Does platelet-rich plasma promote remodeling of autologous …coimplante.odo.br/Biblioteca/Enxertos...

Does platelet-rich plasma promoteremodeling of autologous bone graftsused for augmentation of the maxillarysinus floor?

Gerry M. RaghoebarJurjen SchortinghuisRobert S. B. LiemJan L. RubenJacqueline E. van der WalArjan Vissink

Authors’ affiliations:Gerry M. Raghoebar, Jurjen Schortinghuis, ArjanVissink, Department of Oral and MaxillofacialSurgery and Maxillofacial Prosthetics, UniversityHospital Groningen, Groningen, the NetherlandsRobert S. B. Liem, Section of Electron Microscopy,Department of Cell Biology, University ofGroningen, Groningen, the NetherlandsJan L. Ruben, Department of Oral Function andProsthetic Dentistry, Dental School, Faculty ofMedical Sciences, University of Groningen,Groningen, the NetherlandsJacqueline E. van der Wal, Department ofPathology, University Hospital Groningen,Groningen, the Netherlands

Correspondence to:G. M. RaghoebarDepartment of Oral and MaxillofacialSurgery and Maxillofacial ProstheticsUniversity Hospital GroningenPO Box 30.0019700 RB GroningenThe NetherlandsTel.: þ31 50 3613840Fax: þ31 50 3611161e-mail: [email protected]

Key words: autologous bone, edentulous maxilla, endosseous implants, platelet-rich

plasma, sinus floor elevation surgery

Abstract: The aim of this study was to evaluate the effect of platelet-rich plasma (PRP) on

remodeling of autologous bone grafts used for augmentation of the floor of the maxillary

sinus. In five edentulous patients suffering from insufficient retention of their upper

denture related to a severely resorbed maxilla, the floor of both maxillary sinus was

augmented with an autologous bone graft from the iliac crest. Randomly, PRP was added to

the bone graft used to augment the floor of the left or right sinus (split-mouth design).

Three months after the reconstruction, bone biopsies were taken with a trephine from the

planned implant sites (N¼30). Subsequently, three implants were placed in the left and

right posterior maxilla. Microradiograms were made of all biopsies (N¼30), whereafter the

biopsies were processed for light microscopic examination. In addition, clinical parameters

were scored. Wound healing was uneventful, clinically no difference was observed between

the side treated with PRP or not. Also microradiographical and histomorphological

examination of the biopsies revealed no statistical difference between the PRP- and non-

PRP side. One implant placed in the PRP side of the graft was lost during the healing phase.

Implant-retained overdentures were fabricated 6 months after implantation. All patients

functioned well (follow-up 20.2 � 4.3 months). In this study, no beneficial effect of PRP on

wound healing and bone remodeling was observed. It is posed that PRP has no additional

value in promoting healing of grafted non-critical size defects.

Implant dentistry is a dynamic field, both

from a scientific and clinical point of view.

Many clinicians are in search for rather

simple pre-implant surgical procedures

that are less inconvenient to the patient,

but possess the ability to create optimal

circumstances for implant placement. Vari-

ous augmentation techniques are in use to

create sufficient bone volume for reliable

insertion of endosseous implants in the

severely resorbed maxilla (Raghoebar

et al. 2001).

Today, reconstruction of the jaws re-

quires transplantation of osteocompetent

cells. These cells are expected to survive,

produce bone, and finally mature into

a functioning bony mandible or maxilla.

Although elevation surgery of the maxil-

lary sinus floor has proven to be a reliable

method with good results, bone healing is

not always predictable and occasionally the

bone volume at the time of placement of

the implants is not sufficient for predict-

able implant placement.

To improve soft-tissue healing and bone

remodeling, platelet-rich plasma (PRP) has

been introduced as a new and potentially

useful adjunct in oral and maxillofacial

bone reconstructive surgery. Platelets play

an important role in wound healing. TheyCopyright r Blackwell Munksgaard 2005

Date:Accepted 20 June 2004

To cite this article:Raghoebar GM, Schortinghuis J, Liem RSB, Ruben JL,van der Wal JE, Vissink A. Does platelet-rich plasmapromote remodeling of autologous bone grafts used foraugmentation of the maxillary sinus floor?Clin. Oral Impl. Res. 16, 2005; 349–356doi: 10.1111/j.1600-0501.2005.01115.x

349

arrive quickly at the wound site and begin

coagulation. They release multiple growth

factors and cytokines involved in wound

healing, including platelet-derived growth

factor, transforming growth factors, vascu-

lar endothelial growth factor, platelet-

derived endothelial cell growth factor, in-

terleukin-1, basic fibroblast growth factor,

and platelet activating factor-4 (Aghaloo et

al. 2002; Weibrich et al. 2002). These

growth factors are thought to contribute

to bone regeneration and to increase vascu-

larity, both of which are considered vital

features of a healing bone graft.

Up to now, only one study has been

reported in the literature evaluating the

effect of PRP on bone density and healing

time following reconstruction of mandibu-

lar continuity defects with autogenous

bone. The authors claimed a 1.62–2.16-

fold increase in bone density when PRP

was added to an autogenous bone graft

(Marx et al. 1998). Although this beneficial

effect has not been proven in other clinical

studies yet, it already has been proposed to

utilize PRP in combination with alloplasts,

xenografts or other non-autogenous mater-

ials, even without combination with a

bone graft (Furst et al. 2003).

Preliminary case reports claim formation

of some osteoid material or bone using

such a technique, but the preliminary re-

sults are not equivocal and sometimes

conflicting (Anitua et al. 1999; Kassolis

et al. 2000; Rosenberg & Torosian 2000;

Shanaman et al. 2001; Vanassche & De-

francq 2001; Froum et al. 2002; Wiltfang

et al. 2003). No scientific conclusions can

be drawn from these preliminary reports.

Additional studies are needed. Therefore,

the aim of this study was to evaluate the

effect of PRP on remodeling of autologous

bone grafts used for augmentation of the

floor of the maxillary sinus.

Patient and methods

Patients

Five consecutive patients referred to the

Department of Oral and Maxillofacial Sur-

gery of the University Hospital, Groningen

because of insufficient retention of their

upper denture related to a severely resorbed

maxilla were selected on basis of the fol-

lowing inclusion criteria:

� severely resorbedmaxilla (classes V–VI,

Cawood & Howell 1991) with reduced

stability and retention of the upper

denture;

� comparable bone height between the

maxillary sinus and top of the maxilla

on both sides;

� class IV bone quality (Lekholm & Zarb

1985);

� edentulous period of at least 1 year;

� no history of radiotherapy in the head

and neck region;

� no history of reconstructive, pre-pros-

thetic surgery or previous oral implant-

ology.

In all patients, two superstructures were

planned supported by three implants to

obtain an optimal aesthetic and phonetic

result (Fig. 1).

Informed written consent to participate

in this study was obtained from all patients

(three women, two men; mean age

58.4 � 1.9 years at time of surgery, range

57–62 years). The patients had been edent-

ulous in the maxilla for 5–12 years. Ortho-

pantomograms, lateral cephalograms, and

postero-anterior oblique radiographs were

made to assess the height of the maxillary

alveolar bone, the dimensions of the max-

illary sinus, and the antero-posterior rela-

tionship of the maxilla to the mandible.

The radiographs were also screened for

sinus pathology. The mean vertical height

of the alveolar bone on the orthopantomo-

gram between the most caudal part of the

maxillary sinus and the oral cavity was in

the premolar and molar 3 � 2mm (range

1–4mm) and 2 � 1 (range 1–3mm), re-

spectively.

Platelet-rich plasma

During the time needed for harvesting bone

from the iliac crest, PRP was made using a

commercially available Platelet Concen-

tration Collection System kit (PCCS kit,

3i Implant Innovations Inc., Palm Beach

Gardens, FL, USA). Before the surgical

procedure, 6ml of anticoagulant citrate

dextrose-A was collected in a 60ml syr-

inge. From the venipuncture the syringe

was filled with whole blood up to 60ml.

Immediately following the whole blood

collection, the blood-filled syringe was in-

verted six times to ensure the anticoagulant

has been evenly dispersed. Using the plate-

let concentration system, the 60ml of

whole blood mixed with coagulant was

processed to a PRP solution. As a control

for the effectiveness of the work-up of PRP,

the transforming growth factor (TGF)-bconcentration of each PRP sample was

measured according to the method de-

scribed by Waarde et al. (1997).

To promote the release of growth factors

from the platelets, 10% calcium chloride

solution and the patient’s serum, as source

of autologous thrombin, were added before

actual reconstruction of the defects with

the bone graft. The resulting gel was mixed

with the bone graft and some gel was

applied at the closure of the wound at the

side reconstructed with the bone graft

mixed with PRP.

To check whether applying a bone graft

mixed with PRP does not result in a sys-

temic rise of the concentration of growth

factors released by platelets making a split-

mouth design less applicable in patients

locally treated with PRP, whole-blood

samples were collected just before applica-

tion of the bone graft mixed with PRP,

immediately after placement of the bone

grafts mixed with PRP and 24h after

surgery.

Surgical protocol

The maxilla of the patients was recon-

structed with autologous anterior medial

iliac crest bone grafts under general an-

Fig. 1. A 56-year-old female with severe resorption

of the maxilla and mandible. The floor of the

maxillary sinus was augmented with autologous

bone grafts derived from the anterior iliac crest. On

the left side the bone graft was mixed with platelet-

rich plasma. (a) Orthopantomogram showing severe

resorption of the maxilla and mandible. (b) Ortho-

pantomogram 1 year after fabrication of the prosthe-

tic construction. No differences were observed

between the left and the right side.

Raghoebar et al . Platelet-rich plasma and remodeling of bone grafts

350 | Clin. Oral Impl. Res. 16, 2005 / 349–356

esthesia. In all cases, bilaterally a two-stage

procedure (first stage, bone grafting; second

stage, placement of implants) was per-

formed because the height of the maxillary

bone and/or the width of the alveolar crest

were less than 5mm. A bone height of

5mm or more is a prerequisite for implant

placement with sufficient primary stability

(Raghoebar et al. 2001). In addition to

elevation of the floor of the maxillary

sinus, the width of the alveolar crest was

reconstructed too. An osteotomy was pre-

pared in the lateral wall of the maxillary

sinus using the surgical procedure de-

scribed by Raghoebar et al. (2001). After

harvesting of the bone grafts from the iliac

crest, the bone was split into two equal

parts. Randomly, one side was recon-

structed with autologous bone mixed with

PRP gel and one side with autologous bone

only. The floor of the maxillary sinus was

augmented with bone blocks and the re-

maining space occupied by cancellous bone

particles that were obtained by grounding

the graft in a bone mill (Leibingers, Frei-

burg, Germany). Subsequently, placing

monocortico-cancellous bone blocks buc-

cally of the cortex of the alveolar defect

increased the width of the superior alveolar

process. The cancellous side of the bone

graft was in contact with the jawbone and

again cancellous bone particles were used

to fill the small gaps between the bone graft

and the alveolar crest. The grafts were fixed

with titanium screws to the alveolar bone.

PRP gel was applied over the graft at the

PRP side. No membranes were used to

cover the lateral wall defect after the bone

graft was placed. PRP gel was also applied

over the wound after closure with sutures

at the PRP side.

Before harvesting bone grafts, the pa-

tients received broad spectrum antibiotics,

starting 1h preoperatively (intravenously)

and continued orally for 2 days after sur-

gery. Postoperatively, the patients received

a 0.2% chlorhexidine mouth rinse (1min,

five times daily) for 2 weeks. One month

postoperatively, the edentulous patients

were allowed to wear dentures if possible,

after relining them in the operated areas

with a soft liner.

After a healing period of at least 3

months, the implant placement procedure

was performed. A surgical template was

used. Using the template and a trephine

bur (+ 2mm) biopsies were taken in the

region of the canine, the first premolar and

first molar on the same spot as the endoss-

eous implants will be placed (Fig. 2a, c).

The length of the biopsy was the same as

the length of the implant (at least 13mm).

The implants were inserted at the biopsy

locations after widening these holes to

the required dimensions using the standard

burs for the implant system chosen. In all

cases, the bone volume was sufficient. Six

months after insertion, the implants were

uncovered, the oral mucosa was thinned

where applicable and the abutments con-

nected and the prosthetic construction was

fabricated.

Evaluation

The investigators were blinded for both the

clinical and laboratory investigations with

regard to the PRP-treated side. Clinically,

all patients were evaluated according to a

standardized protocol 1, 3, 6 and 12 weeks

after surgery. The clinical protocol in-

cluded assessment of complications during

surgery and postoperative healing (inflam-

mation, wound dehiscence, sequestration,

and loss of bone particles). In addition,

TGF-b concentration of PRP and blood

were measured and the bone biopsies

were studied by microradiography and light

microscopy.

Microradiography

An X-ray source (Philips PW 1730, Eind-

hoven, the Netherlands) was used that

produced monochromatous radiation with

a specific wavelength of 1.537 A. The X-

ray radiation used is Cuka radiation with a

Cu (copper) X-ray tube and a nickel filter.

The wavelength produced is especially

sensitive to be absorbed by calcium. The

biopsies were placed between the 35mm

film (Fuji B&W POS/71337, Rotterdam,

the Netherlands) and the X-ray source and

exposed for 25 s, with a tube charge of

Fig. 2. Bone biopsies and microradiographs of the premolar region 3 months after grafting. (a) Bone biopsy of the platelet-rich plasma (PRP) side. (b) Microradiograph of

the biopsy of the PRP side. (c) Bone biopsy of the non-PRP side. (d) Microradiograph of the biopsy of the non-PRP side.



25kVand 25mA. Tominimizemagnifica-

tion effects, the distance was kept small

(0.3mm) between the specimen and the

film and large (300mm) between the X-ray

source and the specimen. Film was used

instead of radiographic plates because of a

much higher resolution of the film. After

development of the film with a D-19

developer (Kodak, Amsterdam, the Nether-

lands) for 10min, fixating, rinsing, and

drying, the film was placed on a light

box. A digital image of the biopsy on film

was recorded with a stereo microscope

(Wild/Leitz M7 S, Heerburg, Switzerland)

with a magnification � 10 and a CCD

camera (Teli CS 8310, Tokyo, Japan).

The camera was linked to a personal com-

puter equipped with a framegrabber. The

magnified microradiographs were stored as

images with a size of 640 � 480 pixels

and with a resolution of 256 gray values

ranging from 0 (white) to 256 (black).

Histological examination

Immediately after taking, the biopsies were

fixed in 2% glutardialdehyde in 0.1M

sodium cacodylate buffer, pH 7.4, at 41C

for at least 2 days. During this period,

microradiography of the biopsies was

performed. Subsequently, after rinsing in

0.1M sodium cacodylate buffer, the sam-

ples were dehydrated in a graded con-

centration of ethanol and embedded

in glycolmethacrylate. Two micrometer-

thick serial sections were obtained using a

Jung 1140 autocut microtome with a D-

hard metal knife (Shandon, Life Sciences

International Ltd, Cheshire, UK). The

sections were mounted on glass slide and

stained with toluidine blue and alkaline

fuchsin (Merck, Darmstadt, Germany).

All sections were studied lightmicroscop-

ically on the following items: quality of

bone biopsy, ratio bone–bonemarrow, type

of bone marrow (loose connective tissue,

fibrous, fat), presence of hematopoietic

tissue, presence of bone formation, osteo-

blastic rimming, and presence of bone

resorption.

Histomorphometric analysis of the bi-

opsies was performed using Leica Qwins

image analysis software (Leica Microsys-

tems Image Solutions, Leica, Switzerland).

Under a magnification of � 100 (Leica

DM RA microscope, Leica, Switzerland),

every image field of the histological section

was digitized by a Leica DC 200 digital

camera. Subsequently, the percentage of

bone area was determined in each image

field using the Leica Qwins image analy-

sis software and then averaged. The bone

area in an image field was determined by

setting a threshold to the color of the pixels

of the bone, whose area then could be

measured.

Statistical analysis

The data were analyzed using t-test. A

significance level of 0.05 was chosen.

Results

Clinical assessments

One sinus membrane was perforated dur-

ing surgery. Healing was uneventful and

loss of bone particles through the nose was

not observed. A small incision breakdown

occurred in the first week in one patient in

the non-PRP side. This patient was put on

a regimen of rinsing with a chlorhexidine

mouth rinse four times daily. The dehis-

cence healed within 2 weeks.

A total of 30 implants (length 13 or

15mm, Branemarks, Nobel Biocare, Go-

teborg, Sweden) was placed in augmented

maxillae (Fig. 1). Before the prosthetic

phase, one implant was mobile on the

PRP side and was removed. No other im-

plants were lost during the follow-up

(20.2 � 4.3 months).

Comparison of the clinical features at the

PRP and non-PRP sides revealed no differ-

ences with regard to wound healing, com-

plications during or postsurgery and loss of

implants.

PRP

The procedure for working up whole blood

to PRP resulted in a significant increase in

TGF-b concentration (60.6 � 23.6mg/ml)

when compared with the TGF-b concen-

tration of plasma. The level of TGF-b in

the plasma of the patients before apply-

ing PRP, immediately after applying PRP

and 24h after surgery were 3.4 � 1.5,

3.3 � 1.7 and 3.6 � 2.1 mg/ml, respect-

ively. Thus, the procedure applied did not

result in an increase in the TGF-b concen-

tration in serum.

Microradiography

The microradiographs revealed no statis-

tical difference between the PRP and non-

PRP side (P40.05, t-test) (Fig. 2). The

average density on the microradiographs

(arbitrary gray values) at the first premolar

and first molar region was at the PRP side

91 � 23.1 and 71.8 � 23.8, and at the

non-PRP side 84.6 � 19.6 and 90.7 �13.5, respectively. No density data for

bone biopsies derived from the implant

sites in canine region are given because

light microscopic evaluation had revealed

that these biopsies, in contrast to the biop-

sies taken from the (pre)molar region, lar-

gely consisted of pre-existing bone.

Light microscopy

All except one biopsies were of excellent

quality. In all cases, the bony tissue was

predominantly vital, with just a few small

non-vital parts. No differences were ob-

served between the PRP and the non-PRP

group. The bone–bone marrow ratio ranged

from 50–50% to 40–60%, again not show-

ing a difference between the PRP and the

non-PRP group. The same holds true for

the aspect of the bone marrow, which

contained loose or fibrous connective tis-

sue, or consisted of fat cells. Focally, hema-

topoietic tissue was found. Around the

grafted bone particles, active bone forma-

tion with osteoblastic rimming was seen in

both the PRP and the non-PRP group (Figs

3 and 4). Histomorphometric analysis re-

vealed no differences in areas occupiedwith

bone between PRP- and non-PRP-treated

sides. Again because of the fact that biop-

sies derived from the canine region largely

consisted of pre-existing bone no histomor-

phometric data are given for this region.

The average area occupied by bone in

the augmented (pre)molar region was

41.1 � 8.3% at the non-PRP treated

and 38.4 � 11.3% at the PRP-treated

side (Table 1).

Discussion

Researchers in oral and maxillofacial sur-

gery continuously strive to improve bone-

grafting techniques and to providemeans to

obtain a faster and denser bony regenerate.

This study did not show a significant

increase in bone formation by adding PRP

to an autogenous bone transplant used to

augment the floor of a maxillary sinus and

to increase the width of the alveolar pro-

cess. Although the sample size is small and



biopsies were taken at insertion of the

implants only (all placed in a grafted area),

some conclusions may be drawn from this

study. The small sample size might have

contributed to the fact that no differences

in remodeling of the grafts between the

PRP- and non-PRP-treated sides were ob-

served, but even no tendency of improved

healing could be shown. An explanation for

the lack of difference between the PRP- and

non-PRP sides might be that the majority

of the bony regeneration takes place within

the first month of healing. This would be

in line with the mode of action of platelet

growth factors. Degranulation and release

of growth factors occurs within 3–5 days

and the growth factor activity may end in

as soon as 7–10 days (Marx 2001; Froum

et al. 2002).

Consistent with the outcome of our

human study, also in animal experiments

no significant differences in wound healing

between autogenous bone and autogenous

bone mixed with PRP were observed 1, 2,

and 4 months after grafting (Aghaloo et al.

2002). The grafting material used in latter

study was cortical membranous bone from

the rabbit cranium, which differs from the

bone used in this study, the latter being

cancellous endochondral bone from the

iliac crest. More recently, Jakse et al.

(2003) published a study in which they

augmented the floor of the maxillary sinus

with autologous bone in sheep, either with

or without PRP. These authors also con-

cluded that the regenerative capacity of

PRP is of quite low potency. Finally Furst

et al. (2004) failed to show an effect of

platelet-released growth factors on bone

regeneration of cortical mandibular defects

in rats. Based on their and our results, we

like to pose that addition of PRP to a bone

transplant used for sinus floor elevation

surgery has apparently no adjuvant clinical

value.

In contrast to the above-mentioned re-

ports, other authors proposed that adding

PRP to bone grafts will result in an increase

the bone density of the reconstructed defect

(Marx et al. 1998; Vanassche & Defrancq

2001). Furthermore, it has been claimed

that platelets can act as local regulators of

fracture repair and bone regeneration (Gru-

ber et al. 2002). Vanassche & Defrancq

included no controls in their study, how-

ever, Marx et al. (1998) showed the bene-

ficial effect of adding PRP in mandibular

continuity defects of 5 cm or greater. Our

study as well as the studies by Aghaloo

et al. (2002) and Jakse et al. (2003) did not

confirm the observation of Marx et al.

(1998) in defects of a lower magnitude.

Therefore, we like to pose that PRP, be-

cause of its effect as local regulators of bone

regeneration, may have a beneficial effect

on bone healing in critical size defects and

defects with compromised vascularization,

while it has no adjuvant value in smaller

defects like in sinus floor elevation surgery.

In the current study, using a very sensi-

tive microradiography method assessing

the density of bone at the implant side,

no differences between the PRP- and non-

PRP sides were observed. Quantitative mi-

croradiography is a commonly used tech-

nique to measure mineral distributions

(calcium, phosphate) and mineral amounts

of carious lesions in enamel and dentin

(Ruben & Arends 1993; de Josselin de

Fig. 3. Histologic examination of the bone biopsy of

Fig. 2a (platelet-rich plasma side). (a) Overview.

Magnification, � 20. (b) Detail of (a) showing

remodeling of bone. Both osteoclast and osteoblast

activity was present around the grafted bone particle.

Osteoblastic rimming is clearly visible on the left

side of the bone particle. Magnification, � 200.

Fig. 4. Histologic examination of the bone biopsy of

Fig. 2c (non- platelet-rich plasma side). (a) Over-

view. Magnification, � 20. (b) Detail of (a) show-

ing remodeling of bone. Osteoblastic rimming is

clearly visible on the right side of the bone particle.

Magnification, � 200.

Table 1. Histomorphometrical analysis ofthe specimen

Patient Non-PRP side PRP side

#1P1 47.8 � 14.5 53.9 � 12.9M1 45.9 � 20.6 52.2 � 5.5

#2P1 57.3 � 11.8 34.7 � 8.8M1 29.6 � 14.4 49.3 � 11.1

#3P1 42.2 � 17.6 33.8 � 22.7M1 36.2 � 13.7 32.3 � 12.6

#4P1 33.1 � 7.5 29.6 � 11.4M1 37.5 � 7.7 46.6 � 15.9

#5P1 47.7 � 21.5 23.8 � 11.4M1 36.7 � 10.5 25.1 � 6

Overall 41.1 � 8.3 38.4 � 11.3

The relative area occupied with bone in the

first premolar (P1) and first molar (M1) region

(%; mean � SD) is given.

PRP, platelet-rich plasma.



Jong et al. 1987). The technique has also

been used to measure mineral distributions

in bone (Hobson & Beynon 1997; Hobson

1998; Biovin & Meunier 2002). Microradio-

graphy has the advantage over histology that

an image is obtained from the entire speci-

men, making it possible to both locate and

measure areas of bone growth (Schortinghuis

et al. 2003). Although the study by Marx

et al. (1998) reported a 1.62–2.16 times

greater radiographic maturation rate in PRP-

treated reconstruction sites as measured on

panoramic radiographs, in the current study,

using a much more sensitive method no

difference in bone density was observed

between the PRP- and non-PRP sides. This

again supports our hypothesis that PRP has

no adjuvant value in sinus floor elevation

surgery, while it still may have an adjuvant

value in major reconstructive surgery.

With regard to grafting with bone sub-

stitutes, Kassolis et al. (2000) reported

some beneficial effects of the use of PRP.

They used PRP in combination with free-

dried bone allografts in maxillary sinus

floor elevation surgery. Histologic sections

revealed numerous areas of osteoid and

bone formation around freeze-dried bone

allograft particles. Histomorphometry was

not performed and there were no controls.

This makes their results questionable as

in our study; using autogenous bone,

however, we also see proper ostoid and

bone formation in the non-PRP-treated

areas grafted with iliac crest bone. Kassolis

et al. (2000) recognized this flaw in their

experimental setup, as they did not draw

firm conclusions from their study. They

mentioned a need for studies to determine

whether PRP enhances new bone forma-

tion or maturation with allogenic grafts or

not. A recent study indeed indicated that

addition of PRP to grafts of anorganic

bovine bone used for sinus floor elevation

surgery that contained minimal or no auto-

logous bone did not make a significant

difference either in vital bone or in inter-

facial bone contact on the test implants

(Froum et al. 2002). Also, combination of

PRP with bovine hydroxyapatite was not

demonstrably superior to hydroxyapatite

alone (Furst et al. 2003). These are not

surprising observations as PRP acts on

healing capable cells to increase their num-

bers (mitogenesis) and stimulate vascular

ingrowth (angiogenesis) (Marx 2001) that

are not present in acellular bone substi-

tutes. PRP is not osteo-inductive and

must be used in combination with living

bone cells. Therefore, it is unlikely to sig-

nificantly promote bone substitutes and

other non-cellular graft materials.

An effective way to evaluate the effects

of PRP on the formation of bone is to study

the effect in bilateral sinus grafts, with the

addition of PRP being the only controlled

variable. This is the first study to be

performed in this manner with autologous

bone. In our study a beneficial effect of

PRP on bone healing and remodeling could

not be shown. In critical size defects, in

compromised bone after radiotherapy and

in large bony defects, PRP still might have

some value, as has been observed by some

authors in the treatment of such a category

of patients (Marx et al. 1998; Fennis et al.

2002). Furthermore, in the current study

the non-PRP-supported bone graft and

PRP-supported bone graft were left unfunc-

tioned. Implants were placed 3 months

after reconstruction. At that time the grafts

showed comparable signs of remodeling.

This does not exclude a possible beneficial

effect of PRP on early bone healing making

earlier placement of implants after grafting

possible. In such a case, the possible early

enhancing effects of PRP on bone healing

might play a role.

Controlled clinical trials are necessary to

determine whether addition of PRP signifi-

cantly enhances bone formation and ma-

turation or not. Up to now, we like to pose

that PRP has no additional value in pro-

moting healing of grafted non-critical size

defects. As there is a strong clinical poten-

tial associated with supplementing growth

factors in healing wounds, there is a great

need for well-designed studies.

Acknowledgements: Mrs I. R. Zerbo,

Department of Oral Cell Biology, ACTA,

Free University of Amsterdam,

is gratefully acknowledged for her

assistance in the histomorphometry

measurements and Mrs M. A. W. H. van

Waarde is gratefully acknowledged for

measuring the TGF-b concentrations in

blood and PRP.

Resume

Le but de cette etude a ete d’evaluer l’effet du plasma

riche en plaquettes sur le remodelage de greffons

osseux autogenes utilises pour l’epaississement du

plancher sinusal. Chez cinq patients edentes souffr-

ant d’une retention insuffisante de leur prothese

superieure en relation avec unmaxillaire severement

resorbe, les planchers sinusaux des deux maxillaires

ont ete epaissis avec un greffon d’os autogene pro-

venant de la crete iliaque. Au hasard, du plasma

riche en plaquettes (PRP) a ete ajoute au greffon

osseux utilise pour epaissir le plancher du sinus

gauche ou droit (modele de bouche divisee). Trois

mois apres la reconstruction, des biopsies osseuses

ont ete obtenues avec un trepan des sites planifies

pour placer des implants (N¼ 30). Ensuite, trois

implants ont ete places dans les parties maxillaires

gauches et droites. Des microradiogrammes des 30

biopsies ont ete effectuees, ces dernieres ont ensuite

ete utilisees pour l’examen au microscope optique.

De plus, des parametres cliniques ont ete enregis-

tres. La guerison a ete parfaite, cliniquement aucune

difference n’a ete observee entre les sites traites avec

PRP ou sans. L’examen microradiographique et

histomorphologique des biopsies n’a revele aucune

difference significative entre les sites PRP et non-

PRP. Un implant place dans le site PRP du greffon a

ete perdu durant la phase de guerison. Des protheses

retenues sur implants ont ete fabriquees six mois

apres l’insertion des implants. Tous les patients ont

une mise en fonction excellente apres un suivi de

20 � 4,3 mois. Dans cette etude, aucun effet ben-

efique additionnel du PRP sur la guerison et le

remodelage osseux n’a ete observe. Le PRP n’aurait

aucune valeur supplementaire a promouvoir la guer-

ison dans ce type d’operation.

Zusammenfassung

Fordert plattchenreiches Plasma die Remodellier-

ung von autologen Knochentransplantaten, welche

fur die Augmentation des Sinusbodens vom Sinus

maxillaris verwendet werden?

Das Ziel dieser Studie war, den Einfluss von

plattchenreichem Plasma auf die Remodellierung

von autologen Knochentransplantaten, welche fur

die Augmentation des Sinusbodens vom Sinus max-

illaris verwendet wurden, auszuwerten.

Bei 5 zahnlosen Patienten, welche aufgrund einer

stark resorbierten Maxilla uber einen ungenugenden

Halt der Oberkieferprothese klagten, wurde der

Sinusmaxillaris mit autologem Knochen vom Beck-

enkamm augmentiert. Zufallig wurde dem Kno-

chen, der zur Augmentation des rechten oder

linken Sinusbodens verwendet wurde, plattchen-

reiches Plasma (PRP) hinzugefugt (unterschiedlich

behandelte Seiten). Drei Monate nach der Aug-

mentation wurden mittels Hohlfrasen Biopsien an

den geplanten Implantatlokalisationen entnommen

(N¼ 30). Danach wurden je drei Implantate in die

rechte und linke posteriore Maxilla eingesetzt.

Von allen Biopsien wurde Mikrorontgenbilder ange-

fertigt (N¼30), danach wurden die Biopsien fur

die lichtmikroskopische Untersuchung aufgearbei-

tet. Zusatzlich wurden klinische Parameter

aufgenommen.

Die Wundheilung war unauffallig. Klinisch konnten

keine Unterschiede zwischen den mit und ohne

PRP behandelten Seiten beobachtet werden. Ebenso

ergab die mikroradiographische und histomorpho-



metrische Untersuchung der Biopsien keine

statistisch signifikanten zwischen der PRP und

nicht-PRP Seite. Ein Implantat, welches in eine

PRP Seite eingesetzt worden war, ging wahrend

der Einheilphase verloren. Die implantatgetragenen

Hybridprothesen wurden 6 Monate nach Im-

plantation angefertigt. Alle Patienten funktionierten

problemlos (Beobachtungszeit bis 20.2 � 4.3

Monate).

In dieser Studie konnte kein positiver Einfluss des

PRP auf die Wundheilung und die Knochenremo-

dellierung beobachtet werden. Es wird vermutet,

dass PRP keinen zusatzlichen Effekt bei der Forder-

ung der Heilung von Transplantaten in Defekten

mit nicht-kritischer Grosse hat.

Resumen

La intencion de este estudio fue evaluar el efecto del

plasma rico en plaquetas en el remodelado de injertos

de hueso autologo usado para aumento del suelo del

seno maxilar.

Se aumento el suelo de ambos senos maxilares con

injertos de hueso autologo de la cresta iliaca en 5

pacientes edentulos que padecıan de insuficiente

retencion de su dentadura superior relacionada con

un maxilar severamente reabsorbido. Aleatoria-

mente, se anadio plasma rico en plaquetas (PRP)

al injerto oseo usado para aumentar el suelo del

seno derecho o izquierdo (diseno de boca partida).

Tres meses tras la reconstruccion, se tomaron

biopsias de hueso con un trepano de los lugares

de implantes planificados (N¼30). Subsecu-

entemente se colocaron tres implantes en el

maxilar posterior derecho e izquierdo. Se hicieron

microrradiogramas de todas las biopsias (N¼ 30),

posteriormente las biopsias se procesaron para mi-

croscopıa optica. Ademas se tomaron parametros

clınicos.

La cicatrizacion de la herida tuvo lugar sin

incidentes. Clınicamente no se observo diferencia

alguna entre el lado tratado con PRP o no. Tampoco

el examen microrradiografico e histomorfologico

de las biopsias revelaron diferencias estadıstica-

mente significativas entre los lados con o

sin PRP. Un implante colocado en el lado del

PRP se perdio durante la cicatrizacion. Las

dentaduras implantorretenidas se fabricaron a

los seis meses de la implantacion. Todos los pa-

cientes funcionaron bien (seguimiento de 20.2 �4.3 meses).

En este estudio no se observo ningun efecto bene-

ficioso del PRP sobre la cicatrizacion y sobre el

remodelado oseo. Se plantea que el PRP no tiene

ningun valor adicional en promover la cicatrizacion

de defectos no crıticos injertados.

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