CHAPTER 2 LITERATURE REVIEW

Transcription

1 11 CHAPTER 2 LITERATURE REVIEW 2.1 INTRODUCTION Sutures are the most frequently used textile biomaterial for wound closure and tissue approximation as shown in the Figure 2.1. Sutures are used to close the cuts caused by injuries or to close the incision due to surgery and other medical procedures like wound approximation. They are commonly used on the skin, internal tissues, organs and blood vessels. This chapter deals with an exhaustive review of evolution of sutures, consumption of surgical sutures in India, classification of sutures, properties and different types of suture materials, antimicrobial sutures, suture manufacturing techniques and technical applications of sutures in wound closure. Figure 2.1 Wound Closed With Suture

2 EVOLUTION OF SURGICAL SUTURES The use of sutures for tissue approximation is the oldest and still the most common form of wound closure. The oldest known suturing material used on humans dates back to 1100 BC and the oldest known suturing material used on live human tissue dates back to 600 BC. These ancient sutures comprised of natural material such as linen, human hair, cotton, and flax and did not change until the 1800 s. Through the 1800 s and into the 1900 s rapid improvement and new materials were introduced into the field of sutures. By 1901, sutures could be found in the form of catgut and kangaroo gut kept in sterile glass tubes, gold and silver wire, silkworm gut, silk, cotton, linen, tendon and intestinal tissue from many forms of animals. The first synthetic sutures developed were non-absorbable sutures. These non-absorbable synthetic sutures are made from polymers such as, nylon, polypropylene, and polyester. The first synthetic polymeric sutures were developed around 1930 to create less tissue reaction, drag, and scarring. In 1960 work began on developing synthetic absorbable sutures using polymeric technology. The polyglycolic acid braided suture was introduced in the name Dexon and in 1970 it was accepted by the Food and Drug Administration (FDA) and released for general surgical use as the first polymeric absorbable suture material. In 1975, another absorbable material was introduced for surgical wound closure. This braided suture was chemically comprised of a lactic acid glycolic acid copolymer known as polyglactin. This suture later became known as Vicryl. The braided structure of Dexon and Vicryl has been found to provide sufficient wound holding characteristics. However, their structure can interfere with the healing process. Due to the negative characteristics of braided or sutures, synthetic monofilament absorbable sutures were created to combat these disadvantages (Black 1982).

3 13 In 1981, a new polymer called polydioxanone was introduced for surgical applications. It was a synthetic absorbable monofilament suture with improved handling capabilities and caused minimal tissue inflammation. In 1985, the newest form of a synthetic absorbable monofilament suture extruded from the polymer polytrimethlyene carbonate was introduced. It is claimed to provide the ultimate tensile strength of polydioxanone with improved handling characteristics. Recently antimicrobial sutures have received greater attention due to its unique properties. With a wide array of suture materials to choose from, it is increasingly important to understand the basic properties of sutures materials in order to make the most appropriate suture selection for wound closure. No one suture material is ideal. An ideal suture would be one that could be used under all circumstances in every operation. To date no one suture possesses all these attributes. Therefore compromises must be made in selecting a suture material (Pillai et al 2010). 2.3 CONSUMPTION OF SURGICAL SUTURES IN INDIA Medical textiles include all those textile materials used in health, hygiene, personal care and surgical applications. Materials used include monofilament and yarns, woven, knitted, and nonwoven fabrics, and composite structures. The numbers of applications are huge and diverse, ranging from a single thread suture to the complex composite structures for bone replacement, and from the simple cleaning wipe to advanced barrier fabrics used in operating rooms. The domestic consumption of medical textiles is expected to increase from Rs 1,514 crore in to around Rs 2,263 crore during Under meditech segment, surgical dressings accounts for over 50% of the total medical textile consumption, whereas surgical

4 14 sutures account for around 21% followed by contact lenses and artificial implants with shares of around 12% and 8% respectively. The non-woven fabric in disposables accounts for 2% and sanitary napkins account for 1.65%. In the medium term (next 5 years), the Medical textile industry is expected to achieve growth at the rate of 8-9% year on year. Sutures are absorbable or non-absorbable textile materials widely used in wound closure, to ligate blood vessels and to draw tissues together. Absorbable sutures are used mainly for internal wound closures and nonabsorbable sutures are used to close exposed wounds and are removed when the wound is sufficiently healed. The potential market for surgical suture industry in is estimated at Rs 415 crores from Rs 325 crores in The Table 2.1 shows the expected usage of sutures in India. In volume terms, the usage of surgical suture industry is expected to grow from million dozens in to million dozens in The usage of absorbable sutures and non-absorbable sutures are assessed at around 60% and 40% respectively. Further, the usage of non-absorbable sutures produced using silk accounts for 50 %, nylon 10 % and the remaining 40 % by other sutures such as polyester, polypropylene etc. The annual expenditure of hospitals on sutures has been increasing in the range of percent per annum on account of increased number of operations being performed and the rise in accident cases. Table 2.1 Expected Usage of Sutures in India Years Surgical sutures Quantity Value in Crores Production million dozens 330 Imports million meters 36 Exports 1.15 million dozens 41 Domestic Consumption million dozens 325 Domestic Consumption million dozens 415 Exports potential Data not available 72.3

5 15 The Indian suture market is dominated by Ethicon, division of Johnson and Johnson Limited which enjoys a long standing brand image and has introduced innovative product variants from time to time. It is estimated that around 60% of the market share is enjoyed by Ethicon, India and the rest of the market is ruled by other manufacturers namely Centenial surgical suture Limited, Mumbai, Futura surgicare private limited, Bangalore etc. India is importing non-sterile sutures from various countries. United States of America accounts for over 50-60% share followed by Korea with 30-40% and 5-10% each from China, Germany and Japan. Marginal imports also take place from United Kingdom, Italy, Singapore and Belgium. Mostly sutures are manufactured in India but their raw material is imported except for braided silk sutures and catgut. It is estimated that Bangladesh accounts for around 40-50% of the exports of sutures from India followed by Russia and Philippines with 15-20% share each. India also exports surgical sutures to Hungary, Netherlands, Spain, China, Singapore, Malaysia etc. Exports of surgical sutures are expected to reach a size of Rs 72.3 crores by the year by growing at a Compound annual growth rate of 12%. 2.4 CLASSIFICATION OF SURGICAL SUTURES Wound closure using suture materials is an integral part of the surgical process. Sutures are textile biomaterials widely used in wound closure, to ligate blood vessels and to draw tissues together. Sutures consist of a fibre or fibrous structure with a metallic needle attached at one of the fibre ends and they can be broadly categorized according to their origin, the physical configuration and the spontaneous degradation.

6 Type of Material Based on Origin Natural suture materials are based on natural polymers derived from animals or plants. Manmade suture materials are produced from synthetic polymer by various fibre spinning techniques such as melt, dry, wet and dry-jet-wet spinning process Based on Physical Configuration Suture materials are available in both monofilament configuration. and Monofilament A monofilament with its smooth surface can only be made from synthetic material by polymer extrusion method. The important property of the monofilament is a minimal tissue reaction. This is because of monofilament smooth surface. Also the monofilament suture does not allow any bacteria to survive as compared to sutures. It is also easy to make or place a knot in the depth of the body. However, because they have relatively higher bending stiffness and the tendency to untie, it is hard to deal with it and to form stable knot. In addition, their stiff cut ends could irritate mucosa and cause ulceration (Kim et al 2007) Multifilament Multifilament yarns can be twisted together to form a braided sutures. To form a braided suture, in general, eight to sixteen monofilament yarns are to be used. Obviously, due to the manufacturing method, the braided sutures have rough surface which causes tissue drag to be high. A lubricant is applied on the surface of braided suture material to lower the tissue drag and allow better knotability. Braids are also flexible and easy to

7 17 handle as compared to monofilament sutures. But, their braided structure could offer nidus for food debris or bacteria, which can be a latent infection source (Kim et al 2007). Polyesters, polyamides and silks are commonly used for manufacturing braided sutures Based On Spontaneous Degradation Sutures can also be according to their degradation properties. Sutures that undergo rapid degradation in tissues, losing their tensile strength within 60 days, are considered as absorbable sutures. Sutures that generally maintain their tensile strength for longer than 60 days are non-absorbable sutures (Karaca et al 2005) Absorbable sutures Absorbable sutures may be used to hold wound edges in approximation temporarily, until they have healed sufficiently to withstand normal stress. These sutures are prepared either from the collagen of healthy mammals or from synthetic polymers. They may also be impregnated or coated with agents that improve their handling properties, and colored with a FDA approved dye to increase visibility in tissue. Natural absorbable sutures are digested by body enzymes which attack and break down the suture strand. Synthetic absorbable sutures are hydrolyzed a process by which water gradually penetrates the suture filaments, causing the breakdown of the suture's polymer chain. Compared to the enzymatic action of natural absorbable suture material, hydroxylation results lesser degree of tissue reaction following implantation. During the first stage of the absorption process, tensile strength diminishes in a gradual, almost linear fashion. This occurs over the first several weeks post implantation. The second stage often follows with considerable overlap, characterized by loss of suture mass. Both stages exhibit leukocytic cellular responses which serve to remove cellular

8 18 debris and suture material from the line of tissue approximation. The loss of tensile strength and the rate of absorbtion are separate phenomena. A suture can lose tensile strength rapidly and yet be absorbed slowly or it can maintain adequate tensile strength through wound healing, followed by rapid absorption. In any case, the strand is eventually completely dissolved, leaving no detectable traces in tissue. Although they offer many advantages, absorbable sutures also have certain inherent limitations. If a patient has a fever, infection, or protein deficiency, the suture absorption process may accelerate, causing too rapid a decline in tensile strength. In addition, if the sutures become wet or moist during handling, prior to being implanted in tissue, the absorption process may begin prematurely. Similarly, patients with impaired healing are often not ideal candidates for this type of suture. All of these situations predispose to postoperative complications, as the suture strand will not maintain adequate strength to withstand stress until the tissues have healed sufficiently (Chu 1997) Non-absorbable sutures Non-absorbable sutures are those which are not digested by body enzymes or hydrolyzed in body tissue. They are made from a variety of non- biodegradable materials and are ultimately encapsulated or walled off by the body s fibroblasts. Non-absorbable sutures ordinarily remain where they are buried within the tissues. When used for skin closure, they must be removed postoperatively. Non-absorbable sutures may be used in a variety of applications: Exterior skin closure, to be removed after sufficient healing has occurred. Within the body cavity, where they will remain permanently encapsulated in tissue.

9 19 Patient history of reaction to absorbable sutures, keloidal tendency or possible tissue hypertrophy. Prosthesis attachment. Non-absorbable sutures are composed of single or multiple filaments of metal, synthetic, or organic fibres rendered into a strand by spinning, twisting, or braiding. Each strand is substantially uniform in diameter throughout its length, conforming to the United States Pharmacopeia (USP) limitations for each size. Non-absorbable sutures have been classified by the USP according to their composition. In addition, these sutures may be uncoated or coated, uncolored, naturally colored, or dyed with an FDA approved dye to enhance visibility (Chu 1997). 2.5 PROPERTIES OF SURGICAL SUTURES materials. The following section discusses the various properties of suture Tensile Properties Among the tensile properties tenacity and knot strength have been identified as critical for secured suturing. Tenacity of suture is important for the practitioner making a knot. If the material is too weak and the knotting force is stronger than tensile strength of suture material, suture can easily break while tightening the knot. Therefore it is essential to know the tenacity of sutures. The tensile strength of a material is determined by the weight required to break a suture divided by its cross-sectional area. In selecting sutures, it should be noted that the tensile strength of a suture need not to exceed that of the tissue it is securing.

10 20 Knot strength is a measure of the amount of force necessary to cause a knot to slip and is directly related to the coefficient of friction of a given materials. For a braided structure, the coefficient of friction is higher because the threads in the braids have mobility, which increases the knot holding capacity. Therefore, there is no knot untying before the break for the braided structures. Monofilament sutures however have very smooth surfaces, which allow them to pass easily through the tissue. At the same time, it decreases the knot holding capacity (Bayraktar et al 2001) Suture Size The size of a suture refers to its diameter and can be expressed in code numbers by two different standard systems such as the United States Pharmacopoeia system and the European Pharmacopeia (EP) system. A small range of suture diameters is permitted for each code, as shown in Table 2.2. In the USP system, the code of non synthetic absorbable sutures is different from that of non-absorbable sutures and synthetic absorbable sutures even though they have the same allowable range of diameters. In the EP system, the code numbers range from 0.1 to 10 mm as the diameter of the suture increases and there is no differentiation of synthetic absorbable from non synthetic absorbable sutures. The tensile strength of the suture material increases with the increase in suture size. When sutures are selected, the suture should be as small as possible to minimize the amount of material drawn through the surface of the tissue as well as inside the body. In addition, the amount of foreign material should be as small as possible to minimize complications. An increase in suture size leads to a large increase in knot volume. Therefore, small sutures are desirable if other requirements have been met (Dumitriu 2002).

11 21 Table 2.2 Suture Size Classification Non synthetic absorbable materials USP size codes EP size codes Suture diameter (mm) Non absorbable and synthetic absorbable materials Absorbable and non absorbable materials Minimum Maximum - 11/ / / / /0 07/ /0 06/ /0 05/ /0 04/ /0 03/ /0 02/ / Memory Memory refers to the inherent tendency of a suture material to return to its original shape after being manipulated and is a reflection of its stiffness. A suture with a high degree of memory is stiffer, more difficult to

12 22 handle and more likely to become untied compared with suture material that has less memory Stiffness Stiffness of the suture material determines its handling characteristics, strength of knot and knot security. If stiff suture is used to form small loop, it may results in improper approximation of wound edges for its tendency to spring back. Stiff suture is difficult to tie and to put knot, the knot may not stand for long time, may cause disruption of wound, mechanical irritation, and wound edges may get apart. Stiffness value decreases with reduced suture size. Geometric form is the most important factor in determining the stiffness of a suture. Monofilament sutures are always stiffer than braided suture. Although coating of suture facilitates the smooth passage of suture through tissues, but it results in stiffness than the uncoated one. The polymeric coating forms a thin film over the surface of suture, fills the interstices between the fibres and yarns, and forms bond among the fibres resulting higher stiffness to the suture (Chu 2002) Coefficient of Friction The friction between the tissue and the suture and between sutures influences tissue drag and knot strength as well as knot security. A higher coefficient of friction benefits knot security, resulting in a more secure knot. But at the same time, it is problematic at the knot snug down because it may take more time and energy to tie a knot. Furthermore, a higher coefficient of friction increases tissue drag, which may result in more traumatic wounds and a more severe inflammation response. Sutures with special surface coatings generally gave lower values than did the sutures without any such coatings.

13 23 The differences in frictional profiles are governed by the differences in the viscoelastic nature of the suture materials. A careful study of this parameter under a variety of clinical conditions is essential to gain an understanding of the behavior of surgical knots in clinical practice (Gupta et al 1985) Biocompatibility Tissue reaction to sutures depends on several factors such as the chemical nature of the suture material, the physical form of the suture, the amount of suture in the tissue (suture size and knot volume), and stiffness. Among these, the chemical composition of the suture is considered the most important factor. Usually natural suture materials provoke more severe tissue reactions than synthetic sutures due to the availability of acceptance sites for the enzymes to react with sutures (Dumitriu 2002). 2.6 SUTURE MATERIALS The following section discusses the different types of non-absorbable and absorbable sutures Non-Absorbable Sutures Non-absorbable sutures are those that are not digested by body enzymes or hydrolyzed in body tissue. They are made from a variety of nonbiodegradable materials and are ultimately encapsulated or walled off by the body s fibroblasts. The details of commercially available non-absorbable sutures in the market are shown in the Table

14 24 Table 2.3 Commercial Natural Non Absorbable Sutures Generic name Trade name Physical configuration Surface treatment Manufacturer Silk Surgical Silk Braided Silk Dermal Twisted Silk Virgin Silk Twisted Silk Silk Braided Silk Sofsilk Braided Silk Silk Braided Tru permanizing Tanned gelatin (or other proteins) None Silicone Coated Paraffin wax Ethicon Ethicon Ethicon Ethicon, Davis & Geek US Surgical Society Steril Catgut Cotton Surgical Twisted None Ethicon cotton Cotton Cotton Twisted Linen Linen Twisted None None Davis & Geek Ethicon

15 25 Table 2.4 Commercial Synthetic Non-Absorbable Suture Generic name Trade name Physical configuration Polyester Ethibond Braided Polyester Mersilene Braided Polyester Ethiflex Braided Polyester Dacron Braided Polyester Ticron Braided Polyester Surgidac Braided and monofilament Polyester Silky Polydek Braided Polyester Sterilene Braided Polyester Tevdek Braided Polyester Astralen Braided Surface treatment Polybutylate None Teflon None Silicone Manufacturer Ethicon Ethicon Ethicon Davis & Geek Davis & Geek Coated with US Surgical braid Teflonized Society Steril Catgut Teflonized Society Steril Catgut Teflonized Society Steril Catgut Teflonized Astra Polyester Mirafil monofilament None Braun Melsungen Polyester Novafil monofilament None Davis & Geek Polyamide Ethilon monofilament None Ethicon Polyamide Nurolon Braided Coated Ethicon Polyamide Surgilon Braided Silicone Davis & Geek Polyamide Dermalon monofilament None Davis & Geek Polyamide Bralon Braided Coated US Surgical Polyamide Sutron monofilament None Ethicon Polyamide Supramid Core-sheath None Astra Polypropylene Prolene monofilament None Ethicon Polypropylene Surgilene monofilament None Davis & Geek

16 Silk sutures Silk was first introduced as a suture material in the year 1890s. Silk from the silkworm, Bombyx mori has been used most extensively for wound ligation and became the most common natural suture surpassing collagen used in the biomedical industry over the past 100 years. This reflects the high biocompatibility of silk, despite silk being a foreign protein to mammals. During the past 25 years, a variety of degradable synthetic sutures have dominated the suture market. However silk is still popular in ocular, neural and cardiovascular surgery due to its advantageous characteristics such as good knot tying ability, easy handling characteristics and a minimum tendency to tear through tissue (Altman et al 2003). Various studies have confirmed that silk does not cause severe inflammation or elicit other tissue responses in mammalian tissue. As a substrate, silk protein is good for mammalian cell adhesion and proliferation (Karthikeyan et al 2011). Furthermore, silk is a soft and pliable suture material that is comfortable for patients and unlikely to tear through even delicate tissues. For many surgeons, surgical silk represents the standard handling performance by which newer synthetic materials are judged, especially due to its superior handling characteristics. Surgical silk loses tensile strength when exposed to moisture and should be used dry. Although silk is classified by the USP as a nonabsorbable suture, long-term in vivo studies have shown that it loses most or all of its tensile strength in about 1 year and usually cannot be detected in tissue after 2 years. Thus, it behaves in reality as a very slowly absorbing suture. The silk sutures are usually coated with wax or silicone to enhance the material properties and reduce fraying. On the other hand, coated sutures may provoke inflammatory tissue reactions if the pieces of the coated substances flake off and migrate into surrounding tissues. To reduce this problem,

17 27 coating should have an affinity for suture filaments. The elimination of wax coating significantly diminished the initially high thrombotic response to silk. Silk is also a cost effective suture material (Altman et al 2003) Linen It is made from flax fibres. It is available in twisted form. It can be used for general surgery, gynecology, cardiovascular surgery, gastrointestinal surgery and plastic surgery. The Linen suture is not absorbed and hence it does not loss the tensile strength. It gains 10% of tensile strength when it is wet. It is also available in treated with silicone and polyvinyl solution. It has better handling characteristics and excellent knot security Cotton It was introduced as a suture material in 1939 to replace silk suture during World War II. It is extracted from hairs of seed of cotton plant. It gains tensile strength and knot security when wet. It slowly losses tensile strength after implantation, with 50% loss of tensile strength at 6 months, and 70% loss of tensile strength at 2 years. However it is not absorbable sutures. It has better knot security than silk. Disadvantages of cotton suture are its capillarity, tissue reactivity, inferior handling ability due to electrostatic properties and ability to potentiate infection (Boothe 1993) Nylon Nylon was the first synthetic non-absorbable suture introduced in the year It is most commonly used in dermatologic surgery. It is available in both monofilament and forms. It has high tensile strength, minimal tissue reactivity, excellent elastic properties and low cost. The nylon sutures retain approximately two-thirds their original strength after

18 28 11 years. The major drawback to nylon is its high degree of memory. Furthermore nylon is very stiff and it needs to be carefully tied in order to avoid the untying of the knot and the possibility of cutting through the tissues (Gupta et al 2008) Polyester Polyester braided sutures are very similar to silk in their tying ease, workability and knot security. It is available in both coated and uncoated form. One disadvantage of the uncoated polyester sutures is that they have a relatively rough surface that produces drag when brought through tissues and when knots are set. Therefore coated polyester suture were developed to overcome the above mention problem. The coating substances such as teflon and silicone were problematic due to their instability. Fragments of this coating can tear and migrate into surrounding tissues, thus provoking inflammatory reactions. The relatively high cost and the fact that the coating may crack after the knots are tied prevent them from being frequently used (Gupta et al 2008). In a recent study a chitosan treated antimicrobial polyester suture was prepared by Gupta et al (2010). The graft modification of polyester monofilament was performed in such a way that the filament retains its physical and mechanical properties and attains antimicrobial nature Polypropylene Polypropylene sutures are sutures with extremely low tissue reactivity. Although they have slightly more memory than nylon monofilament, they possess high tensile strength and provide the best resistance to infections. The unique smoothness of the polypropylene suture surface makes it simple to tie and enhances suture removal. On the other hand, such a high rate of smoothness results in low knot security and therefore knots have a tendency to slip (Gupta 2008).

19 29 Smit et al (1991) evaluated the tissue reactivity of various suture materials such as silk, polyester, polypropylene, nylon in vivo on rats using the histological method. Their results showed that there was no significant difference in tissue reaction among the different sutures and the surgical trauma had a greater influence on tissue reaction than the material itself. Karaca et al (2005) studied the in vivo tissue reactions of silk, polyester, polyamide, and polypropylene sutures and found that all the sutures showed tissue reaction to some extent but in general braided sutures induced more tissue reaction than monofilament sutures Stainless steel Stainless steel is the only metallic suture still widely used. It is available in both monofilament and braided form. It is biologically inert and non-capillary in nature. It can be easily sterilized by autoclaving process. It has the highest tensile strength and greatest knot security of all suture materials and maintains this strength on implantation in tissues. It is good for suturing tissues that heal slowly. The monofilament form stainless sutures are used effectively in contaminated and infected wounds, because it does not support infection. Disadvantages of stainless steel suture are its tendency to cut tissues, poor handling characteristics (especially in knot tying) and diminished ability to withstand repeated bending without breaking Absorbable Sutures Sutures that undergo rapid degradation in tissue and lose most of their tensile strength within 60 days are considered as absorbable sutures. An advantage of absorbable suture is that they generally do not require removal. However, these materials incite varying degrees of tissue response due to their degradation by hydrolysis, enzymatic digestion or phagocytosis. The speed of this hydrolysis depends on the temperature and the ph of the tissue

20 30 or the liquids surrounding the suture material. Proteolytic enzymes in the body digest catgut suture material. Other synthetic absorbable sutures are absorbed via hydrolytic degradation. Enzymatic degradation elicits more reaction than other (Kim et al 2007). The details of commercially available natural and synthetic absorbable sutures in the global market are shown in the Table 2.5 and 2.6 respectively Catgut Catgut is derived from sheep intestinal submucosa. Its use at present is declining due to its poor tensile strength, poor knot security in vivo and high tissue reactivity. It retains significant tensile strength for only four to five days and wound security essentially disappears within two weeks. Catgut treated with chronic acid has delayed absorption time and decreased tissue reactivity as compared to untreated catgut, and can be used as the top layer of skin closure. A major problem associated with this type suture is high inflammatory reactions which interferes the wound healing process (Chu 1997). Table 2.5 Commercial Natural Absorbable Sutures Generic name Catgut Trade name Surgical gut Physical configuration Twisted Catgut Surgigut Twisted Catgut Softgut Twisted Reconstituted collagen Collagen Twisted Surface treatment Plain and chromic Plain and chromic Glycerin coated Plain and chromic Manufacturer Astra, Ethicon, Davis & Geek, US Surgical Davis & Geek Ethicon

21 31 Table 2.6 Commercial Synthetic Absorbable Sutures Generic name Polyglycolic acid Polyglycolic acid Trade name Physical configuration Dexon S Braided Dexon plus Braided Polyglycolic acid Dexon II Braided Poly(glycolidelactide)(polyglactin 910) Poly(glycolidelactide)(polyglactin 910) Poly(glycolidelactide)(polyglactin 910) Vicryl Braided Vicryl plus Braided Vicryl Rapide Panacryl Polysorb Braided Braided Braided None Surface treatment Poly(oxyethyleneo xypropylene) Polycaprolate Polyglactin 370 and calcium stearate Triclosan Coated None Coated Manufacturer Davis & Geck Davis & Geck Davis & Geck Ethicon Ethicon Ethicon Ethicon US Surgical Poly-p-dioxanone PDS II Monofilament None Ethicon Polydioxanone PDS plus Monofilament Triclosan Ethicon Poly(glycolide-Llactide) Poly(glycolide-Llactide) Poly(glycolide-cotri methylene carbonate) Poly(glycolide-cocaprolactone) (Polyglec prone 25) Maxon Monofilament None Davis & Geck Monocryl Monofilament None Ethicon Glucomer 631 Biosyn Monofilament None US Surgical Collagen It was evolved to overcome the disadvantages of conventional catgut. The flexor tendons of beefs were converted into dispersed fibrils. The

22 32 dispersed fibrils were then extruded and reconstituted to form collagen sutures Polyglycolic acid suture The first synthetic absorbable surgical suture was introduced in 1970, polyglycolic acid, a homopolymer of glycolic acid. The commercial name of polyglycolic acid is Dexon. It was known for its excellent tensile strength, knot strength, delayed absorption and markedly diminished tissue reactivity compared with catgut. In animal studies, the absorption of Dexon suture was found to be about 40 percent after seven days. By 15 days, it has lost more than 80 percent of its original strength. By 28 days, this material retains only 5 percent of its original tensile strength, and it is completely dissolved by 90 to 120 days. Dexon is absorbed by hydrolysis, reducing the inflammatory response. As a monofilament, Dexon is stiff and difficult to work with. Therefore, it is available in braided form for easier handling. Dexon also comes with a synthetic coating (Dexon Plus) to ease of passage through tissue and good handling characteristics (Chu 1997) Polyglactic acid suture Polyglactic acid, the second synthetic suture material was introduced in The commercial name of polyglactic acid suture is Vicryl. It is a copolymer of lactide and glycolide, manufactured with a coating composed of polyglactin 370 and calcium stearate. This lubricant coating gives Vicryl excellent handling and smooth typing properties. Like Dexon, Vicryl material retains only 8 percent of its original tensile strength by 28 days. However, complete absorption of Vicryl is more rapid, occurring between 60 and 90 days (Craig et al 1975). Like all synthetic polyesters, Vicryl degrades by hydrolysis and causes minimal tissue reaction. Vicryl is a braided suture, and comes in violet-dyed and undyed forms. Vicryl also

23 33 comes with other two types namely Vicryl plus antibacterial suture introduced in the year 2004 and Vicryl rapide coated suture introduced in the year To date, the most commonly used antibacterial suture is the triclosan coated polyglycolic acid suture only. Recently, literature suggests that the triclosan based surgical sutures has significant limitations and complications (Aiello et al 2011) Polydioxanone suture In 1981, a new polymer, Polydioxanone (PDS) was introduced for surgical applications. PDS is a polymer made from polydioxanone and is manufactured in monofilament form. It retains 74 percent of its original strength at two weeks, 58 percent at four weeks and 41 percent at six weeks. (Gupta et al 2008). Thus, PDS is a useful suture in situations where extended wound tensile support is needed. Although PDS is hydrolyzed much more slowly than the other synthetic absorbable sutures, foreign body reactions to this material are judged to be minimal. Unlike Dexon or Vicryl, PDS is a monofilament and should have less affinity for microorganisms. PDS is stiffer than the braided synthetics and more difficult to handle, and costs about 14 percent more than Vicryl or Dexon. PDS is also comes with PDS plus, an antimicrobial suture introduced in the year Polytrimethylene carbonate suture In 1985, another synthetic absorbable suture Polytrimethylene carbonate suture was introduced. The commercial name of Polytrimethylene carbonate is Maxon. It is a monofilament that was designed to combine the excellent tensile-strength retention properties of PDS with improved handling characteristics. Like PDS, Maxon provides wound support over an extended period of time, with average strength retention of 81 percent at 14 days, 59 percent at 28 days and 30 percent at 42 days. Complete absorption occurs

24 34 between 180 and 210 days, with minimal tissue reaction. Moreover, Maxon is much more supple and easier to handle than PDS, with 60 percent less rigidity (Rodeheaver et al 1987). Compared with Dexon or Vicryl, Maxon has a smoother knot run down and an excellent first-throw holding capacity, thus simplifying tissue approximation and minimizing the need for knot repositioning. Maxon costs approximately 7 percent more than Dexon or Vicryl (Gupta et al 2008) Poliglecaprone Suture The suture comprised of a copolymer of glycolide and epsiloncaprolactone, it is virtually inert in tissue and absorbs predictably. The commercial name of Poliglecaprone is Monocryl. This monofilament suture features superior pliability for easy handling and tying. The surgeon may prefer Monocryl sutures for procedures which require high initial tensile strength diminishing over 2 weeks postoperatively. These include subcuticular closure and soft tissue approximations and ligations, with the exception of neural, cardiovascular, ophthalmic, and microsurgical applications. Monocryl suture is available in dyed (violet) and undyed (natural) form. Dyed Monocryl suture retains 60% to 70% of its original strength at 7 days post implantation, reduced to 30% to 40% at 14 days, with all original strength at 7 days post implantation, reduced to 30% to 40% at 14 days, with all original strength lost by 28 days. At 7 days, undyed Monocryl suture retains approximately 50% to 60% of its original strength, and approximately 20% to 30% at 14 days post implantation. All of the original tensile strength of undyed Monocryl suture is lost by 21 days post implantation (Gupta et al 2008). Absorption is essentially complete at 91 to 119 days. In the year 2008, Monocryl plus antibacterial suture was launched by ethicon. It showed good antibacterial characteristics.

25 DEVELOPMENTS IN SURGICAL SUTURES Antimicrobial Sutures Wound infection is considered to be one of the most common complications in all types of injuries. The presence of foreign materials in wound has been known to enhance the surrounding tissues to wound infection. Suture materials are the probably the most important textile materials in wound infection because the infection begins along or near suture lines. In addition, the suture knot can provide a vehicle for bacterial colonization and replication that can ultimately result in surgical site infections. There are about 2.4 million cases of hospital-acquired infections each year in the United States alone, of which approximately 15% are surgical site infections. Infections associated with medical devices and sutures account for 66% of all of the infections. In some cases, the problems caused by such infections are difficult to resolve, which need extended hospitalization, antibiotic therapy, and additional surgical procedures. Therefore incorporation of some antimicrobial drugs or therapeutic agents like growth factors into the suture materials to accelerate wound healing and prevent wound infection has gained recent attentions (Mingmalarik et al 2011). Microbes are the tiniest creatures not seen by the naked eye. They include a variety of micro-organisms like bacteria, fungi, algae and viruses. In the majority of polymeric implants and intravenous catheters, staphylococci play a predominant role. Staphylococci is the most frequently implicated microorganisms in infection occurring in the drainage system of cerebrospinal fluid, venous catheters sutures, continuous ambulatory catheters, heart valves and in hip as well as knee prosthesis. Negative effect on the vitality of the microorganisms is generally referred to as antimicrobial.

26 36 A living microbe typically has an outermost cell wall which is mainly composed of polysaccharides. This cell wall maintains the integrity of cellular components and shields the cell from the extracellular environment. Immediately beneath the cell wall is a semi-permeable membrane which encloses intracellular organelles and a numerous of enzymes and nucleic acids. The enzymes are responsible for the chemical reactions that take place within the cell, and the nucleic acids store all of the genetic information of the organism. The survival or growth of microorganisms depends on the integrity of the cell and the concerted action and proper state of all of these components. Antimicrobial agents either inhibit the growth (biostatic) or kill (biocidal) the microorganisms. The manner in which antimicrobial agents inhibit or kill can be attributed to cell wall damage or inhibition of cell wall synthesis, alteration of cytoplasmic membrane permeability, alteration of the physical or chemical state of proteins and nucleic acids, inhibition of enzyme action and inhibition of protein or nucleic acid synthesis. following methods: The antimicrobial activity in sutures can be achieved by the Blending or incorporation of volatile or nonvolatile antimicrobial agent while processing Coating or absorption of the antimicrobial agent onto the filament Graft polymerization followed by immobilization of antimicrobial agents onto the grafted surface Incorporation of bioactive agents including antimicrobial agents into polymers by blending has been commercially applied in surgical implants

27 37 and other biomedical devices. This is a pretreatment technology, where the antimicrobial agent is introduced during the processing stages. For this, the additive characteristic has to be compatible with blending conditions. Heavy metals, such as gold, silver and copper have also been used to introduce antimicrobial activity in suture. Povidone-Iodine (PVP-I) complex is also one of the most widely used products in the sphere of surgery. The slow release of free iodine from the complex gives prolonged antimicrobial activity from the doped material. Antimicrobial nylon sutures have been prepared by blending of Nylon-6 with PVP-I complex using a melt spinning process (Gupta et al 2008). Depending upon the blend ratio, a preweighed quantity of chips was added to the saturated solution of the PVP-I complex and these chips were then spun and drawn at the temperature to obtain a monofilament with good strength. The sutures have polar bonding between nylon and PVP-I complex, which results in the slow and controlled release of iodine from the sutures and exhibit antimicrobial nature. In the post processing technology, the most common technique for applying the antibacterial agent is coating. Antimicrobial agents that cannot tolerate the temperature used in polymer processing are often coated onto the material after fabrication. The antimicrobial agents linked to the surface through physical bonds or anchored by the cross linking on the fibre. Antimicrobial suture having long lasting antimicrobial properties and good physical properties are prepared by coating a suture with a solution of an antimicrobial agent and segmented urethane polymer. Antimicrobial coating on polyester suture were carried out by depositing an antimicrobial biocompatible metal by vapor deposition technique. Polyester sutures were coated by magnetron sputtering silver-copper alloy of inhibition results showed presence of clear zone inhibiton (Gupta et al 2008).

28 38 Blacker et al (2004) used silver doped bioactive glass powder to coat absorbable Vicryl and non-absorbable Mersilk surgical suture. Stable homogeneous coating on the surface of the suture was achieved by using an optimised aqueous slurry dipping technique. The in-vitro bioactivity of the suture was tested by immersion in simulated body fluid (SBF). After 3 days of immersion in SBF, bone like hydroxyapatite formed on the coated suture indicating the enhanced bioactive behaviour. In vitro antimicrobial evaluation of polyglactin 910 suture coated with triclosan has shown attractive results. The antibacterial activity of the coated suture was evaluated against S. aureus and Staphylococcus epidermis and produced zones of inhibition after 5 and 10 passes through fascia and subcutaneous tissue (Gupta et al 2008). Iodine can be attached to polyamide suture to provide them antimicrobial property. Antimicrobial nylon suture has been prepared by coating the monofilament with iodine (Gupta et al 2008). Nylon-6 monofilament was treated with iodine by immersing the filament in a saturated solution of iodine in acetone and was tested for iodine release and antimicrobial properties against E. coli and S. aureus by zone of inhibition method. It was observed that a clear zone of inhibition was formed around 6 mm in the case of E.coli and 8 mm in the case of S. aureus (Gupta et al 2008). The radiation, plasma and chemical methods of grafting have occupied the attention of numerous researchers for many years (Gupta et al 2008). Graft polymerization offers an effective approach to introduce desirable properties into the polymers without affecting the architecture of the polymer backbone (Gupta et al 2000). Grafting of hydrophilic monomers provides a good platform for the introduction of antimicrobial activity. The grafted side chains contain functional groups to which various bioactive materials can be attached. These functional groups include amine, carboxylic acid and hydroxyl groups, which can be utilized further for the attachment on antimicrobial drug (Singh and Ray 1994). This approach of graft

29 39 fictionalization has been successfully used for the development of polypropylene sutures by incorporating acrylonitrile and vinylimidazole grafts into the suture matrix. Both the tetracycline hydrochloride and ciprofloxacin have been immobilized onto the modified sutures and their effectiveness against different microbes has been evaluated (Gupta et al 2007). Antimicrobial polyester suture is prepared by graft modification of the filament in such a way that the filament retains its physical properties and attains antimicrobial nature. In a recent study antimicrobial polyester suture is prepared by graft polymerization of acrylic acid on the surface of the suture, in order to keep the bulk unaltered the grafting was carried out by using vacuum plasma (Gupta et al 2008). As a result, polyester surface acquire functionality of carboxyl group while the bulk remain unaltered. It has been observed that the monomer concentration plays a crucial role in the graft management and a maximum in the grafting is achieved at a monomer concentration of 40% monomer concentration as shown in Figure MONOMER CONCENTRATION [%] Figure 2.2 Variation of Degree of Grafting With Monomer Concentration

30 40 The acrylic acid grafted surface offers excellent functionality for the interaction with chitosan molecules which is an attractive route to produce antimicrobial suture material. Atomic Force Microscopy studies have been done for untreated polyester, grafted polyester and chitosan coated polyester samples and it was found that the roughness of the surface increases with the grafting but the surface of the coated suture is smoother compared to the grafted sutures due to uniform coating of chitosan all over the surface (Gupta et al 2010). The chitosan coated sutures were loaded with ciprofloxacin as the antimicrobial drug. This loading helps in the enhancement in the antimicrobial nature of the suture and hence provides better healing process. Ciprofloxacin has been observed to be released slowly from the suture and continued up to 3-4 days as shown in Figure 2.3. This is interesting from the point of view of drug availability at the wound site till the suture is removed in 4-5 days TIME ( hrs.) Figure 2.3 Amount of Drug Release with Time

31 Barbed Bidirectional Sutures In 1992, Dr. Gregory Ruff of Duke University Medical Center started working on an idea of a barbed suture for cosmetic applications. Dr. Ruff took the idea of a barbed suture and applied it to an absorbable suture material made of polydioxanone. The advantage of using an absorbable polymer suture is that it does not need to be removed and it does not require knots to make it secure. The knotless design has significant potential in reducing scar tissue due to the absence of a significant foreign- body reaction caused by knots. The barbed configuration anchors the suture into the tissue and provides adequate tissue adhesion while the wound heals under minimum residual tension and pressure (Dattilo et al 2002). The success of this novel wound closure device requires the suture geometry to be well characterized and monitored during manufacture for two reasons: quality control (measuring uniformity of the barb geometry) and the need to determine the effect of tissue holding capacity and the barb geometry. Quill Medical, Inc. currently produces this barbed monofilament suture from polydioxanone in size 0, (size 0 has a diameter of 0.30 to 0.39 mm), while other sizes are under development. Figure 2.4 shows the barbed bidirectional monofilament polydioxanone suture. Figure 2.4 Barbed Polydioxanone Suture The monofilament sutures contain up to 78 barbs manufactured in a spiral pattern around the circumference of the suture. The barbs are divided into two groups facing each other in opposing directions around the mid-point as shown in Figure 2.5. The two sets of barbs divide the suture into two

32 42 sections, right and left. Internal wound closure yields the best results when using an absorbable material. Figure 2.5 Bidirectional Barbed Suture Showing Midpoint Using non-absorbable wound closure material requires removal of the device after the wound has healed. This can lead to additional visits to the physician or surgeon and the use of more invasive surgical procedures. The fact that polydioxanone is absorbable makes it an ideal candidate for internal wound closure. Current sutures require the tying of surgical knots. The throws of these knots are often pushed through a transdermal cannula, which can be tedious and difficult for the surgeon as well as resulting in inferior knot performance. The knotless barbed suture can also be applied through a cannula and, without the need for tedious knot throwing and pushing, it is likely to reduce surgery time and create a more consistent method for tissue approximation. Mckenzie (1967) described the use of a nylon-barbed suture for repair of the long flexor tendon of the hand as shown in Figure 2.6. Figure 2.6 Barbed Sutures in Tendon Repair Application The knotless designed suture increases the flexibility and longitudinal movement of the tendon that would normally be limited by the

33 43 presence of knots. The polymer suture can be engineered to maintain the required strength for the duration of the complete healing process. In addition, the absorbable barbed suture does not require removal after the repair is healed, thus reducing the number of visits to the surgeon as well as the trauma associated with a follow-up intervention. 2.8 SUTURE MANUFACTURING TECHNIQUES Spinning Technology The production method currently used for almost all synthetic sutures is melt spinning or solution spinning. In melt spinning process, polymer chips or pellets are melted using heat, and then the molten polymer is forced through a spinneret to form filaments. Immediately after the filaments are extruded from the spinneret, cool air passes through and solidifies the filaments. The fibres can be drawn before and after being solidified to obtain the desired degree of molecular chain orientation, crystallinity, and desired fibre diameter. The diameters of fibres produced by melt spinning range from 10 µm to 50 µm. This production method prohibits the incorporation of bioactive agents and temperature-sensitive antibiotics as the high temperatures necessary to melt the polymers may cause these agents to lose their functional activity. In this circumstance wet spinning, dry-jet-wet spinning or electro spinning can be employed to manufacture the sutures. The manufactured monofilaments by any one of the above technique may be used directly as monofilament sutures or subjected to another process called braiding. The spinning methods, including dry spinning, wet spinning, and melt spinning, use only mechanical forces to produce fibres from a polymer melt or solution. However, in electrospinning, both mechanical and electrical forces are applied to produce fine fibres. In this process, a

34 44 high voltage supply is applied to produce a strong electric field. The polymer solution or polymer melt is contained in a syringe with a thin tip. It is from the syringe tip that polymers are drawn into fibres. Usually, either a metal needle tip is used or a metal wire is inserted into the polymer solution at the tip of the syringe to charge the polymers positively or negatively. As a result, the polymer solutions or polymer melt at the tip is subjected to both surface tension and mutual charge repulsion. The direction of the surface tension opposes the direction of the mutual charge repulsion. As the intensity of the electric field is increased, and the mutual charge repulsion of the liquid overcomes the surface tension, the solution at the tip of the capillary is ejected. The fibres are formed upon the evaporation of the solvent or upon the cooling of the polymer melt. The diameters of fibres manufactured by electrospinning range from several microns to several hundredths of a micron or even several nanometers Braiding Technology Braiding is a textile structure formation process which is known for its simplicity and versatility. A braid structure is formed by the diagonal intersection of yarns. Braiding is more significant for industrial textiles than consumer textiles. Although the volume of braided structures is small compared to weaving and knitting in consumer textiles, braiding is one of the major fabrication methods for technical and industrial fabrics (Amit et al 2012). Braiding can be classified as two and three dimensional braiding. Two dimensional braid structures can be circular or flat braids. Although circular and flat braids have thickness, it is small compared to the other two dimensions, therefore they are considered as two dimensional. Three dimensional braiding is relatively new and was developed mainly for composite structures (Adanur 1995). A two dimensional circular or flat braid

35 45 is formed by crossing a number of yarns diagonally so that each yarn passes alternatively over and under one or more of the others. The most common designs in two dimensional braids are diamond braid (1/1 repeat) and regular or plain (2/2 repeat). The Figure 2.7 shows the different braid patterns. (a) (b) Figure 2.7 Different Braid Patterns (a) 1/1 Pattern (b) 2/2 Pattern Circular braiding arrangement consists of a track plate, yarn carriers, braid ring, and a mandrel. A diagram of minitype circular braiding machine is shown in the Figure 2.8. Figure 2.8 Minitype Circular Braiding Machine

36 46 The track plate supports two sets of yarn carriers rotating on a circular track, one set rotating in the clockwise direction and the other in the counterclockwise direction, and during this process, they interlace with each other to form a braided structure over a mandrel. A braid ring controls the shape and dimension of the braid at the point of braiding. The type of design is one of the factors which affect the mechanical properties of the braided structure. Braid structures are specified by the line and pick numbers. One repeat of the braid measured along the braid axis is called a pick (S). Pick count is the number of S per unit length in a single line parallel to the braid axis. One repeat of the braid across the braid normal to the braid axis is called a line (L) (Figure 2.9). The braid angle,, is half of the angle made by crossing filaments in the braid. It is one major factor to be considered when designing braids, since it has a significant effect on the mechanical properties. Braid angles of 10 to 85 are achievable. The ratio of the speed of the carriers to the take-up device determines the braid angle. Since the speed of the yarn carriers is constant, the braid angle can be controlled by changing the take-up rate on the braiding machine. Figure 2.9 Schematic Illustrations of Structural Parameters of a Braid

37 47 Flat braids are made in the form of a flat strip or tape. In flat braiding, instead of following two continuous paths, the carriers turn around or reverse direction at two given points called terminals and then continue on the opposite track. The size of a braid is governed by the following factors: The number of carriers The diameter of the yarns The number of yarn end per carrier The number of yarns per unit length Two dimensional braided circular structures have been successfully used in various technical applications. Surgical suture is one of the applications of this form of structures. Hristov et al (2004) studied the mechanical behavior of circular braids made from polypropylene and polyester. In a recent study the tensile and knot behavior of polyester braided sutures (Abdessalem et al 2009). Three dimensional braiding is a relatively new compared to two dimensional braiding. The first three dimensional braiding machine was developed in 1960s. The three dimensional braiding concept has been developed mainly for textile structural composites. There is no three dimensional braiding machine that is commercially available. The main reason for this is that every different three dimensional braided structure requires a different machine with specific characteristics and dimensions. Therefore, companies and research institutions custom-build their three dimensional braiding machines.

38 TECHNICAL APPLICATIONS OF SUTURES FOR WOUND CLOSURE There are primarily four categories for classifying the use of sutures: dermal closure, internal closure, tendon repair, and fastener. Dermal closure uses the suture to approximate the tissue at the site of the wound. Absorbable sutures predominate mostly in internal wound closure. Internal closure from a wound or incision uses an absorbable suture because it eliminates additional surgical procedures that would be needed for removal of non absorbable sutures. Tendon repair uses sutures to join the two-ruptured ends of the tendon or ligament. Either absorbable or non-absorbable sutures are used in this procedure. Finally, sutures can be used as fasteners to attach implantable devices to their intended position. In an application where sutures are used to fasten a warp knitted polyester cardiac support jacket around the heart to restrict expansion of a diseased heart. Dermal and internal wound closure requires the physician to decide on a specific type of technique for approximation of the wound edges. The type of suturing technique depends on the configuration of the wound, the environment of the wound, and the type of physical properties the wound shape will inflict on the suturing material (Moy et al 1992). An ideal wound closure will leave little scar tissue and suturing marks. The most common forms of suturing technique for dermal and internal wounds are the simple interrupted, intra dermal, simple continuous, continuous intra dermal, interrupted horizontal mattress and interrupted vertical mattress as shown in the Figure 2.10.

39 49 (a) (b) (c) (d) (e) (f) Figure 2.10 Suturing Techniques (a) Simple Interrupted (b) Simple Intra Interrupted Dermal (c) Simple Continuous (d) Continuous Intradermal (e) Interrupted Horizontal Mattress (f) Interrupted Vertical Mattress

40 50 Procedures for tendon and ligament repair use sutures that run through each ruptured end, pull the ruptured ends together, and are fastened with knots or other methods The use of sutures requires some form of surgical knot to fasten the suture into place. The perfect combination of material and suture technique is worthless unless the tissue is approximated and held for the appropriate duration of the healing process. Surgical knots are the only way to hold sutures in place. However, as reported earlier, they come with adverse effects SURGICAL NEEDLES AND SUTURES PACKAGING SYSTEM Surgical Needles Surgical needles are usually produced from stainless steel alloys, which have excellent resistance to corrosion. All true stainless steels contain a minimum of about 12% chromium, which allows a thin, protective surface layer of chromium oxide to form when the steel is exposed to oxygen. Since their development during the early 1960s, high-nickel maraging stainless steels have found extensive use in structural materials in many applications requiring a combination of high strength and toughness. A high-nickel maraging stainless steel, comprises % nickel, % titanium, and % chromium. In contrast, stainless steel comprises 12 14% chromium without nickel or titanium. Scientists have successfully employed the concept of high-nickel maraging stainless steels to develop stainless steel wires with superior strength and ductility for use as surgical needles. Surgical needles made of high-nickel maraging stainless steel have a greater resistance to bending and breaking than stainless steels without nickel (Robin et al 2002).

41 51 Suture selection is dependent on the anatomic site, surgeon s preference, and the required suture characteristics. No standardized sizing system or nomenclature is available for needles or needle holders. The main consideration in needle selection is to minimize trauma. The length, diameter, and curvature of the needle influence the surgeon s ability to place a suture. Figure 2.11 shows the different types of surgical needles. Figure 2.11 Different Types of Surgical Needles The ideal surgical needle has the following characteristics: High-quality stainless steel Smallest diameter possible Stable in the grasp of the needle holder Capable of implanting suture material through tissue with minimum trauma