Jan Lindhe. Clinical Periodontology

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REGENERATIVE PERIODONTAL THERAPY •

Fig. 28-5. Microphotographs show-

ing the histological features after 6

months of healing, under the four

experimental conditions (a-d) il-

lustrated in Fig. 28-4. The teeth in

(

b) and (d) are those root planed

their coronal portion, and the

teeth (

a) and (b) are those reim

planted in

sockets with normal

bone height. A

fibrous reunion

was established in

areas where the connective tissue

attachment was

retained (a and c)

while the epithe

lium has migrated

to the apical ex-tension of root

instrumentation (a

RP) where the

attachment was re-

moved (b and d).

CEJ: cemento

enamel junction.

Fig. 28-6. Microphotograph of a

tooth retained in its labially dis-

placed position (a) and a tooth (b)

moved back to its original posi

tion.

The level of alveolar bone (ar

row) is

reduced in (a) while it has

regenerated to its normal level (ar-

row) in (b). The apical termination

the junctional epithelium is at the

cemento-enamel junction (CEJ) in

both situations.

656 • CHAPTER

Fig. 28-7. Microphotograph of furcation 6 weeks after grafting with iliac crest marrow (a). The furcation is com

pletely filled with bone (B), but ankylosis (AN) and root resorption (RS) can be seen. (b) Higher magnification

the area in (a) showing ankylosis and resorption. OC: osteoclasts.

Fig. 28-8. Microphotograph of a healed bifurcation defect following transplantation of non-vital bone grafts (a). The

grafts (G) have not been reached by bone formation from the interradicular septum (S), but occur as isolated parti

cles surrounded by "cementu

. Cementum (C) and new connective tissue attachment formation have taken place

along the entire circumference of the bifurcation. (b) High magnification of isolated bone grafts (G) with newly

formed "cementum" on the surface.

Ellegaard et al. (1973, 1974, 1975, 1976) and Nielsen

et al. (1980) reported that grafting materials in peri-

odontal bony defects may be:

osteoproliferative

(osteogenetic), which means that

new bone is formed by bone forming cells con-

tained in the grafted material

osteoconductive,

which means that the grafted mate-

rial does not contribute to new bone formation

per

but serves as scaffold for bone formation origi

nating

from adjacent host bone

osteoinductive,

which means that bone formation is

induced in the surrounding soft tissue immediately

adjacent to the grafted material.

These studies, where various types of bone graft were

placed in intrabony defects or interradicular lesions,

revealed that only iliac bone marrow grafts survived

transplantation. Transplantation of iliac bone marrow

grafts almost consistently resulted in bone fill in the

experimental defects, but healing was frequently ac-

companied by ankylosis and root resorption (Fig. 28-

7).

The iliac bone marrow grafts exerted an osteo

geneic

effect, and it was suggested that this was re-

REGENERATIVE PERIODONTAL THERAPY • 657

Fig. 28-9. Cleared specimen from a 1-week-old bifurca

tion defect treated with bone grafts. Judged from the

course of the blood vessels, the granulation tissue in

the defect has developed mainly from the periodontal

ligament (arrows) and only to a minor extent from the

interradicular septum (IS).

Fig. 28-10. Microphotograph of a

reimplanted root after 3 months of

healing (a). A periodontal liga

ment

(PL) has become re-estab

lished in

the apical portion of the

root

whereas ankylosis (A) and

root

resorption (R) is the predomi

nant

feature in the coronal por

tion. (b)

High magnification of the

ankylosis

seen in (a).

sponsible for the induction of root resorption (Elle-

gaard et al. 1973, 1974). Jaw bone grafts and xenografts

did not actively contribute to bone formation but

served as a scaffold for bone regeneration (i.e. osteo-

conductive effect). Often, however, these bone grafts

were not reached by the new bone growing out from

the host bone, but occurred as isolated particles sur-

rounded by a bone-like or cementum-like substance

(

Fig. 28-8). It was found that the treated bifurcation

defects became filled mainly with granulation tissue

derived from the periodontal ligament (Fig. 28-9). The

authors (Nielsen et al. 1980) suggested that this in-

growth of ligament tissue inhibited bone formation

and

that the new cementum on the root surface in the

bifurcation defects, including the cementum-like sub-

stance observed around the implanted bone particles,

were formed by periodontal ligament cells (Fig. 28-8).

Thus, it appeared from these studies that the key cells

in periodontal regeneration are periodontal ligament

cells rather than bone cells.

Regenerative capacity of bone cells

The ability of newly formed tissue originated from

bone

to produce a new connective tissue attachment

was

examined in a study by Karring et al. (1980). Roots

periodontitis-affected teeth were extracted and

placed

in surgically created sockets in edentulous ar

eas of

dogs. The implanted roots were covered with

tissue

flaps (submerged) and the results of healing

were

examined histologically after 3 months. A peri

odontal

ligament was re-established in the apical por

tion of

the reimplanted roots where, at the time of

implantation, remnants of periodontal ligament tissue

were preserved. In the coronal portion of the roots

which were previously exposed to periodontitis and

then scaled and planed, healing had consistently re-

sulted in ankylosis and root resorption (Fig. 28-10). On

the basis of this finding, it was concluded that tissue

derived from bone lacks cells with the potential to

produce a new connective tissue attachment.

658 • CHAPTER 28

Fig. 28-11. Microphotograph of root (R) which has been

reimplanted with its surface facing the gingival connec-

tive tissue (GCT). The surface exhibits extensive resorp-

tion.

Fig. 28-12. Microphotograph showing new attachment

formation (between the arrows) on a submerged root

with a non-impaired periodontal ligament. Coronal to

the cementum, root resorption is the predominant fea-

ture.

Fig. 28-13. Microphotograph of a

titanium implant placed in contact

with retained root tips (a). A dis-

tinct cementum layer (arrows)

and

periodontal ligament (PL) in

continuity with that on the roots

(

R) is visible on the implant sur-

face. (b) High magnification in po-

larized light of the periodontal

ligament formed around the im-

plant seen in (a). A cementum

layer

(arrows) with Sharpey's fi

bers is

present at the implant sur

face.

Principal fibers, oriented per-

pendicular to the surface, are run-

ning across the ligament space

(

LS) and are inserting in the op-

posing bone (B) as in natural teeth

(see Fig. 1-71).

Regenerative capacity of gingival connective

tissue cells

Another experiment (Nyman et al. 1980) was carried

out

in order to examine the potential of gingival con

nective

tissue to produce a new connective tissue

attachment.

The teeth were treated as described in the

experiment

above but were not transplanted into

sockets. Instead

they were placed in bone concavities

prepared on the

buccal aspect of the jaw and sub

sequently covered by

tissue flaps. Thus, half the cir

cumference of the roots

was in contact with bone while the remaining part was

facing the gingival connective

tissue at the subsurface of

the flaps. Histologic exami-

nation after 3 months of healing showed areas with

periodontal ligament in the apical portion of the roots

where, at the time of implantation, periodontal ligament

tissue was preserved. In the coronal, previously

exposed

part of the roots, no signs of new connective

tissue

attachment were present. The root portion lo

cated in

contact with gingival connective tissue dem

onstrated a

connective tissue with fibers oriented par

allel to the

root surface and without attachment to the

root.

However, root resorption occurred at the majority of the

surfaces (Fig. 28-11). On the basis of this

result it was

concluded that gingival connective tissue also lacks cells

with the potential to produce a new

connective tissue

attachment.

REGENERATIVE PERIODONTAL THERAPY •

Regenerative capacity of periodontal

ligament cells

In the experiments described above, root resorption

was observed occasionally, also in the apical portion

of the extracted and reimplanted roots (Karring et al.

1980, Nyman et al. 1980). It was suggested that this

occurred because the periodontal ligament tissue re-

tained on this part of the root had become injured

during extraction, thereby allowing bone or gingival

connective tissue to contact the root surface during

healing and induce resorption. It was assumed that

this damage of the retained periodontal ligament tis-

sue had also restricted its potential of proliferating in

the coronal direction along the root surface. Indeed, in

a later study (Karring et al. 1985), where periodonti-

tis-involved roots were retained in their sockets and

subsequently submerged, significant amounts of new

connective tissue attachment formed on the coronal

portion of the roots (Fig. 28-12). The finding of new

attachment only on the roots with a non-impaired

periodontal ligament, but never on the extracted and

reimplanted roots with an impaired ligament, indi-

cates that periodontal ligament tissue contains cells

with the potential to form a new connective tissue

attachment on a detached root surface.

Active root resorption occurred consistently at the

root surfaces above the coronal extension of new at-

tachment. It was suggested that this resorption was

induced by gingival connective tissue which had pro-

liferated apically from the covering tissue flap. Thus,

only cells in the periodontal ligament seem capable of

regenerating lost periodontal attachment.

The final evidence that the progenitor cells for new

attachment formation are residing in the periodontal

ligament was provided in studies in which titanium

dental implants were placed in contact with retained

root tips whose periodontal ligament served as a

source for cells which could populate the implant

surface during healing (Buser et al. 1990a,b, Warrer et

al. 1993). Microscopic analysis revealed that a distinct

layer of cementum with inserting collagen fibers had

formed on the surfaces of the implants (Fig. 28-13a),

and that these fibers, often oriented perpendicularly

to the surface, were embedded in the opposite bone

(

Fig. 28-13b). Control implants (Fig. 28-14) placed

without contact with retained roots healed with the

characteristic features of osseointegration (i.e. direct

contact between bone and the implant surface). These

results prove that the progenitor cells for periodontal

attachment formation reside in the periodontal liga-

ment and not in the alveolar bone as previously as-

sumed (Melcher et al. 1987).

Role of epithelium in periodontal wound

healing

Some of the roots in the experiment described above (

Karring et al. 1985) penetrated the covering mucosa

Fig. 28-14. Microphotograph of a titanium implant

placed without contact with retained roots (control).

This implant has healed with a direct contact between

the bone and the implant surface (osseointegration)

at early stages of healing, thereby allowing the epithe-

lium to grow apically along the root surface. The

amount of new connective tissue attachment on these

roots was considerably smaller than that formed on

the roots which remained submerged throughout the

study. This finding and those of other investigators

(Moscow 1964, Kon et al. 1969, Proye & Polson

1982)

indicate that the apical migration of

epithelium re-

duces the coronal gain of attachment,

evidently by preventing periodontal ligament cells

from repopulat-

ing the root surface (Fig. 28-15).

Downgrowth of epithelium into the periodontal

lesion has most likely occurred to a varying extent

during healing following most flap and grafting pro-

cedures applied in regenerative periodontal therapy,

which may explain the varying results reported. This

view is supported by the results of the monkey study

by Caton et al. (1980). These investigators examined

healing in ligature-induced periodontal lesions fol-

lowing treatment with four different modalities of

regenerative surgical procedures:

root planing and soft tissue curettage

Widman flap surgery without bone grafting

Widman flap surgery with the placement of frozen

autogeneous red bone marrow and cancellous

bone, or

beta tricalcium-phosphate in intrabony defects.

Healing following all treatment modalities resulted in

the formation of a long junctional epithelium extend-

ing to or close to the same level as before treatment.

66o •

CHAPTER

Fig. 2845. Microphotograph illustrating an intrabony

defect after regenerative treatment. New bone (NB) has

formed in the defect but epithelium has migrated api-

cally along the root surface to the notch (arrow) in the

root surface indicating the bottom of the defect before

treatment.

Root resorption

In the experimental studies described previously,

granulation tissue, derived from gingival connective

tissue or bone, produced root resorption when con-

tacting the curetted root surface during healing fol-

lowing surgery (Karring et al. 1980, 1985, Nyman et

al.

1980). It should be expected, therefore, that this

phenomenon would occur as a frequent complication

to regenerative periodontal surgery, particularly fol-

lowing those procedures which include the placement

of grafting materials to stimulate bone formation. The

reason that root resorption is rarely seen is most likely

that postoperatively, the dento-gingival epithelium

migrates apically along the root surface, forming a

protective barrier towards the root surface (Fig. 28-15).

This view is supported by the results of an experimen-

tal study in monkeys (Karring et al. 1984) in which

roots, which previously had been subjected to liga-

ture-induced periodontitis, were extracted and reim-

planted into contact with bone and connective tissue

and covered with a tissue flap (submerged). After

varying time intervals the submerged roots were ex-

posed to the oral cavity by a second incision (wound-

ing) through the covering mucosa, thereby permitting

the epithelium to migrate into the wound. In speci-

mens where the wounding occurred within 2 weeks

(

Fig. 28-16), the previously diseased part of the roots

Fig. 28-16. Microphotograph of an implanted root (R)

where epithelium was allowed to migrate into the

wound after 2 weeks. The epithelium has migrated

along the coronal, previously periodontitis-involved

root surfaces down to the level indicated by the arrows.

In the areas covered by epithelium, there are no signs

of resorption. Apical to this level the root surfaces dem

onstrate root resorption.

Fig. 28-17. Microphotograph of an implanted root (R)

where epithelium was allowed to migrate into the

wound after 4 weeks. The epithelium (arrows) covers

only the coronal cut root surface. Extensive resorption

is seen on the surface facing the gingival connective tis

sue (GCT) and resorption and ankylosis are seen on the

surface facing the bone tissue (B).

REGENERATIVE PERIODONTAL THERAPY • 661

Fig. 28-18. Progression of perio-

dontitis at a different rate on

neighboring tooth surfaces results

in the development of intrabony

defects. Based on the number of

surrounding bone walls such de-

fects are classified as one-wall (a),

two-wall (b) or three-wall (c) de-

fects.

was covered by epithelium and showed no signs of

resorption. With increasing intervals between implan-

tation of the roots and the wounding, a steadily dimin

ishing part of the diseased root surface was covered

by epithelium, and root resorption and ankylosis be-

came progressively pronounced (Fig. 28-17). This ob-

servation concurs with results presented by Bjorn et

al. (1965) who treated 11 periodontally diseased teeth

in seven human volunteers, using the submerging

technique which prevented apical migration of the

dentogingival epithelium. The authors reported that

root resorption was indeed a common complication

following this kind of therapy.

REGENERATIVE PROCEDURES

One of the first methods used in attempts to obtain

new attachment was scaling and root planing com-

bined with soft tissue curettage (i.e. mechanical re-

moval of the diseased root cementum and the pocket

epithelium). Studies in humans (e.g. Younger 1899,

McCa111926, Orban 1948, Beube 1952, Waerhaug 1952,

Schaffer & Zander 1953, Carranza 1954, 1960) and in

animals (e.g. Beube 1947, Ramfjord 1951, Kon et al.

1969) showed that this type of periodontal therapy

resulted not only in the establishment of gingival

health but also in a reduction of the initially recorded

pocket depth. This decrease in the depth of the peri-

662 • CHAPTER 28

odontal pocket was assumed to be partly the result of

shrinkage of the initially inflamed gingiva, but partly

also the effect of the formation of a new connective

tissue attachment in the apical part of the pocket.

The possibility of obtaining new attachment be-

came widely accepted with the work of Prichard

(

1957a,b) in which new attachment formation in in-

trabony periodontal lesions was reported as a predict

able outcome of treatment. Seventeen cases were pre-

sented out of which four were subjected to a re-entry

surgical procedure, revealing that these defects were

filled with bone. The technique of Prichard (1957b,

1960) was only used for the treatment of three-wall

intrabony defects, and the results obtained suggested

that the morphology of the periodontal bony defect

was essential for the establishment of a predictable

prognosis. Goldman & Cohen (1958) introduced a

classification of periodontal intrabony defects which

was based on the number of osseous walls surround-

ing the defect, being either three-wall, two-wall or

one-wall defects or a combination of such situations

(

Fig. 28-18).

The technique of Prichard (1957a,b, 1960) included

the elevation of tissue flaps in order to get access to

the defect. All granulation tissue in the defect was

removed and the root surface was scaled and planed.

In order to enhance regeneration of bone, small perfo

rations were made with a bur at several sites of the

bone walls. The flaps were sutured to accomplish

complete coverage of the defect. Many clinical inves-

tigators have claimed that new attachment resulted

following this type of treatment but there is little

quantitative or qualitative documentation (Patur &

Glickmann 1962, Wade 1962, 1966, Ellegaard & Loe

1971, Yukna et al. 1976). Patur & Glickmann (1962)

reported a clinical study including 24 intrabony de-

fects treated according to the Prichard technique

(

1957a,b). The outcome was evaluated by comparing

preoperative and postoperative radiographs, meas-

urements of the alveolar bone level adjacent to the root

and study casts taken during operation and postop-

eratively after reflecting buccal and lingual flaps. The

authors reported that new attachment had occurred in

two-wall and three-wall intrabony defects but not in

one-wall defects. Results from a study by Ellegaard &

Loe (1971) comprising 191 defects in 24 patients with

periodontal disease indicated that complete regenera-

tion, determined radiographically and by periodontal

probing, had occurred in around 70% of the three-wall

defects, in 40% of the combined two-wall and three-

wall defects and in 45% of the two-wall defects.

In a later study by Rosling et al. (1976), 124 in-

trabony defects in 12 patients were treated by means

of the modified Widman flap procedure (Ramfjord &

Nissle 1974). Following treatment the patients were

recalled twice per month for professional tooth clean-

ing. Re-examination performed clinically and on ra-

diographs 2 years after therapy demonstrated bone fill

in two-wall as well as three-wall defects. The authors

suggested that this regrowth of bone was also associ

ated with the formation of new connective tissue at-

tachment and ascribed the successful healing mainly

to the optimal standard of oral hygiene which was

maintained in all patients during healing. A clinical

study with almost identical results was presented by

Polsen & Heijl (1978). The results of several histologic

studies in animals and humans, on the other hand,

indicate that formation of new periodontal attach-

ment is by no means predictable following subgingi-

val curettage or flap surgery (Listgarten & Rosenberg

1979, Caton & Nyman 1980, Caton et al. 1980, Steiner

et el. 1981, Stahl et al. 1983, Bowers et al. 1989a).

Grafting procedures

In a number of clinical trials and animal experiments,

the flap approach was combined with the placement

of bone grafts or implant materials into the curetted

bony defects with the aim of stimulating periodontal

regeneration. The various graft and implant materials

used so far can be placed into four categories:

1. Autogenous grafts:

Grafts transferred from one po-

sition to another within the same individual. This

type of graft comprises (1) cortical bone or (2) can-

cellous bone and marrow, and is harvested either

from intraoral or extraoral donor sites.

Alto ;eneic grafts: Grafts transferred between

geneti

cally dissimilar members of the same

species. (1) Frozen cancellous bone and marrow, and

(2) freeze

dried bone have been used.

3. Xenogencic grafts:

Grafts taken from a donor of an-

other species.

4. Alloplastic materials:

Synthetic or inorganic implant

materials which are used as substitutes for bone

grafts.

The rationale behind the use of bone grafts or alloplas

tic materials is the assumption that both the regrowth

of alveolar bone and the formation of new attachment

would be stimulated because these materials may

either (1) contain bone forming cells (osteogenesis), or

(

2) serve as a scaffold for bone formation (osteocon-

duction), or because (3) the matrix of the bone grafts

contains bone-inducing substances (osteoinduction)

(

Urist 1980, Brunsvold & Mellonig 1993). Such com-

plete regeneration of the periodontal attachment ap-

paratus following grafting procedures would imply

that cells derived from bone possess the ability to form

new cementum with inserting collagen fibers on a

previously periodontitis-involved root surface (Mel-

cher et al. 1987).

The value of using bone grafts or alloplastic mate-

rials for periodontal regeneration has mainly been

examined in case reports, while histologic evidence of

new attachment and controlled clinical studies is lim-

ited. The results from such reports vary and the docu

mentation presented usually consists of preoperative

REGENERATIVE PERIODONTAL THERAPY •

663

and postoperative probing attachment levels, radio-

graphic interpretations or re-entry procedures.

Autogenous grafts

Autogenous grafts (autografts) may retain some cell

viability and are considered to promote bone healing

mainly through osteogenesis and/or osteoconduc-

tion. They are gradually resorbed and replaced by

new viable bone. In addition, potential problems of

histocompatibility and disease transmission are elimi

nated with autogenous grafts. Autogenous grafts can

be harvested from intraoral or extraoral sites.

Intraoral autogenous grafts

Intraoral autogenous grafts obtained from edentulous

areas of the jaw, healing extraction sites, maxillary

tuberosities or the mandibular retromolar area were

commonly used in periodontal regenerative surgery

(

Mann 1964, Ellegaard & Loe 1971, Rosenberg 1971a,b,

Dragoo & Sullivan 1973a, b, Hiatt & Schallhorn 1973,

Froum et al. 1983, Stahl et al. 1983). Generally cancel

lous bone is preferred as graft material but cortical

bone, applied as small chips (Rosenberg et al. 1979),

or mixed with blood prior to the placement in the

defects (Robinson 1969, Froum et al. 1976), was also

reported to be effective in producing regeneration in

periodontal intrabony defects.

The effect of intraoral autogenous grafts has been

evaluated in both animals and humans. In a study in

monkeys, Rivault et al. (1971) observed that intrabony

defects filled with intraoral autogenous bone chips

mixed with blood (osseous coagulum) healed with

new bone formation, but no more bone was found in

such experimental defects than was observed in simi

lar control defects treated with surgical curettage.

Other studies in monkeys and dogs also failed to

demonstrate significant differences in bone formation

between grafted and non-grafted intrabony or furca-

tion defects (Ellegaard et al. 1974, Coverly et al. 1975,

Nilveus et al. 1978).

In clinical case-series where intraoral autogenous

grafts were used for the treatment of intrabony peri-

odontal defects, a mean bone fill ranging from 3.0 mm

to 3.5 mm was reported (Nabers & O'Leary 1965,

Robinson 1969, Hiatt & Schallhorn 1973, Froum et al.

1975). Hiatt & Schallhorn (1973) treated 166 intrabony

lesions with intraoral autogenous cancellous bone.

They reported a mean increase in bone height of 3.5

mm, evaluated by clinical measurements. One-wall,

two-wall and three-wall defects were included, and

the largest bone fill was observed in defects with the

highest number of bone walls. A block section ob-

tained from a patient treated in this study presented

histologic evidence of new cementum, bone and peri-

odontal ligament formation. In controlled clinical

studies, intraoral autogenous grafts were found supe

rior to surgical debridement alone in terms of bone fill

(Froum et al. 1976), or probing attachment (PAL) gain

(Carraro et al. 1976) in two-wall defects. However,

there are controlled studies that demonstrate more

modest results regarding bone fill or PAL gain after

intraoral grafting when compared to ungrafted con-

trols (Ellegaard & Loe 1971, Renvert et al. 1985).

Ross & Cohen (1968) reported new bone and ce-

mentum formation in a human histologic specimen

from an intrabony defect retrieved 8 months following

debridement and placement of intraoral autogenous

grafts. They also found that the grafts were without

osteocytes and that the deposition of new alveolar

bone had taken place around the grafts. Nabers et al.

(

1972) observed that new cementum and functionally

oriented periodontal ligament fibers were present in

half the length of a defect which was biopsied about

years after treatment with intraoral autogenous

bone grafts. In other human histologic reports, bone

fill and new attachment were observed coronal to

reference notches placed on the treated roots at the

apical termination of root planing (Hiatt et al. 1978) or

at the most apical level of previously existing calculus

(Froum et al. 1983, Stahl et al. 1983). Other investiga

tors, however, observed an epithelial lining which

occupied a varying portion of the previously diseased

part of the root (Hawley & Miller 1975, Listgarten &

Rosenberg 1979, Moscow et al. 1979). The results from

these studies indicate that the treatment of periodon

tal osseous defects with intraoral bone grafts may

result in periodontal regeneration, but not

predictably.

Extraoral autogenous grafts

Schallhorn (1967, 1968) introduced the use of auto-

geneous hip marrow grafts (iliac crest marrow) in the

treatment of furcation and intrabony defects. Later

several studies were published demonstrating the

osteogenic potentials of this material (Schallhorn et al.

1970, Schallhorn & Hiatt 1972, Patur 1974, Froum et al.

1975), and as much as 3-4 mm gain in crestal bone was

reported following the treatment of intrabony defects

with hip marrow grafts. The effect of iliac crest mar-

row and of intraoral cancellous bone grafts in one-

wall, two-wall and three-wall bony defects in humans

was evaluated by Patur (1974). He reported that bone

fill occurred to a varying extent with both types of

graft. The amount of bone fill in one-wall bony defects

was larger with iliac crest marrow than with cancel-

lous bone or when no grafts were used. Some defects

within all three groups showed bone fill, and no dif-

ference was observed between the control defects and

those treated with intraoral cancellous bone grafts.

The author stated that even with fresh iliac crest mar

row, bone regeneration is variable and unpredictable.

Healing of interradicular and intrabony lesions fol

lowing placement of iliac crest marrow was evaluated

in monkeys by Ellegaard et al. (1973, 1974). Regenera

tion occurred more frequently with the use of grafts,

but iliac crest marrow frequently resulted in ankylosis

and root resorption (Fig. 28-19).

Histologic evidence of periodontal regeneration in

humans following the use of iliac crest marrow grafts

was provided by Dragoo and Sullivan (1973a,b). At 8

months following therapy a mature periodontal liga-

664 • CHAPTER 28

Fig. 28-19. Photomicrograph illustrating an intrabony

defect 2 months following grafting with iliac crest mar

row. The defect is completely filled with bone, but new

cementum (c) is lacking on the root surface except for

the most apical part (n) of the defect. Note that anky-

losis and root resorption (arrows) are occurring in the

coronal part of the defect.

ment was present at the grafted sites and about 2 mm

supracrestal new attachment had also formed. Clini-

cal evidence of root resorption was noted in 7 of the

250 grafted sites.

Due to the morbidity associated with the donor site

and that root resorption sometimes results, iliac crest

marrow grafts are not used in regenerative periodon-

tal therapy today.

Allogeneic grafts

Allogeneic grafts (allografts) were utilized in attempts

to stimulate bone formation in intrabony defects in

order to avoid the additional surgical insult associated

with the use of autogenous grafts. However, the use

of allogeneic grafts involves a certain risk regarding

antigenicity, although, in order to suppress foreign

body reactions, the grafts are usually pretreated by

freezing, radiation or chemicals.

The types of allogeneic grafts used are frozen iliac

cancellous bone and marrow, mineralized freeze-

dried

bone grafts (FDBA) and decalcified freeze-dried bone

grafts (DFDBA). The need for cross-matching to

decrease the likelihood of graft rejection as well as the

risk of disease transmission virtually eliminated the

use of frozen iliac allogeneic grafts in periodontics.

FDBA is a mineralized bone graft, which through

the manufacturing process loses cell viability and,

therefore, is supposed to promote bone regeneration

through osteoconduction (Goldberg & Stevenson

1987). The freeze drying also markedly reduces the

antigenicity of the material (Turner & Mellonig 1981,

Quattlebaum et al. 1988). The efficacy of freeze-dried

bone allogeneic grafts (FDBA) was evaluated in a

study

which included 89 clinicians (Mellonig 1991). At

re-

entry surgery it was found that 67% of the sites

treated with FDBA alone and 78% of the sites treated

with FDBA plus autogenous bone grafts demon-

strated complete or more than 50% bone fill. Thus,

FDBA plus autogenous bone appeared more effective

than FDBA alone. In split-mouth studies where FDBA

was combined with autogenous grafts or tetracycline

powder (Sanders et al. 1983, Mabry et al. 1985), a

defect fill of 60% and 80% of the initial lesion was

reported. In a split-mouth study it was also shown that

FDBA implantation had a similar effect on defect reso

lution as that achieved by DFDBA (Rummelhart et al.

1989) or granular porous hydroxyapatite (Barnett et

al. 1989). However, the only controlled clinical trial

comparing treatment of intrabony defects with FDBA

implantation versus flap surgery failed to demon-

strate any difference in terms of clinical attachment

gain and bone fill between test and control sites at 1

year re-entry examination (Altiere et al. 1979). In ad-

dition, human histologic specimens demonstrated

that implantation of FDBA in intrabony defects

yielded no periodontal regeneration but resulted in a

long epithelial attachment on the previously diseased

root surface (Dragoo & Kaldahl 1983).

Several animal studies suggested that deminerali-

zation of a cortical bone allograft (DFDBA) enhances

its osteogenic potential by exposing bone morpho-

genic proteins (BMPs) which presumably have the

ability to induce host cells to differentiate into

osteoblasts (Urist & Strates 1970, Mellonig et al. 1981).

Several case reports presented clinical improvements

and bone fill after implantation of DFDBA into in-

trabony defects (Quintero et al. 1982, Werbitt 1987,

Fucini et al. 1993, Francis et al. 1995), and controlled

clinical studies documented considerable gain of at-

tachment and bone fill in sites treated with DFDBA as

compared with non-grafted sites (Pearson et al. 1981,

Mellonig 1984, Meadows et al. 1993). However, no

statistical differences regarding attachment level

changes and bone fill were found when comparing

sites treated with FDBA and sites treated with DFDBA

(Rummelhart et al. 1989).

Histologic evidence of regeneration following

grafting with DFDBA was provided by Bowers et al.

(

1989b,c). Complete regeneration with new cemen-

tum, periodontal ligament and bone amounting to

80% of the original defect depth was reported at sites

treated with DFDBA, which was considerably more

than that observed in defects treated with surgical

debridement alone. However, animal experiments