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Original Article |

Osteopontin and Bone Sialoprotein Distribution at the Bone Graft Recipient Site FREE

Per Alberius, DMD, MD, PhD; Monica Gordh, DMD, PhD
[+] Author Affiliations

From the Department of Plastic Surgery, University Hospital MAS (Dr Alberius), and the Department of Oral Surgery, Centre for Oral Health Sciences, Lund University (Dr Gordh), Malmö, Sweden.


Arch Otolaryngol Head Neck Surg. 1998;124(12):1382-1386. doi:10.1001/archotol.124.12.1382.
Text Size: A A A
Published online

AUTOGENEIC BONE grafts are used in reconstructive craniofacial procedures to facilitate union between skeletal segments and to create improved contour and shape. In many respects, their predictability in terms of incorporation and volumetric persistence is still unclear. Multiple investigators have tried to find means to improve graft survival and operative success. Several factors have been identified that are considered to influence the long-term outcome, such as the embryonic origin of the graft,1,2 its extent of revascularization,1,36 its architectural features,1,3 and fixation.58

One factor of fundamental importance to this issue is the recipient site–graft interface and its acceptance of the new graft. Surprisingly, despite the numerous articles published in this field, this issue has frequently been neglected. Theoretically, an increased tissue pressure resulting from the introduction of a more or less voluminous graft may change the normal recipient bone remodeling response to a more aggressive bone resorption and bone loss. Large grafts in a nonresilient tissue environment would then promote bone resorption and negatively influence the ultimate and hoped-for result.

This investigation aimed to study the reactions at the recipient site after various bone grafting procedures. This was accompished by descriptively analyzing the distribution of 2 noncollagenous phosphoproteins, osteopontin and bone sialoprotein (BSP), which are believed to be involved in the regulation of bone formation.

ANIMALS AND ANESTHESIA

Twenty-two male isogeneic adult Lewis rats, with a mean (SD) weight of 359 (34) g, were used. Four additional animals of identical size were used to obtain donor tissue. Sedation, anesthesia, and animal care were provided as described previously.913 The animals were killed 4 or 20 weeks after grafting. Institutional guidelines regarding animal experimentation were followed. All research protocols were approved by the Animal Ethics Committee at Lund University, Lund, Sweden.

SURGICAL PROCEDURE

The surgical protocol has been described previously.9,10 Briefly, identical-size bone blocks, 4 mm in length, from the femur and tibia (without their periosteum), were harvested from donors using a low-speed trephine mounted in a dental drill. During drilling, the surgical field was continuously irrigated with sterile saline to reduce thermal damage. A paramedian skin incision was made to expose the cranial vault. On one side, a fascial incision parallel to the temporal line was made, and a tight pocket was produced under the temporal muscle. On the contralateral side, a subperiosteal pocket was created. At some sites (Table 1), the recipient bed was gently ground under irrigation to expose the marrow of the recipient bed to an area corresponding to the size of the graft. All animals received 2 bicortical bone grafts, except for 2 animals that only received 1 graft (the contralateral side received unicortical grafts for a pilot study). The experimental design is presented in Table 1.

HISTOLOGIC EXAMINATION

At autopsy, the bone grafts and the recipient bed were carefully excised en bloc without stripping away the soft tissues, immediately frozen in isopenthane, and stored at −70°C. Six-micrometer sections were prepared using a cryostat. The sections were incubated with rabbit antibodies against proteins prepared from rat bone matrix, ie, BSP14 and osteopontin.15 Immunolabeling was performed with antiserum (diluted 1:50-1:200) from immunized rabbits.16 The sections were stained using the peroxidase-antiperoxidase procedure.17 Additional sections were stained with hematoxylin-eosin, safranin O, and van Gieson stain. Also, a control specimen without antibody labeling was prepared. The specificity of the immunolabeling was checked as described by Hulth et al.18 All histologic examinations were performed by an investigator who was not informed about which specimens belonged to which group. The analysis focused on the recipient site, but the interface region and the graft contact area were also included. Detailed studies in identical circumstances on the specific maintenance of various onlay bone graft regimens have been reported elsewhere.913

All animals tolerated the operative procedure without complications. All wounds healed uneventfully. Macroscopically, the bone grafts seemed incorporated into the recipient bone without evidence of infection or graft dislodgment.

HISTOLOGIC FINDINGS

At 4 weeks, integration of subperiosteal grafts to the recipient bed was most pronounced peripherally adjacent to the periosteum but was incomplete along the remainder of the graft-host interface. Areas of localized bone resorption were distributed over the host bed, but the graft's surface facing the interface was mainly intact and seemed relatively nonreactive. Ground areas were fairly intact superficially, with new bone trabeculae reaching toward the interface region, while more resorptive activity, appearing like vacuoles, was found deeper in the recipient bone. Graft integration was markedly more pronounced in this group. Submuscular grafts were more integrated than the subperiosteal ones, but otherwise disclosed the same histologic pattern. The ground areas below submuscular grafts showed excellent bony union to the graft (Figure 1). Rich new bone production from the recipient bed and remodeling at the graft's contact surface were evident (Figure 1).

Place holder to copy figure label and caption
Figure 1.

Submuscular graft (g) after 4 weeks. The recipient bone (r) was grounded. A rich network of bone trabeculae emanating from the recipient bed is distinctly labeled (labeling with antibodies to osteopontin, original magnification ×100).

Graphic Jump Location

At 20 weeks, the recipient site was very thin after subperiosteal placement of the grafts. The inner cortical layer was reduced in height, and moderate remodeling and, occasionally, corticalization of the remaining diploic space were observed. The grafts demonstrated restricted thinning with ongoing remodeling. Graft integration was moderate. In contrast, ground specimens showed complete integration (Figure 2). Their recipient site disclosed marked progressive thinning, and the remaining bone layer often was lamellar.

Place holder to copy figure label and caption
Figure 2.

Submuscular graft (g) after 20 weeks. The rich bone formation in the interface is distinctly illustrated. The asterisk indicates artifact (bone sialoprotein, original magnification ×100).

Graphic Jump Location

Submuscular grafts were completely integrated. The newly formed bone at the graft and host bed was fairly mature, but showed some height reduction. Ground surfaces often showed near or restricted complete penetration to the central nervous system.

IMMUNOHISTOCHEMICAL FINDINGS
Osteopontin

Labeling was fairly uniform between groups. Submuscular grafts disclosed slightly more intensive labeling. In general, osteocytes were distinctly labeled. After 4 weeks, the soft tissue in the interface between the graft and host bed was almost nonlabeled, while the newly formed trabeculae and the undersurface of the graft revealed distinct labeling (Figure 1). After 20 weeks, the labeling pattern was identical to that described above, but less intensive (Figure 3). The recipient bone showed a nonlabeled outer zone, which demonstrated a lamellar structure but was dissimilar in appearance from the remaining external cortical layer. Below that, a zone of more intensive labeling was detected, its bone structure being more immature, with large vascular channels. Most inferiorly (closest to the brain), the lamellar bone was vaguely labeled. In some specimens, small triangular tongues, with their base at the interface and demonstrating more labeling peripherally, were directed endocranially.

Place holder to copy figure label and caption
Figure 3.

Subperiosteally placed onlay (g) after 20 weeks. The host bed (r) was not surgically manipulated. An intensive remodeling area (i) is situated between a fairly nonlabeled zone at the interface region and the original host bone (osteopontin, original magnification ×100).

Graphic Jump Location
Bone Sialoprotein

Labeling generally showed low intensity (Figure 2 and Figure 4). The findings were almost identical regardless of group, except that submuscular groups disclosed slightly more labeling. The BSP was localized below the external zone of the recipient site, with activity concentrated in the central part and less activity more peripherally (Figure 4). No labeling was observed at the host bed's surface Figure 2). All osteocytes were distinctly labeled. Labeling was less pronounced after 20 weeks.

Place holder to copy figure label and caption
Figure 4.

Submuscular graft (g) after 4 weeks. The recipient bone (r) was not grounded, but the outer cortical plate is markedly reduced in height. Labeling is weak, but slightly more prominent in an intermediate zone (arrows) of newly formed bone and old diploic bone (labeling for bone sialoprotein, original magnification ×100).

Graphic Jump Location

Onlay bone grafts are widely used in the restoration and augmentation of the craniofacial skeleton. However, an initial satisfactory result is sometimes followed by a less than optimal long-term outcome because of graft resorption or recipient site remodeling causing loss of contour and volume. Consequently, prognostic assessment of graft success is difficult, and various techniques and experimental protocols have been tested to improve the procedure; yet, the problem remains partly unsolved. The present study focused on the bone remodeling activities of the graft–host bed interface, and with the use of immunolabeling to localize 2 proteins believed to be important markers for various aspects of osseous response, a detailed analysis of the problem was expected.

In previous reports on onlay integration, sparse comments on the status of the recipient bed have been provided. For example, Goldstein et al19 noted intensive bone remodeling after 15 days in the recipient nasal dorsum of rabbits after placement of grafts from the zygomatic arch, as well as multiple areas of bone formation in both graft and host bed after 40 days. Ermis and Poole20 observed, after 16 weeks, resorption of the underlying mandible in most rabbits receiving bicortical iliac grafts. Similarly, Phillips and Rahn8 described resorptive areas in the underlying mandible for nonfixed (but not fixed) rib and skull grafts in sheep after 20 weeks. Chen et al3 observed vigorous osteoclastic activity in the recipient surface 10 days after subperiosteal placement of unicortical iliac and calvarial rigidly fixed grafts to the rabbit snout. Lin et al5 postulated that once a graft becomes adherent enough to the recipient bone to resist outside mechanical forces acting on it, the type of fixation used would make little difference. This conclusion was based on the findings that fixed or nonfixed iliac unicortical and full-thickness calvarial grafts transplanted to the snout or femur in rabbits resulted in no significant difference in residual graft volume for neither host bed. Finally, Gosain et al21 observed conversion from a cortical to a trabecular bone structure in vascularized bone transfers and their recipient zygomas in rabbits after 1 year. Consequently, information is rhapsodic, incomplete, and contradictory, and further data are necessary to achieve a full understanding of this important issue.

THE MAJOR constituent of bone matrix is hydroxyapatite, and the most abundant organic constituent is type I collagen. The extracellular matrix contains several noncollagenous proteins that appear to serve important functions in the regulation of mineralization, collagen fiber growth, and cell-matrix interactions.22 Osteopontin and BSP are the major phosphorylated proteins of mammalian bone, and both are produced by the osteoblasts. These proteins function in the initiation of mineralization, bind tightly to hydroxyapatite, and possess cell attachment activity via an RGD (arginin-glycine-aspartic acid) amino acid sequence.15 However, they are different in many respects.

Osteopontin is abundantly present in both membranous and enchondral bone, primarily in osteoblasts and osteocytes, but also in osteoprogenitor cells.23 It is less acidic than BSP and is present not only in bone but also in other tissues, such as the kidney, placenta, and some parts of the central nervous system.23 The protein presently is believed to have a dual function. First, it has been shown to recruit both osteoclast precursor cells and osteoclasts and to bind them to the mineralized matrix of bone.24,25 Second, the protein is enriched at the mineralization front in enchondral bone26 and is supposed to regulate the mineralization process by inhibiting calcification and crystal growth.27

Bone sialoprotein is present only in bone and dentin.28 It is apparently restricted to osteoblasts in areas of initial bone formation.2931 In vitro, it promotes nucleation and crystal growth32 and hence appears to be a marker of new bone formation. After the osteoblasts have been embedded in the mineralized matrix of enchondral bones as osteocytes, labeling is markedly reduced.31 Interestingly, the osteocytes of the membranous bones studied (the parietal and temporal bones) were distinctly labeled, even in the adult animals used.

In accord with the findings of our previous studies,9,10 in which immunolabeling of osteopontin and BSP were localized mostly to a bicortical graft's interior during the investigation periods, in the present study we found labeling in general to be weak in the areas investigated. The recipient site, however, disclosed quite dramatic anatomical changes. Generally, it was markedly and quite rapidly reduced in height, while the contact surface of the graft appeared relatively nonreactive. Mostly, the outer surface (zone) of the host bed was intact and nonlabeled, although rich remodeling activity and bone protein labeling were observed in a subzone paralleling the surface. Seemingly, the resorptive activity is concentrated some distance away from the actual interface region. Also, in ground specimens, the endocranial surface was quite undisturbed and kept its lamellar structure. The resorptive activity therefore seems to be quite strictly localized. Both osteopontin and BSP labeling clearly supported this conclusion and highlighted the subzone activity. It is possible that the triangular bone formations observed in some specimens might participate in such a localized manner of transferring the resorptive signals to the bone tissue interior.

The graft's contact surface to the interface showed marked local remodeling and resorptive activity. This remodeling was more pronounced after submuscular placement of the graft, a finding that was apparent for both intervals. Maturation was slow for the bicortical grafts irrespective of placement. Surprisingly, full bone maturation was not observed in any group, but after 20 weeks reduced labeling was observed for both proteins investigated. This indicates that maturation of the recipient bone with decreased bone turnover was approaching.

The spectrum of successful graft incorporation ranged from the subperiosteally placed graft, which obtained improved integration after the recipient bed was ground, to the submuscular graft, with further improvement after grinding. This pattern was applicable for both intervals tested. Also, the early dramatic gain in bone production obtained after grinding was only temporary, as this bone was resorbed later. The reason for the divergent response between the submuscular- and subperiosteal-placed grafts is unclear. The influence of graft fixation was probably negligible; both placements clinically seemed quite stable during operation, and all grafts were fixed to the host bed at the end of the study.

The periosteum is a vascular membrane that consists of a fibrous layer and a cellular cambium layer. It gets less osteogenic with age.33,34 Interestingly, its osteogenic potential seems to be dependent on the type of bone (membranous or enchondral) being covered.35,36 Speculatively, the passive nature of the periosteum does not produce very much tension or pressure on an onlay graft. In contrast, a more or less continuously moving muscle must exert an intermittent stress, which should negatively affect graft size. However, to what extent this muscle activity will affect the integration per se is not known. LaTrenta et al7 emphasized the importance of 2 factors, apart from the physiologic stress placed on the graft, that affect the extent of bone graft resorption (and integration): the vascularity of the host bed and the recipient-to-host bone contact. The recipient-to-host bone contact was presumably identical with both graft positionings, while the extent of revascularization may have been different. As theorized by Ermis and Poole,20 the increase in vascularity noted for submuscularly placed grafts may promote rapid and optimal graft incorporation. The graft resorption induced by stress implies that relatively larger grafts should be used when they are being placed below muscle, rather than subperiosteally positioned, to acquire the desired graft volume.

Different views prevail concerning the importance of revascularization for survival and volumetric maintenance of the graft. Speculatively, the slow revascularization of a devascularized free bone graft may hamper its resorption, while the richly vascularized calvarial bone, constituting the recipient site, is more vulnerable to pressure and local stress. This conclusion agrees with Albrektsson's37 observation that neither osteogenesis nor resorption occurs before a bone is revascularized. Consequently, recipient site failure rather than graft volumetric changes may be a logical explanation in many cases of loss of skeletal contour after bone transplantation. Furthermore, the positive impact on graft integration that was observed after grinding secondarily facilitated graft revitalization and, in turn, resorption, which induces doubts as to its long-term benefits.

Accepted for publication July 8, 1998.

The study was supported in part by Åke Wibergs Stiftelse, Stockholm, Sweden.

Reprints: Per Alberius, DMD, MD, PhD, Department of Plastic Surgery, University Hospital MAS, SE-205 02 Malmö, Sweden.

Hardesty  RAMarsh  JL Craniofacial onlay bone grafting: a prospective evaluation of graft morphology, orientation, and embryonic origin. Plast Reconstr Surg. 1990;855- 14
Link to Article
Zins  JEWhitaker  LA Membranous versus endochondral bone: implications for craniofacial reconstruction. Plast Reconstr Surg. 1983;72778- 784
Link to Article
Chen  NTGlowacki  JBucky  LPHonh  H-ZKim  W-KYaremchuk  MJ The roles of revascularization and resorption on endurance of craniofacial onlay bone grafts in the rabbit. Plast Reconstr Surg. 1994;93714- 722
Link to Article
Kusiak  JFZins  JEWhitaker  LA The early revascularization of membranous bone. Plast Reconstr Surg. 1985;76510- 516
Link to Article
Lin  KYBarlett  SPYaremchuk  MJFallon  MGrossman  RFWhitaker  LA The effects of rigid fixation on the survival of onlay bone grafts: an experimental study. Plast Reconstr Surg. 1990;86449- 456
Link to Article
Phillips  JHRahn  BA Fixation effects on membranous and endochondral onlay bone graft revascularization and bone deposition. Plast Reconstr Surg. 1990;85891- 897
Link to Article
LaTrenta  GSMcCarthy  JGBreitbart  ASMay  MSissons  HA The role of rigid fixation in bone-augmentation of craniofacial skeleton. Plast Reconstr Surg. 1989;84578- 588
Link to Article
Phillips  JHRahn  BA Fixation effects on membranous and endochondral onlay bone-graft resorption. Plast Reconstr Surg. 1988;82872- 877
Link to Article
Alberius  PGordh  MLindberg  LJohnell  O Influence of surrounding soft tissues on onlay bone graft incorporation. Oral Surg Oral Med Oral Pathol. 1996;82 (1) 22- 33
Link to Article
Alberius  PGordh  MLindberg  LJohnell  O Onlay bone graft behavior after marrow exposure of the recipient rat skull bone. Scand J Plast Reconstr Hand Surg. 1996;30257- 266
Link to Article
Gordh  MAlberius  PLindberg  LJohnell  O Bone graft incorporation after cortical perforations of the host bed. Otolaryngol Head Neck Surg. 1997;117664- 670
Link to Article
Alberius  PGordh  MLindberg  LJohnell  O Cortical perforations of both graft and host bed improve onlay incorporation to the rat skull. Eur J Oral Sci. 1996;104554- 561
Link to Article
Gordh  MAlberius  PJohnell  OLindberg  LLinde  A Osteopromotive membranes enhance onlay integration and maintenance in the adult rat skull. Int J Oral Maxillofac Surg. 1998;2767- 73
Link to Article
Franzén  AHeinegård  D Isolation and characterization of two sialoproteins present only in bone calcified matrix. Biochem J. 1985;232715- 724
Oldberg  ÅFranzén  AHeinegård  D Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence. Proc Natl Acad Sci U S A. 1986;838819- 8823
Link to Article
Klareskog  LForsum  UWigren  AWigzell  H Relationship between HLA-DR expressing cells and T-lymphocytes of different subsets in rheumatoid synovial tissue. Scand J Immunol. 1982;15501- 507
Link to Article
Hsu  S-MRaine  LFanger  H Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981;29577- 580
Link to Article
Hulth  AJohnell  OLindberg  LHeinegård  D Sequential appearance of macromolecules in bone induction in the rat. J Orthop Res. 1993;11367- 378
Link to Article
Goldstein  JMase  CNewman  MH Fixed membranous bone graft survival after recipient bed alteration. Plast Reconstr Surg. 1993;91589- 596
Link to Article
Ermis  IPoole  M The effects of soft tissue coverage on bone graft resorption in the craniofacial region. Br J Plast Surg. 1992;4526- 29
Link to Article
Gosain  AKMcCarthy  JGStaffenberg  DGlat  PMSimmons  DJ The histomorphologic changes in vascularized bone transfers and their interrelationship with the recipient sites: a 1-year study. Plast Reconstr Surg. 1996;761001- 1013
Link to Article
Oldberg  ÅFranzén  AHeinegård  D The primary structure of a cell-binding bone sialoprotein. J Biol Chem. 1988;26319430- 19432
Young  MFKerr  JMIbaraki  KHeegaard  A-MRobey  PG Structure, expression, and regulation of the major noncollagenous matrix proteins of bone. Clin Orthop. 1992;281275- 294
Heinegård  DOldberg  Å Structure and biology of cartilage and bone matrix noncollagenous macromolecules. FASEB J. 1989;32042- 2051
Reinholt  FPHultenby  KOldberg  ÅHeinegård  D Osteopontin: a possible anchor of osteoclasts to bone. Proc Natl Acad Sci U S A. 1990;874473- 4475
Link to Article
Hultenby  KReinholt  FOldberg  ÅHeinegård  D Ulrastructural immunolocalization of osteopontin in metaphyseal and cortical bone. Matrix. 1991;11206- 213
Link to Article
Hunter  GKKyle  CLGoldberg  HA Modulation of crystal formation by bone phosphoproteins: structure specificity of the osteopontin-mediated inhibition of hydroxyapatite formation. Biochem J. 1994;300723- 728
Fisher  LWWhitson  SWAvioli  LVTermine  JD Matrix sialoprotein of developing bone. J Biol Chem. 1983;25812723- 12727
Chen  JShapiro  HSSodek  J Developmental expression of bone sialoprotein mRNA in rat mineralized connective tissues. J Bone Miner Res. 1992;7987- 997
Link to Article
Hultenby  KReinholt  FPNorgård  MOldberg  ÅWendel  MHeinegård  D Distribution and synthesis of bone sialoprotein in metaphyseal bone of young rats show a distinctly different pattern from that of osteopontin. Eur J Cell Biol. 1994;63230- 239
Shen  ZHeinegård  DSommarin  Y Distribution and expression of cartilage oligomeric matrix protein and bone sialoprotein show marked changes during rat femoral head development. Matrix Biol. 1994;14773- 781
Link to Article
Hunter  GKGoldberg  H Nucleation of hydroxyapatite by bone sialoprotein. Proc Natl Acad Sci U S A. 1993;908562- 8565
Link to Article
Urist  MRMcLean  FC Osteogenic potency and new bone formation by induction in transplants to anterior chamber of the eye. J Bone Joint Surg. 1959;34A443
Eyre-Brook  AL The periosteum: its function reassessed. Clin Orthop. 1984;189300- 307
Uddströmer  L The osteogenic capacity of tubular and membranous bone periosteum: a qualitative and quantitative experimental study in growing rabbits. Scand J Plast Reconstr Surg. 1978;12195- 205
Link to Article
Uddströmer  LRitsilä  V Osteogenic capacity of periosteal grafts: a qualitative and quantitative study of membranous and tubular bone periosteum in young rabbits. Scand J Plast Reconstr Surg. 1978;12207- 214
Link to Article
Albrektsson  T Repair of bone grafts: a vital microscopic and histological investigation in the rabbit. Scand J Plast Reconstr Surg. 1980;141- 12
Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Submuscular graft (g) after 4 weeks. The recipient bone (r) was grounded. A rich network of bone trabeculae emanating from the recipient bed is distinctly labeled (labeling with antibodies to osteopontin, original magnification ×100).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Submuscular graft (g) after 20 weeks. The rich bone formation in the interface is distinctly illustrated. The asterisk indicates artifact (bone sialoprotein, original magnification ×100).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Subperiosteally placed onlay (g) after 20 weeks. The host bed (r) was not surgically manipulated. An intensive remodeling area (i) is situated between a fairly nonlabeled zone at the interface region and the original host bone (osteopontin, original magnification ×100).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

Submuscular graft (g) after 4 weeks. The recipient bone (r) was not grounded, but the outer cortical plate is markedly reduced in height. Labeling is weak, but slightly more prominent in an intermediate zone (arrows) of newly formed bone and old diploic bone (labeling for bone sialoprotein, original magnification ×100).

Graphic Jump Location

References

Hardesty  RAMarsh  JL Craniofacial onlay bone grafting: a prospective evaluation of graft morphology, orientation, and embryonic origin. Plast Reconstr Surg. 1990;855- 14
Link to Article
Zins  JEWhitaker  LA Membranous versus endochondral bone: implications for craniofacial reconstruction. Plast Reconstr Surg. 1983;72778- 784
Link to Article
Chen  NTGlowacki  JBucky  LPHonh  H-ZKim  W-KYaremchuk  MJ The roles of revascularization and resorption on endurance of craniofacial onlay bone grafts in the rabbit. Plast Reconstr Surg. 1994;93714- 722
Link to Article
Kusiak  JFZins  JEWhitaker  LA The early revascularization of membranous bone. Plast Reconstr Surg. 1985;76510- 516
Link to Article
Lin  KYBarlett  SPYaremchuk  MJFallon  MGrossman  RFWhitaker  LA The effects of rigid fixation on the survival of onlay bone grafts: an experimental study. Plast Reconstr Surg. 1990;86449- 456
Link to Article
Phillips  JHRahn  BA Fixation effects on membranous and endochondral onlay bone graft revascularization and bone deposition. Plast Reconstr Surg. 1990;85891- 897
Link to Article
LaTrenta  GSMcCarthy  JGBreitbart  ASMay  MSissons  HA The role of rigid fixation in bone-augmentation of craniofacial skeleton. Plast Reconstr Surg. 1989;84578- 588
Link to Article
Phillips  JHRahn  BA Fixation effects on membranous and endochondral onlay bone-graft resorption. Plast Reconstr Surg. 1988;82872- 877
Link to Article
Alberius  PGordh  MLindberg  LJohnell  O Influence of surrounding soft tissues on onlay bone graft incorporation. Oral Surg Oral Med Oral Pathol. 1996;82 (1) 22- 33
Link to Article
Alberius  PGordh  MLindberg  LJohnell  O Onlay bone graft behavior after marrow exposure of the recipient rat skull bone. Scand J Plast Reconstr Hand Surg. 1996;30257- 266
Link to Article
Gordh  MAlberius  PLindberg  LJohnell  O Bone graft incorporation after cortical perforations of the host bed. Otolaryngol Head Neck Surg. 1997;117664- 670
Link to Article
Alberius  PGordh  MLindberg  LJohnell  O Cortical perforations of both graft and host bed improve onlay incorporation to the rat skull. Eur J Oral Sci. 1996;104554- 561
Link to Article
Gordh  MAlberius  PJohnell  OLindberg  LLinde  A Osteopromotive membranes enhance onlay integration and maintenance in the adult rat skull. Int J Oral Maxillofac Surg. 1998;2767- 73
Link to Article
Franzén  AHeinegård  D Isolation and characterization of two sialoproteins present only in bone calcified matrix. Biochem J. 1985;232715- 724
Oldberg  ÅFranzén  AHeinegård  D Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence. Proc Natl Acad Sci U S A. 1986;838819- 8823
Link to Article
Klareskog  LForsum  UWigren  AWigzell  H Relationship between HLA-DR expressing cells and T-lymphocytes of different subsets in rheumatoid synovial tissue. Scand J Immunol. 1982;15501- 507
Link to Article
Hsu  S-MRaine  LFanger  H Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981;29577- 580
Link to Article
Hulth  AJohnell  OLindberg  LHeinegård  D Sequential appearance of macromolecules in bone induction in the rat. J Orthop Res. 1993;11367- 378
Link to Article
Goldstein  JMase  CNewman  MH Fixed membranous bone graft survival after recipient bed alteration. Plast Reconstr Surg. 1993;91589- 596
Link to Article
Ermis  IPoole  M The effects of soft tissue coverage on bone graft resorption in the craniofacial region. Br J Plast Surg. 1992;4526- 29
Link to Article
Gosain  AKMcCarthy  JGStaffenberg  DGlat  PMSimmons  DJ The histomorphologic changes in vascularized bone transfers and their interrelationship with the recipient sites: a 1-year study. Plast Reconstr Surg. 1996;761001- 1013
Link to Article
Oldberg  ÅFranzén  AHeinegård  D The primary structure of a cell-binding bone sialoprotein. J Biol Chem. 1988;26319430- 19432
Young  MFKerr  JMIbaraki  KHeegaard  A-MRobey  PG Structure, expression, and regulation of the major noncollagenous matrix proteins of bone. Clin Orthop. 1992;281275- 294
Heinegård  DOldberg  Å Structure and biology of cartilage and bone matrix noncollagenous macromolecules. FASEB J. 1989;32042- 2051
Reinholt  FPHultenby  KOldberg  ÅHeinegård  D Osteopontin: a possible anchor of osteoclasts to bone. Proc Natl Acad Sci U S A. 1990;874473- 4475
Link to Article
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