostino et al. Hydroxyapatite for Malar Augmentation. J Oral Maxillofac Surg 2016.

1.e12 HYDROXYAPATITE FOR MALAR AUGMENTATION

derivatives and to a chronic inflammatory reaction to

extraneous bodies (chronic inflammatory

peripheral reaction).

As in the cases cited earlier, Medpor (porous poly-

ethylene) is a material that is widely used for surgical

purposes and in trauma patients. It is preshaped and

Table 3. HISTOLOGIC EVALUATION OUTCOMES

2-yr Postoperative Histologic

Findings (19 Specimens) %

Hydroxyapatite granules 100

Macrophages (foreign body

reaction)

100

Fibrous stroma 50

New bone formation and

mature trabecular bone

70

D’Agostino et al. Hydroxyapatite for Malar Augmentation. J Oral

Maxillofac Surg 2016.

stable over time, but it is difficult to position,13

because of its rigidity, and to contour surfaces of com-

plex skeletal structures. It needs to be stabilized with

screws. The complication rate varies from 5 to 20%

and it is associated with a relatively large percentage

of early- and late-onset infections (1 to 12%).33,34

Medpor creates a fibrous capsule, it is notosteoconductive, and it is not very inert with respect

to immunologic responses.14

Different researchers have described using porous

HA as onlay bone grafts for the facial skeleton.35,36 In

a study by Moreira-Gonzales et al17 on the use of HA

in procedures to contour the face, the percentage of

complications was relatively small (5.6%); more specif-

ically, 4.3% had contour irregularities and 1.3% hadinfection and extrusion of granules requiring overcor-

rection of 15% of the required volume. An animal study

showed that, in contrast to the rapid resorption of

autologous grafts, porous HA matrix had long-term

permanencewith maintenance of contour and osseous

FIGURE 10. Zygomatic bone specimen harvested 24 months afterprosthesis placement. The bone maturation gradient proceeds fromthe periosteal (asterisk) to the deep side (hematoxylin and eosinstain; magnification, �10).

D’Agostino et al. Hydroxyapatite for Malar Augmentation. J Oral

Maxillofac Surg 2016.

D’AGOSTINO ET AL 1.e13

incorporation.37 Concerning the biocompatibility of

HA, the results of a study by Campioni et al38

showed that porous HA plus microfibrillar collagen

was characterized by a high rate of cell proliferation

and favored cell adhesion (Saos-eGFFP) on its own sur-

face. This would seem to satisfy the criteria necessaryfor biocompatibility, that is, the absence of toxicity

and being chemically inert. Concerning long-term sta-

bility, porous HA seems to be stable in some condi-

tions, such as not being placed under a functional

load,19 which, of course, is the case at the zygomatic re-

gion or other areas subject to facial contouring. The

FIGURE 11. Osteoclast activity localized around hydroxyapatite residue�20).

D’Agostino et al. Hydroxyapatite for Malar Augmentation. J Oral Maxill

authors also used porous HA for mandibular recontour-

ing and paralateronasal and infraorbital augmentation,

with satisfactory results. Another condition for stability

is that it should not be attained by osteosynthesis. Sta-

bility seems to depend on an adequately sized subper-

iosteal pocket that holds the graft in place and prevents

the granules from migrating to the soft tissues and

adequate hemostasis at the recipient site; this willdecrease intra- and postoperative bleeding so that the

initial prosthetic volume is decreased. The graft’s stabil-

ity also depends on the surgeon’s proficiency in viewof

the findings of malposition and partial resorption

found in the present sample (1.36%) that were prob-

ably linked to a too-small or too-large subperiosteal

pockets or inappropriate management of hemostasis.

In the present cases, secondary correction wasachieved by fat grafts harvested under local anesthesia.

Fat grafts represent a good option for facial recontour-

ing in orthognathic surgery, as discussed by others.39

Lipofilling generally presents with low morbidity,

with only superficial bruising of the harvested areas

or other minor complications, such as acute edema,

ecchymosis, and redness, which have been

described as relatively frequent. However, majoradverse effects, such as blindness, also can occur,

although at a much lower rate.40 Firm knowledge

of the vascular anatomy is mandatory to prevent

related complications. A certain amount of unpre-

dictable resorption also has been observed.41,42

Compared with HA, the indications for fat grafting

focus more on minor defects and on other areas of

the face, such as nasolabial folds, marionette lines,cheeks, upper and lower lips, and labial tubercles.

When using fat grafts for severe malar deficiency, it

is generally difficult to achieve a satisfactory and

stable result in symmetry and projection.43,44 The

stability of HA appears to be linked to the

material’s osteoconductive properties because it is

gradually replaced by native bone tissue with a

colonization gradient from the periosteum to the

s (immunohistochemistry with cathepsin K; magnification, �10 and

ofac Surg 2016.

FIGURE 12. Osteoblasts identified with CD56 antibody. Greaternew osteogenesis activity at the side of the biopsy sample adjacentto native bone (immunohistochemistry; magnification, �1 and�20).

D’Agostino et al. Hydroxyapatite for Malar Augmentation. J Oral

Maxillofac Surg 2016.

1.e14 HYDROXYAPATITE FOR MALAR AUGMENTATION

basal cortical bone, as shown by the study’shistologic findings, which are in accord with the

morphologic volumetric data described by

Mendelsson et al18 and Grybauskas et al.45

The present radiologic findings confirmed that the

prosthetic material changes over time; initially, it is

radiotransparent with a granular structure, but over

time shows increasing uniformity and radiopacity,

which presupposes that the material will be resorbedand eventually replaced by cortical bone. A volumetric

reduction of approximately 10 to 20% of the original

volume 18 to 24 months after the procedure was

described by Mendelsson et al18 and Grybauskas

et al,45 and this is a factor that should be considered

at the preoperative planning stage. The studies cited

earlier also described how the biomaterial, after an

initial compaction period of approximately 4 months,tends to achieve remarkable volumetric stability, with

a negligible decrease in size during the follow-up obser-

vation period. The first cases of malar augmentation

using HAwere reported 10 years ago; those clinical out-

comes are in line with the findings of the present study.

However, the data could not be considered because of

the lack of adequate records, mostly because at the time

standard preoperative radiographic measurementswere taken in 2 dimensions. Concerning the technical

characteristics, the material is shaped by hand, which

implies that it is possible to achieve various forms and

dimensions according to the needs of the individual

patient; this is particularly useful in cases of asymmetry

of the zygomatic region. On the one hand, the prepara-

tion of the prosthesis has a relatively long learning

curve compared with other preshaped biomaterials;

on the other hand, the resulting naturalness and sym-

metry are excellent given the patients’ high VAS scores.

Shortening intraoperative time might be possible with

the use of preoperative CT planning of custom-made

prostheses, although this would increase the overallcost of the treatment plan. A possible compromise

might be the adoption of a ready-to-use prosthesis

that can be adapted according to the patient’s needs.

In contrast to other biomaterials, HA seems to be char-

acterized by a low rate of early- and late-onset infections

(0.2%). This finding has been confirmed by other

reports17 and is in agreement with the hypothesis

that porous HA has an antibacterial effect.46 Coloniza-tion of bone tissue, the fact that screws are not needed

to fix the prosthesis, and a high degree of biocompati-

bility47 contribute to limiting the occurrence of postop-

erative and long-term infectious phenomena.

Concerning 1-piece and segmental Le Fort I osteoto-

mies of the upper jaw, it should be remembered that

healing of the osteotome site is seldom complete

because of the long-term possibility of bacterialcontamination through the nasal passages.

The present results represent the conjoined efforts

of 2 centers specializing in the treatment of dentoske-

letal deformities and harmonization of facial contours.

The large number of patients makes it one of the most

extensive studies on this procedure found in the liter-

ature. In light of what has emerged from this study,

porous HA seems to have excellent biocompatibleand osteoconductive properties. In fact, the low rate

of complications found and the radiologic, histologic,

and molecular biological findings support this affirma-

tion and are in agreement with data of other studies

found in the literature. Porous HA prostheses for zygo-

matic augmentation led to long-term stable esthetic re-

sults, and most patients expressed a high degree of

satisfaction. These advantages are counterbalancedby the relatively long time needed to prepare the pros-

theses and the long learning curve involved in creating

the subperiosteal pocket and a slight hypercorrection,

which seem necessary to address the short-term volu-

metric reduction. Given the characteristics described

in this study, porous HA granules with microfibrillar

collagen seems to be an excellent choice when

surgery to harmonize the zygomatic region and tocorrect facial asymmetry is being planned.

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