Use of N-Butyl-2-Cyanoacrylate in Oral Surgery:Biological and Clinical Evaluation

*Mayra Perez, *Iraida Fernandez, *Daysi Marquez, and †Rosa Mayelın Guerra Bretana

*Clınica Estomatologica Docente de Bauta, Provincia Habana; and †Centre of Biomaterials of Havana University,Havanna, Cuba

Abstract: N-butyl-2-cyanoacrylate based tissue adhesive,Tisuacryl, was employed as a nonsuture method for closingwounds in oral surgery. One hundred thirty patients weretreated with the adhesive and 30 with suture. The surgicalprocedures were apicectomy, extraction of molars, andmucogingival grafting. The studied product was well tol-

erated by the tissue and permitted immediate hemostasisand normal healing of incisions. When Tisuacryl was usedas dressing material for donor sites and mucosal ulcer-ations, pain relief was observed. Key Words: Cyanoac-rylate—Tissue adhesive—Oral surgery.

Cyanoacrylate adhesives have been extensivelyused for closure of cutaneous wounds and in a widevariety of surgical procedures (1–6). Herod (7) haspublished a review of the uses of cyanoacrylates indentistry. More recently cyanoacrylates are beingused for preparation of drug-containing nanopar-ticles (8). Tisuacryl is a medical-grade tissue adhe-sive developed at the Centre of Biomaterials of Ha-vana University. N-butyl-2-cyanoacrylate and gentianviolet as a colorant basically compose this product.Tisuacryl was approved for clinical use at the begin-ning of 1996 and is becoming an increasingly popularmethod for closure of superficial lacerations underlow tension. The use of the adhesive reduces treat-ment time and is a pain-free method of closure, al-lowing good cosmetic results. More than 1,000 pa-tients were treated with Tisuacryl for the closure ofsurgical and traumatological cutaneous wounds dur-ing the last 3 years with no adverse reports. Theobjective of the present study was to assess the effi-cacy of Tisuacryl in the management of wounds inoral surgery.

MATERIALS AND METHODS

Tissue adhesiveN-butyl-2-cyanoacrylate is synthesized by a Kno-

venagel condensation of N-butyl cyanoacetate (Pro-bus, S.A. Badalona, Barcelona, Spain) with formal-dehyde (Probus, S.A. Badalona), in the presence ofa base catalyst, and using toluene as an azeotrope-forming solvent for removal of water from the con-densates. The reaction is followed by pyrolisis of theresulting polycyanoacrylate to obtain the reactivemonomer.

Biological evaluationFollowing the recommendations outlined by the

International Organization for Standards (ISO) forthe assay of material biocompatibility (9) for theclinical applications tested, the product is catego-rized as a medical device contacting with mucosalmembranes and breached surfaces. Assays for cyto-toxicity, genotoxicity, histotoxicity, skin and mucosalirritation and sensibilization, and systemic toxicitywere conducted to evaluate the biocompatibility ofTisuacryl.

Clinical study protocolsThe study was divided into two stages. In the first

stage, a prospective, randomized, controlled trial wasconducted with 60 patients, 30 in the experimentalgroup and the rest in the control group. In the sec-

Received August 1999.Presented in part at the 1st Latin American Congress for Ar-

tificial Organs and Biomaterials—COLAOB-98, held in BeloHorizonte, Brazil, December 10–13, 1998.

Address correspondence and reprint requests to Dr. Rosa May-elın Guerra Bretana, Centro de Biomateriales, Universidad de LaHabana, Habana 10400, Cuba. E-mail: biomat@comuh.uh.cu

Artificial Organs24(3):241–243, Blackwell Science, Inc.© 2000 International Society for Artificial Organs

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ond stage, 100 more patients were included only inthe experimental group.

The controlled trial was conducted in two institu-tions in Havana and Pinar del Rıo. Three physiciansof each medical institution participated in the study.The coordinator of the study trained all the physi-cians involved. The study included patients from 18to 65 years of age who came to the medical institu-tions for molar extractions or periapical surgery thatinvolved four or less teeth. Exclusion criteria in-cluded pregnancy, diabetes, cancer, and mental ill-ness. Informed consent was acquired for all patients,who were then randomly allocated in the 2 groups:experimental and control.

Surgical procedures were performed in the stan-dard manner in both groups. In the experimentalgroup, hemostasis was obtained, the edges of theincision were manually apposed, and the adhesivewas accurately placed in small drops covering 2–3mm in a lineal fashion, with care taken to not applyadhesive between the wound edges. Manual approxi-mation of the wound was maintained for 30 s toallow complete polymerization. The control woundswere closed with 3–0 suture by standard techniques.

All patients were asked to return if complicationssuch as infection, wound dehiscence, or abnormalpain developed. Follow up of the wounds was doneat two periods: during the first 30 min after the sur-gical procedure and 7–9 days later. The variablesassessed were hemostasis (immediate or mediate),dehiscence (yes or no), inflammation (normal or ab-normal), and infection (yes or no).

Three other medical institutions in Havana, San-tiago de Cuba, and Matanzas were included in thesecond stage of the study. The medical personnelwho entered at this stage were also previouslytrained. In this period, 100 patients between 15 and65 years of age who needed periapical, periodontalsurgery, or extractions were included. Oral ulcer-ations were also topically treated.

RESULTS AND DISCUSSION

The results of the biological evaluation ofTisuacryl were completely satisfactory, demonstrat-ing the similarities in the response of Tisuacryl withproducts commercially available in other countries(i.e., Histoacryl, Braun, Helsungen, Germany).Tisuacryl has no genotoxic activity over a Stock D-7of Saccharomyces Cerevisae, with genotype a/a ade2–40/ade 2–119 trp5–12/trp5–27 ile 1–92/ile 1–92, inconcentrations between 1 and 83 mg/ml of culture. Inthe skin irritation test performed on rabbits, no irri-tating response, erythematous reaction, or edema

was observed. In addition, the product did not pro-duce cutaneous sensitivity, systemic toxicity, or mu-cosal irritation. After implantation of material inpolymeric form on the rabbits’ spines, minimal toxiceffects in the surrounding tissue were observed.Moreover, the implantation of the monomer in vari-ous vascularized subcutaneous tissues produced aweak, transitory, inflammatory reaction that latercontinued with the reparative response with intensefibroblastic proliferation, and a complete and lateelimination of the material through the histocyticand giantocellular reaction.

The first 60 patients were enrolled in the clinicaltrial between February and April 1997. No patientwas lost from the follow-up. The 2 groups, Tisuacryland suture, had similar demographic characteristics(Table 1). There were differences between the 2groups only with respect to the immediate hemosta-sis. In the experimental group, complete hemostasiswas obtained immediately. In the control group,complete hemostasis was obtained only after 20–30min. A small amount of bleeding occurred during theremoval of suture, which caused brief discomfort.Differences in healing rates were not observed. Noadverse effects appeared in either group.

In the second stage of the study, 100 more patientswere included between September and December1997. In all the clinical procedures tested (Table 2),healing of wounds was very good, bleeding was rap-idly controlled, and no adverse effects were ob-served. Two Newman lineal incisions of more than 6cm were done. In those cases, less than 50% of thesuture needed in conventional methods was applied.

The main result of the present study is thatTisuacryl required much less time for initial hemo-stasis than suture. The treatment with the syntheticadhesive is also superior in the application ease. An-other advantage is the elimination of follow-up visitsand the discomfort caused due to the removal ofsuture. The adhesive flaked off entirely within 1week without causing any more tissue reaction thanthe normal healing response. Especially interestingresults were obtained in the fixation of mucogingival

TABLE 1. Characteristics of the 2 study groups in thecontrolled trial

Tisuacryl Suture

Patient characteristicsNumber 30 30Mean ± SD age in years 34.7 ± 12.5 32.9 ± 11.4Sex, %M 30 33

Surgical proceduresApicectomy, number 15 10Extraction, number 15 20

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grafts. The application of the adhesive seemed to beless time consuming and easier than suturing. Bleed-ing was also rapidly controlled.

As a protective covering of the donor sites andmucosal ulcerations, patient acceptance of the tech-nique was high because of pain relief and less eatingdiscomfort when the adhesive was placed over thedamaged tissue.

CONCLUSIONS

In this study, Tisuacryl was well tolerated by thetissue. Treatment with adhesive was, in general, com-parable with classical suturing. However, Tisuacrylis superior in the immediate hemostasis as well as

less time consuming, easier to apply than suture, andmore comfortable to patients.

REFERENCES

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2. Kamer FM, Joseph JH. Histoacryl: Its use in aesthetic facialplastic surgery. Arch Otolaryngol Head Neck Surg 1989;115:193–7.

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4. Quinn JV, Drzewiecki A, Li MM, Stiell IG, Sutcliffe T,Elmslie TJ, Wood WE. A randomized, controlled trial com-paring a tissue adhesive with suturing in the repair of pediatricfacial lacerations. Ann Emerg Med 1993;22:1130–5.

5. Quinn JV, Wells J, Sutcliffe T, Jarmuske M, Maw J, Stiell IG,Johns P. Randomized trial comparing octylcyanoacrylate tis-sue adhesives and sutures in the management of lacerations.JAMA 1997;277:1527–30.

6. Papatheofanis FJ, Barmada R. The principles and applica-tions of surgical adhesives. Surg Ann 1993;25:49–81.

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8. Fresta M, Cavallaro G, Giammona G, Wehrli E, Puglisi G.Preparation and characterization of polyethyl-2-cyanoacrylatenanocapsules containing antiepileptic drugs. Biomaterials1996;17:751–8.

9. International Organization for Standards (ISO 10993). Bio-logical evaluation of medical devices. Part 1. Guidance onselection of tests. 1992.

TABLE 2. Clinical characteristics of the patients in thenoncontrolled trial

Clinical characteristics

Patients characteristicsNumber 100Mean ± SD age in years 31.5 ± 14.5Sex, %M 45

Surgical proceduresApicectomies, number 32Mucogingival grafts, number 19Ulcerations, number 8Extractions, number 41

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