Morphologie (2017) 101, 113—119

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GENERAL REVIEW

Filling bone defects with �-TCP inmaxillofacial surgery: A reviewComblement osseux par �-TCP en chirurgie maxillofaciale :revue des indications

B. Guillaumea,b,∗

a Collège Francais d’Implantologie (CFI), 6, rue de Rome, 75005 Paris, Franceb Groupe Études Remodelage Osseux et bioMatériaux (GEROM), Institut de Biologie en Santé (IRIS-IBS),LUNAM Université, CHU d’Angers, 49933 Angers cedex, France

Available online 29 May 2017

KEYWORDSTricalcium phosphate;�-TCP;Bone graft;Sinus lift;Biomaterial

Summary Reconstruction of bone defects prior to implant placement now involves syntheticsubstitutes such as �-TCP because of its ability to promote bone remodeling. Its capacity tobe progressively substituted by the patient’s bone allows to regenerate a dense bone volume.In addition, its availability in large quantities, avoiding the morbidity observed with harvest-ing autogenous bone, widens the operative indications. In this paper, the main indicationsof �-TCP in maxillofacial surgery (dentistry, parodontology and dental implant surgery) arereviewed. They include periodontal bone disease, bone disjunction, pre-implant surgery (sinusfloor elevation and lateralization of the inferior alveolar nerve).© 2017 Elsevier Masson SAS. All rights reserved.

MOTS CLÉS�-TCP ;Biomatériau ;Greffe osseuse ;

Résumé La reconstruction des déficits osseux avant la pose d’implant fait appel désormais àdes matériaux de substitution synthétique comme le �-TCP de par ses capacités à favoriser leremodelage osseux. Il est progressivement substitué par l’os du patient permettant de régénérerun volume osseux dense. Enfin, sa disponibilité en grande quantité, évitant la morbidité liéeà un site de prélèvement d’autogreffe, élargit les indications opératoires. Dans ce travail,les principales indications d’utilisation du �-TCP en chirurgie maxillofaciale (chirurgie den-

Sinus lift ;

Tri calcium phosphate taire, parodontologie et implantation dentaire) sont revues. Elles comprennent la maladieosseuse parodontale, la disjonction osseuse, la chirurgie pré-implantaire (élévation de sinuset latéralisation du nerf alvéola© 2017 Elsevier Masson SAS. Tou

∗ 6, rue de Rome, 75005 Paris, France.E-mail address: doct.guillaume@wanadoo.fr

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http://dx.doi.org/10.1016/j.morpho.2017.05.0021286-0115/© 2017 Elsevier Masson SAS. All rights reserved.

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n dental and maxillofacial surgery, the repair of boneefects aims at recreating a bony site that is suitable for

114 B. Guillaume

Figure 1 Scanning electron microscopic image of beta-tricalcium phosphate (�-TCP). A. A scaffold suitable for bonegrafting with an interconnected macroporosity. B. High magni-fit

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graft depend on the volumes to be filled (alveolar area) or tobe restored (vertical or horizontal ridge insufficiency, bonecyst or sinus lifting). The volume and form of the defectinfluence the choice of the grafting material. A consider-able number of possibilities are available: e.g., harvestingautologous bone particles to fill a post-extraction socket [3],thickening of a thin ridge caused by hypodontia [4], bone dis-junction [5], sinus lifting [6] or lateralization of the inferioralveolar nerve [7]. Surgical techniques also use various sur-gical protocols with a local or a general anesthesia; it shouldbe noticed that local anesthesia is being practiced more andmore frequently. Although autologous bone grafts and allo-grafts have been a recognized surgical modality for severaldecades, the use of synthetic biomaterials has continued todevelop as substitute products, especially in the context ofpre-implant surgery.

Definitions of graft-related criteria

A bone substitute must be biocompatible and fill severalcriteria: bio-inertia is defined as the absence of physico-chemical reaction of the product in direct contact withbone. Bioactivity is the capacity to develop reactions favor-ing osseointegration of the product and the adaptation of the

cation of the surface of a wall of this scaffold showing theypical surface of sintered grains with microporosity (arrows).

orphological, prosthetic or implant-prosthetic rehabilita-ion [1,2]. Causes of bone deficiency are numerous: genetic,

ost-traumatic, secondary to tooth removal, infectious oratrogenic. The volume of bone to reconstruct varies accord-ng to the anatomical situation. The characteristics of the

igure 2 Filling a bone socket and reconstruction of the corti-al side with beta-tricalcium phosphate (�-TCP) granules after

tooth extraction. Insert: CT analysis of the reconstructed boneeveral months after the graft, note the high bone density.

Figure 3 A. Disjunction on a premolar zone. B. Beta-tricalcium phosphate (�-TCP) granules (1000—2000 �m) withhigh porosity are inserted in the gap created between the twocortices.

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Bone filling with �-TCP

receiving tissue. Osteoinduction is defined as the ability toinduce bone formation in an extra-skeletal area. Osteocon-duction is the ability of the recipient bone cells to colonizethe graft. An evolution in the choice of materials to fill bonedefects occurred in the past few years. Autologous graft isconsidered as the ‘‘gold standard’’ in terms of osteogenic-ity but its main disadvantage is that obtaining a sufficientvolume of bone is sometimes a problem (except when largebone samples are harvested but with a significant increasein morbidity) [8,9]. So, due to the justified reluctance to useextra-oral bone grafts and the medicolegal constraints, theinterest for synthetic bone substitutes is increasingly grow-ing. Most surgical teams seek to restore sufficient amountsof high quality bone allowing implant placement by usingbiomaterials to restore a part or the whole bone. Beta-tricalcium phosphate (�-TCP) is now one of the most usedsynthetic materials for bone reconstruction in orthopedicand maxillofacial surgery and now in pre-implant surgery.In implantology, the resorbable or non-resorbable natureof the grafted material appears of the upmost importance.Some materials are resorbable but there are considerabledifferences in term of disappearance upon time, some ofthem can persist indefinitely. The use of a biomaterial in a

maxillary or mandibular site after a tooth extraction mustallow implant placement in a second surgical time. In addi-tion, synthetic biomaterials preserve the macroarchitecture

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Figure 4 Sinus lift elevation. A. The sinus membrane is gently pusC. Beta-tricalcium phosphate (�-TCP) granules (1000—2000 �m) withplaced in the grafted area 9 months later, note the increase density

115

f the implanted areas and they can be produced in largeuantities by industry.

haracteristics of �-TCP

-TCP - Ca3(POH4)2 - belongs to the family of tricalciumhosphates in the beta phase. Being considerably much moreesorbable than hydroxyapatite, this biomaterial is highlyiocompatible when implanted in bone; it is resorbableithin 6 to 9 months as shown in animal and human his-

ological studies [10]. One of the main characteristics ofhe biomaterial is to be commercially available as scaf-olds with a macroporosity of 100 to 600 �m that ensuressteoconduction and can reach 85% of the total mass of therafted material (Fig. 1A). �-TCP has also a microporosity< 100 �m) due to sintering of elementary grains, which facil-tates the exchange of extracellular fluxes of Ca2+ and PO4

3−

ons (Fig. 1B). This ensures an optimal bone remodelingith increased osteoblastic apposition and the appositionf lamellar bone. Its biocompatibility, its bioresorption andsteoconductive properties from the recipient bone make

ockets of variable sizes. In addition, reconstruction of aaxillary sinus in a pre-implantation step can also be easily

btained. �-TCP can also be prepared in the form of plates

hed away. B. The space available for grafting is then exposed. a high porosity are used to fill this area. D. Implants have been

of the grafted zone.

116

to fill the sinus ceiling. Such plates also allow to densify theunderlying graft with granules and can be used to protect thesinus mucosa (Schneider’s membrane) in case of perforation.

Clinical indications of bone filling biomaterials

Periodontics and pre-implant surgery

Periodontal bone diseaseIt has been proposed for more than 15 years to fill peri-odontal pockets with biomaterial granules. Loss of theperi-radicular bone tissue induces mobility of the dental rootand can cause loss of the tooth. Under local anesthesia, theprocedure consists in detaching the full thickness of the gin-giva to scrap the inflammatory tissues and cementum alongthe root and to fill the defect. �-TCP is available in variousgranule sizes varying from 550—1000 �m to 1000—2000 �m.

Figure 5 Histological analysis of a bone biopsy harvestedin a patient six months after grafting with beta-tricalciumphosphate (�-TCP) granules. A. Mineralized bone is apposeddirectly onto the biomaterial surfaces. (Goldner’s trichrome,calcified bone is in green osteoid tissue in red). B. Remodel-ing of implanted �-TCP granules by osteoclasts. Histoenzymaticidentification of these cells by their tartrate resistant acidphosphatase (TRAcP) content; osteoclasts are in brown, newly-apposed bone is counterstained in blue and �-TCP remainsunstained.

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he characteristics of �-TCP scaffolds prepared with a highorosity by industry are to promote reconstruction withamellar bone. In case of apicoectomy and elimination ofhe cystic tissues at the apex of the tooth, a bone loss mayccur with a variable volume ranging from a few mm3 to 1r 2 cm3. The cystic tissue is removed by a careful curettagend 1000—2000 �m granules of high porosity �-TCP are usedo fill the cavity.

re-implant surgeryncreasing the volume of the dental arch will allow thelacement of dental implants. In implant surgery, it is oftenandatory to respect the healing time necessary for the

rafted area to be remodeled before placing an implant in bone environment that is sufficient in volume and willemain stable over time. Post-extraction sockets, as peri-dontal pockets, can benefit from the use of �-TCP granuleso support bone reconstruction (Fig. 2).

one disjunctionhether at the maxilla or the mandible, insufficient thick-

ess of the ridge imposes to recreate the bone thickness.pposition graft is an alternative technique but requires aecond site to harvest the autogenous bone; sometimes thiss not possible or rejected by the patient. Bone disjunctionepresents in fact a greenstick fracture [11]. With a bonehisel or with a fissure burr, vertical sections are done at theesired height (Fig. 3A). Similarly, a cleavage plane is maden the whole thickness of the ridge. Finally, the cortical bones gradually moved away while maintaining its apical inser-ion. The gap (4 to 5 mm in thickness) is then filled with-TCP 1000—2000 �m granules, this prevents the vestibularortical bone from returning in place (Fig. 3B). This allowsone remodeling and osseointegration of the biomaterial bysteoconduction in 8 to 9 months.

inus floor elevation

lacement of an implant in the posterior zone of the upperaw is often challenging because bone loss is observed inost patients with edentulation and thickness of the sinusoor may be reduced up to 5 to 6 mm. It is evident thatuch a reduced vertical bone height limits implant place-ent since an 8 to 10 mm of bone height is required to allow

mplant placement. Thus, elevation of the maxillary sinusoor is a recently described solution to restore a suitable 5o 10 mm height of available bone for implant placement.inus lifting was first reported by Boyne and James in the960s [12]. Sinus floor elevation for dental implant place-ent is obtained by detachment of the sinus mucosa using

lateral maxillary window approach (lateral anthrotomy, inost cases) or by the crestal route, followed by the filling by

grafting material [13—15]. A crestal incision of the max-lla is made on the alveolar ridge with a vertical dischargencision in the canine region and opposite to the posterioruberosity. The gingival flap is then reclined to ensure goodisibility of the anterior surface of the sinus and allow the

ealization of a bone window whose upper limit is 15 mmrom the crest. The bone window is done with a diamondound bur under irrigation (Fig. 4A). The central trapdoorf cortical bone is preserved to maintain a bone layer for

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Bone filling with �-TCP

the mucosa during the other surgical steps. The sinus mem-brane is then gently raised from the bone floor to delimit asufficient volume. At this stage, one should carefully checkthe presence of any perforation of the membrane becausethey can lead to complications at the time of placementof the biomaterial (Fig. 4B). A suture may be done with a6/0 thread or a �-TCP plate (Sinus-upTM, Kasios, France) toensure a complete closure of the sinus. The cavity is thenfilled with a biomaterial that will latter provide the bony bedsuitable for implant placement. Autogenous bone chips havelong been considered as the gold standard due to their pre-sumptive maintenance of cellular viability [12]. The choiceof a biomaterial must fulfill several qualities: it should bebiocompatible in the grafted site and should not inducean inflammatory reaction of the sinus mucosa, which couldbe deleterious to the whole surgical procedure. It must beintegrated within the grafted areas by combining its resorp-tion and its substitution by new bone. Resorption shouldbe progressive to allow bone remodeling with appositionof lamellar bone. Non-resorbable hydroxyapatite should beavoided [16]. Macroporosity of the grafted biomaterial playsa key role in bone osteoconduction because it determinesthe invasion of vascular and cellular sprouts [17,18]. Lastly,

the grafting material must be provided in sufficient volumeto allow an easy adaptation in these complex surgical areasto fill volumes up 3 to 6 cm3. Over the years, several typesof materials including allografts and xenografts of various

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Figure 6 Lower alveolar nerve (IAN) lateralization. A. X-ray of alarge bone defect. B. A significant bone defect is obtained and the em(�-TCP) granules (1000—2000 �m) with a high porosity are used to fiIAN and placement of four implants is now possible.

117

rigins have been used either alone or mixed with morcel-ized autogenic bone [19]. �-tricalcium phosphate was therst synthetic bone substitute to be proposed for sinus floorlevation [14]. The use of 1000—2000 �m granules of highorosity �-TCP HP is recommended nowadays [20]. Anthrallling begins by placing granules on the posterior wall thenn the latero-anterior and anteroposterior walls withoutxcessive compression of the biomaterial (Fig. 4C). Thenterior wall is then filled and a resorbable SurgicelTM mem-rane (Ethicon, Johnson and Johnson) to avoid migrationf granules and sutured with Vicryl 5/0TM thread (Ethicon,ohnson and Johnson). A computed tomographic analysis issually done 8 months later. There is a marked densificationf the grafted area filled by the biomaterial and no edemaf the sinus membrane can be evidenced (Fig. 4D).

The grafted area appears to be more radio-opaque thanhe surround bone tissue (due to the greater calcium contentf �-TCP). The density will progressively decrease as theiomaterial is replaced by bone [21]. Histological analysisonfirmed the direct bonding of mineralized bone matrixo �-TCP granules together with the biomaterial resorptionFig. 5A) [10,22,23]. Depending on the area, the bone has aatrix of lamellar or non-lamellar texture. The detection of

key enzyme present in the osteoclasts (tartrate resistantcid phosphatase [TRAcP]) evidences these cells at the sur-ace of the newly formed bone and at the surface of �-TCPranules (Fig. 5B).

patient with an included canine whose ablation will create aergence of the IAN is evidenced. C. Beta-tricalcium phosphatell this area. D. X-ray of the patient after lateralization of the

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ateralization of the inferior alveolar nerve (IAN)

ertical atrophy of alveolar ridge is encountered at theandible as a sequela of dental extractions (Fig. 6A) or inatients with a long history of wearing a removable pros-hesis. An onlay graft allows bone reconstruction in theertical direction but requires the use autologous cortico-rabecular bone harvested at the calvarium, iliac crest,ibia or mandibular symphysis, retromolar area, mandibularamus [24]. The use of allogenic or xenogenic bone par-icles has also been suggested. In all cases, the graft isaintained to the alveolar ridge by osteosynthesis using tita-

ium screws. The IAN remains one of the main anatomicalimitation to the placement of implants in the poste-ior mandibular zone. Another alternative is to move theAN laterally from its canal by nerve lateralization andepositioning to provide a bone area suitable for implantlacement [25]. The displacement of the IAN can be pro-osed in several situations: in case of compression of theerve sheath following a trauma, when a removable prosthe-is exerts compressive strains on the IAN or when an implantpex directly compresses the nerve [7,11,26]. Lateraliza-ion of the IAN radically changes the nature of the prostheticoncept where only the anterior region is usually concerned.isplacement of the nerve allows the placement of implants

n the posterior zone with a removable prosthesis with an O-ing system or a posterior bar. In fixed dental prosthesis, theosterior implants increase the holding of an overdenturer a fixed bridge by providing supporting pillars. In case of aemovable prosthesis, attachment of the prosthesis is con-iderably improved when an O-ring system or a posterior bars used.

The surgical technique is based on a vestibular osteotomyf the external cortical bone in front of the mental fora-en, and extended by fashioning of a bone flap towards the

ear [27—29]. The cortico-trabecular bone block is removedo gain access to the nerve and to gently tease it out ofhe mandible (Fig. 6B). The bone block is both removedn toto or morcellized and kept until the end of the inter-ention. Replacement of the bony flap allows an underlyingone growth and prevents the nerve from returning to theandibular canal. Nevertheless, displacement of the IAN

reates a bone void. It can be filled with �-TCP particlesFig. 6C) held in place with a SurgicelTM membrane. Compactlocks of �-TCP can also be implanted. After an 8-monthone healing period, the mandibular bone has been recon-tituted and offers a suitable site for implant placementFig. 6D). High porosity �-TCP granules plays an essentialole in the local remodeling of bone volume and lead to theormation of a quality site.

onclusion

one remodeling is an essential step in the healing processf a grafted area. The contribution of synthetic biomaterialss now confirmed and guarantees an optimal reconstruc-

ion that allows implant placement in a second step. Thevailability of �-TCP in the form of granules or compactlabs offers new therapeutic perspectives in maxillofacialnd pre-implant surgery.

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B. Guillaume

isclosure of interest

he author declares that he has no competing interest.

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