SIMULTANEOUS VERTICAL GUIDED BONEREGENERATION AND GUIDED TISSUEREGENERATION IN THE POSTERIOR MAXILLAUSING RECOMBINANT HUMANPLATELET-DERIVED GROWTH FACTOR: ACASE REPORTIstvan Urban, DMD, MD; Nicholas Caplanis, DDS, MS; Jaime L. Lozada, DDS

This clinical case report describes and demonstrates successful use of recombinant human platelet-

derived growth factor (rhPDGF-BB) in conjunction with autogenous bone, anorganic bone mineral,

and barrier membranes to reconstruct severe alveolar bone defects. A combined sinus augmentation

and vertical alveolar ridge augmentation was successfully performed. In addition, a significant

amount of periodontal bone gain was achieved in close apposition to a previously denuded root

surface, which is significant from a periodontal standpoint, given the possibility of vertical

periodontal regeneration.

Key Words: guided bone regeneration, vertical ridge augmentation, sinus augmentation,PDGF, barrier membranes, periodontal regeneration, GBR, GTR

INTRODUCTION

Vertical and horizontal alveolar ridge aug-mentation utilizing guided bone regen-eration (GBR) has become a significanttreatment option to provide optimalbone support for osseointegrated dentalimplants. The surgical technique and

application of GBR for supracrestal regeneration havebeen described previously,1 and the first animal andhuman histologic studies demonstrated successfulvertical bone augmentation.2,3 Long-term resultsconcluded that vertically augmented bone usingGBR techniques responds to implant placement in asimilar fashion to native, nonregenerated bone.4,5

The GBR technique for vertical bone augmentationwas used in combination with a subantral augmenta-tion procedure for posterior maxillary reconstructionutilizing machined surface implants. However, implantsurvival and success rates were 92.1% and 76.3%,which conflicted with previously reported results onvertical and horizontal GBR.6

A potential solution for overcoming this differencein results could be the use of bone inductive growthfactors. This may enhance the development of mature

Istvan A. Urban, DMD, MD, is Assistant Professor, Graduate ImplantDentistry, Loma Linda University, Loma Linda, Calif, and is in privatepractice in Periodontics and Implant Dentistry in Budapest, Hungary.Address correspondence to Dr Urban at Sodras utca 9, Budapest,Hungary 1026. (e-mail: istvan@implant.hu).Nicholas Caplanis, DDS, MS, is Assistant Professor, Graduate ImplantDentistry, Loma Linda University, Loma Linda, Calif, and is in privatepractice in Periodontics and Implant Dentistry in Mission Viejo, Calif.Jaime L. Lozada, DDS, is Professor, Department of RestorativeDentistry, Director of Graduate Implant Dentistry, Loma Linda University,Loma Linda, Calif.

CLINICAL

Journal of Oral Implantology 251

lamellar bone, which possibly could support dentalimplants sooner and more predictably.

The safety and efficacy of recombinant humanplatelet-derived growth factor (rhPDGF-BB) have beendemonstrated for periodontal regeneration.7 Resultsof a preclinical canine study demonstrated thatpurified recombinant PDGF-BB, used in combinationwith a deproteinized bovine block, and withoutplacement of a barrier membrane, has the potentialto regenerate significant amounts of new bone insevere mandibular ridge defects.8

Several case studies utilizing various combinationsof autogenous bone, anorganic bovine-derived bonemineral (ABBM) (Bio-Oss, Geistlich Pharma AG, Wolhu-sen, Switzerland), and rhPDGF-BB were publishedrecently and report successful histologic and clinicalresults.9,10

This clinical case report describes and demon-strates the successful use of rhPDGF-BB in conjunctionwith autogenous bone, anorganic bone mineral, andbarrier membranes to reconstruct severe alveolarbone defects.

CASE PRESENTATION

A 30-year-old healthy female patient presented for anevaluation of her posterior right maxilla, which had ahistory of dentoalveolar infection. Significant clinicalfindings included several fistulous tracts and peri-odontal probing depths of up to 10 mm around teethNos. 2, 3, and 4. Although the 3 teeth were splintedtogether, advanced mobility of the entire 3-unitprosthesis was evident. Radiographic examinationrevealed advanced periodontal bone loss with associ-ated periapical lesions (Figure 1).

The prognosis was poor, and extraction wasperformed. Following a 2-month healing period, asevere vertical ridge defect was noted as anticipated,which also was visible during her smile. This caused anesthetic concern for the patient (Figure 2). The verticaldefect in close proximity to the floor of the sinussignificantly compromised the site with regard toimplant reconstruction (Figure 3). The patient desireda fixed reconstruction; therefore, the clinical plan wasto regenerate the alveolar defect to ideally reconstructform and esthetics and subsequently place implants tosupport a fixed prosthetic restoration.

SURGICAL PROCEDURE

The patient was premedicated with amoxicillin 2 g1 hour before surgery and was given 500 mg penicil-lin 3 times a day for 1 week following the surgery. The

patient rinsed with 0.12% chlorhexidine solution(Peridex) for 1 minute; the patient’s skin surroundingthe surgical site was disinfected, and a sterile surgicaldrape was applied to minimize potential contamina-tion from extraoral sources. A full-thickness, midcrestalincision was made in the keratinized gingiva on thealveolar crest. For adequate surgical access, a diver-gent vertical incision was made at the mesial lineangle of tooth No. 6. After primary incisions weremade, periosteal elevators were used to reflect a full-thickness flap beyond the mucogingival junction andat least 5 mm beyond the bone defect. A rectangularantrostomy with rounded corners was created with around diamond bur at the lateral wall of the maxillarysinus. The sinus window was infractured and the sinusmembrane was reflected carefully with sinus curettesand was elevated with care to prevent perforations(Figure 4). With a small round bur, the recipient bonybed was prepared with multiple decortical holes toexpose the medullary space. Autogenous bone washarvested from the right ascending ramus and wasparticulated in a bone mill (R. Quetin Bone-Mill,Roswitha Quetin Dental Products, Leimen, Germany).The autogonous bone was mixed with ABBM (Bio-Oss,Geistlich Pharma AG) and then was hydrolyzed inrhPDGF-BB (Gem 21, Osteohealth, Shirley, NY). Anappropriate-sized, titanium-reinforced expanded poly-tetrafluoroethylene membrane (e-PTFE) (GORE-TEXRegenerative Material Titanium Reinforced, W.L. Gore& Associates, Flagstaff, Ariz) was selected and trimmedwith consideration of graft volume. The membranewas fixated first on the palatal side using multipletitanium pins. The bone graft then was placed withinthe subantral space and appositionally on the verticalalveolar defect. The membrane was folded over ontothe buccal alveolus and fixated with additional titaniumpins (Figure 5). The mesial border of the e-PTFEmembrane was placed 4 mm from the distal surfaceof tooth No. 4 to prevent membrane exposure. Themesial end of the membrane was unfilled for about2 mm supracrestally (Figure 6). This area was filled withadditional bone graft, connecting the denuded rootsurface to the open end of the membrane (Figure 7). Aresorbable collagen membrane (Bio-Gide ResorbableBilayer Membrane, Osteohealth) then was applied toprotect and contain this area in an attempt to minimizepostoperative complications (Figure 8). An additionalcollagen membrane was applied to cover the sinuswindow. Periosteal releasing incisions were made toprovide adequate flap reflection for tension-free primaryclosure. The flap was closed (GORE-TEX CV-5 Suture,W.L. Gore & Associates) in 2 layers with the use ofhorizontal mattress and single interrupted sutures.

SIMULTANEOUS VERTICAL GUIDED BONE REGENERATION

252 Vol. XXXV / No. Five / 2009

Medications were followed as described earlier. Inaddition, an anti-inflammatory medication, 50 mgdiclofenac (Voltaren XR) was prescribed 3 times a dayfor 1 week following surgery. For chemical plaquecontrol, 0.12% chlorhexidine solution was used dailyfrom 24 hours post surgery until the time of sutureremoval. Postoperative swelling was remarkable, reach-ing maximum at 48 hours postoperatively. Swellinggradually subsided but was still visible at 1 week anddisappeared completely after 10 days. Postoperativediscomfort usually was associated with tension fromthe swelling. Pain was negligible, however. No othersymptoms occurred during the postsurgical period.

To avoid postsurgical trauma, a removable appli-ance was not utilized. After a previously described 9months of uneventful healing, the area was exploredemploying the same full-thickness flap design.3 Themembrane had maintained its original position, andbone growth was evident over the membrane in the

area where the resorbable collagen membrane wasutilized (Figure 9). After removal of the titanium pinsand the e-PTFE membrane, complete vertical boneregeneration was observed. The defect between thedistal surface of tooth No. 4 and the e-PTFE membranealso demonstrated complete bone fill. About 2 mm ofthe previously denuded root surface of tooth No. 4 wasalso in intimate contact with bone (Figure 10).

Three Branemark TiUnite implants were placed(Nobel Biocare, Yorba Linda, Calif) in accordance withthe manufacturer’s protocol (Figure 11). Duringimplant placement, a collagen membrane (Bio-GideResorbable Bilayer Membrane, Osteohealth) wasplaced empirically over the newly formed crestal boneto protect the graft from possible early resorption.

The implants were submerged through a 2-stagetechnique for 6 months and then were uncovered andrestored with a splinted, 3-unit implant supportedfixed partial denture (Figures 12 and 13).

FIGURES 1–4. FIGURE 1. Failing dentition on the right posterior maxilla. FIGURE 2. Esthetically and functionally demanding severe vertical defect.FIGURE 3. Deficient alveloar ridge revealed following full-thickness flap elevation. FIGURE 4. Sinus proximity managed with combined sinusfloor elevation procedure.

Istvan Urban et al

Journal of Oral Implantology 253

DISCUSSION

rhPDGF-BB has demonstrated safety and efficacy forperiodontal regeneration in previous studies.7 It hasbeen shown both in a preclinical canine study8 and insubsequent case reports that PDGF has the potentialto regenerate significant amounts of supracrestalbone in conjunction with ABBM and autogenousparticulated bone.9,10

This case report demonstrates that significantvertical bone regeneration is possible in a demandingclinical defect in the posterior maxilla. Conflictingresults of posterior maxillary vertical regenerationhave been reported previously. In one study,5 100%success rates were reported using enhanced surfaceimplants (Ti-Unite, Nobel Biocare) after vertical GBR,whereas another study reported implant survival andimplant success rates of 92% and 76%, respectively,when machined surface implants were used.6 Bothstudies used the success criteria delineated by Albrekts-

son et al.11 In this case report, a combined subantralaugmentation and vertical alveolar ridge augmentationwas performed successfully, leading to 100% implantsuccess11 and survival over 12 months for these 3implants. In addition, a significant amount of periodon-tal bone gain was achieved in close apposition to apreviously denuded root surface, which is significantfrom a periodontal standpoint, given the possibility ofvertical periodontal regeneration.

This limited case report demonstrates remarkablevertical bone regeneration and perhaps periodontalregeneration using rhPDGF-BB in conjunction withautogenous bone, anorganic bone mineral, and barriermembranes. No controls were included in this casereport. In the future, controlled studies are needed toevaluate the extent of benefit derived when PDGF isused. Continued follow-up will be necessary toinvestigate long-term implant success, as well asstability of the newly regenerated bone around theimplants and the natural tooth.

FIGURES 5–8. FIGURE 5. Equal volumes of particulate autogenous bone with an anorganic bone mineral, combined with recombinant humanplatelet-derived growth factor, are applied to defect. FIGURE 6. The membrane is secured over the graft with titanium pins. FIGURE 7. Theresidual defect between the applied titanium reinforced expanded polytetrafluoroethylene membrane is filled with additional graftmaterial. FIGURE 8. The treatment area and the sinus window are protected with a resorbable collagen membrane.

SIMULTANEOUS VERTICAL GUIDED BONE REGENERATION

254 Vol. XXXV / No. Five / 2009

FIGURES 9–13. FIGURE 9. Following 9 months of uneventful healing, the expanded polytetrafluoroethylene membrane (e-PTFE) membrane hasmaintained its position with excellent bone regeneration between the distal surface of the previously denuded tooth No. 4 and thetitanium reinforced e-PTFE membrane. FIGURE 10. Clinical view of the regenerated alveolar crest. FIGURE 11. Occlusal view of 3 implants placedinto ideal positions. FIGURE 12. The final reconstruction demonstrates a functional and esthetic outcome. FIGURE 13. Stable crestal bone aroundthe implants and regenerated bone in close apposition with previously denuded tooth No. 4.

Istvan Urban et al

Journal of Oral Implantology 255

This treatment modality has the potential toeliminate completely the need for bone harvesting;preliminary results are encouraging. However, theclinician should recognize that clinical informationregarding this technique, including information onresorption of the regenerated bone, implant survival,and crestal remodeling around the implants, iscurrently limited. Further documentation using con-trolled long-term, randomized, clinical trials is neces-sary before this new treatment technique can berecommended for routine clinical practice.

REFERENCES

1. Tinti C, Benfenati SP. Vertical ridge augmentation: surgicalprotocol and retrospective evaluation of 48 consecutively insertedimplants. Int J Periodontics Restorative Dent. 1998;18:435–443.

2. Jovanovic SA, Schenk RK, Orsini M, Kenney EB. Supracrestalbone formation around dental implants: an experimental dogstudy. Int J Oral Maxillofac Implants. 1995;10:23–32.

3. Simion M, Trisi P, Piattelli A. Vertical ridge augmentationusing a membrane technique associated with osseointegratedimplants. Int J Periodontics Restorative Dent. 1994;14:497–512.

4. Simion M, Jovanovic SA, Tinti C, Benfenati SP. Long-termevaluation of osseointegrated implants inserted at the time or aftervertical ridge augmentation: a retrospective study on 123 implantswith 1–5 year follow-up. Clin Oral Implants Res. 2001;12:35–45.

5. Urban IA, Jovanovic SA, Lozada JL. Vertical ridge augmen-tation using guided bone regeneration (GBR) in 3 clinical scenarios:a retrospective study of 35 patients 12 to 72 months after loading.Int J Oral Maxillofac Implants. 2009;24:502–510.

6. Simion M, Fontana F, Rasperini G, Maiorana C. Long-termevaluation of osseointegrated implants placed in sites augmentedwith sinus floor elevation associated with vertical ridge augmen-tation: a retrospective study of 38 consecutive implants with 1 to7-year follow-up. Int J Periodontics Restorative Dent. 2004;24:208–221.

7. Nevins M, Giannobile WV, McGuire MK, et al. Platelet-derivedgrowth factor stimulates bone fill and rate of attachment level gain:results of a large multicenter randomized controlled trial. JPeriodontol. 2005;76:2205–2215.

8. Simion M, Rocchietta I, Kim D, Nevins M, Fiorellini J. Verticalridge augmentation by means of deproteinized bovine bone glockand recombinant human platelet-derived growth factor-BB: ahistological study in a dog model. Int J Periodontics RestorativeDent. 2006;26:415–423.

9. Simion M, Rocchietta I, Dellavia C. Three-dimensional ridgeaugmentation with xenograft and recombinant human platelet-derived growth factor-BB in humans: report of two cases. Int JPeriodontics Restorative Dent. 2007;27:109–115.

10. Simion M, Rocchietta I, Monforte M, Maschera E. Three-dimensional alveolar bone reconstruction with a combination ofrecombinant human platelet-derived growth factor BB and guidedbone regeneration: a case report. Int J Periodontics Restorative Dent.2008;28:239–243.

11. Albrektsson T, Zarb G, Worthington P, Eriksson B. The long-term efficacy of currently used dental implants: a review and proposedcriteria of success. Int J Oral Maxillofac Implants. 1986;1:11–25.

SIMULTANEOUS VERTICAL GUIDED BONE REGENERATION

256 Vol. XXXV / No. Five / 2009