Growth Factor-Mediated Sinus Augmentation Grafting With ... · survival following sinus augmentation, a far narrower body of literature exists examining similar parameters for mineralized

CASE REPORT

Growth Factor-Mediated Sinus Augmentation Grafting WithRecombinant Human Platelet-Derived Growth Factor-BB (rhPDGF-BB):

Two Case ReportsE. Todd Scheyer* and Michael K. McGuire*

Introduction: In the following two case reports, growth factor-mediated sinus augmentation surgery is used to treat sig-nificant posterior maxillary alveolar bone deficiency. At initial examination, preexisting subsinus alveolar bone height was £3mm. A composite graft of anorganic bovine bone mineral (ABBM) þ mineralized bone allograft was combined with recombinanthuman platelet-derived growth factor-BB (rhPDGF-BB) for augmentation grafting via a traditional maxillary lateral wall osteotomyapproach to the sinus. In both cases, early implant placement and loading following sinus grafting, as well as long-term clinicalfollow-up, document potential benefits of growth factor-mediated bone regenerative sinus augmentation procedures. The signif-icantly abbreviated durations seen in these two cases between sinus augmentation grafting and implant placement and prostheticrestoration, to the best of our knowledge, have not been previously reported in the literature.

Case Presentations: Two adult males presented with severe posterior maxillary alveolar bone atrophy, with a maximumsubsinus bone height of 3mm in patient #1 and<1mm in patient #2. For each patient, a 50:50 particulate composite graft of ABBMand mineralized allograft was hydrated with 1 mL of 0.3 mg/mL rhPDGF-BB. Four and one-half (4.5) and 3.5 months followinggrafting in patient #1 and #2, respectively, implants were placed and core biopsy specimens obtained. Histologic examinationof osteotomy cores demonstrated significant amounts of vital bone for each patient. Definitive implant-supported restorationsin full occlusion were placed 8.5 and 7.5months following sinus grafting for patient #1 and #2, respectively. Three (3) and 2.4 yearsfollowing implant placement, all implants were well integrated, with no evidence of radiolucency at the implant-to-bone interface.

Conclusion: The addition of tissue-engineered proteins, i.e., rhPDGF-BB, to sinus augmentation protocols may allow ear-lier implant placement secondary to accelerated bone formation following grafting in the severely pneumatized sinus andmay pro-vide for increased long-term positive clinical outcomes. Clin Adv Periodontics 2011;1:4-15.

Key Words: Bone regeneration; maxillary sinus augmentation; recombinant human platelet-derived growth factor-BB (rhPDGF-BB).

*PerioHealth Professionals, Houston, TX.

Submitted December 9, 2010; accepted for publication February 9, 2011

doi: 10.1902/cap.2011.100001

4 Clinical Advances in Periodontics, Vol. 1, No. 1, May 2011

BackgroundWith the Sinus Consensus Conference of 1996, sinusaugmentation procedures became validated as effectivetreatment for posterior maxillary alveolar bone volumedeficiency prior to placement of osseointegrated implants.1

Today, sinus grafting has become standard-of-care treatmentfor the surgical management of the deficient posteriormaxilla. Robust, vital bone regenerative outcomes, criticalto long-term implant survival and function, help definesuccessful surgical endpoints for sinus grafting procedures.An awareness of those procedural variables affecting vitalbone regenerative outcomes in sinus grafting is a necessaryrequisite for surgical success. Such variables include lengthof time between sinus grafting and implant placement,2-11

type of graft matrix used,2,4-12 presence or absence of oc-clusive membranes over the lateral window osteotomysite,13-17 and the addition of bioactive signaling molecules,i.e., bone morphogenetic protein-2 (BMP-2), platelet-richplasma, and recombinant human platelet-derived growthfactor-BB (rhPDGF-BB), to osteoconductive graft matri-ces.18-21

Anorganic bovine bone mineral (ABBM)† has beenused widely as an osteoconductive grafting matrix in sinusaugmentation procedures, either alone or as a compositegraft with other materials. Two systematic reviews ofrandomized controlled clinical trials appear to verify thetherapeutic effectiveness of ABBM in sinus augmentationprocedures.16,22 Implant survival rates in both reviewsfor 100% xenograft augmented sites are seen as equal toor better than 100% particulate autogenous bone graftsand superior to composite grafts of ABBMplus autogenousbone. Additional studies examining long-term implant sur-vival rates in ABBM-grafted sinus further verify ABBM’seffectiveness in sinus augmentation surgery.12,23-25

In addition to implant survival, numerous published stud-ies examine the quantity and quality of bone regeneration atvarious time points in ABBM-grafted sinus sites.2,4,6,7,10,11,14

Such studies are primarily small case series that tend to re-port a range of vital bone formation, determined in largepart by the times chosen for core biopsy and varying fromapproximately 19% at 3 to 4 months to approximately70% at ‡1 year.2,4,6,7,10,11,14 Since ABBM has been shownto have a relatively slow rate of resorption, the percentageof residual ABBM particles integrated with newly formedbone is generally reported as high.

In contrast to the relatively wide body of literature ex-amining ABBM-mediated bone regeneration and implantsurvival following sinus augmentation, a far narrowerbody of literature exists examining similar parameters formineralized allogenic sinus grafts, the majority of whichfocuses on percent vital bone regeneration at various post-grafting timepoints.6,8,26-28As inABBMstudies,mineralizedallograft investigations tend to be small case series witha range of percent vital bone formation varying from ap-proximately 18% at 6 to 8months28 to 42% at 36months.8

Compared to ABBM, particulate mineralized allograft re-sorption rates are relatively rapid, yielding less residualgraft material at comparable time points.6,8,26 Data for im-plant survival in mineralized allografted sinuses are lessavailable than forABBM-grafted sinuses andarederivedpri-marilyfromsmallclinicalcaseseries.However,anumberofstu-dies with data up to 36 months suggest survival rates rangingfrom 93% to 97% in 100% allogenic-grafted sinuses.29-31

Advances in tissue engineering and recombinant growthfactor technology may provide opportunities for improvedregenerative outcomes in sinus augmentation procedures.rhPDGF-BB, in its integral role in promoting neovasculari-zation, as well as its mitogenic and chemotactic effects onosteoblast-lineage cells, may serve an important role in pro-moting improved regenerative outcomes in sinus augmenta-tion procedures.32-34 In vitro and in vivo studies confirmeffective attachment and release of rhPDGF-BB when com-bined with ABBM, human bone allograft, and other matri-ces.35,36 A recent proof-of-principle study examining thepotential role of rhPDGF-BB when combined with ABBMparticulate grafts in human sinus augmentation surgeriesnoted increased osteogenic activity at 6 to 8 months whencompared to ABBM-grafted sites alone. In addition, moreefficient replacement resorption of ABBM particles wasapparent in a number of sites when ABBM was saturatedwith rhPDGF-BB.18 Additional studies examining graftsof either ABBM or mineralized allograft combined withrhPDGF-BB, but for procedures other than sinus augmen-tation, appear to verify the potential for improved boneregenerative outcomes over ABBM or allograft matricesalone.37-46

In the following two case reports, composite grafts ofABBM, mineralized bone allograft, and rhPDGF-BB were

†Bio-Oss, Osteohealth, Shirley, NY.

FIGURE 1a At baseline, patient #1 with £3 mm of right subsinus alveolar bone. 1b Enhanced cross-sectional view at baseline, patient #1.

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Scheyer, McGuire Clinical Advances in Periodontics, Vol. 1, No. 1, May 2011 5

used in sinus augmentation surgeries to treat significantposterior maxillary alveolar bone deficiencies. In bothcases, early implant placement and loading following sinusgrafting, as well as long-term clinical follow-up, documentpotential benefits of growth-factor mediated bone regen-erative sinus augmentation procedures. Histologic andhistomorphometric examinations at the time of implantplacement provide additional insight into the potential rolegrowth factors may play in the management of the atro-phied posterior edentulous maxilla.

Clinical Presentation andCase ManagementTwo mature adult males were referred for correctionof severe posterior maxillary alveolar bone deficiencyprior to prosthetic rehabilitation with implant-supportedrestorations. At the initial visit, in addition to a comprehen-sive dental examination, full-mouth periapical radiographs,clinical photographs, and maxillary computerized tomo-graphic scans were obtained. Any necessary periodontalor restorative care was conducted prior to surgery. In eachcase subsinus bone height was negligible, varying froma maximum of 3 mm in patient #1 (Figs. 1a and 1b) to

<1mm in patient #2 (Figs. 2a and 2b). Except for amucousretention cyst in patient #2, both maxillary sinuses werehealthy and disease free.

At surgery, following elevation of a full-thickness muco-periosteal flap, a traditional maxillary lateral wall osteo-tomy approach to the sinus was used in each case. Priorto grafting, a 50:50 particulate composite graft of ABBMand mineralized allograft‡ was hydrated with US Foodand Drug Administration (FDA) off-label dose of 1 mLof 0.3 mg/mL rhPDGF-BB for a minimum of 10 minutesto allow for adequate growth factor attachment to the graftmatrix. Following careful sinus membrane elevation andremoval of the mucous retention cyst from patient #2, in-cremental quantities (approximately 3 to 4 g per sinus) ofthe graft material were placed into the newly formedsubsinus space. A resorbable collagen membranex wasplaced over each lateral window osteotomy site and themucoperiosteal flaps closed via multiple expanded poly-tetrafluoroethylene suturesk (Figs. 3a through 3d). Patientswere placed on amoxicillin/clavulanate potassium 875mg,

FIGURE 2a Patient #2 at baseline, with <1 mm of subsinus bone height and a mucous retention cyst in the left sinus. 2b Enhanced cross-sectional view atbaseline from the #14 position. (Please note large mucous retention cyst).

‡LifeNet, Virginia Beach, VA.xBio-Gide, Osteohealth.kCV, Gore-Tex, W.L. Gore & Associates, Flagstaff, AZ.

FIGURE 3a Removal of mucous retention cyst. 3b ABBM þ mineralizedallograft þ rhPDGF-BB composite graft placed within the newly createdsubantral space. 3c Resorbable collagen membrane placed over the lateralwall window. 3d Full-thickness mucoperiosteal flaps closed primarily viamultiple expanded polytetrafluoroethylene sutures.

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6 Clinical Advances in Periodontics, Vol. 1, No. 1, May 2011 Growth Factor-Mediated Sinus Augmentation

1 tablet twice a day starting 2 days prior to surgery and con-tinuing for 8 days following surgery. Ibuprofen 800mgwasprescribed for pain and inflammation, and the patientswere prescribed 0.12% chlorhexidine rinses and instructednot to brush or floss at the surgical sites until after sutureremoval.

Postoperatively, each patient was seen at 1 week and thenmonthly until implant placement. For patient #1 and patient#2, implants{ were placed and core biopsies obtained 4.5months and 3.5 months, respectively, following sinus graft-ing. At insertion, each implant achieved 25 Newton cm(Ncm) of torque. In addition to the implant core biopsies,a lateral wall osteotomy biopsy was obtained for patient#2 (Figs. 4a through 4d and Figs. 5a through 5d).

Clinical OutcomesPatient #1Given the accelerated implant insertion time following sinusgrafting, each patient received careful long-term follow-up.For patient #1, 3months after implant placement bothmax-illary right implants successfully tolerated a 25 Ncm torquetest.Onemonth later adefinitive cement retained restorationin full occlusion was inserted. For patient #1, 8.5 monthselapsed between sinus augmentation surgery and final place-ment of the definitive, implant-supported restoration. Aradiograph taken 3 years following implant placement dem-onstrates well-integrated implants with no evidence ofradiolucency at the implant-to-bone interface (Fig. 6).

Patient #2As in patient #1, 3 months following implant insertion, allthree implants for patient #2 successfully tolerated the

manufacturer’s recommended 25 Ncm torque test. At thissame visit, cement retained restorative abutments wereplaced and an interim restoration inserted (Figs. 7a through7c). One month later the maxillary left posterior quadrantwas definitively restoredwith single unit implant-supportedcrowns (Figs. 8a and 8b). For patient #2, approximately 7.5months elapsed between sinus augmentation surgery andplacement of definitive, implant-supported restorations.Clinical and radiographic examination 2.4 years followingimplant placement demonstrates well-integrated implantswith no evidence of radiolucency at the implant-to-bone in-terface (Fig. 9).

Histologic OutcomesPatient #1: 4.5 Months Following Sinus GraftingFigure 10 represents a relatively intact core specimenat 2.5�magnification. The left portion of the slide demon-strates dense lamellar bone representative of native, alveo-lar crestal bone. The right or apical portion of the slidereveals a number of residual ABBM particles integratedwith relatively dense vital regenerated bone.Newly formedbone bridging adjacent ABBM particles is seen throughoutthe specimen. Both residual particles and regenerated boneare surrounded by fatty marrow. Complete resorption ofthe mineralized allograft occurred, with no evidence of al-lograft particles present.

At 5� and 10�magnification, newly regenerated boneis seen intimately integrating with residual ABBM graftparticles. Abundant amounts of osteoid are evident, indic-ative of ongoing active osteogenesis (Figs. 11a and 11b).At 20� magnification, osteoblasts are seen rimming theadvancing front of newly formed osteoid, indicating

{OsseoSpeed Implants, Astra Tech, Waltham, MA.

FIGURE 4a At 4.5 months following grafting, radiographic evidence of a well-consolidated graft, right posterior maxilla. 4b At 4.5 months, restoration of bonyvolumetric and linear requirements for proper implant placement within right posterior maxilla. 4c For patient #2, at 3.5 months a significant increase insubsinus bony height without evidence of slumping. 4d Sufficient augmented height at 3.5 months for implant placement. (Please note complete resolution ofpreoperative sinus pathology).

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increased metabolic activity and bone regeneration (Fig.12).

Finally, at moderate magnification (10�), blood vesselscan be observedwithin some of the residual ABBM-graftedparticles (Fig. 13). As in the previous views, newly formedbone is seen bridging gaps between ABBM particles.

FIGURE 5a Core specimen retrieval at ridge crest, 3.5 months postgraft-ing. 5b Lateral window core biopsy at 3.5 months postgrafting. 5c Properimplant position confirmed. 5d Implant fixtures in place and lateral windowbiopsy site evident, 3.5 months postgrafting.

FIGURE 7a At 6.5 months following sinus augmentation grafting, cementretained restorative abutments were placed and an interim prosthesisinserted. 7b Stable bone-to-implant contact 3 months following implantinsertion. 7c Occlusal view of interim restoration.

FIGURE 6 Stable bone-to-implant interface 3 years following implantplacement.

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Osteoid, with adjacent osteoblasts, can again be seen,indicative of active, continuing osteogenesis.

Patient #2: 3.5 Months Following Sinus GraftingLateral Window Bone CoreAt 3.5 months post-sinus grafting, an intact lateral windowosteotomy core reveals significant amounts of newly regen-erated bone throughout the specimen (Fig. 14). Importantly,since the core was obtained from the lateral window area,all bone present represents newly formed hard tissue. Asin patient #1, residual ABBMparticles remain, but allograftparticulate appears completely absent at 3.5 months. At in-creased magnification, considerable amounts of osteoid areevident, indicative of ongoing bone formation (Fig. 15). At

FIGURE 11a Patient #1. Newly formed bone is seen integrating withresidual ABBM particles. (5�) Sanderson’s rapid bone stain þ van Giesonpicro fuchsin. NB ¼ new bone; O ¼ osteoid. 11b Patient #1. Osteoid,indicative of ongoing osteogenesis, is clearly visible at higher magnifica-tions. (10�) Sanderson’s rapid bone stain þ van Gieson picro fuchsin.NB ¼ new bone; O ¼ osteoid.

FIGURE 8a Definitive single unit implant-supported crowns 7.5 monthsfollowing sinus grafting. 8b Occlusal view of definitive restoration.

FIGURE 9 At 2.4 years following implant placement, well-integratedimplants with no evidence of radiolucency at implant-to-bone interface.

FIGURE 10 Patient #1. Intact core at 4.5 months post sinus graftingdemonstrates dense, newly formed bone bridging adjacent residual ABBMparticles. Allograft has been completely resorbed. (2.5�) Sanderson’s rapidbone stain þ van Gieson picro fuchsin.

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FIGURE 13 Patient #1. Well-formed bone bridges the gaps betweenABBM graft particles. Osteoid and osteoblasts are seen, as well as bloodvessels forming within some of the residual ABBM particles. (10�)Sanderson’s rapid bone stain þ van Gieson picro fuchsin. BV ¼ bloodvessel; NB ¼ new bone; O ¼ osteoid; OB ¼ osteoblasts.

FIGURE 12 Patient #1. Residual ABBM particles are in intimate contactwith dense regenerated bone. Osteoblasts are seen at the advancing frontof newly formed osteoid. (20�) Sanderson’s rapid bone stain þ van Giesonpicro fuchsin. BV = blood vessel; NB ¼ new bone; O ¼ osteoid; OB ¼osteoblasts.

FIGURE 16 Patient #2. Osteoblastic rimming along the advancing front ofosteoid demonstrates continued osteogenesis at the lateral windowosteotomy site. Sanderson’s rapid bone stain þ van Gieson picro fuchsin(10x). O ¼ osteoid; OB ¼ osteoblasts.

FIGURE 15 Patient #2. At increased magnification, osteoid is seenadjacent to newly regenerated bone, indicative of ongoing bone formation.(5�) Sanderson’s rapid bone stain þ van Gieson picro fuchsin. NB ¼ newbone; O ¼ osteoid.

FIGURE 17 Patient #2. At 3.5 months post-sinus grafting, significantamounts of newly regenerated bone are seen throughout the intact implantcore. Residual particles of ABBM remain. (2.5�) Sanderson’s rapid bonestain þ van Gieson picro fuchsin. NB ¼ new bone.

FIGURE 14 Patient #2. At 3.5 months following sinus grafting, an intactlateral window core reveals significant amounts of well-formed regeneratedbone in close apposition with residual ABBM particles. (2.5�) Sanderson’srapid bone stain þ van Gieson picro fuchsin. NB ¼ new bone.

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yet higher magnification, osteoblastic rimming along theouter edges of osteoid becomes apparent, emphasizing in-tense osteogenesis at the lateral window sinus osteotomysite (Fig. 16).

Implant CoreAs in the lateral windowbone core, considerable quantitiesof newly regenerated bone are seen throughout an intactimplant core at 3.5 months following grafting. Since theinitial height of native crestal alveolar bone was no morethan 1 mm, all bone present in this core specimen is newlyformed following grafting (Fig. 17). Once again, ABBMparticles are evident but mineralized allograft appearscompletely resorbed. At higher magnification, consider-able amounts of osteoid line well-formed trabeculae ofnewly regenerated woven bone, indicating ongoing osteo-genic activity (Fig. 18).

Histomorphometric OutcomesPatient #1: Implant Core – Table 1As noted in Table 1, at 4.5 months following grafting withABBM, mineralized human allograft, and rhPDGF-BB,43% of the implant core consisted of bone. Since no allo-graft remained, 100% of the bone present was vital.Although ABBMparticles remained, only 7%of the exam-ined core represented ABBM particulate by 4.5 months.

Patient #2Lateral Window Bone Core – Table 2At 3.5 months postgrafting, 33% of the core removedfrom the lateral window osteotomy site consisted ofnewly regenerated bone. No allograft particles remained.Twenty-six percent (26%) of the intact core at this 3.5-month time point represented residual ABBM particulategraft.

Implant Core – Table 2At 3.5 months, 15% of the subantral grafted implant siteconsisted of newly regenerated bone. Again, since no allo-graft particulate remained, 100% of the examined bonewas vital. ABBM occupied 41% of the volume of the im-plant-related bone core.

DiscussionRegeneration of vital, well-vascularized bone is central tolong-term positive clinical outcomes following maxillarysinus augmentation procedures.2-18 With the introductionof such bioactivemolecules as BMP-2 and rhPDGF-BB intoclinical practice, opportunities may now exist to improvelong-term clinical outcomes in sinus augmentation proce-dures by including tissue-engineered proteins into ourgrafting regimens.18 Inclusion of tissue-engineered proteinsmay also allow procedural modifications to current sinusaugmentation protocols, i.e., variations in graft matrices,loading times, and potential elimination of barrier mem-branes placed over the lateral osteotomy site.

FIGURE 18 Patient #2. At higher magnification, osteoid is readily apparentlining newly formed bony trabeculae. (10�) Sanderson’s rapid bone stain þvan Gieson picro fuchsin. NB ¼ new bone; O ¼ osteoid.

TABLE 2 Patient 2 – Lateral Window and Implant Cores

Core BiopsySpecimen

% of Specimen ¼Bone

% Total Bone ¼Vital

% Total Bone ¼Nonvital (Allograft)

% Marrow orFibrous Tissue % Specimen ¼ ABBM

LateralWindow

33% 100% 0% 40% 26%

OcclusalImplant Site

15% 100% 0% 44% 41%

TABLE 1 Patient 1 – Implant Core

Core Biopsy Specimen% of Specimen ¼

Bone% Total

Bone ¼ Vital% Total Bone

¼ Nonvital (Allograft)% Marrow or Fibrous

Tissue% Specimen¼ ABBM

43% 100% 0% 51% 7%

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In the current cases, rhPDGF-BBwas added to sinus aug-mentation composite grafts of ABBM and mineralized al-lograft. Stronglymitogenic and chemotactic for osteoblastsand osteoblastic precursor cells, as well as integral in pro-moting neovascularization, the addition of rhPDGF-BBmay have played important roles in allowing acceleratedtreatment times as well as supporting stable long-term clin-ical outcomes.32-34 In both cases, native subsinus alveolarbone height at initial examination was minimal: <3 mmin one patient and<1 mm in the other. With such minimalalveolar bone height, initial implant stabilization in bothcaseswas completely dependent upon thequality andquan-tity of newly regenerated bone.

Both ABBM and mineralized allograft have been asso-ciated with positive bone regenerative outcomes in sinusaugmentation procedures. Depending upon the durationbetween sinus grafting and implant placement, percent-ages of new bone formation vary, with greater amountsof regenerated bone generally seen at longer intervals be-tween grafting and implant insertion.2,4,6-8,10,11,14,26-28 Inboth of the current cases, the addition of rhPDGF-BB sug-gested the possibility of abbreviated intervals between si-nus grafting and implant placement. In patient #1, 4.5months elapsed between grafting and implant placementand in patient #2, 3.5 months between augmentation andimplant placement. Despite accelerated implant insertiontimes, percentages of vital bone formation varied from43% in patient #1 to 33% at the lateral window osteot-omy site and 15% at the implant placement site in patient#2. Reported vital bone percentages for ABBM and min-eralized allograft without growth factors are generallylower at similar time points.2,5-8,10-12,17,26-28 Moreover,the abundance of osteoid seen histologically for both pa-tients suggests further ongoing bone regeneration and in-creased amounts of new vital bone over time within bothgrafted sites.

Although the attachment and release kinetics forrhPDGF-BBwhen combined with ABBMandmineralizedallograft are similar, normal resorption times of each ma-trix tend to differ, more rapidly for mineralized allograft

and rather prolonged for ABBM.6,8,10,11,26-28 Understand-ing that both matrices appear to have equivalent attach-ment and release kinetics for rhPDGF-BB, more rapidallograft resorption might allow for additional spacefor bone regeneration to occur, while the much slowerresorption rate of ABBM might help maintain graftheight by preventing slumping consolidation. Notably,at both early implant insertion time points, only ABBMparticulate remained, with mineralized allograft com-pletely resorbed at early time points. In each case, graftheight was maintained without evidence of slumping. In-terestingly, however, in patient #1 only 7% of the ABBMgraft remained at 4.5 months, suggesting growth factormay have accelerated resorption of ABBM matrices asseen in other studies.18,37,40 This is particularly interestinggiven the prolonged resorption times of ABBM normallyreported in the literature. The positive regenerative find-ings seen for each patient are equally matched by positivelong-term clinical outcomes. Despite early implant place-ment into a grafted sinus, at 3 months following implantinsertion all implants successfully tolerated a 25 Ncm tor-que test. In each case, insertion of definitive final implant-supported restorations was accelerated relative to normalclinical practice following sinus augmentation grafting.Eight and one-half (8.5) months and 7.5 months elapsedbetween augmentation surgery and placement of defini-tive final restorations in full functional occlusion for pa-tient #1 and patient #2, respectively. Long-term clinicaland radiographic follow-up at 3 years (patient #1)and 2.4 years (patient #2) following implant placementdemonstrated well-integrated implants, no evidence ofbreakdown at the bone-to-implant interface, and wellfunctioning implant-supported restorations. While bothcases suggest significant benefits with the addition of tis-sue-engineered proteins to sinus augmentation protocols,final confirmation of efficacy can come only from ade-quately powered, randomized, controlled clinical trials.Nevertheless, tissue engineering technologies hold greatpromise to shorten healing times and increase treatmentpredictability. n

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Summary

Why is this case new information? Tissue engineering & recombinant growth factor technology may lead tothe following improved sinus augmentation outcomes:n Accelerated bone regenerationn Abbreviated interval between sinus grafting and implant placementn Abbreviated interval between implant placement and definitiveimplant-supported prosthetic restoration

n Improved long-term implant survival

What are the keys to successfulmanagement of these cases?

Proper management includes the following key items:n Choosing carrier matrices with proper attachment & release kineticswhen combined with rhPDGF-BB

n Allowing sufficient time for attachment of rhPDGF-BB to carriermatrices

n Choosing carrier matrices with different resorption ratesn Carefully elevating the sinus membrane to avoid perforationn Thoroughly grafting the entire subsinus space

What are the key limitations tosuccess in these cases?

Key limitations include the following:n Little available data from prospective clinical trials documenting theshort and long-term efficacy of growth factor-mediated procedures insinus augmentations with rhPDGF-BB þ ABBM þ mineralizedallograft

n Study is off-label, without current FDA approval for present study graftcomposition in sinus augmentation procedures

AcknowledgmentsThe authors would like to acknowledge the following indi-viduals for their help in this project: Jennifer Gramazio(Osteohealth, Shirley, NY) for her assistance with the im-ages. Special thanks to Dr. Stuart Kay, science writer andconsultant (Huntington, NY) for his help with the organi-zation and production of this manuscript; Drs. MichaelRoyer and Hari Prasa from the University of MinnesotaDepartment of Histology for the histological processingand analysis; and special thanks also to Dr. James T.

Mellonig (University of Texas Health Science Center atSan Antonio, Department of Periodontics) for his histolog-ical review of the samples. Osteohealth has provided hon-oraria for lectures, as well as financial support for clinicalresearch trials, but the authors received no support for thecases in this report. Osteohealth provided financial assis-tance for the preparation of the manuscript and histology.

CORRESPONDENCE:Dr. E. Todd Scheyer, 3400 S. Gessner Rd., Suite 102, Houston, TX 77063.E-mail: [email protected].

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References1. Jensen OT, Shulman LB, Block MS, Iacono VJ. Report of the Sinus

Consensus Conference of 1996. Int J Oral Maxillofac Implants 1998;13(Suppl.):11-45.

2. Froum SJ, Wallace SS, Cho SC, Elian N, Tarnow DP. Histomorpho-metric comparison of a biphasic bone ceramic to anorganic bovine bonefor sinus augmentation: 6- to 8-month postsurgical assessment of vitalbone formation. A pilot study. Int J Periodontics Restorative Dent2008;28:273-281.

3. Yamamichi N, Itose T, Neiva R, Wang HL. Long-term evaluation ofimplant survival in augmented sinuses: A case series. Int J PeriodonticsRestorative Dent 2008;28:163-169.

4. Iezzi G, Degidi M, Scarano A, Petrone G, Piattelli A. Anorganic bonematrix retrieved 14 years after a sinus augmentation procedure: Ahistologic and histomorphometric evaluation. J Periodontol 2007;78:2057-2061.

5. Gapski R, Neiva R, Oh TJ, Wang HL. Histologic analyses of humanmineralized bone grafting material in sinus elevation procedures: A caseseries. Int J Periodontics Restorative Dent 2006;26:59-69.

6. Froum SJ, Wallace SS, Elian N, Cho SC, Tarnow DP. Comparison ofmineralized cancellous bone allograft (Puros) and anorganic bovinebone matrix (Bio-Oss) for sinus augmentation: Histomorphometry at26 to 32 weeks after grafting. Int J Periodontics Restorative Dent 2006;26:543-551.

7. Lee YM, Shin SY, Kim JY, Kye SB, Ku Y, Rhyu IC. Bone reaction tobovine hydroxyapatite for maxillary sinus floor augmentation: Histo-logic results in humans. Int J Periodontics Restorative Dent 2006;26:471-481.

8. Cammack GV 2nd, Nevins M, Clem DS 3rd, Hatch JP, Mellonig JT.Histologic evaluation of mineralized and demineralized freeze-driedbone allograft for ridge and sinus augmentations. Int J PeriodonticsRestorative Dent 2005;25:231-237.

9. Zerbo IR, Zijderveld SA, de Boer A, et al. Histomorphometry of humansinus floor augmentation using a porous beta-tricalcium phosphate: Aprospective study. Clin Oral Implants Res 2004;15:724-732.

10. Fugazzotto PA. GBR using bovine bone matrix and resorbable andnonresorbable membranes. Part 1: Histologic results. Int J PeriodonticsRestorative Dent 2003;23:361-369.

11. Tadjoedin ES, de Lange GL, Bronckers AL, Lyaruu DM, Burger EH.Deproteinized cancellous bovine bone (Bio-Oss) as bone substitute forsinus floor elevation. A retrospective, histomorphometrical study of fivecases. J Clin Periodontol 2003;30:261-270.

12. Ferreira CE, Novaes AB, Haraszthy VI, Bittencourt M, Martinelli CB,Luczyszyn SM. A clinical study of 406 sinus augmentations with 100%anorganic bovine bone. J Periodontol 2009;80:1920-1927.

13. Froum SJ, Tarnow DP, Wallace SS, Rohrer MD, Cho SC. Sinus floorelevation using anorganic bovine bone matrix (OsteoGraf/N) with andwithout autogenous bone: A clinical, histologic, radiographic, andhistomorphometric analysis d Part 2 of an ongoing prospective study.Int J Periodontics Restorative Dent 1998;18:528-543.

14. Tarnow DP, Wallace SS, Froum SJ, Rohrer MD, Cho SC. Histologicand clinical comparison of bilateral sinus floor elevations with andwithout barrier membrane placement in 12 patients: Part 3 of anongoing prospective study. Int J Periodontics Restorative Dent 2000;20:117-125.

15. Tawil G, Mawla M. Sinus floor elevation using a bovine bone mineral(Bio-Oss) with or without the concomitant use of a bilayered collagenbarrier (Bio-Gide): A clinical report of immediate and delayed implantplacement. Int J Oral Maxillofac Implants 2001;16:713-721.

16. Wallace SS, Froum SJ. Effect of maxillary sinus augmentation on thesurvival of endosseous dental implants. A systematic review. AnnPeriodontol 2003;8:328-343.

17. Wallace SS, Froum SJ, Cho SC, et al. Sinus augmentation utilizinganorganic bovine bone (Bio-Oss) with absorbable and nonabsorbablemembranes placed over the lateral window: Histomorphometric andclinical analyses. Int J Periodontics Restorative Dent 2005;25:551-559.

18. Nevins M, Garber D, Hanratty JJ, et al. Human histologic evaluationof anorganic bovine bone mineral combined with recombinant humanplatelet-derived growth factor BB in maxillary sinus augmentation:Case series study. Int J Periodontics Restorative Dent 2009;29:583-591.

19. Triplett RG, Nevins M, Marx RE, et al. Pivotal, randomized, parallelevaluation of recombinant human bone morphogenetic protein-2/absorbable collagen sponge and autogenous bone graft for maxillarysinus floor augmentation. J Oral Maxillofac Surg 2009;67:1947-1960.

20. Torres J, Tamimi F, Martinez PP, et al. Effect of platelet-rich plasma onsinus lifting: A randomized-controlled clinical trial. J Clin Periodontol2009;36:677-687.

21. Boyapati L, Wang HL. The role of platelet-rich plasma in sinusaugmentation: A critical review. Implant Dent 2006;15:160-170.

22. Del Fabbro M, Testori T, Francetti L, Weinstein R. Systematic review ofsurvival rates for implants placed in the grafted maxillary sinus. Int JPeriodontics Restorative Dent 2004;24:565-577.

23. Hallman M, Sennerby L, Lundgren S. A clinical and histologicevaluation of implant integration in the posterior maxilla after sinusfloor augmentation with autogenous bone, bovine hydroxyapatite, ora 20:80 mixture. Int J Oral Maxillofac Implants 2002;17:635-643.

24. Valentini P, Abensur D. Maxillary sinus floor elevation for implantplacement with demineralized freeze-dried bone and bovine bone (Bio-Oss): A clinical study of 20 patients. Int J Periodontics RestorativeDent 1997;17:232-241.

25. Hising P, Bolin A, Branting C. Reconstruction of severely resorbedalveolar ridge crests with dental implants using a bovine bone mineralfor augmentation. Int J Oral Maxillofac Implants 2001;16:90-97.

26. Kolerman R, Tal H, Moses O. Histomorphometric analysis of newlyformed bone after maxillary sinus floor augmentation using groundcortical bone allograft and internal collagen membrane. J Periodontol2008;79:2104-2111.

27. Noumbissi SS, Lozada JL, Boyne PJ, et al. Clinical, histologic, andhistomorphometric evaluation of mineralized solvent-dehydrated boneallograf (Puros) in human maxillary sinus grafts. J Oral Implantol2005;31:171-179.

28. Sohn DS, Lee JK, An KM, Shin HI. Histomorphometric evaluation ofmineralized cancellous allograft in the maxillary sinus augmentation: A4 case report. Implant Dent 2009;18:172-181.

29. Chaushu G, Mardinger O, Calderon S, Moses O, Nissan J. The use ofcancellous block allograft for sinus floor augmentation with simulta-neous implant placement in the posterior atrophic maxilla. J Perio-dontol 2009;80:422-428.

30. Minichetti JC, D’Amore JC, Hong AY. Three-year analysis of taperedscrew vent implants placed into maxillary sinuses grafted withmineralized bone allograft. J Oral Implantol 2008;34:135-141.

31. Aghaloo TL, Moy PK. Which hard tissue augmentation techniques arethe most successful in furnishing bony support for implant placement?Int J Oral Maxillofac Implants 2007;22(Suppl.):49-70 (erratum 2008;23:56).

32. Mariotti M, Maier J. Angiogenesis: An overview. In: New Frontiers inAngiogenesis. Forough R, ed. Netherlands:Springer Verlag; 2006:1-29.

33. Li WW, Tsakayannis D, Li VW. Angiogenesis: A control point fornormal and delayed wound healing. Contemp Surg 2003;(Suppl.):5-11.

34. Giannobile W. Periodontal tissue regeneration by polypeptide growthfactors and gene transfer. In: Lynch SE, Genco RJ, Marx RE, eds. TissueEngineering Applications in Maxillofacial Surgery and Periodontics.Chicago:Quintessence; 1999:231-243.

35. Jiang D, Dziak R, Lynch SE, Stephan EB. Modification of anosteoconductive anorganic bovine bone mineral matrix with growthfactors. J Periodontol 1999;70:834-839.

36. Nevins M, Hanratty J, Lynch SE. Clinical results using recombinanthuman platelet-derived growth factor and mineralized freeze-driedbone allograft in periodontal defects. Int J Periodontics RestorativeDent 2007;25:421-427.

37. Simion M, Rocchietta I, Kim D, Nevins M, Fiorellini J. Vertical ridgeaugmentation by means of deproteinized bovine bone block andrecombinant human platelet-derived growth factor-BB: A histologicstudy in a dog model. Int J Periodontics Restorative Dent 2006;26:415-423.

38. Simion M, Rocchietta I, Dellavia C. Three dimensional ridge augmen-tation with xenograft and recombinant human platelet-derived growthfactor-BB in humans: Report of two cases. Int J Periodontics Re-storative Dent 2007;27:109-115.

39. Cardaropoli D. Vertical ridge augmentation with the use of recombi-nant human platelet-derived growth factor-BB and bovine bonemineral: A case report. Int J Periodontics Restorative Dent 2009;29:289-295.

40. Nevins ML, Camelo M, Schupbach P, Kim DM, Camelo JMB, NevinsM. Human histologic evaluation of mineralized collagen bone sub-stitute and recombinant platelet-derived growth factor-BB to createbone for implant placement in extraction socket defects at 4 and 6months: A case series. Int J Periodontics Restorative Dent 2009;29:129-139.

41. Simion M, Rocchietta I, Monforte M, Maschera E. Three-dimensionalalveolar bone reconstruction with a combination of recombinant

C A S E R E P O R T


human platelet-derived growth factor BB and guided bone regenera-tion: A case report. Int J Periodontics Restorative Dent 2008;28:239-243.

42. Nevins M, Camelo M, Nevins ML, Schenk RK, Lynch SE. Periodontalregeneration in humans using recombinant human platelet-derivedgrowth factor-BB (rhPDGF-BB) and allogenic bone. J Periodontol2003;74:1282-1292.

43. Fagan MC, Miller RE, Lynch SE, Kao RT. Simultaneous augmentationof hard and soft tissues for implant site preparation using recombinanthuman platelet-derived growth factor: A human case report. IntJ Periodontics Restorative Dent 2008;28:37-43.

44. Nevins ML, Camelo M, Nevins M, et al. Minimally invasive alveolarridge augmentation procedure (tunneling technique) using rhPDGF-BB

in combination with three matrices: A case series. Int J PeriodonticsRestorative Dent 2009;29:371-383.

45. McGuire MK, Scheyer T, Nevins M, Schupbach P. Evaluation of humanrecession defects treatedwith coronally advanced flaps and either purifiedrecombinant human platelet-derived growth factor-BB with beta trical-cium phosphate or connective tissue: A histologic and microcomputedtomographic examination. Int J Periodontics RestorativeDent2009;29:7-21.

46. McGuire MK, Scheyer ET, Schupbach P. Growth factor-mediatedtreatment of recession defects: A randomized controlled trial andhistologic and microcomputed tomography examination. J Periodontol2009;80:550-564.

indicates key references.

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Growth Factor-Mediated Sinus Augmentation Grafting With ... · survival following sinus augmentation, a far narrower body of literature exists examining similar parameters for mineralized