IITTE EINEMANN

RTH

Biomoterids 16 (1995) 1141-1148 0 1995 Elsevier Science Limited Printed in Great Britain. All rights reserved
014%9612/95/$10.00

Monocryl@ suture, a new ultra-pliable absorbable monofilament suture

Rao S. Bezwada, Dennis D. Jamiolkowski, In-Young Lee, Vishvaroop Agarwal, Joseph Persivale, Susan Trenka-Benthin, Modesto Emeta, Jogendra Suryadevara, Alan Yang and Sylvia Liu
Research and Development Division, Ethicon, Inc., P.O. Box 151, Somerville, NJ 08876-0151, USA

Synthetic absorbable sutures are available as braided constructions or as monofilaments. Braided absorbable sutures are made either from 9O:lO poly(glycolide-co-L(-)-lactide), sold by Ethicon, Inc. under the trade name Vicryl@, or from polyglycolide, as sold, for instance, by Davis and Geck under the trade name Dexon@. There are, however, some concerns with braided sutures that relate to tissue drag and the trauma this may cause, as well as the possible potentiation of infection through the interstices of the braid structure. Absorbable monofilaments, such as the monofilament sutures derived from p-dioxanone homopolymer (PDS IIa, an Ethicon, Inc. product), or a copolymer of trimethylene carbonate and glycolide (Maxor?, a Davis and Geck product), eliminate many of these concerns, but generally monofilaments do not handle as well as braids. This paper describes the research leading to the introduction of Monocryl (poliglecaprone 25) monofilament sutures, based on segmented block copolymers of &-caprolactone and glycolide. Monocryl sutures will be shown to display excellent handling properties, minimal resistance during passage through tissue and excellent tensile properties. These sutures provide an in vivo breaking strength retention of approximately 2030% after 2 weeks, considered by many to be the critical wound healing period. Absorption data on these sutures are presented; absorption is complete between the 91st and 119th days of implantation, with slight or minimal tissue reaction.
Keywords: Sutures, absorbable sutures, synthetic absorbable sutures, monofilament

Received 1 July 1994; accepted26 January 1995

Synthetic absorbable sutures are available as braided constructions or as monofilaments. Braided absorbable sutures are made either from polyglactin-910, a 90:lO copolymer of glycolide and lactide, sold by Ethicon, Inc. under the trade name Vicryl, or from polyglycolide, sold, for instance, by Davis and Geck under the trade name Dexon. Except for fine sizes, the monofilaments derived from these polymer systems are relatively stiff and, thus, mainly braided sutures are produced from polyglactin-910 and its variants. There are, however, some concerns with braided sutures that relate to tissue drag and the trauma this may cause. Consequently, braided sutures are generally coated to help minimize tissue drag. Other concerns with braided sutures include the possible potentiation of infection through the interstices of the braid structure. To eliminate some of the concerns of braided sutures, absorbable monofilament sutures, PDS II (a homopolymer of p-dioxanone; an Ethicon, Inc. product) and Maxon [a copolymer of trimethylene carbonate and glycolide; a Davis and Geck product) have been introduced2*3. Even though some advances have been made with these monofilaments, generally speaking, Correspondence to Dr R.!3. Bezwada.
1141

monofilaments do not handle as well as braids and further improvements in handling and package memory are desired. Although the natural absorbable suture, catgut, is still being used, it has several drawbacks, including low tensile strength and significant tissue reaction during the critical wound healing period. The latter causes non-uniform surgical performance. In order to overcome these shortcomings, a major research programme was initiated which led to the development of Monocryl (poliglecaprone 251, the most pliable synthetic absoibable monofilament suture marketed. These monofilaments are derived from a segmented copolymer of &-caprolactone and glycolide4. This complex polymeric system contains soft segments of a random copolymer of &-caprolactone and glycolide which provide good handling characteristics, and hard segments of polyglycolide which provide high strength. The hard and soft segments are combined in the same polymeric chain in such a way so as to lead to the unique properties of Monocryl. In this study, the in vivo characteristics of breaking strength retention, absorption, tissue reaction, as well as the pharmacokinetics and surgical functionality of Monocryl monofilament sutures, are described. These
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Monocryl suture, an absorbable

monofilament:

R.S. Bezwada

et al.

biological parameters, as well as certain physical and handling properties (i.e. strong initial strength, little or no tissue drag, good knot security), are considered important to surgical performance. Additionally, studies were conducted (but are not described here) to evaluate the toxicity potential of Monocryl suture and its components. In these studies Monocryl suture, or where appropriate, extracts thereof, were shown to lack genotoxic, cytotoxic, teratogenie, irritating or allergenic effects. The suture demonstrated no pyrogenic or haemolytic potential. Monocryl suture did not potentiate the development of bacterial infection in mice or interfere with the tissue defence to bacterial contamination.

MATERIALSANDMETHODS Polymer preparation

A prepolymer of s-caprolactone and glycolide was first prepared to give chains of a soft segment nature. In a second stage of the polymerization, more glycolide was added to create hard segments attached to the already-formed soft segments. The resulting polymer is a segmented block copolyester. The composition of the prepolymer, and its complete solubility in glycolide, as well as the final composition of the copolymer, were found to be the critical factors in obtaining strong pliable monofilaments. The overall optimum composition of the copolymer was about 25 mol% s-caprolactone and 75 mol% glycolide repeating units. The chemical formula of the segmented block copolyester is shown below:

prepolymer in the reaction flask. The temperature of the reaction mixture was raised to 230C to dissolve the prepolymer into the molten glycolide. After about 10min at 230C the copolymer looked uniform; the temperature of the reaction mixture was dropped to 200C and maintained there for about 2 h. The copolymer was isolated and ground. It was dried by heating for 16 h at 110C at a pressure of 0.1 mm Hg to remove any unreacted monomers. Total conversion was 99.6%. Proton nuclear magnetic resonance (lH NMR) was run at a field strength of 300MHz using a Varian Model XL-300 instrument. The solvent system used was hexafluoroacetone sesquideuterate-deuterobenzene. Mole fractions, as determined by NMR, of polymerized caprolactone, polymerized glycolide, unreacted caprolactone and unreacted glycolide were found to be 0.250, 0.746, 0.02 and 0.02, respectively. The copolymers were generally found to have complete solubility in only a limited number of solvents. The fluorinated solvents HFIP and hexafluoroacetone were found to be useful. The IV of the copolymer was 1.65 dig- (HFIP). Copolymers with weight average molecular weights between about 60000 and 100 000 (as determined by gel permeation chromatography, and corresponding to IVs of about 1.5-1.8 dig-) were found to be quite suitable for melt spinning. Large scale polymerizations were conducted using the general scheme presented above.

Filament preparation
Copolymers were melt spun into monofilament on a small scale using a In&on Capillary Rheometer as an extruder5. Copolymer to be extruded was packed in a preheated extrusion chamber and extruded through a 40 mil die (L/D 24.1) after a dwell time of 9-13 min at the extrusion temperature and a ram speed of 2 cm min- and shear rate of 213 s-l, While extrusion temperatures depended both on the polymer T, and on the melt viscosity of the material at a given temperature, extrusion of these copolymers at temperatures of about lo-50C above their melting point was often found satisfactory. The above described copolymer was extruded at a temperature of about 230C. The extrudates were generally taken up through an ice water bath at 24 ft min-, although other bath temperatures and take-up speeds were occasionally used. The extrudate filaments, often requiring up to 2 weeks at room temperature to crystallize, were subsequently drawn about x 5 to x 7 in multi-stage drawing processes in order to achieve molecular orientation and improved tensile properties. Large scale drawing was accomplished using industrial fibre spinning techniques. After cutting the strands to the required lengths, needles were attached. The sutures were then wound, put into folders and placed in aluminium foil-laminated packages. The sutures were sterilized with ethylene oxide, thoroughly degassed and sealed in a dry atmosphere.

Typical polymerization

scheme

Segmented copolymers of s-caprolactone/glycolide were made using the general scheme shown below for the polymer, with a 45:55 middle block and a 25:75 overall composition5. A flame dried, 250 ml, three-neck, roundbottomed flask was charged with 28.54g (0.250 mol) Ecaprolactone, 35.52g (0.306 mol) glycolide, 0.114ml distilled diethylene glycol (1.2mmol per mole of total monomer) and 0.0505 ml of stannous octoate (0.33 M in toluene, 60 0OO:l molar ratio of monomer:catalyst). The flask was fitted with a flame-dried mechanical stirrer and an adaptor. The reaction vessel was purged by evacuating the flask followed by venting with nitrogen; this was repeated three times. The reaction mixture, under a nitrogen pressure of 1 atm, was heated to 190C and maintained at this temperature for about 17 h with slow stirring. The conversion of monomer to prepolymer was over 99 mol%. The inherent viscosity (IV) of the resulting prepolymer was 1.44 dl g-l, as determined in hexafluoroisopropanol (HFIP) at 25C, at a concentration of 0.1 g dl-l. In the second stage of the polymerization, 51.54g (0.444 mol) of molten glycolide was added to the
Biomaterials 1995, Vol. 16 No. 15

Mechanical properties
Randomly selected strands from multiple lots of a given suture type and size were tested for physical and mechanical properties. The diameters of the sutures

Monocrvl

suture,

an absorbable

monofilament:

R.S. Bezwada

et a/.

1143

were measured in accordance with USP XXI16. Straight tensile strength, knot strength, elongation-to-break and Youngs modulus were measured on a constant rate-ofextension universal tensile testing machine with suitable clamps for holding the specimens firmly.

Gut sutures were determined; four lots of each suture were evaluated. The results obtained on dyed PDS II suture from another set of experiments are also reported; two lots of size 2-0 were tested. In these comparative studies, as before, eight suture strands per time period were tested for each lot.

Tissue drag
The frictional forces encountered -during passage through tissue werle estimated by recording the force required to pull 20cm of suture through the tissue at the rate of 30 cm min- using an Instron tensile testing machine. In this experiment, surgically prepared posterior dorsal rat skin was used. A square section of this tissue was stretched and mounted on a frame. The frame was mounted to a pulley device that was attached to the lower jaw of the tensile testing machine. A length of suture was attached to the upper jaw of the machine and then passed through the tissue guided by a set of pulleys. An appropriate minimum weight was attached to the end of the suture strand to just keep the complete suture strand assembly under tension. The In&on machine was activated and as the lower jaw moved down, the response at the suturetissue interface was recorded as a computer trace. The system recorded the real-time plot of force versus pulllength as the suture passed through the tissue.

Tissue reaction and absorption

Female Long-Evans rats used in the tissue reaction and absorption study were acclimatized, anaesthetized and prepared as described earlier for aseptic surgery. A midline incision was made on the skin over the sacral spine parallel to the vertebral column. Following retraction of the skin laterally, sterile suture strands were drawn into the right and left gluteal muscles. Two suture segments, each approximately 2 cm long, were implanted per muscle. The skin incisions were then closed and the rats retained up to 116 d. At the predetermined periods of in vivo residence, predesignated rats were killed by carbon dioxide asphyxiation. Gluteal muscles containing the implanted suture samples were excised, examined grossly and preserved in 10% buffered formalin fixative. A transverse section of each formalin-fixed sample was trimmed and processed for paraffin embedding, sectioning, and staining with haematoxylin and eosin. Histological examination of the implant sites was conducted using cross-sections 6pm in thickness. To assess absorption, the average cross-sectional area of the suture sample was calculated from suture diameters obtained with the use of an ocular micrometer. Data from the 3 day period were considered to represent 100% remaining and were used as such in calculating the median percentage suture area remaining at subsequent periods. The tissue reactions were quantitatively evaluated by using a modified method of Sewell and associates7. Table 1 details the histological grading and scoring system used.

Breaking strength retention

Female Long-Evans rats weighing between 250 and 300g were utilized. to evaluate the in tivo breaking strength of Monocryl suture (sizes 5-O to 1). The rats were each anaesthetized with an intraperitoneal injection of a mixture of ketamine hydrochloride (60 mg kg-l) and x:ylazine hydrochloride (10 mg kg-) and prepared for surgery by clipping the hair from the dorsal cervical area to the dorsal lumbosacral area. The skin of the clipped area was then scrubbed with an antiseptic solution. A small transverse skin incision (2 cm) was made in the dorsal subcutis of each rat, immediately posteri.or to the scapula. Suture segments, each approximately 10 cm in length, were implanted by grasping both ends of each with haemostatic forceps, inserting the forceps into the dorsal subcutis through the transverse skin incision, releasing the sutures and withdrawing the forceps. Two suture segments were implanted in each rat, one in the right and one in the left posteriodorsal subcutis. The skin wounds were closed and the rats retained for up to 3 weeks. At the end of scheduled test periods (typically i and 14 d), the appropriate rats were killed by carbon dioxide asphyxiation, The suture ,strands were carefully recovered following the transverse incision of the skin in the dorsoscapular area a.nd reflection of the skin posteriorly. For each size, multiple suture lots were evaluated; for each lot, eight suture strands per time period were tested for breaking strength on a calibrated In&on Universal Testing Instrument. The strength of unimplanted samples was determined similarly. The average breaking strength remaining was calculated as the percentage of the original, unimplanted strength. Pooled standard deviations were calculated. In a separate study, the breaking strength retention profiles of size 2-0 Monocryl, dyed Vicryl and Chromic

Table 1

Histological

grading

system

of tissue

reaction Weighting factor 5 3 6 2 1 1 1 1

Characteristic

Width of zone Overall cell density Neutrophils Giant cells Lymphocytes/plasma Macrophages Eosinophils Fibroblastslfibrocytes A sample Parameter

cells

score is completed Grade

as shown: Weighting factor 5 3 1 2 1 Score

Zone Cell density Macrophages Giant cells Fibroblasts Total

2 2 2 1 2

10 6 2 2 2 22

Each characteristic is assigned a grade of W based upon dimension or density. The grade is then multiplied by the weighting factor to obtain the final score. Adjectival ratings were assigned to the reaction scores within these limits: 0, none, l-8, minimal; g-24, slight, 25-40. moderate; 41-56, marked; greater than 56, extensive.

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Monocryl

suture, an absorbable
Physical property

monofilament:
comparison

R.S. Bezwada et al.

of size 2-O absorbable

Surgical finctionality
The performance of Monocryl suture for urocystotomy closure, gastrotomy closure, closure, hysterotomy small intestinal anastomosis, colonic anastomosis, vascular ligation (splenectomy, ovariohysterectomy), joint capsule closure (arthrotomy) and laparotomy closure was evaluated in Beagle dogs. Blood samples were obtained from all dogs for determination of clinical chemistry and haematology parameters the week before surgery and approximately 1 week postoperatively. In the urocystotomy study, urine samples were collected from all dogs during surgery and at necropsy. In all studies, vital signs body temperature, respiration rate) were (pulse, measured prior to surgery and daily for the first week postoperatively. Dogs were observed daily during the postoperative period for general health. Twenty-eight days after surgery, dogs were killed and a gross examination was performed.

Table 3 sutures

Material

Diameter (mils)

Straight-pull strength (psi) (lb) 16.14 10.77 9.07 15.28 91 100 70700 46700 103000

Knot-pull strength (lb) (psi) 8.11 7.37 4.51 7.97 45700 48400 23 200 54000

Elongation (%) 39 51 22 24

Monocryl PDS II Chromic

15.03
13.93 15.70 13.74

Vicryl

gut

Pharmacokinetics
A size Z-O, 14C-labelled Monocryl suture was prepared of [2,6-14C] caprolactone and from a copolymer glycolide. The synthesis of the [2,6-14C] caprolactoneglycolide copolymer and the preparation of the 14Clabelled Monocryl suture were conducted at Ethicon. [2,6-14C] Caprolactone was purchased from Du Pont NEN Products. A total of 64 rats was used in the study. A 31 inch suture was strand of the 14C-labelled Monocryl implanted surgically into the dorsal subcutis of each animal, immediately posterior to the scapular. The mean radioactivity per suture strand corresponded to 19.8 &i. Following the implantation of 14C-labelled Monocryl suture, a group of six animals, three per sex, was killed at weeks 1, 2, 3, 4, 6, 8, 9, 10 and 14. The remaining 10 animals, five per sex, were killed at the end of the study (week 16). Radioactivity levels in the blood and various tissues were measured by liquid scintillation counting. Urine, faeces and expired air were also collected from these animals, and the weekly output of radioactivity up to the time of killing was determined.

properties of size 2-O Monocryl suture are compared in Table 3 to the following commercial absorbable sutures: Vicryl, PDS II and Chromic Gut. Figure 1, a graphical representation of the tensile strengths of all commercial size 2-0 absorbable monofilaments, normalized for cross-sectional area, shows that Monocryl suture is the strongest of all the absorbable monofilament sutures. Suture stiffness is an important parameter that significantly influences the handling properties of a suture. Pliability or lack of stiffness is the quality of being sufficiently flexible or supple to accomplish surgical suturing, ligating or for knot tying. Suture stiffness can be calculated from the product of the suture area moment of inertia and the Youngs modulus of the material as obtained from stress-strain charts. The assumption was made that the suture materials were homogeneous throughout their crosssectional area. Table 4 shows the stiffness values calculated for Monocryl suture as compared to Maxon, Chromic Gut and PDS II suture. Maxon is 4.1 times as stiff as Monocryl suture; Chromic Gut suture and PDS II suture were found to be 3.8 and 1.4 times as stiff, respectively. The lower stiffness of. Monocryl suture, i.e. its pliability, results in excellent handling during surgical use with the added benefit of minimal out-of-package memory when compared to other sutures.

RESULTS AND DISCUSSION Mechanical properties

The physical property test results for size 2-O and 4-O Monocryl suture are shown in Table 2. The physical

//

Table 2 and 4-O Physical

Physical

properties

of Monocryl

suture,

sizes

2-O

I
/
YONOCRYL

property

Size 2-O 15.03 16.14 91100 8.11 45 700 39 113000

Size 4.0 8.55 6.76 117400 3.01 52 500 37 156000

Diameter (mils) Straight tensile strength (lb) Straight intrinsic strength (psi) Knot tensile strength (lb) Knot intrinsic strength (psi) Elongation (%) Youngs modulus (psi)

Figure 1 A graphical representation of strengths, normalized for cross-sectional commercial size 2-O absorbable monofilaments.

the area,

tensile of all

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R.S. Bezwada et al.

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Table 4 Handling characteristics monofilament sutures Suture Diameter (mils) 15.03 15.81 15.70 13.93 Youngs (psi) 113000 380 000 358 000 211000

of

size

2-O

absorbable
. MONOCRYL VICRYL

modulus

Stiffness (lb in2 x 104) 2.8 11.8 10.7 3.9

*Dyed

Monocr I@ Maxon J Chromic gut PDS II@

Tissue drag
The frictional forces produced by a suture during passage through tissue is an important consideration. Surgeons prefer a suture which can pass smoothly through tissue, minimizing tissue trauma. A rough strand presents considerable resistance during tissue passage, making it difficult to use as a continuous running suture. Synthetic monofilaments, because of their smooth surface, have less tissue drag compared to, for instance, braids, which have relatively high surface roughness. Even within the monofilament family, there may be considerable differences in smoothness. Figure 2, for example, compares the tissue drag characteristics of size 2-O Monocryl suture with a gut suture of similar size, demonstrating that the Monocryl suture passes through the tissu.e with greater ease.

WEEKS AFTER SUTURE IMPLANTATION

Figure 3 Average breaking strength of size 2-O Monocryl@, dyed Vicryl@, dyed PDS II@ and chromic cut sutures, as a function of implantation time in the subcutis of rats.

Breaking strength retention

The in tivo breaking strength retentions of various sizes of Monocryl suture are shown in Table 5. Fourteen days postoperatively, Monocryl suture retained approximately 20-30% of its initial tensile strength. The breaking strengih retention profiles of size 2-O Monocryl, PDS II, Vicryl and Chromic Gut suture are compared in Figure 3.

tissue reactions for Monocryl sutures were in the slight or minimal ranges throughout (Table 6), and were characterized primarily by the presence of macrophages and fibroblasts, fewer lymphocytes and plasma cells, small numbers of polymorphonuclear leucocytes and occasional giant cells (see Figure 4). These cells gradually diminished in concentration during the 119d study period. The absorption of Monocryl sutures was complete between 91 and 119 d.

Tissue reaction and absorption

Microscopic examination with tissue reaction grading was performed on all .slides of the implant sites. The

Table 5 In viva breaking Monocryl@ sutures Suture size

strength

retention

of various

sizes of

Mean breaking strength, 0 days (p.s.d.) (lb) 4.55 6.55 10.92 15.59 19.43 25.60 0.16 0.30 0.74 0.94 1.30 1.65

Mean breaking strength, 14 days (pad.) (lb) 1.19 1.45 2.81 3.86 4.85 6.20 0.15 0.22 0.25 0.58 0.55 1.08

l3sd
(%I
26.3 22.2 25.8 24.7 24.9 24.2

5-o 4-O 3-o 2-o 0 1

Pooled standard deviation. t Breaking strength retpntion.

Table 6 Median tissue reaction after intramuscular implantation

scores* in rats

for Monocryl@

sutures

Days postimplantation Size 0 5

10

Time to complete absorption 63 15 11.5 91 20 0 119 2.5 0 (d) 119 91

3 17 10

7 9 12.5

28 7.5 6

15

20

25

Pull Length
Figure 2 Monocryl@

(cm)
drag

2-o 6-O

A comparison of the tissue and gut sutures.

traces of size 2-O

Scores are as follows: 0, no reaction: l-6, minimal reaction; g-24, slight reaction; 2540, moderate reaction; 41-56, marked reaction; 56+, extensive reaction.

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Monocryl

suture, an absorbable

monofilament:

R.S. Bezwada et al.

Figure 4 Tissue reaction and absorption of size 2-0, dyed, monofilament Monocryl@ suture at 3, 7, 28,63, 91 and 119 d postimplantation. Haematoxylin and eosin stained paraffin embedded rat gluteal muscle. a, Monocryl suture at 3d surrounded by an irregular zone of oedema and inflammatory cells, primary macrophages and neutrophils, separating skeletal muscle cells. b, Monocryl suture at 7d with a minimal inflammatory reaction zone composed of macrophages and fibroblasts. c, Monocryl suture at 28 dwith a slight inflammatory reaction zone composed primarily of macrophages and fibroblasts with a scattering of eosinophils. d, Monocryl suture at 63d with a slight inflammatory reaction zone composed primarily of macrophages, fibroblasts, lymphocytes and plasma cells. e, At 91 d, the Monocryl suture has been completely absorbed. There is a slight inflammatory reaction zone composed of large, foamy macrophages centrally with fibroblasts, lymphocytes and plasma cells at the periphery. f, At 119d, the Monocryl suture has undergone complete absorption. There is a minimal inflammatory reaction composed of macrophages, fibroblasts, lymphocytes and plasma cells. a-f, Haematoxylin and eosin, original magnification x 150. Biomaterials 1995, Vol. 16 No. 15

Monocryl suture, an absorbable

monofilament:

R.S. Bezwada et al.

ii? 601 B 8

1147

Surgical functionality
Intraoperatively, Monocryl suture passed through the tissues with very little resistance. Knot security was felt to be very good based on the tactile feedback from the suture. All dogs recovered uneventfully from surgery without evidence of pain or discomfort. Body weights remained stable and no treatment-related changes in pulse rate, body temperature, respiratory rate or clinical laboratory values were apparent. Upon necropsy, all surgical incision lines were shown to be healing normally with no evidence of dehiscence.

50.

a. in urine

Pharmacokinetics
The absorption of the 14C-labelled glycolyl moiety in a glycolide-based copolymer suture was reported by Katz et ~1.~. They iround that at 22-24 weeks after subcutaneous implantation, nearly all of the radioactivity disappeared from the implantation site and appeared in expired air, urine and faeces. The present paper reports the results of a pharmacokinetic study carried out with radioactive Monocryl suture in which the caproyl moiety was 14C labelled. Figure 5 shows the absorption profile of this 14C-labelled Monocryl suture, as measured by the disappearance of radioactivity from the implantation site. There was an initial lag period of about 3 weeks. Thereafter, the radioactivity decreased linearly (zero-order kinetics) up to week 10. The radioactivity in the implantation site at week 10 corresponded to 5.6% and 9.4% of the implanted dose in males and females, respectively. By week 14, the radioactivity corresponded to 0.15% and 0.24% of the implanted dose in males and females, respectively. These results demonstrated that the Monocryl suture is absorption of 14C-labelled essentially complete 14 weeks after subcutaneous implantation. The radioactivity in the plasma reached peak levels at week 6, but completely returned to baseline levels at

a
a c B
8

WEEKS AFTER SUTURE IMPLANTATION

60
5om b. in expired air

* Yd* + Female

i
2 0

0:
0

10

12

14

16

WEEKS AFTER SUTURE IMPLANTATION

i.:

5
C

10

12

14

16

WEEKS AFTER SUTURE IMPLANTATION

WEEKS AFTER SUTURE IMPLANTATION Figure 5 Amounts of radioactivity in ihe surgical implantation site of rats, male and female as indicated, followin& subcutaneous implantation of C-labelled Monocryl suture. Expressed as the percentage of the total radioactivity dose administered per animal.

6 Cumulative amounts of radioactive output from rats following subcutaneous implantation of C-labelled Monocryl@ suture. Expressed as the percentage of the total radioactivity dose administered per animal. a, In the urine; b, in the expired air; c, in the faeces of the rat. Figure Biomaterials 1995, Vol. 16 No. 15

1148

Monocrvl suture, an absorbable monofilament: R.S. Bezwada

et al.

week 16. The tissue radioactivity reached peak levels at week 6 in the liver, kidney and testes, at week 8 in the brain, heart, lungs and spleen, and at weeks 8-10 in muscles, fat, lymph nodes, eye lenses and ovaries. Throughout the entire study period of 16 weeks, the radioactivity content in the tissues and organs was less than 0.75% of the total implanted dose. These results indicate that there was no unusual accumulation of radioactivity in the tissues and organs after suture implantation. Figure 6 shows the elimination profiles of radioactivity from implanted animals. Approximately 96% of the implanted dose (95.1% in males and 97.0% in females) was eliminated from animals within 14 weeks. Approximately 49% of the radioactivity was excreted in the urine (48.8% in males and 49.8% in females), 41% was recovered in the expired air (40.4% in males and 42.5% in females) and 5% was eliminated in the faeces (5.0% in males and 4.1% in females). The results indicate that the major routes of elimination of 14C-labelled Monocryl suture are urinary excretion and pulmonary elimination of 4coz.

sutures. The use of Monocryl sutures for urocystotomy, laparotomy, hysterotomy, intestinal anastomosis, gastrotomy, vascular ligation and joint capsule closure were satisfactory based upon the intraoperative, postoperative and necropsy results.

ACKNOWLEDGEMENTS The authors are deeply indebted to Dr Constance L. Ace for her NMR characterization of the polymers. The authors also wish to acknowledge the help of Dr Irene Nozad with this project.

REFERENCES
Craig PH, Williams JA, Davis, KW et al. A biological comparison of polyglactin 919 and polyglycolic acid synthetic absorbable sutures. Surg Gynecol O&et 1975; 141:1-10. Ray JA, Doddi A, Regula D, Williams JA, Melveger A.

Polydioxanone (PDS), a novel monofilament synthetic absorbable suture. Surg Gynecol Obstet 1981;153:497507.

CONCLUSIONS A new synthetic absorbable monofilament suture derived from a segmented copolymer of s-caprolactone and glycolide, Monocryl suture, is presented. The physical and biological properties of Monocryl suture are discussed. Monocryl suture possesses the highest straight tensile strength and best handling properties of all the available monofilament absorbable sutures. The in viva performance of the suture was evaluated for breaking strength retention, absorption, tissue reaction, pharmacokinetics and surgical functionality. Tissue reaction and absorption were assessed by intramuscular implantation of sizes 2-O and 6-O Monocryl suture into rats. The tissue reactions of the sutures were in the slight or minimal ranges and were of a foreign body nature. Absorption of the sutures was complete between 91 and 119 d. Multiple surgical procedures were performed in Beagle dogs to judge the surgical performance of the

Katz AR, Mukhejee DP, Kaganov AL, Gordon S. A new synthetic monofilament absorbable suture made from polytrimethylene carbonate. Surg Gynecol Obstet 1985;
161:213-222.

Sewell WR,. Wiland J and Craver BN. New methods of comparing sutures of ovine catgut with sutures of bovine catgut in three species. Surg Gynecol Obstet 1955: 100:483-494. Rodeheaver GT, Thacker JG, Owen J, Strauss M, Masterson T, Edlich RR. Knotting and handling characteristics of coated synthetic absorbable sutures. j Surg Res 1983; 35: 525-530.

Bezwada RS, Jamiolkowski DD. Segmented copolymers of &-caprolactone and glycolide for new absorbable monofilament sutures. Transactions of the Society of Biomaterials (Annual Meeting, 28 April-2 May 1993), XVI: 40. Bezwada RS, Jamiolkowski DD, Shalaby SW. Segmented copolymers of &-caprolactone and glycolide. US Patent 5,133,739, July 1992. Pharmacopeia of the United States, Vol. XXII. Easton, PA: Mack, 1989: 1614-1615.

Biomaterials 1995, Vol. 16 No. 15