U s e of a h y d r o p h i l i c
as a root canal filling material Bernard H. Benkel, DDS; David W. Risinq, DMD; Lawrence B. Goldman, DMD" Herbert Rosen, DMD; Melvin Goldman, DDS; and Joseph H. Kronman, DDS, PhD, Boston
H y d r o n w a s u s e d a s a filling m a t e r i a l in the anterior teeth of m o n k e y s . T h e material s h o w e d that at p e r i o d s of 103 to 348 d a y s there w a s , in the m a j o r i t y of c a s e s , c o m p l e t e h e a l i n g of both vital a n d pulpless cases; biocompatibility with tissue; c o m p l e t e filling of all irregularities; a n d calcification of e x c e s s m a t e r i a l in the p e r i a p i c a l areas.
During the past few years several papers have been published that have detailed the complex anatomy of the prepared root canaP and the inadequacy of presently used root canal filling materials. '-',a These studies showed that there are many fins, lateral and accessory canals, and culde-sacs present in many endodonticatly prepared root canals, 1 and that guttapercha laterally condensed or used with chloroform or Kloropercha does not closely proximate the ultimate shape of the canal. 2,3 To fill these irregularities by using presently available materials, it is necessary to use a sealer. All endodontic sealers have been shown to be irritating when forced into the periapical tissues. 4-s
Great care is thus necessary to avoid overfilling with either the filling material or the sealer. With this in mind, we recently published a paper 9 histologically appraising three rubbery, biocompatible, plastic filling materials. Silastic 382 and Silastic Adhesive were well tolerated in the vital cases. In the pulpless cases with radiographic areas of periapical rarefaction, however, they seemed to interfere with healing. Hydron, on the other hand, showed biocompatibility and no interference with healing in either vital or pulpless cases. The present investigation is a further histologic study of Hydron, its biocompatibility, and its efficacy as a root canal filling material.
Methods and M a t e r i a l s Hydron," or poly (2-Hydroxyethyl methacrylate) (poly [HEMA]), is a gel based on products of the alcoholic reesterification Of methyl methacrylate with ethylene glycol. Polymerization of the mixture proceeds in an aqueous environment. The water content of the final polymer is constant for a given temperature and depends on the relative amount of water present during polymerization and the physical structure and number of cross-linkages present.
When the material polymerizes in the presence of water in the excess of its equilibrium capacity, a porous or spongy structure results because of the coalescence of water droplets into the intrapolymer channels. Conversely, when the material polymerizes in a relatively more anhydrous environment and it is subsequently placed in a more aqueous one, it will swell until the equilibrium water content level is reached. At that stage, it will remain dimensionally stable. Thus, Hydron is soft in tissue and hard under atmospheric conditions. The setting time is retarded by atmospheric oxygen, and, therefore, the material sets more rapidly in the canal than on the mixing slab. Working time varies from 8 to 15 minutes in the canal. This study involved the incisor teeth of six healthy, mature rhesus monkeys of the Macaca mulatta species. A total of 48 incisor teeth was selected for the experiment. The eight incisors of each monkey were overfilled with the experimental materials. Each monkey was premedicated With 1 to 2 m g / k g body weight of phencyclidine hydrochloride (Sernylan) and then anesthetized to a surgical level with 15 m g / k g body weight of pentobarbital sodium.
JOURNAL OF ENDODONTICS I VOL 2, NO 7, JULY 1976
A complete intraoral and radiographic examination was accomplished to evaluate the pulpal vitality of the teeth and the health of the surrounding 9oral tissues. In all cases the initial visual evaluation and study of the periapical radiographs indicated that the pulps were vital and that the oral tissues were not involved with any obvious pathologic condition. It was decided at the outset of the study that the pulps of four teeth of each monkey would be extirpated and the root canals left open to the saliva fluids for at least 60 days before treatment. These were randomly selected by using a table of random units. The pulps of all odd-numbered teeth were extirpated, and the even-numbered teeth were left intact temporarily. All those teeth in which the pulps were extirpated received the following treatment: access was achieved with high-speed burs, and a routine pulpectomy was performed. These teeth were left open to the oral fluids for at least 60 days or until there was obvious radiographic evidence of periapical pathologic change. All teeth then were treated endodontically. All endodontic procedures were performed in a manner that was routine for the investigator. Standard incremental instrumentation of both the vital and pulpless teeth was accomplished with endodontic files. Copious irrigation with 2.5% sodium hypochlorite was used throughout the preparation of the teeth to achieve the optimum canal debridement possible. Periapical radiographs were taken to ensure proper measurement. All canals were instrumented to at least a no. 40 file 1 mm beyond the radiographic apex of the tooth. The canals were overprepared in an effort to ensure that appreciable quantities of Hydron would be delivered through the apex into the surrounding periapical tissues, and to remove as much necrotic tissue as possible. The canals
were dried and the pulpless teeth medicated with camphorated monochlorophenol on a squeezed sterile cotton pledger, and then sealed with Cavit.t Vital teeth were similarly medicated with metacresylacetate. A b o u t one to four weeks after the canals were prepared, the canals were reentered, irrigated, and dried; all eight teeth in each monkey were filled with one of three experimental mixtures of Hydron that differed only in rheologic properties. H y d r o n was mixed on a glass slab with a metal spatula according to the manufacturer's directions. The material was delivered through a 1-cc disposable plastic syringe with a 25- or 27-gauge needle, with hand pressure. The teeth then were radiographed to ensure that appreciable quantities of Hydron were delivered into the periapical tissues. W a r m gutta-percha was used in an effort to deliver Hydron through the apex by using the gutta-percha as a pressure plug. The coronal excess of gutta-percha and Hydron then was removed, and a final filling of amalgam was placed. In addition, the pulps of four maxillary and mandibular premolars of two monkeys were extirpated six months before killing the animals; these teeth served as controls. After periods ranging from 103 to 348 days, the periapical areas of the teeth again were radiographed and the animals were killed. Surgical anesthetic doses of pentobarbital sodium were administered and maintained through an intravenous catheter with a saline drip. Block sections of the anterior areas of the maxilla and mandible were taken. The animals then were killed with excess pentobarbital sodium. Tissue blocks were immersed immediately in 10% neutral buffered Formalin in volumes at least 20 times in excess of that of the specimen. Individual teeth were separated from
the gross specimen, with 0.012-mm vertical cuts made by a water-cooled diamond-impregnated cutting wheel mounted on an electric lathe. Individual teeth also were immersed in 10% neutral buffered Formalin in volumes 20 times in excess of that of the specimen. All cutting of block sections into individual tooth sections was done within a half hour of the surgical removal of the specimen. Specimens were immersed in F o r malin for periods of 24 to 36 hours. They then were washed and decalcified in 25% citrated formic acid or ethylenediaminetetraacetic acid and then processed routinely. The specimens were mounted in paraffin blocks and serially sectioned from 5/zm to 7/xm. The sections then were stained with hematoxylin-eosin or Masson trichrome stain.
Results A t 103 to 165 days, Hydron was found to be biocompatible. Except for three cases there was a singular absence of inflammation, resorption of bone or cementum, or any other degenerative process. In all three cases cited, only mild inflammation was observed. In all of these necrotic tissue was observed in the apical area of the canal. There was no apparent difference between the vital and pulpless cases or between the 103- and 165day specimens. The periapical areas showed practically no inflammation except for occasional inflammatory ceils. The material that had been forced through the apex was extremely well tolerated at all time periods, and in most cases there was not even capsule formation (Fig 1). Although the material had been deliberately forced into the periapical tissue and periodontal membrane, there was no inflammatory reaction and it seemed to be quite inert (Fig 2). There were some collections of cells present with what seemed to be many
JOURNAL OF ENDODONTICS I VOL 2, NO 7, JULY 1976
Fig 3 - - P h a g o c y t i c cells (C) containing ]ine particulate matter. These cells abut normal - appearing bone (B) (H&E, orig X480).
Fig 1---Low-power view of apex (tl) and periapical area of vital case at 103 days. Hydron (H) is present in canal and is also distributed in periapical tissues (H&E, orig mag X40).
same lack of inflammation as the earlier ones. Areas that appeared to be Hydron in various stages of calcification were numerous (Fig 11). Invasion by fibroblasts and collagen fibers was more pronounced. Fig 2---Higher-power view of periapical tissue (PT) in intimate contact with Hydron (H) in vital case at 103 days. Inflammatory reaction or capsule absent (H&E, orig mag X 480).
small granules in the cytoplasm. They did not appear to be giant cells because there were discrete cell membranes and one nucleus (Fig 3). It is possible that this was a phagocytic response of fixed tissue histiocytes. Osteoblasts and osteocytes with the distinctive granular appearance aforementioned (Fig 3) were evident (Figs 4 and 5). This was indicative of new bone formation in these areas. The growth of new connective tissue was not hampered, and normalappearing fibroblasts appeared to be invading the collections of Hydron 198
(Fig 6). Sections through the periodontal membrane showed the presence of Hydron with no inflammatory reaction (Fig 7). The interface between the canal wall and the material was excellent, and in some cases granules appeared in the dentin adjacent to the canal wall (Fig 8). It was suspected that Hydron was in the dentinal tubules, and this was confirmed by staining sections with Masson trichrome stain. Hydron took a bluish green stain and was clearly evident in the dentinal tubules (Figs 9 and 10). The 348-day specimens showed the
Wichterle and Lim first described Hydron in 1960 (Nature 185:117, 1960). They were looking for an alloplastic material that could be safely implanted in tissue. Other materials such as methyl methacrylate were erratic in their tolerance because of the continued diffusion of low molecular weight substances from the polymer matrix, their impermeability to metabolites, and foreign body reactions to mechanical irritation. They postulated that a more suitable implant polymer would have a structure permitting more intimate contact with the host tissue, would have a water content similar to that of tissue, would be permeable to metabolites, and would be inert to biodegradation by normal or pathologic processes. Thus, the currently used poly (2~ methacrylate) evolved in an attempt to meet these requirements. Hydron has been severely tested for its alleged superior biocompatibility, with encouraging results. Dreifus 1~ performed cytotoxicity studies by using
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Fig 4 - - R o w of osteoblasts (0) on surface of newly formed bone (B). Granules (G) similar to those observed in Figure 3 can be seen in osteoblasts ( H & E , orig mag • 600).
Fig 6--One hundred three-day specimen. Section shows presence and/or invasion of fibrous connective tissues (CT) into accumulation of Hydron (H). No pathologic changes were noticed (H&E, orig mag • 480).
Fig 5--One hundred sixty-five-day specimen. Another example of normally aligned osteoblasts (0) in contact with freshly f o r m e d bone (B) (H&E, orig mag X 480).
small pieces of polymerized Hydron in a newborn rat's kidney cell culture and found no evidence of inhibition of cellular growth for periods up to three days. Barvic n conducted an exhaustive in vivo tissue tolerance study comparing 18 hard and soft polymethyl methacrylate or copolymer systems, including Hydron. He implanted the materials subcutaneously, intraperitoneally, and intramuscularly into rabbits and rats for periods from two weeks to three years. He noticed a uniformly innocuous tissue response to Hydron within 48 hours, and encapsulation by connective tissue elements on the third day. Because of Hydron's unique prop-
erties and alleged excellent tolerance by tissue, many potential medical applications of the material have been investigated, 12-14 showing uniformly innocuous responses. Other investigators 15-1r have described the pathogenesis of the implant and the early histologic picture. During the first days after implantation, the implant becomes surrounded by a thin, fibrous layer with occasional polymorphonuclear leukocytes. As these disappear from the implant area, collagen fibers and fibrocytes appear. By the 90th day the lesion has stabilized. The implant is surrounded by a fine, fibrous capsule consisting of collagen fibers arranged parallel to the implant margin. It may be vascular-
Fig 7--Pulpless case at 165 days. Hydron (H) present in periodontal membrane. Alveolar bone (B) is for orientation. No inflammatory changes were ob.~erved (H&E, orig mag • 199
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Fig 8--Hydron granules (HG) in dental tubules. Notice excellent adaptation o/ Hydron (H) to root canal wall (W) (H&E, orig mag •
Fig 9--Dentinal tubules containing Hydron (T). Hydron (H) also present in root canal (Masson trichrome, orig mag • 480). 200
Fig lO--Pulpless case at 348 days. Varying stages o/calcification are observed. Heterotropic bone (HB) and mature bone (MB) as well as Hydron (H) are all present (H&E, orig mag • 480).
ized, particularly during the earlier periods, after implantation. There is no giant-cell reaction and no deposition of calcium. Homogeneous or microporous material differs in its reaction from macroporous material. The capsule decreases as the porosity increases. Sprincl, Kopecek, and Lfm la showed that the vessels from the newly formed fibrous capsule penetrate into the implant at higher porosities. The higher the porosity is, tile greater the depth of cellulization and new capillaries and the greater the calcification. Winter and Simpson (Nature 223: 88, 1969) implanted Hydron sponge in the backs of 13-week-old large, white pigs and observed definite bone formation in 62 days; when implanted in rats, bone formed in six months. The new bone had sharply defined
borders and was lined by a layer of osteoblasts, is Winter and Simpson postulated that the few multinucleated giant cells that were seen were caused by the deposition of calcified salts and not the polymer. In this study a very similar reaction was observed (Fig 4). Although we could not show giant cells, there were bone formations in the early and later stages of calcification. Because earlier studies dealt with soft tissue, the presence of hard tissue has been considered undesirable. However, under the conditions of this s t u d y - - i n b o n e - - i t is a most desirable finding. Rubin and MarshalP 9 found that Hydron did not enhance the ingrowth of bone into Dacron for prosthetic anchorage in the knee, but they did observe bony incorporation of portions of Hydron. They said, "Hydron| sponge is capable of eliciting an unusual phenomenon of woven bone formation . . . which certainly requires further study. ''1:' The presence of many granules in the local histiocytes and in the osteoblasts and osteocytes have several interesting implications: - - N o w h e r e in the literature is there any description of a similar phenomenon. The material in this investigation contained barium sulfate to render it radiopaque. Material in all other studies did not contain BaSO~. Because the monomer is water soluble, and the polymer has extremely large molecules and is quite inert, one can speculate that the particles are BaSO4. Further investigations are being conducted to confirm this speculation. - - T h e particles do not interfere with normal cell function because the osteoblasts and the later osteocytes both contain the granules, giving evidence that normal bone formation proceeded undisturbed. - - T h e r e was no evidence of any degenerative or inflammatory changes in the vast majority of specimens.
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Fig l l - - V i t a l case at 348 days. Tooth instrumented and canal filled with Hydron (H). Dentinal tubules (DT) stained darkly with green material, w h i c h is H y d r o n (Masson t r i e h r o m e , orig mag • 480).
Fig 1 4 - - H y d r o n model of root canal space. Root canal has been filled with Hydron and tooth then was dissolved. Model obtained is pictured. Notice sharpness o/ /ins (F) and spurs (S), which accurately fill irregularities present (Orig mag •
Fig 1 2 - - V i t a l case at 103 days. Hydron filling in canal (H) and small mass of necrotic tissue (N) remaining at apex (A). Notice small area o/ in/lammation (INF) and abscess cavity (C) (H&E, orig mag •
Fig 1 3 - - T h r e e hundred forty-eight-day specimen. Control tooth: pulp was extirpated and canal was l e f t o p e n to o r a l fluids. Dentinal tubules (DT) stained lightly as compared to those in Figure 11. Hydron was not present in either canal or tubules. Pulp tissue debris (PTD) remains (Masson trichrome, orig mag • 480). --BaSO~ has no known toxicity. In all time periods and in vital and pulpless cases, the material was extremely well tolerated and the histologic picture showed zero to minimal inflammation, no degenerative changes, and normal periodontal membranes. Three teeth did show some periapical inflammation; however, this was closely related to necrotic tissue left behind in the canal (Fig 12). The material in the dentinal tubules was definitely shown to be Hydron. A single tissue block contained two
teeth. One tooth was a control; the pulp had been extirpated and the canal left open to oral fluids. It had not been instrumented or filled. The other tooth had been instrumented and filled with Hydron. Figures 13 and 14 clearly show the green-stained Hydron in the tubules in the one case and empty tubules in the other. This seems to indicate that Hydron may be an excellent canal filling material. Hydron
models (Fig 12) made according to the method of Davis, Brayton, and Goldman 1 clearly show the irregular space of the root canal and the close adaptation of the material to the walls of the canal. Hydron appears to be quite promising as a root canal filling material. However, if the canal is not thoroughly cleansed, a filling of Hydron will be no better than any other filling. 201
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A continuing study of the use of a soft, rubbery, hydrophilic, plastic mat e r i a l - - H y d r o n - - a s a filling was conducted with the use of anterior teeth of monkeys. The material showed that at periods of 103 to 348 days there was, in the majority of cases, complete healing of both vital and pulpless cases; biocompatibility with tissue; complete filling of all irregularities; and calcification of excess material in the periapical areas. *National Patent Developing Corp., New York. tPremier Dental Products Co., Philadelphia. Drs. Benkel and Rising are former graduate students in endodontics; Drs. L. B. Goldman and Rosen are clinical instructors in endodontics; Dr. M. Goldman is clinical professor in endodontics and director of postgraduate endodontics; and Dr. Kronman is professor in orthodontics, Tufts University School of Dental Medicine. l~.:~luestsfor reprints should be directefi to: Dr. Melvin Goldman, Tufts University School of Dental Medicine, 136 Harrison Ave, Boston, 02111. References
11 Davis, S.R.; Brayton, S.M.; and Goldman, M. The morphology of the
prepared root canal: a study utilizing injectable silicone. Oral Surg 34:642 Oct 1972. 2. Brayton, S.M.; Davis, S.R.; and Goldman, M. Gutta-percha root canal fillings. An in vivo analysis. I. Oral Surg 35:226 Feb 1973. 3. Goldman, M. Evaluation of two filling methods for root canals. J Endod 1:69 Feb 1975. 4. Guttuso, J. Histopathologic study of rat connective tissue responses to endodontic materials. Oral Surg 16:713 June 1963. 5. Rappaport, H.M.; Lilly, G.E.; and Kapsimalis, P. Toxicity of endodontic filling materials. Oral Surg 18:785 Dec 1964. 6. Spangberg, L. Biologic effects of root canal filling materials. Odontol Revy 20:(suppl) 16, 1969. 7. Seltzer, S.; Green, D.B.; Weiner, N.; and DeRenzis, F. A. scanning electron microscope examination of silver cones removed from endodontically treated teeth. Oral Surg 33:589 April 1972. 8. Erausquin, J., and Muruzfibal, M. Tissue reaction to root canal fillings with plastic cements. Oral Surg 29:91 Jan 1970. 9. Rising, D.W.; Goldman, M.; and Brayton, S.M. Histologic appraisal of three experimental root canal filling materials. J Endod 1:172 May 1975. 10. Dreifus, M.; Holeckova, E.; and Wichterle, O. Evaluation of hydrocolloid plastic substances on tissue cultures. Cesk Oftal 18:268 July 1962.
11. Barvic, M. Reaction of the living organism to the presence of acrylic allografts and possible carcinogenic effects of such grafts. Acta Univ Carol Med 8:707, 1962. 12. Kocvara, S.; Kliment, K.; Kubat, J.; Stol, M.; Ott, Z.; and Dvorak, J. Gelfabric prosthesis of the ureter. J Biomed Meter Res 1:325, 1967. 13. Singh, M.P. Hydron in the right antrum. Biomed Eng 4:68, 1969. 14. Tollar, M.; Stol, M.; and Kliment, L. Surgical suture materials coated with a layer of hydrophilic hydron gel. J Biomed Mater Res 3:301, 1969. 15. Sprincl, L.; Kope~ek, J.; Lim, D. Effect of porosity of heterogeneous poly (glycol monomethacrylate) gels on the healing-in of test implants. J Biomed Mater Res 5:447 Sept 1971. 16. Sprincl, L.; Kope~ek, J.; and Lim, D. Effect of the structure of poly (glycol monomethacrylate) gel on the calcification of implants. Calcif Tissue Res 13:63, 1973. 17. Sprincl, L.; Vacik, J.; and Kope~ek, J. Biological tolerance of ionogenie hydrophilic gels. J Biomed Mater Res 7:123 Jan 1973. 18. Winter, G.D. Heterotopic bone formation in synthetic sponge. Proc R Soc Med 63:1111, 1970. 19. Rubin, R.M., and Marshall, J.L. Porous hydrophilic polymer: good and bad news in the orthopedic application of cruciate ligament substitution. J Biomed Mater Res 9:375, 1975.