Advanced technologies and polymer materials for surgical sutures

Sterilization techniques used forsutures have also been discussed in this chapter.1.2 Polymers as suture materialsIn the past sutures made of natural materials like dried animal gut, ani

CHAPTER Advances in biopolymer based surgical sutures Blessy Joseph1, Jemy James2, Nandakumar Kalarikkal3 and Sabu Thomas3 1Business Innovation and Incubation (BIIC), Mahatma Gandhi University, Kottayam, Kerala, India; 2University Bretagne Sud, Lorient, France; 3International and Inter University Centre for Nanoscience and Nanotechnology, Mahatma Gandhi University, Kottayam, Kerala, India 1.1 Introduction Over the years, there has been a dramatic growth of the wound closure market Traditionally materials like silk, cotton, horsehair, animal tendons and intestines, and wire made of precious metals were in operative pro- cedures The limitations and risks associated with such wound closure devices demanded the need for efficient and cost-effective techniques for wound healing Although there have been significant advances in tissue adhesives and other mechanical wound closure devices, sutures have been the preferred choice for surgeons Sutures can be defined as the materials used to uphold tissues together normally after a trauma or surgery [1] They can be natural or synthetic materials that can provide adequate mechanical strength during tissue fixation The art of suturing can be found in the Egyptian mummified resins, in which they have used woolen threads, plant fibers, hair, and tendons Suturing techniques were documented in 500 BCE (Before Common Era) by Indian surgeon Sushruta in “Sushruta Samhita [2].” Metal wires were first applied in the human body by French physicists Lapayode and Sicre in 1775 to set a broken humerus (upper arm bone)[3] A fundamental change was witnessed following Second World War, after which polymer sutures and stainless steel became superior The se- lection of suture material is dependent on the physical and biological characteristics of the suture as well as the type of tissue to be healed Sutures are made from synthetic or natural polymers Synthetic polymers are not readily degradable They accumulate and can have a long-term detrimental effect on ecosystems The tunable physical characteristics of biopolymers make them a reliable material for the fabrication of sutures Biopolymers can be obtained from natural sources or synthesized chemically from Advanced Technologies and Polymer Materials for Surgical Sutures © 2023 Elsevier Ltd ISBN 978-0-12-819750-9 https://doi.org/10.1016/B978-0-12-819750-9.00008-5 All rights reserved Advanced Technologies and Polymer Materials for Surgical Sutures biological material or entirely biosynthesized by living organisms[4] They are easily biodegradable as they are obtained from renewable sources The term “biodegradation” generally refers to degradation by microorganisms The polymer is broken down into carbon dioxide and water which forms food for microorganisms[5] Biopolymers as surgical sutures have gained considerable attention because of their unique properties like biocompat- ibility and biodegradability Biopolymers can adopt more precise and defined 3D shapes and structures when compared to synthetic polymers having more simple and random organization[6] This makes biopolymers attractive for in vivo applications They are generally classified into three categories based on the nature of repeating units they are composed of (i) polysaccharides, often carbohydrate structures (cellulose, chitin, starch, alginate, etc.); (ii) polypeptides made of amino acids (collagen, actin), and (iii) polynucleotides deoxynucleic acid (DNA) and ribonucleic acid (RNA)) (Fig 1.1) This chapter intends to provide an overview of the biopolymers used for suture fabrication, their physical and biological properties, and how these properties facilitate wound repair Sterilization techniques used for sutures have also been discussed in this chapter 1.2 Polymers as suture materials In the past sutures made of natural materials like dried animal gut, animal hair (e.g., horse hair), silk, tendons, and plant fibers (e.g., linen, cotton) were widely used [7,8] The technological advancements in polymer sci- ence paved way for the development of sutures with diverse materials having excellent mechanical and physical properties There has been a large-scale expansion and evolution of the research and business in the area of materials for biomedical applications Still, sutures and staples are the most used material in the biomedical industry Sutures are to be used in many cases where natural wound closure is difficult and external Figure 1.1 Classification of biopolymers according to their structure Advances in biopolymer based surgical sutures reinforcement is highly essential Biopolymer based absorbable sutures are much preferred to nonabsorbable sutures Sutures are generally classified as absorbable and nonabsorbable based on whether they degrade or not after performing the intended function Nonabsorbable sutures need to be removed by doctors, hence causing additional discomfort to patients Whereas absorbable sutures degrade within the body usually by hydrolysis or with the aid of proteolytic enzymes[9] 1.3 Biopolymers Environmental problems arise with the continued use of synthetic poly- mers Intensive research has been carried out in this direction, possibly replacing synthetic polymers with natural ones As mentioned above, biopolymers are obtained from biological sources Hence, the use of bio- polymers offers an eco-friendly approach They are decomposed by mi- croorganisms or natural processes like availability of moisture, sunlight, etc which is environmentally friendly when compared to petroleum based synthetic polymers releasing toxic byproducts into the surroundings Bio- polymers are employed in diversified fields such as food packaging, drug delivery, tissue engineering, etc Although they are biocompatible, many of them lack sufficient mechanical properties desired for medical applications Most often they are crosslinked or modified with materials like glutaral- dehyde, citric acid, poly (carboxylic acids), and so forth[10] Crosslinkers like glutaraldehyde can be cytotoxic hence greener approaches are also being explored Nanoparticles are also used to enhance the properties of biopolymers The interaction between biopolymers and nanoparticles re- sults in nanocomposites with improved functionalities like antimicrobial property, tensile strength, thermal stability, or water resistance Many re- searchers have investigated the ability of silver nanoparticles (AgNPs ) to improve the antimicrobial properties of biopolymers, wherein cost-effective methodologies could be formulated for developing wound dressings or food packaging films Cellulose paper coated with silver-gold nanoparticles displayed improved antibacterial activity against E.coli [11] Another work reported the synthesis of silver-cellulose hybrids which showed excellent antibacterial activity against E.coli and S.aureus whereas pure cellulose (Microcrystalline cellulose) didn’t exhibit any activity against the respective microbial strains[12] Although several biopolymers find promising appli- cations in the biomedical sector, we will be concentrating on polymers like cellulose, collagen, silk, chitosan, chitin, polyhydroxyalkanoates (PHA), and PLA which particularly fit well for the suture industry Advanced Technologies and Polymer Materials for Surgical Sutures Cellulose is the naturally occurring homopolymer consisting of b-1, linked glucan chains Being inherently biodegradable and low-cost material, cellulose finds immense application in healthcare [13] Cellulose materials try to self-assemble and form an extended network by both intramolecular and intermolecular hydrogen bonds, which makes them relatively stable Chitin is a sustainable biopolymer due to its abundance Structurally, chitin is N-acetyl glucosamine and the main source are crustaceans like crabs, shellfish, etc The deacylated form of chitin known as chitosan consists of N-acetyl glucosamine and glucosamine moieties Both chitin and chitosan are versatile enough to be processed to any form like sponges, gels, or scaffolds, thereby finding many applications in tissue engineering and drug delivery[14] Natural silk fibers are produced by arthropods like silkworms or spider Mulberry silkworms (Bombyx mori) are most commonly reared to produce silk They have a core-shell structure con- sisting of components, a heavy chain fibroin, a light chain fibroin, and a third small glycoprotein, known as the P25 protein These proteins are coated with hydrophilic sericins Silk materials are used as sponges, films, or sutures for applications like ligament tissue engineering, hepatic tissue en- gineering, cartilage tissue engineering, and so on [15e17] Poly(lactic acid) (PLA) is a biodegradable polyester produced from the monomer, lactic acid (LA) by mechanisms like direct polycondensation (DP) and ring-opening polymerization (ROP) The tunable physicochemical properties and biocompatibility of PLA make it suitable for biomedical applications Collagen is a major structural protein in animals and forms a vital part of the extracellular matrix It provides tensile strength to tendons and ligaments and also elasticity to the skin It has a 3D architecture comprising of a right- handed bundle of three parallel, left-handed poly proline II-type helices [18] Source of collagen includes bovine skin and tendons, porcine skin, marine organisms like sponges, fish, and jelly fish It is used for soft tissue repair, dental applications, and as scaffolds for tissue engineering [19,20] Polyhydroxyalkanoates (PHA) are naturally synthesized polyesters accu- mulated as energy storage material inside the cellular structure of various microorganisms 1.4 Biopolymers for sutures 1.4.1 Collagen Collagen nanofibrils (CoNF) have a great potential for being mechanically strong but biodegradable sutures They play a major role in tissue Advances in biopolymer based surgical sutures engineering as being the key component of the extracellular matrix It is the most abundant protein in the human body and imparts structural integrity and strength to the tissues[21] The use of collagen as a modern biomaterial began in 1881 Joseph Lister and William Macewen (Fig 1.2) reported the advantages of catgut, a collagen-rich biomaterial prepared from the small intestine of sheep[23] Untreated catgut sutures are often processed from dead animal tissue, hence causing infections[24] They are often used in the case of subcutaneous or fatty tissue[25] Collagen sutures were modified with heparin for sustained release of platelet-derived growth factor-BB (PDGF-BB) Tendon-derived cells seeded on PDGF-BB incorporated collagen sutures showed 50% greater proliferation than untreated collagen sutures[26] This could be because collagen provides active chemical sites for conjugating growth factors Collagen has also been used to coat surgical sutures to improve their functionalities Polyester/polyethylene sutures coated with collagen were evaluated for their response to bone and tendon cells[27] Collagen coating was found to stimulate proliferation and adhe- sion of cells in collagen coated sutures when compared to uncoated one 1.4.2 Polylactic acid (PLA) PLA is one of the most popular biodegradable and bio-based polymers PLA is used to prepare biodegradable polymer sutures [28] The biocom- patibility of the polymers has been extensively studied, and it has been proven to be one of the best biopolymers for biomedical applications like sutures etc [29] PLA is a polymer derived from LA and its structure makes it easily breakable during metabolism and thereby making it easier to be excreted from the body [30] Degradation occurs through enzymatic or hydrolytic scission of ester bonds The degradation of PLA depends on its Figure 1.2 SEM images of PLA suture loaded with PM-Ds: (A) 100 Â times, (B) 1000Â times (Reproduced with permission from Ref [22].) Advanced Technologies and Polymer Materials for Surgical Sutures molecular weight, crystallinity, presence of fillers, etc Recently, Liu et al reported the fabrication of PLA sutures loaded with PLA microspheres containing drug[22] Initially PLA microspheres containing drug genta- micin sulfate was prepared (PM-Ds) Further, this drug loaded microspheres were loaded onto the PLA sutures (PM-Ds/PLA) The mechanical prop- erties were analyzed which showed an increase in the properties of the drug loaded suture when compared to the neat suture A sustained release of the drug up to days could be achieved As evident from the scanning electron microscopy images, the microspheres entered the gaps of the suture fibers, and stuck to them firmly which could have resulted in the prolonged release of the drug (Fig 1.2) In another study, biopolymers like chitosan, alginate, and the blends of these polymers were coated on the surface of PLA sutures The mechanical studies were carried out Some of the drugs based on antibiotic sensitivity was chosen and was introduced into the sutures using surface treatment method like dip coating The drug release studies and antimicrobial activity proved that the drug-coated bio polymeric sutures were effective in wound closing and wound healing [31] Poor biocompatibility and cellular affinity are major problem encountered with PLA sutures To improve the surface hydrophilicity, PLA sutures were initially treated with lipase followed by grafting with chitosan [32] It’s evident from the SEM images that initially the untreated sutures had a smooth surface Once grafted with chitosan, in some places chitosan united and led to a rougher surface and large friction coefficient However, hydrophilicity was greatly improved Blends of PLA and polycaprolactone compatibilized with Ethyl Ester L- Lysine Triisocyanate (LTI) were melt-spun to produce suture threads of diameter 0.3 mm 1.0 phr of LTI was found to be the most suitable composition for producing sutures, at higher loadings the sutures were too rigid The suture threads didn’t induce any bacterial growth [33] 1.4.3 Silk Silk is a protein polymer whose characteristics are slow degradation and good mechanical strength Silk is preferred for cardiovascular, neurological, and ophthalmic procedures [34] The ease of handling and improved knot security properties makes silk superior among other sutures But their use is hindered due to the high inflammatory reactions posed by them [35,36] Bacterial attachment to silk sutures was compared to commercially available Monocryl Plus suture [37] From Fig 1.3 it is evident that the Advances in biopolymer based surgical sutures Figure 1.3 Scanning electron microscope images of (A) silk suture knot material and (B) Monocryl Plus suture knot material Microorganisms and cellular detritus are highly visible in silk sutures (Reproduced with permission from Ref [37].) microorganisms were highly colonized around the suture knot of silk suture when compared to that of Monocryl Plus suture Maintaining sterile conditions in the wound has always been a hurdle after suturing Medical devices and sutures contribute about 45% of nosocomial infections or hospital-acquired infections [38] Antibacterial sutures play a pivotal role in combating surgical site infections[39] Once a biofilm is formed on the surface of a suture, it becomes resistant to tradi- tional antimicrobials Once bacteria colonize a suture, local methods to treat bacterial in- fections become inadequate Hence, several strategies to prevent bacterial adherence have been proposed by researchers including the addition of antibiotics, nanoparticles, biomaterials, etc Sutures impregnated with an- tibiotics have been found to prevent the adherence of bacteria and biofilm formation [40] Tetracycline hydrochloride (TCH), a bacteriostatic drug is found to exhibit activity against a wide range of gram-positive and gram-negative microorganisms[41] The efficacy of TCH-treated sutures was studied by Viju and Thilagavathi [42] As was expected, untreated silk sutures promote the growth of E.coli and S.aureus Synergistic chitosan and TCH drug was exploited to develop antimi- crobial silk sutures for preventing microbial infections [43] Such combi- nations can provide a prolonged antibacterial effect AgNPs have been widely used as an antibacterial agent[44,45] AgNPs exhibits their antimi- crobial potential through various mechanisms The anchoring of AgNPs to Advanced Technologies and Polymer Materials for Surgical Sutures microbial cells, followed by penetration into the cells, reactive oxygen species and free radical generation, and modulation of microbial signal transduction pathways have been recognized as the most prominent ways of antimicrobial action [46] AgNPs were coated on silk sutures to impart antibacterial properties [47] Mechanical strength was retained after the addition of AgNPs; however, a significant reduction in bacterial growth was achieved Cytotoxicity studies using 3T3 mouse embryonic fibroblast cells showed 82% cell viability for silver treated samples This showed that the silver treatment did not affect their proliferative capacity Surface modification of silk fibroin suture, AASF (antheraea assama, popularly known as golden silk; found only in certain parts of Assam) was achieved by grafting polypropylene (PP) onto silk fibroin sutures[48] Here the sutures were first sterilized using argon and then low-temperature plasma grafting of PP onto sterilized sutures was done to achieve the desired biofunctionalities Here the modified suture showed more biocompatibility and improved wound healing when compared to the untreated ones In vivo studies were conducted in three groups The first group was sutured with AASF, the second with argon plasma-treated AASF (AASFAr) and the third group with PP grafted AASF sutures (PP-AASF) The histopathology studies on the 14th postoperative day show the pres- ence of inflammatory cells in group A characterized by lesser collagen formation (Fig 1.4) Group B shows a considerably fair amount of collagen formation with slight infiltration in and around hair follicles Whereas PP- AASF sutured group (Group C) shows highly accelerated wound healing activity Moreover, a greater amount of hair follicles was also present when compared to the other groups Figure 1.4 Histologic evaluation of wound healing on 14th postoperative day His- topathological section of the sample collected from the incised wound of (A) group A, (B) group B, and (C) group C animals shows inflammatory cell inflammation (IN) in and around the hair follicle (HF) as well as subepidermal tissue Proliferation of fibrous connective tissue (CT) indicates faster healing of group B and group C as compared to group A animals (Reproduced with permission from Ref [48].) Advances in biopolymer based surgical sutures 1.4.4 Chitin & chitosan Chitin and chitosan are polymers derived from marine animals and is some of the most available biopolymers other than cellulose However, some of the challenges make its usage cumbersome [49] Though chitin is highly biocompatible, nontoxic, and biodegradable, along with its antimicrobial effect, there are still more challenges to overcome to exploit its huge po- tential for prospective applications [50] Chitosan is a potent antimicrobial agent and its antimicrobial activity can be attributed to its cationic nature [51] The positively charged chitosan molecules interact with negatively charged microbial cell membranes leading to the disruption of the microbial membrane [52] Sutures were fabricated from chitin having good me- chanical strength [53] No allergic reactions or inflammation was seen The chitin suture was absorbed in about months in rat muscles The accel- erated degradation can be mainly due to the action of lysozyme Chitin nanofibrils are used as nanofillers for reinforcing polymers to obtain nanocomposites with enhanced stability, especially in the case of bio- resorbable sutures [54] Chitosan stimulates tissue regeneration and prevents scar formation The mechanical strength of chitosan is very low; hence, it is mainly exploited as suture coatings Chitosan has been used for coating silk sutures [55] Silk sutures coated with chitosan also showed excellent anti- bacterial efficacy [56] A modified derivative of chitosan known as hydroxyl propyl trimethyl ammonium chloride (HACC) chitosan coated on Vicryl suture showed excellent antibacterial activity and also displayed good biocompatibility [57] HACC is a water-soluble modified derivative of chitosan that exhibits good antibacterial activity [58,59] HACC coated sutures effectively prevented biofilm formation when compared to triclosan-coated sutures Prabha et al showed that extracted chitosan (EC) from crab shells showed higher inhibition of biofilm formed by mixed species[60] The antibacterial and antifungal effects of Vicryl absorbable sutures coated with chitosan, uncoated sutures, and commercially available triclosan-coated sutures were studied against S epidermidis and C albicans (Fig 1.5) The uncoated suture (control) and sutures soaked with acetic acid (Vehicle control) did not show any antibacterial or anticandidal activity The commercial triclosan-coated sutures exhibited only antibacterial ac- tivity and did not show any anticandidal activity EC immobilized sutures exhibited good antimicrobial activity against both strains compared to commercially available chitosan (CC) 10 Advanced Technologies and Polymer Materials for Surgical Sutures Figure 1.5 Antimicrobial activities of the impregnated suture against S epidermidis and C albicans: (A) Control; (B) VC; (C) EC (400 mg/mL); (D) CC (400 & 450 mg/mL); (E) Triclosan coated Reproduced with permission from Ref [60] 1.4.5 Polyhydroxyalkanoate (PHA) PHA is a microbial polyester having excellent biocompatibility and biodegradability Poly(3-hydroxybutyrate) (PHB) is the most widespread member of the polyhydroxyalkanoate family and is produced under un- balanced growth conditions like depletion of essential nutrients such as nitrogen, phosphorus, or magnesium [61] Poly (4-hydroxybutyrate) (P4HB) is a typical PHA type used for the fabrication of surgical materials The most well-known product, and the first approved by the US Food and Drug Administration, is the TephaFLEX suture fabricated from P4HB [62] In vivo studies of PHA sutures implanted intramuscularly over year showed that animals that received the sutures were in good health condi- tion during the period of study No adverse reactions were observed, and functional characteristics of the animals were also not affected [63] Poly- hydroxyalkanoate sutures decreased tendency to curl were fabricated by extrusion and orientation of the fibers [64] The resulting fibers had an elongation to break from about 17% to about 85% and Young’s modulus of less than 350,000 psi He et al evaluated the biocompatibility of mono- filament made from poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and a multifilament made from poly(3-hydroxybutyrate-co-3- hydroxyvalerate) (PHBV) and PLA blend [65] The PHBHHx fiber and the PHBV/PLA fiber showed remarkable biocompatibility to be used as sur- gical sutures