Histologic reaction to four synthetic micro sutures in the rabbit*

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1 FERTILITY AND STERILITY Copyright e 1983 The American Fertility Society Vol. 4, No.2, August 1983 Printed in U.s A. Histologic reaction to four synthetic micro sutures in the rabbit* Luc o. Delbeke, M.D. t Victor Gomel, M.D.:j: Peter F. McComb, M.B.:j: Nazma Jetha, M.D.II Rijksuniversiteit Gent Akademisch Ziekenhuis, Gent, Belgium, The University of British Columbia, and Shaughnessy Hospital, Vancouver, British Columbia, Canada Histologic reaction to nylon, polypropylene, polyglactin-91, and polydioxanone microsutures was assessed in the uterine horn of the rabbit. At 24 days after insertion of the microsuture, a marked infiltration of histiocytes was seen around the nylon, polypropylene, and polydioxanone microsutures, whereas the reaction to polyglactin-91 was characterized by the presence of giant cells. At 8 days after insertion of the microsutures, the polydioxanone was almost entirely absorbed and the reaction to polyglactin-91o was minimal. Moderate histiocytic infiltration persisted around the nylon and polypropylene sutures. Fibrosis was also detected around the nylon and polypropylene sutures at 8 days, but not at all around the polydioxanone and polyglactin-91 sutures. We conclude that polydioxanone leaves little or no tissue reaction at 8 days in the uterine horn of the rabbit. Fertil Steril4:248, 1983 In this study, the histologic reaction to four synthetic microsutures was evaluated. The optimal properties required for a microsuture to be used in gynecologic infertility microsurgery are (1) tensile strength, (2) sterilizability, (3) lack of toxicity, and (4) degradation and/or absorption within a predictable and appropriate time span. 1 Received February 16, 1983; revised and accepted April 18, *Supported by the British Columbia Health Care Research Foundation. tdepartment of Obstetrics and Gynaecology, Rijksuniversiteit Gent Akademisch Ziekenhuis. :j:department of Obstetrics and Gynaecology, Faculty of Medicine, The University of British Columbia. Reprint requests: Dr. Peter McComb, Department of Obstetrics and Gynaecology, Grace Hospital, Vancouver, B.C., Canada V6H 3V5. IIDepartment of Pathology, Shaughnessy Hospital. It is essential that tissue reaction to the suture material be minimal so that any deleterious effects can be avoided. We undertook the present prospective study to evaluate the histologic reaction to four synthetic suture materials of 8- weight. This weight of suture was chosen because 8- suture swaged onto a taper-point needle 13 fj. in diameter is the suture used most widely in infertility microsurgery.2 We studied the histologic reaction to polypropylene (Prolene), nylon (Ethilon), polyglactin- 91 (Vicryl), and the new material, polydioxanone (PDS), all manufactured by Ethicon, Somerville, NJ; each was swaged onto a 13-fJ. taperpoint needle. Polypropylene and nylon are nonabsorbable sutures, whereas polydioxanone and polyglactin-91 are absorbable materials. Only polyglactin-91 is braided; the other three are monofilament sutures. 248 Delbeke et ai. Histologic reaction to synthetic microsutures Fertility and Sterility

2 Table 1. Tissue Reaction to Four Microsutures at 24 Days Rabbit no. Nylon Polypropylene Polyglactin-91 Polydioxanone Histiocytes Giant cells Histiocytes Giant cells Histiocytes Giant cells Histiocytes Giant cells /+ MATERIALS AND METHODS Four sexually mature female New Zealand White rabbits weighing 3.5 kg were caged individually under standard conditions 3 for 2 weeks before the onset of the study. Anesthesia was induced and maintained by intermittent boluses of sodium pentobarbital solution intravenously. The abdominal wall was depilated, and the bicornuate uterus was displayed through a lower midline incision. Under magnification (Zeiss OPMI 6SF operating microscope, Zeiss Oberkochen, West Germany), the four types of suture material were sewn in parallel rows, 5 mm apart, of continuous stitches over a 3-cm segment of each proximal uterine horn. The two rows of absorbable sutures were placed between the two rows of nonabsorbable sutures to facilitate later histologic localization. To place each stitch, the 13-j.L taper-point needle was passed through the serosa into the muscularis to exit 1.5 to 2 mm distally; this was repeated along the 3-cm segment. At the beginning and at the end of each row of stitches the suture was anchored with a threethrow surgical knot. The abdominal incision was then closed in two layers with interrupted stitches of 3- polyglactin-91. After 24 and 8 days, the left and the right uterine horns, respectively, were excised and fixed in formalin solution. The central 1.5-cm portion of the segment of uterus containing the four sutures was sectioned transversely in a serial fashion. A minimum of 12 representative sections per uterine horn were stained with hematoxylin and eosin. Additional representative sections from the 8-day specimens were stained by the van Gieson's technique and studied for evidence of fibrosis. In the 8-day sections, a polarizing microscope system allowed detection of even the tiniest remnant of absorbable suture. All the slides were examined concomitantly by the same two observers, and the histologic reactions were graded to according to (1) the degree of infiltration by mononuclear histiocytes, (2) the multinucleated giant cell reaction, and (3) the presence of fibrosis. The absence of any detectable histologic reaction or fibrosis was classified as O. Tissue reaction or fibrosis that extended into the surrounding tissue for a distance less than the suture diameter was classified as +, that extended the same distance as the width of the suture as + +, and that extended for a distance greater than the width of the suture material as RESULTS The findings are collated in Tables 1 and 2 and summarized in Table 3. MONONUCLEAR HISTIOCYTE REACTION Infiltration by mononuclear histiocytes is equally pronounced around both of the nonabsorb able sutures at 24 days (Figs. 1 and 2) and 8 days (Figs. 3 and 4). The infiltration is sparse around polyglactin-91 and polydioxanone sutures. Whereas at 24 days polydioxanone (Fig. 5) incites a more marked histiocytic infiltration than does polyglactin-91 (Fig. 6), the opposite occurs at 8 days (Figs. 7 and 8). Table 2. Tissue Reaction to Microsutures at 8 Days Nylon Polypropylene Polyglactin-91 Polydioxanone Rabbit no. Histio- Giant Fibrosis Histio- Giant Fibrosis Histio- Giant Fibrosis Histio- Giant Fibrosis cytes cells cytes cells cytes cells cytes cells Nsa NS NS NS NS NS NS NS NS NS NS NS /+ ano suture seen. Vol. 4, No.2, August 1983 Delbeke et al. Histologic reaction to synthetic microsutures 249

3 Table 3. Summarized Data from Tissue Reactions at 24 Days and 8 Days Histiocytes 24 Days Giant cells Nylon ++ Polypropylene ++ Polyglactin Polydioxanone ++ /+ 8 Days Histiocytes Giant cells Fibrosis + +/ /+ I GIANT CELL REACTION Abundant numbers of giant cells are seen with polyglactin-91, occasionally with polydioxanone and nylon but not polypropylene, at both 24 and 8 days. FIBROSIS Fibrous reaction is the hallmark of nonabsorbable suture materials but is absent with polyglactin-91 and polydioxanone suture remnants. ABSORPTION At 8 days polydioxanone was absent in all but one uterus (Fig. 7; rabbit 4), whereas polyglactin-91 remnants were found by polarizing microscopy in three of the four uterine horns. However, these remnants were completely fragmented and could not be detected by nonpolarizing light microscopy. Nylon and polypropylene suture materials persisted at 8 days in all rabbits. Although there is a general tendency to less histiocytic infiltration and to less giant cell formation at 8 days to all of the sutures, the absorbable sutures do incite less tissue reaction overall and specifically no detectable fibrosis. DISCUSSION Postlethwait 3 and Case and co-workers 4 observed that tissue responsiveness to the same suture material varied from animal to animal, and also between different tissues in the same animal. This 'Variability renders precise investigation of tissue-suture reaction difficult, especially in this case, where there is a relative lack of inflammatory response to any of the sutures. In the present study and in our previous investigation,5 we have minimized such inherent variability by standardizing the prevailing conditions. One further change that we have incorporated is the placement of a continuous suture rather than individual knotted stitches. The location of suture materials, even after absorption of much of the substance of the suture, has thus been far more easily determined. Furthermore, this technique avoids suture crowding and minimizes any possible effect on local blood flow and tissue metabolism. Despite our attempts to standardize, it is of interest that one animal (rabbit 4) mounted a greater tissue reaction (Figs. 7 and 8) to all suture materials, especially at 8 days. Despite the more evident tissue reaction that rabbit 4 exhibited to all four sutures, it is noteworthy Figure 1 Nylon suture at 24 days (H & E, original magnification, Figure 2 Polypropylene suture at 24 days (H & E, original magnification, x 18), 25 Delbeke et al. Histologic reaction to synthetic microsutures Fertility and Sterility

4 Figure 3 Nylon suture at 8 days (H & E, original magnification, Figure 6 Polyglactin-91O suture at 24 days (H & E, original magnification, Figure 4 Polypropylene suture at 8 days (H & E, original magnification, Figure 7 Polydioxanone suture at 8 days (rabbit 4) (H & E, original magnification, Figure 5 Polydioxanone suture at 24 days (H & E, original magnification, Figure 8 Polyglactin-91 suture at 8 days (rabbit 4) (H & E, original magnification, Vol. 4, No.2, August 1983 Delbeke et al. Histologic reaction to synthetic microsutures 251

5 that there was no fibrosis associated with the polyglactin-91 and polydioxanone sutures. Histiocytes are associated with simple phagocytosis, whereas giant cells are formed in an inflammatory area containing particulate matter too large to be phagocytized by a single mononuclear cell. The somewhat increased histiocytic infiltration around the polyglactin-91 and polydioxanone sutures at 24 days suggests active phagocytosis of these absorbable materials, culminating in a paucity of tissue reaction and especially a lack of fibrosis at 8 days. It is difficult to assess any possible deleterious effect that microsutures might have upon oviductal and ovarian function. However, it is reasonable to suppose that such adverse effects might be mediated by excessive tissue reaction. This study shows that polydioxanone leaves little or no tissue reaction at 8 days in the rabbit uterine model. These results warrant a human trial with this suture material. Acknowledgment. We thank Ethicon for the supply of suture materials. REFERENCES 1. Frazza EJ, Schmitt EE: A new absorbable suture. J Biomed Mater Res 5:43, Gomel V: Microsurgery in Female Infertility. Boston, Little Brown & Co., 1983, p Postlethwait RW: Rate of breaking strength loss of absorbable sutures in the stomach. Surgery 78:531, Case GD, Glenn JF, Postlethwait RW: Comparison of absorbable sutures in urinary bladder. Urology 7:165, Gomel V, McComb PF, Boer-Meisel M: Histologic reactions to polyglactin-91o, polyethylene and nylon microsutures. J Reprod Med 25:56, Delbeke et al. Histologic reaction to synthetic microsutures Fertility and Sterility

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