SELECTION AND APPLICATION OF SYNTHETIC POLYMERIC MATERIALS IN SURGICAL SUTURES by KENNETH BRANSON SIMMONS (Under the Direction of Jason Locklin) ABSTRACT Wound closure is a complex process that relies on a variety of tools and materials to produce the best outcome for patients. The use of a single suture for the closure of all fascia is ill advised and should be avoided. This thesis seeks to inform the reader of the characteristics and utility of various synthetic polymeric materials and their application as surgical sutures. INDEX WORDS: Surgical Sutures, Synthetic, Absorbable, Nonabsorbable SELECTION AND APPLICATION OF SYNTHETIC POLYMERIC MATERIALS IN SURGICAL SUTURES By KENNETH BRANSON SIMMONS B.S., The University of Georgia, 2012 A Thesis Submitted to the Graduate Faculty of The University of Georgia in Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE ATHENS, GEORGIA 2017 © 2017 Kenneth Branson Simmons All Rights Reserved SELECTION AND APPLICATION OF SYNTHETIC POLYMERIC MATERIALS IN SURGICAL SUTURES by KENNETH BRANSON SIMMONS Major Professor: Jason Locklin Committee: Jonathan Amster Jeffrey Urbauer Electronic Version Approved: Suzanne Barbour Dean of the Graduate School The University of Georgia August 2017 iv DEDICATION To my father, Kenneth Simmons, who taught me the importance of an education. To my fiancée, Laura Anne Cotney, for bringing music to my life and helping me to keep my wits about me. v ACKNOWLEDGEMENTS I would like to acknowledge the support and guidance given by my major professor, Dr. Jason Locklin, for his guidance and support in my graduate studies. Additionally, I would like to acknowledge all members of the Locklin group for their input and support during group meetings, literature talks, and seminar. I would like to thank my committee members, Dr. Jonathan Amster and Dr. Jeffrey Urbauer, for their support. Finally, I would like to thank my employer, Ethicon – A Johnson & Johnson Company, for providing funding throughout my studies. vi TABLE OF CONTENTS Page ACKNOWLEDGEMENTS………………………………………………………………………………v CHAPTER 1 INTRODUCTION ………………………………………………………………………………………1 Absorbable vs Non-Absorbable Suture ………………………………………………………. 2 Monofilament vs Multifilament Suture ………………………………………………………… 3 Coated vs Non-Coated Suture ………………………………………………………………… 4 Suture Sizes……………………………………………………………………………………... 4 2 MONOMERS ……………………………………………………………………………………………5 Lactide …………………………………………………………………………………………….5 Glycolide ………………………………………………………………………………………….6 p-Dioxanone ……………………………………………………………………………………...7 Trimethylene Carbonate ……………………………………………………………………......8 ε-Caprolactone ………………………………………………………………………………......9 3 HOMOPOLYMERS .…………………………………………………………………………………. 10 Polyglycolide ……………………………………………………………………………………10 Polylactide ………………………………………………………………………………………11 Poly(p-dioxanone) ……………………………………………………………………………...12 Poly(4-hydroxybutyrate) ……………………………………………………………………….12 4 COPOLYMERS OF TWO MONOMERS …………………………………………………………...14 Poly(glycolide-co-lactide) ……………………………………………………………………...14 Poly(p-dioxanone-co-glycolide) ……………………………………………………………… 16 Poly(p-dioxanone-co-trimethylene carbonate) ……………………………………………...16 vii Poly(glycolide-co-trimethylene carbonate) …..……………………………………………... 16 Poly(glycolide-co-ε-caprolactone) …………………………………………………………… 17 Poly(lactide-co-ε-caprolactone) ……………………………………………………………… 18 5 COPOLYMERS OF THREE MONOMERS …………………………………………………………19 Poly(glycolide-co-trimethylene carbonate-co-ε-caprolactone) …………………………….19 Poly(glycolide-co-trimethylene carbonate-co-p-dioxanone) ……………………………….19 Poly(ε-caprolactone-co-trimethylene carbonate-co-p-dioxanone) ……………………….. 20 6 COPOLYMERS OF FOUR MONOMERS …………………………………………………………. 22 Poly(glycolide-co-L-lactide-co-trimethylene carbonate-co-ε-caprolactone) ……………...22 7 NONABSORBABLE SUTURE ……………………………………………………………………....23 Polyamides …………………………………………………………………………………….. 23 Polyesters ……………………………………………………………………………………… 24 Poly(vinylidene fluorides) …………………………………………………………………….. 25 Poly(tetrafluoroethylene) ………………………………………………………………………26 Polyolefins ………………………………………………………………………………………27 Ultra-high molecular weight polyethylene ……………………………………………………28 8 FUTURE DIRECTIONS ………………………………………………………………………………30 Barbed Suture …………………………………………………………………………………..30 Poly(propylene oxide) Suture …………………………………………………………………30 Diacetyl Chitin Coated Suture …………………………………………………………………31 Antibiotic Eluting Suture ……………………………………………………………………….31 Amino Acid Based Nanogel Conjugated Suture …………………………………………….32 REFERENCES ………………………………………………………………………………………….33 1 Introduction: Needles wrought from bone, tendons of a kangaroo, lining of a cow’s stomach. Despite the macabre sounding nature of this list, as if they are the components of some witch’s brew, these items help to illustrate the history of surgery and surgical suture. From the first eyed needles, approximately 50,000 years ago1, to the use of kangaroo tendons and bovine serosa as wound closure materials, surgery has employed a wide array of materials to facilitate wound approximation and promote healing. Currently, the field relies heavily on synthetic materials as replacements to these seemingly antiquated, naturally occurring materials. Wound closure requires numerous materials of varying composition and geometry dependent upon the location and nature of the surgery. To rely solely on one type of suture would result in decreased quality of care and increased complications. For this reason, a wide array of wound management solutions are currently available. The intent of this review is to highlight and differentiate the options that are currently available to physicians, and to provide a prospectus on future suture materials. As with any review, this work draws on information from previous reviews2-8 of available materials and seeks to provide an update on the current state of available biomaterials. A suture is a strand or fiber used to sew parts of the living body9. Given the broad nature of the definition, it is natural that many differing types of suture exist. While many sutures are made from natural materials (silk and catgut), this review will focus mainly on synthetic materials. The ubiquitous nature of surgery ensures the 2 large size of the market for surgical suture. The market for surgical suture in 2016 exceeded $3.46 billion, and is expected to reach $4.40 billion by 202110. During this time, expected growth is 5% per year, due to an increase in the number of surgeries and the launch of new suture materials10. In order to discuss the varying synthetic sutures, the types will be bifurcated into absorbable and nonabsorbable. The composition, geometry, and utility of each suture family will be discussed to act as a useful reference for those seeking to compare the characteristics of different suture materials. This will include features such as size, color, and any specialized features used to distinguish the suture. In addition to the distinction between absorbable and nonabsorbable suture, a distinction also exists between braided and monofilament suture. This will be included in the discussion of each suture material. Absorbable vs Non-Absorbable Suture: The choice between an absorbable and nonabsorbable suture depends largely on the amount of time required for proper wound healing, whether the suture will need to be removed, and the location of the tissue approximation. Absorbable suture is designed to be implanted into the body and degrade over time without the need for later removal. These suture materials are designed to be susceptible to hydrolysis and enzymatic attack within the body and to exhibit a certain tensile strength profile at given times post implantation. Absorbable sutures are manufactured using materials that are easily metabolized by the body and that do not produce hazardous byproducts. In general, absorbable sutures are used for the approximation of fascia within the body where tensile strength is required for a period 3 between a few days and several months. Synthetic polyesters are most often employed for absorbable sutures, but natural products like catgut can also be used. Non-absorbable sutures are manufactured using materials that will not degrade when implanted into the body. Rather, they become encased in the tissue as the wound heals and are left in place. For this reason, they must be manufactured from materials that will not cause adverse reaction. Polypropylene, nylon, and silk are common materials used for the manufacture of nonabsorbable suture. Nonabsorbable sutures can be used for surface approximations or internal wound closure where an extended healing time is required. This type of suture is often used for cardiovascular and neurological surgeries, external wound closure, wound closure within the body cavity, and for prosthesis attachment11. Monofilament vs Multifilament Suture: Sutures can be divided into monofilament and multifilament or braided sutures. Monofilament sutures are composed of a single strand of material and are often uncoated and nonabsorbable. Since they are monofilament, they tend to invoke less of an inflammatory response than braided suture due to the reduced surface area of the suture. While they move through tissue more easily than braided suture, they do suffer from poorer handling characteristics. Monofilament suture typically requires more knots to ensure secure placement and maintain memory when removed from packaging. Multifilament sutures are composed of numerous monofilament strands that are braided together. Braided sutures are often coated and absorbable. The