J Oral Maxillofac Surg 48:1305-1309 1990

Poly(L-Lactide) Implants in Repair of Defects of the Orbital Floor: An Animal Study FRED R. ROZEMA, DDS,* RUDOLF R.M. BOS, DDS, PHD,t ALBERT J. PENNINGS, MS, PHD,~ AND HENK W.B. JANSEN, MS, PI-IDS Because of the life-long presence of alloplastic, nonresorbable orbital floor implants and the complications of their use mentioned in literature, the use of a resorbable material appears to be preferable in the repair of orbital floor defects. A high-molecular-weight, as-polymerized poly(Llactide) (PLLA) was used for repair of orbital floor defects of the blowout type in goats. An artificial defect was created in the bony floor of both orbits. Reconstruction of the orbital floor was then carried out using a concave PLLA implant of 0.4-mm thickness. At 3, 6, 12, 19, 26, 52, and 78 weeks postoperatively, one goat was killed. Microscopic examination showed full encapsulation of the implant by connective tissue after 3 weeks. After 6 weeks, resorption and remodeling of the bone at the points of support of the implant could be detected. A differentiation between the sinus and orbital sides of the connective tissue capsule was observed. The orbital side showed a significantly more dense capsule than the antral side, which had a loose appearance. At 19 weeks, a bony plate was progressively being formed, and at 78 weeks, new bone had fully covered the plate on the antral and orbital side. No inflammation or rejection of the PLLA implant was seen.

Many authors have advocated surgery for traumatically induced defects of the orbital floor.‘-6 The main purpose of such surgery is to prevent the patient from having residual diplopia and enophthalmus. In the past, a variety of materials have been used to reconstruct defects of the orbital floor or to support the orbital contents. These include not only autografts, but also xenografts and allografts. The disadvantages of autografts are the additional operation required to procure these grafts and the risk of

rejection. One objection to the use of an allograft such as lyophilized human dura is the insufficient stiffness of the wet material, which can cause difficulties in bridging larger defects of the orbital floor.7~8 Alloplastic materials are popular today because of availability without an additional operation and their ease of use. The alloplastic implants commonly used are of the nonresorbable type. However, materials such as Silastic (Dow Corning, Midland, MI), Teflon (Dow Chemical Co, Wilmington, DE), methylmethacrylate, and polyethylene have been known to cause complications.9-” These include incidental cases of extrusion or migration of the implant, residual diplopia, infection of the foreign-body implant, dental abscess, or infection of the maxillary sinus. Considering the above mentioned complications and the life-long presence of these implants, the use of resorbable alloplastic material appears to be preferable. The resorbable implants should permit sufficient temporary support of the orbital tissues, es-

Received from the University of Groningen, The Netherlands. * Department of Oral and Maxillofacial Surgery. t Department of Oral and Maxillofacial Surgery. $ Department of Polymer Chemistry. § Department of Histology and Cell Biology. Address correspondence and reprint requests to Dr Rozema: Department of Oral and Maxillofacial Surgery, University Hospital Groningen. Oostersingel59.9713 EZ Groningen, The Netherlands. 0 1990 American

Association

of Oral

and Maxillofacial

Sur-

geons 0278-2391/90/4812-0010$3.00/O

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1306 pecially during the period of formation of scar tissue or new bone, but disappear after healing is complete. Resorbable alloplastic implants such as polylactic acid,” GeltXm,‘3 polyglactin,14 and polydioxanone (PDS) (Ethicon, Somerville, NJ) have already been used. However, these materials have certain disadvantages, such as rapid resorption, the bulkiness of the implant (up to 2-mm thickness), and inferior mechanical properties. Poly(L-lactide) (PLLA), a new material with improved mechanical properties, has been developed by Leenslag et al. l5 This PLLA has been successfully tested preclinically and clinically in the form of boneplates and screws for internal fixation of mandibular and zygomatic fractures.‘6-20 These favorable results have led us to undertake the present animal study to determine the suitability of high-molecular-weight as-polymerized PLLA implants for repair of orbital floor fractures of the blowout type. Materials and Methods PREPARATION

OF PLLA

IMPLANTS

The shape and dimensions of the implants were based on a study of the anatomical dimensions in the orbital region of both dried goat and human skulls. The implants, which were machined from a block of as-polymerized PLLA,” were concave, 0.4 mm thick, and 30 mm in diameter. Perforations of 2 mm diameter were made to allow tissue ingrowth (Fig 1). ANIMAL

STUDY

A total of 15 goats (European breed, 60 to 80 kg) were used. A study on dried skull collections showed that the goat has an orbital floor with a shape that closely resembles that of humans. After intravenous injection of diazepam (1 mg/kg body weight), glycopyrronium bromide (2 mg), and ketamine hydrochloride 10% (10 mg/kg body weight), intubation was performed and anesthesia was maintained using a nitrous oxide-oxygen-fluothane mixture supplemented with sufficient

ORBITAL FLOOR IMPLANTS

ketamine hydrochloride for relaxation (1,500 mg/500 mL saline, 20 to 30 drops/min). Both eye sockets were operated on using an inferior orbital rim approach. The orbital floor was exposed by incising and elevating the periosteum and an artificial defect, approximately 15 mm in diameter, was created in the bone and sinus epithelium with the aid of a blunt instrument and a rongeur. Care was taken not to damage the infraorbital rim. The orbital contents were allowed to prolapse in the maxillary sinus by perforating the supporting tissues using scissors. A concave implant of PLLA was adapted to the floor of the orbit, taking care that the entire defect was covered. Excess areas of the implant were trimmed with scissors. Just before the implant was inserted, the orbital contents that had prolapsed were repositioned. The implant was fixed to the infraorbital rim with one Dexon (Davis & Geck; Cyanamid, Seoul, Korea) resorbable suture. The wound was closed in layers with Dexon sutures. The operation on both eyes was identical. EVALUATION

OF HEALING

The goats were examined clinically, without measuring diplopia and enophthalmus. They were observed daily during the 1st week, and regularly thereafter. Photographs were taken at 1, 2 and 3 weeks postoperatively. At 3, 6, 12, 19, 26, 52, and 78 weeks postoperatively, one goat was killed using pentobarbital 200 mg/mL intravenously. After the orbital area was excised, it was quick-frozen and sawed in half sagittally through the lens and the artificially created defect. Photographs were taken of each half to record the position of the implant. After fixation in 4% formaldehyde, slices of the orbital region (5 mm) were dehydrated in graded series of ethanol and acetone and embedded in polyester resin. Sections were then made of the region comprising the orbit, periorbit, maxillary sinus, sinus roof, and the fractured area in a plane through the lens and the artificially made defect. After staining of the surface of the block with toluidine blue and basic-fuchsin, 30+m sections were cut with a Leitz 1600 diamond saw (Ernst Leitz, GNBH, Wetzlar, FRG) for light-microscopic evaluation. RemIts

FIGURE 1. Photograph of the PLLA implant. The implant has a glassy appearance.

MACROSCOPIC

FINDINGS

Macroscopic examination of the orbital halves showed that all intra- and periorbital structures were clearly visible, including a cross-section of the implant. The implant was still in place. It was cov-

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ered by a thin layer of fibrous tissue on both the orbital and the maxillary sinus side. From week 12, the orbital tissue covering the implant became somewhat thicker. The maxillary sinus side resembled the epithelial layer seen in a normal sinus. At week 26, 52, and 78, this situation appeared to be stable. No pathologic reactions could be seen. MICROSCOPICFINDINGS

The 3-week sample showed an implant fully covering the defect, totally encapsulated by loose fibrous tissue. No inflammation was seen. At 6 weeks, resorption and remodeling of bone at the points of support of the implant could be detected. The fibrous tissue capsule on the sinus side was very thin. On the orbital side, the capsule was slightly thicker. There was no sign of inflammation. In the 12-week sample, the orbital side showed a significantly more dense capsule than the antral side, which had a loose appearance. Also, ingrowth was observed in the perforations of the implant. Normal sinus epithelium containing goblet cells covered the maxillary sinus side. Capillaries were observed in the loose connective tissue. The number of layers of connective tissue was estimated at 30, with a total thickness of approximately 150 pm. Bone resorption was noted at the points of support of the implant. New bone was being formed, a thin layer of which just covered the outline of the implant. At 19 weeks, a progressive bony plate was found, which partially covered the implant from the border toward the center. This bony plate had been formed in apposition to the outer side of the fibrous connective tissue capsule. It was more prominent on the antral side than on the orbital side. In the perforations, new bone formation was also observed, arising from the antral side. At week 26, the antral side showed a mature connective tissue capsule. The whole implant, including the perforations, was covered with a layer of dense connective tissue. A thin bony plate was seen in apposition to this fibrous complex. In the perforations bone formation could be detected. The defect was healed and the maxillary sinus side was covered with pseudostratified epithelium containing goblet cells. Capillaries were observed in the subepithelial connective tissue (Fig 2). On the orbital side, a thin layer of dense connective tissue was observed. The adjacent orbital fat was normal in appearance. No inflammatory or foreign-body reactions were seen. The 78-week specimen showed a mature connective tissue capsule. New bone had now fully covered the PLLA implant on the antral and orbital

FIGURE 2. Photomicrograph showing the implant (P), fully encapsulated by connective tissue. A thin, newly formed bony plate is in apposition to this fibrous complex. On the bottom side, a layer of the maxillary sinus mucosa containing goblet cells can be recognized (arrows) (26 weeks; hematoxylin-eosin stain, original magnification x 16).

sides. The perforations in the implant also were filled with new bone. Both the orbital aspect and maxillary sinus side had a normal appearance. The orbital fat was also normal. The implant was still in place, with no visible changes (Fig 3). No intlammation or foreign-body reactions were seen (Fig 4). Discussion After 3 weeks, the orbital floor implant was totally encapsulated by connective tissue. Experiments on polymer implants in general, and also in the orbital floor region as reported in literature, showed similar encapsulation patterns. 12~14,18*21*22 As is generally accepted, the implant acts as a foreign body, causing irritation to the surrounding tissue. It is well known that any tissue damage causes a proliferative and reparative connective tissue response. In the first period of implantation, no substantial resorption of the implant occurred. Therefore, no disturbance in capsule formation took place. The formation of fibrous tissue eventually turns into encapsulation of the implant. Davilla et al23 and Matlaga et al” showed that the degree of encapsulation is directly dependent on the size, geometrical shape, and certain physical aspects of the implant. This makes the PLLA implant suitable for application in the orbital floor area. Our experiment has demonstrated that the tissue reaction to the PLLA implant is very mild, causing only a thin capsule of connective tissue. The degree of soft-tissue response can be in&t-

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ORBITAL FLOOR IMPLANTS

FIGURE 3. Photomicrograph showing a PLLA implant in situ 78 weeks after implantation. On the left side, the implant is completely embedded in newly formed bone. On the right side, one of the perforations is visible. Note the tearing artifact in the maxillary sinus mucosa due to cutting (hematoxylin-eosin stain, original magnification X 1).

enced by the surface texture of an polymer implant. Taylor and Gibbon? showed that surface texturing in polytetrafluoroethylene (PTFE) implants increased the number of giant cells and macrophages. The smooth surface of the PLLA implant did not attract giant cells and macrophages. The implant is fixed with only one suture to the infraorbital rim. During postoperative observation, and in the histologic findings, no signs of migration were found. Brown et alz6 observed an increased host-tissue reaction when an implant was mobile for a long time. The histologic examination did not show signs of increased tissue response. There was a striking difference between the tissue reaction on the orbital side, showing a dense appearance, and the loose connective tissue on the

FIGURE 4. High-power photograph of the interface of the PLLA implant. A thin layer of fibrous connective tissue (CT) containing spindle-shaped fibroblasts and collagen fibers is seen between the bone (B) and the implant (P). No signs of intlammation are visible (hematoxylin-eosin stain, original magnification x 160).

antral side. Sevastjanova21 described the biomechanical features that may influence collagen composition and appearance. Eye movement and gravity may be responsible for a more dense composition of the connective tissue covering the orbital side of the PLLA implant. The antral side has no load-bearing function, resulting in a loose connective tissue. After insertion, the implant was covered by periosteum. At 6 weeks, probably due to eye movement and loading of the implant, resorption and remodeling of bone at the points of support of the implant could be detected. Cutright and Hunsuck’* observed similar recontouring and osteoblastic activity using their fast-resorbing implant of compression-molded polylactic acid (PLA). At week 12, the PLLA implant showed new bone formation in apposition to the fibrous tissue capsule. The perforations were also filled with new bone. Both processes started on the antral side. Cutright and Hunsuck12 reported in a monkey experiment that PLA implants do not inhibit new bone formation at the site of the artificially made defect. In a study on osseous repair in discontinuity defects in dog mandibles treated with the copolymer of PLA:PGA (polyglycolic acid), Hollinger2’ showed that these fractures healed more rapidly than untreated defects. A linear increase of bony reparative elements was suggested, but this phenomena might be explained by the combination of the copolymer with a phospholipid. In our study it was difficult to determine the osteogenic or osteoconductive potential of the PLLA. For this purpose, a control side is needed to compare defects treated with PLLA implants with those left untreated. This study showed that in goats, the specially designed PLLA implant, of 0.4-mm thickness, gave sufficient support to the orbital tissue during healing. Histologic analysis showed encapsulation and new bone formation completely covering the im-

ROZEMA ET AL

plant. The PLLA was very well tolerated and did not give rise to any clinically detectable inflammatory or foreign-body reaction. At the end of the longest period of observation (78 weeks), the PLLA implants were not yet completely disintegrated. However, in vitro (phosphatebuffered aqueous saline solution) and in vivo degradation of PLLA samples performed in rats, sheep, and dogs showed a decrease of molecular weight (a,) and tensile strength (ub) up to 95% after 12 weeks. Loss of mass was observed from 26 weeks onward. 18,28Based on the animal studies, it can be estimated that the implant will be fully resorbed in about 3.5 years. It would be preferable to shorten this total resorption time, as the long presence of the implant may result in some of the same complications seen with nonresorbable implants. As clinical examination showed no complications in the healing process, the method of treatment appears to be well tolerated. The implant support was sufficient for the eyeball to assume a normal position. Considering the disadvantages of today’s implant materials, the high-molecular-weight, aspolymerized PLLA appears to have promise in the management of orbital blowout fracture. Acknowledgment The authors wish to thank Professor Geert Boering (head of the Department of Oral and Maxillofacial Surgery) for his ideas and stimulating help, and for critically reviewing the manuscript. The technical assistance of Adams B. Verweij (Department of Polymer Chemistry, University of Groningen) is greatly appreciated.

References I. Converse JM. Smith B, Obear MF, et al: Orbital blowout fractures: A IO-year survey. Plast Reconstr Surg 39:20, 1967 2. Crikelair GF, Rein JM, Potter GD, et al: A critical look at the “blow-out” fracture. Plast Reconstr Surg 49:374, 1972 3. van Herk W, Hovinga J: Choice of treatment of orbital floor fractures as part of facial fractures. J Oral Surg 31600, 1973 4. Hawes JM, Dortzbach RK: Surgery on orbital floor fractures. Ophthalmology 9Ck1066, 1983 5. Bleeker GM, van Ommen B: Early treatment of orbital fractures. Onhthalmoloaica 13840. 1959 6. de Man K: Fractures-of the orbital floor: Indications for exploration and for the use of a floor implant. J Maxillofac Surg 12:47. 1984 7. de Man K: Orbitabodemfracturen. Thesis, Utrecht, Antwerpen, Bohn, Scheltema & Holkema, 1982, p 61 8. Webster K: Orbital floor repair with lyophilized porcine dermis. Oral Surg 65161, 1988

1309 9. Mauriello JA, Flanagan JC, Peyster RG: An unusual late complication of orbital floor fracture repair. Ophthalmology 91:102, 1984 10. Sewall SR, Pemoud FG, Pemoud MJ: Late reaction to silicone following reconstruction of an orbital floor fracture. J Oral Maxillofac Surg 44:821, 1986 11. Mauriello JA, Fiore PM, Ketch M: Late complication of orbital floor fracture repair with implant. Ophthalmology 941248, 1987 12. Cutright DE, Hunsuck EE: The repair of fractures of the orbital floor using biodegradable polylactic acid. Oral Surg 33~28, 1972 13. Burres SA, Cohn AM, Mathog RH: Repair of orbital blowout fractures with Marlex mesh and gelftlm. Laryngoscope 91:1881, 1981 14. Holtje WJ: Wiederstellung von Orbitabodendefekten mit Polyglactin. Eine tierexperimentelle Studie. Fortschritte der Kiefer und Gesichts- Chirurgie Bd 28. Stuttgart, New York, Thieme, 1983, p 65 15. Leenslag JW, Pennings AJ: Synthesis and morphology of high-molecular weight poly-(L-lactide). Makromol Chem 188:1809, 1987 16. Bos RRM, Boering G, Rozema FR, et al: Resorbable Poly(L-lactide) plates and screws for the fixation of Zygomatic fractures. J Oral Maxillofac Surg 45751, 1987 17. Rozema FR, Bos RRM, Boering G, et al: Experimental fractures of the mandibular body of sheep and dogs. A new technique. Br J Oral Maxillofac Surg 27: 163, 1989 18. Bos RRM, Rozema FR, Boering G, et al: Degradation on and tissue reaction to biodegradable poly(L-lactide) for use as internal fixation of fractures. A study on rats. Biomaterials (accepted for publication) 19. Bos RRM, Rozema FR, Boering G, et al: Bone plate and screws of bioabsorbable poly(L-lactide). An animal pilot study. Br J Oral Maxillofac Surg 27:467, 1989 20. Bos RRM, Rozema FR, Boering G, et al: Bio-absorbable plates and screws for the fixation of mandibular fractures. A study in 6 dogs. Int J Oral Maxillofac Surg 18365, 1989 21. Sevastjanova NA, Mansurova LA, Dombrovska LE, et al: Biochemical characterization of connective tissue reaction to synthetic polymer implants. Biomaterials 8:242, 1987 22. Gerlach KL: Biologisch abbaubare Polymere in der Mund-, Kiefer-, Gesichtschirurgie. Tierexperimentelle Untersuchungen. Mtinchen, Wien, Hanser, 1988, p 77 23. Davilla JC. Lautsch EV, Palmer TE: Some physical factors affecting the acceptance of synthetic materials as tissue implants. Ann NY Acad Sci 146:138, 1968 24. Matlaga BF, Yasenchak LP, Salthouse TN: Tissue response to implanted polymers: The significance of sample shape. J Biomed Mater Res 10:391, 1976 25. Taylor SR, Gibbons DF: Effect of surface texture on the soft tissue response to polymer implants. J Biomed Mater Res 17:205, 1983 26. Brown JB, Fryer MP, Ohlwiler DA: Study and use of synthetic materials such as silicone and Teflon, as subcutaneous prostheses. Plast Reconstr Surg 26:264, 1960 27. Hollinger JO, Schmitz JP: Restoration of bone discontinuities in dogs using a biodegradable implant. J Oral Maxillofac Surg 45:954, 1987 28. Bos RRM, Rozema FR, Boering G, et al: In vivo and in vitro degradation of poly(L-lactide) used for fracture fixation, in Putter C de, Lange GL, Groot K de, et al (eds): Implant Materials in Biofunction. Advances in Biomaterials. ~018. Amsterdam, Elsevier, 1988, pp 245-250