Human Clinical and Histologic Responses to the Placement of HTR Polymer Particles in 11 Intrabony Lesions* S.S. Skill/. S.J. Froum, ami D. Tamow ELEVEN INTRABONY PERIODONTAL LESIONS in five volunteer patients received surgical debridcmenl followed hy sile implantation of a porous paniculate polymeric composite i HTR polymer). These patients were observed over lime periods varying from 4 weeks to 2d weeks. At the end ol the individual observation periods, treated sites were surgically removed in block for histologic analysis. Clinical observations indicated a reduction in pocket depth following treatment which consisted of both gingival recession and gain in clinical closure. No untoward effects were observed clinically in any treated patient during the observation periods. Histologic responses varied from gain in closure by epithelial adhesion to new attachment of varying magnitude. Such varied responses were seen within the same patient and between patients. Graft particles were present at sites from 4 weeks to 2(S weeks after implantation and were surrounded by connective tissue capsules. At the periphery of some particles, limited bone formation was present. The alveolar bed was remodeling, at times surrounding specific particles. In our sample, HTR polymer, therefore, appeared to be a well tolerated synthetic graft material when implanted in human intrabony lesions../ Periodontol 1990;61:269-274, Key Words: Periodontal disease "surgery; periodontal pockets/surgery; bone regeneration; denial implants; biocompatible materials. Periodontal treatment goals include attempts at regeneration of lost attachment. This requires new cementum formation accompanied by newly inserted functionally oriented libers at a root site previously exposed to the oral environment. Intrabony lesions have shown such regenerative responses particularly when osseous grafts were placed into the debrided defect to enhance new attachment.1-2 Since human bone graft materials in limited, synthetic grafts have been devised to substitute and/or augmenl human bone material. Among such substitutes are particles composed of hydroxyapatites,- 1 tricalciuin phosphate4 and porous hydroxyapatites/-" In general, these synthetic bone substitutes have not enhanced new attachment, but rather served as well-tolerated fillers. The present series of case reports presents human histologic responses to placement of a non-resorbable, microporous, synthetic bone grafting material in intrabony lesions. The material combines a polymelhylmelhacratate, polyhydroxycthylmethacralalc (PHEMA) and calcium in a patented process which results in a biocompatible composite.7 'Department of Periodonlics, New York University, College of Dentistty, New York, NY. It is marketed as HTR polymer.t In our study HTR-4C was used exclusively. MATERIALS AND METHODS Eleven intrabony lesions in five volunteer patients (ages 33 to 61 years; 3 males and 2 females) were monitored clinically and historically to study the effects of HTR polymer implants on the healing of these lesions. All participants were in good health and every patient received an explanation of the study and signed an informed consent as part of the protocol requirements. Sites/teeth treated in this study were diagnosed as having a hopeless prognosis by an independent dental examination. All clinical measurements and surgical procedures were performed by the same periodontist (S.J.F.). Prior to surgery, initial therapy, oral hygiene procedures, temporary occlusal splinting (where mobility created patient discomfort), and similar cause-related therapy was performed, except at sites selected for HTR polymer implantation. Surgery was performed when the plaque control index was less than L0%. At that lime, radiographs and clinical photographs of tllTR Sciences, Norwalk, CT. © 1990 by the American Academy of Periodontology. 270 ( I.1NU \ l . A M ) I I I M O I ( ) « ; l ( K K S I ' O V S I N T O M I R P O L Y M E R J Periodonlol M i \ 1990 the site were taken. Clinical photographs were also obtained during the surgical procedures for pictorial documentation. Measurements Prior lo surgery and at least f> weeks after initial therapy, a horizontal notch was made in the root ai the level of the gingival margin using a 1/2 round bur. A vertical notch (steering groove) was placed in (he crown of the tooth at each study site to guide the positioning of the silver point used tor measurements. All measurements were made to the nearest 0.1 mm using an endodontic silver point, a locking plier, and a Boley gauge. The distance from the gingival notch to the base of the clinical pocket was then recorded as was the degree of tooth mobilily. Following flap reflection, a second notch was placed through the most apical extent of calculus at the involved root site and the following measurement obtained: I) Distance from calculus notch to deepest point of the osseous defect; ami 2) distance from calculus notch to crest of defect. The defect was also classified according to the number of osseous walls remaining. Surgical Procedure Alter obtaining local anesthesia, a full-thickness mueoperiosleal flap was elevated. After root,calculus notching, the lesion was then thoroughly debrided and measurements taken. Root planing was performed using ultrasonic sealers and hand instruments until ail visible root accretions were removed and the root surface felt smooth lo an explorer. Following inlramarrow penetration, (he site was overfilled with the porous graft material. The llap wall was then positioned as incisally as possible, ; nd complete closure was attempted. Interrupted silk sutures (4.0) were used and a periodontal dressing applied over the sutured site. All preand immediate post-surgical measurements, photographs, and radiographs were taken during this lime. Patients were then placed on penicillin 25(1 mg four times daily for Ml days. Ten to 14 days after graft placemen!, dressings and sutures were removed and the site lightly debrided and irrigated. All patients received weekly professional plaque removal of the surgical si(e for the first 6 weeks and then once every 2 to 4 weeks until the block was removed At the time of block removal, clinical photographs and radiographs were taken of the specific situs and pocket depth, recession, and gain in clinical closure were recorded using the gingival notch as the fixed point of reference. Upon block removal, all specimens were decalcified and prepared for histologic study. Step-serial, mesiodislally cut sections (N|j.) were prepared and selectively stained with hematoxylin-eosin and Mallory-trichrome stains. OBSERVATIONS For both clinical anil histologic observations, the reader niusi note that the data reflect case reports, rather than results of a controlled clinical study. The difficulties in obtaining human blocks for histologic analysis of treatment results limits the controlled trial approach. Hi us, the queslions to be answered by these cases are essentially: 1) What were (he clinical responses to this treatment modality? 2) Was I his material tolerated by (he host? 3) Were there predictable histologic responses? ami 4) Was new attachment par! of these histologic responses1.' Clinical As shown in Table I, preoperative pocket depth at the 1 I sites treated in this series ranged from 7.5 to 15.0 mm (average 4.(1 mm) and the inlraosseous depth ranged from 2.0 to 9.4 mm (average 3.5 mm). The osseous configurations were essentially one lo two wall lesions. Mobility varied from slight to severe (Miller classification). At the time of block removal, pocket depth ranged from 2.1 to 9.2 mm (average 4.d mm) and gingival recession ranged from 0 to 4.1 mm (average 3.0 mm). Gain in clinical closure ranged from 0.5 to 3.4 mm (average l.S mm) Mobility patterns v\ere not altered significantly. Clinical healing responses did not relate to length of observation time. Histologic Cast1 Report I. I'alienl A.A. had two -ales in which HTR polymer was placed. m24 and i!25. Table I records the I: ll't'K Polymer I'rt- iind Post-Surgical Clinical Undines :il Imphnii Silts Patient \..\ D.M. T.T. 1 S. 1 . . < . Average: Range: Age (YtNirs] 61 j | 51 Mi Ir.mh Sile(s) mlM d25 in 3 m 7 d K in 8 in <> d y ill IK m29 ml') Observation Period (weeks) 4 1 I I 18 is is iH 18 18 24 26 Initial Pockel Depth' 10.8 8.0 11.4 s.s 8.6 8.fi 8.2 8.2 7.5 8.0 15.II - > . i i 7.5-15.0 Initial ()>SL-IIUS Depth* 2.7 2.0 "V 2.3 2.4 l.\ i 2 2.8 v l 3.<i 9.4 3.5 2.0-9.4 Final Pockel IXpth 7.1 4.5 s.u 2.1 1,2 2.y 3.0 3.1 4.3 y . : 4.6 2.1-V.2 Final (jinjiiv;il Recession: 1.2 1 i 0.0 3.0 • I I L4 -.1 i 1 3 3.2 4.(1 3.1) 0.0-4.1 Gain in Clinical Closure* 0.5 0.6 3.4 3.4 3.4 | j 2.2 1.1 1.1 i . - [.« 1.8 Volume 61 \umhcr 5 STAHL, FROl M, TARNOW 273 Figure 8. Higher magnification of graft particles shown in Figure 6. Arrow pomts to tunned peripheral osteogenesis at a graft panicle. Orginial magnification, xM. Figure 10. Overview of site tmtfi shown in Figure <i 18 weeks after graft placement. No evidence t>( new attachment is seen. H&E stain. Original magnification. xIO. Figure v. Patient T. T. Oebrided lesions. observed in this patient (Table 1), three sites showed limited evidence of new attachment within the calculus notch area at times associated with root (dentin) resorption, and three sites presented no evidence of new attachment. The reason for this variaiion in healing responses could not be determined at this level of investigation. The clinical gains in closure as reported in Table I did not reflect specific histologic closure mechanisms found at the sites, nor did the longer observation periods indicate a more frequent incidence of new attachment to have taken place within the tested sites. COMMENTS As reported previously/ (he use of HTR polymer graft parlicles in human intrabony lesion led to gains in clinical closure. Similar clinical gains in closure have been reported by debridement alone and with the use of a variety of debridemenl and augmenting procedures.1' Histologically, the most significant eain in new attachment in the human mode) • . < • * • - Figure II. Overview of sue dl> shown in Figure 9 IX weeks after graft placement. Sole cementogenesh at base of notch. IIAE slam. Original magnification .xl (). 272 CLINICAL AND HISTOLOGIC RESPONSES TO HTR POI.VMKK .1 Periodonlol May I WO Figure V. Patient D. \t. Debrided lesion. Figure \ Patient l>. M, Radiogram oj site mX II weeks after wa placement. case was by long J.E. New attachmenl was not present ;md connective tissue encapsulated the particles. Case Ki'port 5. Palienl L.C. had one site (ml9) which was removed alter 2f> weeks. Closure at this site was by epithelial adhesion. Graft particles were found to be surrounded by new bone in some areas within this site. Summary of Ilislolagie Observations. Overall histologic responses demonstrated thai the HTR polymer graft particles were well tolerated by the host and caused no aberrant tissue responses. In most instances, the particles were surrounded by dense collagen and appeared well encapsulated. At times, active bone formation was seen to surround the collagen capsules. At graft peripheries, hone formation was seen occasionally. However, ihe primary question in using synthetic grafts is not whether they act as biocompalible fillers, but rather whether they enhance new attachment and increase bone mass. Histologically, the 1 1 specimens examined showed varying responses at the different sites. Such variations were Figure 6. Overview of histologic appearance of grafted site shown in Figure 4. II weeks after graft placement. \ote epithelial adhesion within calculus notch. Apical In notch, cementogenesis is seen adjacent to graft particle*. II & K smin. Original magnification, xlO. • -m Figure 7. Higher magnification <>( site shown in Figure 6. Note fiber insertion into newly formed cementum. Maflory- Trictirome stain. Original magnification, xM. seen between hosts, and at different sites within the same host. Thus, the clinical gain in closure noted in Table I, consisted of a long epithelial adhesion (J.E.) without evidence of new attachment in seven sites, and limited evidence of new attachment in four sites, 01' particular interest was the response variation within sites of the same host (Patient T.T.) which were removed at ihe same time (IS weeks post surgery). At the six sites Volume hi Number 5 SI AIM., I ROl \ l , TARNOW 271 clinical measurements al these sites. Figure 1 shows the sites debrided and Figure 2 demonstrates (he radiogram of the sites al I he lime of block removal 4 weeks after graft placement. Histologically. closure was by epithelial adhesion (long J . t . ) without evidence of new attachment (Fig. 3). Since marked recession look place, the gingival margin was located apical to the reference notch. (;isi- Report 2. Patient D.M. had one site in which HTR was placed (m3). Table 1 records the clinical measurements. Figure 4 shows the debrided lesion and Figure 5 is the final radiogram, taken at the time of Mock removal 1 I weeks after graft placement. Histologically, the calculus much shows epithelial adherence. Immediately apical to the notch, new cementum has formed adjacent to the graft particles (Fig. 6). The new cementum shows functional fiber orientation (Fig. 7). The particles are surrounded by collagen encapsulation and show bone formation at some of their peripheries (Fig. 8). 4 Case Report 3. Patient I . ! . had six sites in which HTR was placed, |m7, d8, m8, m9, d9, and mlO). They were removed IS weeks after graft placement. Table 1 records the clinical measurements, figure 9 depicts the debrided sites. Figure III shows site m8 in which no new attachment occurred. Closure was by epithelial adhesion which was present al the apical portion of the notch and extended apically. Graft particles were seen at the base of the defect and were surrounded h\ collagen. By contrast, site (.19 (Fig. II) demonstrated functionally oriented, connective tissue attachment to new cemenium in the apical portion of the notch (Fig. 12). Out of six sites observed in this patient, new attachment was seen within or adjacent to the notch in three. No new attachment was observed in the remaining three sites. Case Report 4. Patient J.S. had one site (m2lJ) which was removed 24 weeks after graft placement. Closure in this /•itiitiv 2. Patient -I A, Radiogram of w/c (d25), 4 weeks after graft placement. 1 Figure !. Patient A. I. Debrided lesion. iiguiT 3. Htnck section oj site shown in Figure 1 4 Kecks after graft placement. Closure occurred by epithelial adhesion llongJ.E.). No new attachment t>r significant oxteogenesis was seen. I! tV £ stain. Original magnification, .xl<<. 274 CLINICAL AND H1STOLOGIC RESPONSES TO HI R POLYMER J Periodontol May 1990 . 4 Figure 12. Higher magnification "I area of notch showing cementogenesis seen in Figure I. Fiber insertion inio ihc new cementum can be visualized. Original magnification, x64. has been demonstrated following ikbridement ;md use of human bone graft material.- Synthetic bone substitutes essentially have acted as biocompatible fillers" without evidence of new attachment associated with their use. Since our HTR polymer treated sites provided a gamut of healing responses, they do not allow tor definitive conclusions regarding the predictability of the histologic heating response following the use of this material. Therefore, we are not able to identify a possible "'causative" role played by HTR polymer in enhancing new attachment. This conclusion is particularly important, since human clinical and limited liislologic observations have reported gains in closure by methods ranging from epithelial delay/exclusion at the wound site,1"" to biochemical root treatments;12'13 to use of various grafting materials;1'-14 and to physical manipulation of the wound tissues.1''"' Since these techniques differ markedly from each other in biologic and clinical terms, and yet report gains in closure, we may conclude thai etiologic factors controlling closure and new attachment have not yet been identified. However, research identifying factors responsible for regeneration of periodontal attachment should lead to the development of clinically predictable techniques. Acknowledgments This study was supported in part by grants in aid from HTR Sciences, Norwalk, CT and the Claire and Melvyn Kaufman Institute for Periodontal Research, New York University, College of Dentistry, New York, NY The authors acknowledge with gratitude the ongoing technical assistance of Ms. Gloria Turner in the preparation of this and similar studies. REFERENCES 1. Bowers (iM, Schallhorn RG. Mcllonig JT. Histnlogk1 evaluation of new attachment in human intrabony defects. A literature review. J Periodontol 1982; 53:5(N. 2. Bowers ( i M , I hiidroff B, ( a r m vale R. el a l . H t s t o l o g k evaluation (it a n ew attachment a p p a r a t u s formation in humans, III. I Periodontal L988; 6 0 : 6 8 3 . 3. Froum SJ, Kushner I.. Scopp W, Siahl SS. Human clinical ami hislotogic responses lo Durapalite implants in inlruosseous lesions. ./ Periodontol 19K2: 53:719. 4. Si.ihl SA, Froum SJ. 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Ganles, B.. Garreii S. Egelberg J. Treatment of periodontal furcation defects. 11 Hone regeneration in mandibular Class II defects. J Clin Periodontol 1988; 15:232-234. Send reprinl requests to: Dr. Sigmund Stahl, New York University, David B. Kriser Dental Center. 345 F;aM 24th St.. New York. NY 10(11(1. Accepted for publication Novembei 4,