European Review for Medical and Pharmacological Sciences 2022; 26: 828-845

Surgical site infection and development

of antimicrobial sutures: a review
R.A.H.W. CHUA1,5, S.K. LIM1,3, C.F. CHEE2, S.P. CHIN3, L.V. KIEW4, K.S. SIM5, S.T. TAY1
1
Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur,
Malaysia
2
Nanotechnology and Catalysis Research Centre, Universiti Malaya, Kuala Lumpur, Malaysia
3
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur,
Malaysia
4
Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
5
Institute of Biological Sciences, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia
R.A.H.W. Chua and S.K. Lim equally contributed to this work

Abstract. – Sutures are used to facilitate deeper tissues, for instance, fascial and muscle;
wound healing and play an important role in en- (iii) organ and/or space infection that affects any
suring the success of surgical interventions in site of the body, other than the surgical site1. Pa-
healthcare facilities. Suture-associated surgical tients with SSIs often have a higher risk of hospi-
site infection (SSI) may develop when bacterial
pathogens colonize the suture surface and es- tal re-admittance, longer ICU stay, and postoper-
tablish biofilms that are highly resistant to antibi- ative complications3. Not surprisingly, SSIs also
otic treatment. The outcome of SSI affects post- end up with financial and emotional burdens due
operative care, leading to high rates of morbidity to the high medical cost and poor healthcare qual-
and mortality, prolonged hospitalization, and in- ity3,4. Penel et al5 reported an additional length of
creased financial burden. Antimicrobial sutures hospital stay (16 days) and increased direct med-
coated with antiseptics such as triclosan and ch-
lorhexidine have been used to minimize the oc-
ical costs (17000 Euros) due to SSI after head and
currence of SSI. However, as the efficacy of anti- neck cancer surgery. MRSA SSI was reported to
septic-based sutures may be affected due to the prolong hospital stay by 19.3 days and increased
emergence of resistant bacterial strains, new ap- medical expenditure by $7015 after colorectal
proaches for the development of alternative an- surgery6. Tuon et al7 reported a mortality rate of
timicrobial sutures are necessary. This review 5.4% due to SSIs related to orthopedic trauma.
provides an update and outlook of various ap- The incidences of SSI ranged from 1.2 to 5.2%
proaches in the design and development of an-
timicrobial sutures. Attaining a zero SSI rate will in developed countries8. Ling et al9 described a
be possible with the advancement in suturing reduction in the incidence of SSI, with the cumu-
technology and implementation of good infection lative rates ranging from 0.9% in the United States
control practice in clinical settings. of America (USA) to 2.6% and 2.8% in Italy and
Australia, respectively9. The reduced incidence of
Key Words: SSIs may be attributed to the recent progress in
Antimicrobial sutures, Biofilm, Review, Suture, Sur-
gical site infection.
medical practice; in particular, the introduction of
minimally invasive surgery with smaller incision
size and faster mobilization, better safeguarding
of patient’s immunity, and reduced utilization of
Introduction central venous catheters for parenteral nutrition10.
However, SSI is still amongst the most common
Surgical site infections (SSIs) are surgery-re- type of hospital-acquired infection (HAI) in Eu-
lated infections that occur within 30 days after a rope and the USA11.
surgical intervention, or within one year after the While data on the incidence of SSI in devel-
introduction of a medical implant1-3. Depending oped countries is comprehensive, such data is
on the anatomic sites where the infections take lacking in Asia and low middle-income countries
place, SSIs can present as either (i) superficial (LMIC). In Asia, the incidence of SSI ranged
infection that affects the skin and subcutaneous between 2.0% and 9.7% in Korea12, while in Ja-
tissues; (ii) deep incisional infection that affects pan, the cumulative incidence of SSI was 15.0%

828 Corresponding Author: Tay Sun Tee, Ph.D; e-mail: [email protected]

 Surgical site infection and development of antimicrobial sutures: a review

(6691/44 751 procedures) and 17.8% (3230/18 187 A surveillance study20 in Europe (2010-2011)
procedures) for colon and rectal surgery, respec- showed that the highest cumulative incidence of
tively13. The overall incidences of SSI were 7.8% SSI in patients is colon surgery (9.5% episodes
in South East Asia (SEA)9 and 6.1% in LMIC11. per 100 operations), followed by coronary ar-
SSI was reported as the most common HAI in tery bypass graft (3.5%), and caesarean section
LMICs, with significantly higher risk than in de- (2.9%). Other procedure-related risk factors in-
veloped countries8,14. clude degree of wound contamination and pa-
tients’ clinical condition21,22.
Risk Factors of SSI The age, sex, lifestyle, body mass index,
Multiple procedure- and patient-related risk pre-existing infection, diabetes, comorbidities,
factors are known to cause the initiation and and surgical history are among the patient-re-
progress of SSI9,15,16. The procedure-related risk lated risk factors contributing to SSI2,3. Aga et
factors are associated with the nature of the sur- al23 reported that 22.1% of patients undergoing
gical intervention such as the surgical site, con- abdominal surgery developed SSIs up to 30 days
ditions of wound contamination, and quality of post-surgery. Orthopedic SSIs require a multifac-
pre- and postoperative care17. For instance, colon, eted approach as patients experience a substantial
gastrointestinal and urinary tract surgeries are loss of physical function and an overall poorer
associated with a high risk of SSI due to a heavier quality of life24,25. Li et al26 observed that diabe-
bacterial load at the surgical site; hence, a higher tes mellitus, smoking, operations for >3 hours,
chance of developing intraoperative contamina- absence of antibiotic prophylaxis, and a history
tions18. A correlation between wound category of previous surgery had each contributed to a
and incidence of SSI had been reported whereby significant increase in the risk of SSIs. Additional
the risk of SSIs increased from clean to dirty/ factors that have been reported include move-
infected wound19. ment and number of hospital staff, structural
Additionally, the type of surgery (elective/ features of operating theatre21,27, high body mass
emergency), duration of surgery, the complexity index, and severe scores based on US National
of surgical procedures and length of pre-opera- Nosocomial Infections Surveillance (NNIS) risk
tive hospital stays are also correlated with SSIs. index28,29.

Figure 1. Several mechanisms have been associated with the increased antimicrobial resistance of biofilm-embedded
bacteria: (i) inefficient antimicrobial infiltration through biofilm matrix, (ii) altered physiological responses of microbes to
the heterogeneous environment of biofilm, (iii) emergence of persister or dormant cells, and (iv) presence of polymicrobial
communities in the biofilm environment (i.e. co-infection of bacteria and fungi), which impede the selection of appropriate
antimicrobial therapy for multidrug-resistant bacteria (Image courtesy of Amelia Low CY).

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 R.A.H.W. Chua, S.K. Lim, C.F. Chee, S.P. Chin, L.V. Kiew, K.S. Sim, S.T. Tay

Sutures also provide a conducive surface for tibiotic-resistant bacteria in healthcare facili-
bacterial adherence, colonization, and biofilm ties worldwide. The World Health Organization
formation30-32 (Figure 1). The presence of foreign (WHO) warned that antibiotic-resistant bacteria
materials (suture or medical implants) in a wound may pose severe threats to human health if the
incision provides an anchoring surface for biofilm situation is left uncontrolled41. Bacteria acquire
formation and a reservoir for shielding exogenous antibiotic resistance traits through intrinsic, ac-
bacteria from the host-defense mechanism. The quired, and adaptive mechanisms42,43. Intrinsic
surface conformation of the multifilament suture antibiotic resistance refers to the natural char-
is known to harbor a higher density of bacterial acteristics of bacteria in conferring resistance
cells than monofilament suture31, while the inter- towards certain classes of antibiotics43,44. For in-
stices on suture knots provide a large surface area stance, Gram-negative bacteria are relatively less
for bacterial propagation and colonization33. A sensitive to β-lactam antibiotics as compared to
study34 comparing absorbable and non-absorbable Gram-positive bacteria. The lipopolysaccharide
sutures during dento-alveolar surgery showed cell wall, present only in Gram-negative bacteria,
that non-absorbable sutures were more prone to acts as a physical barrier to prevent the entry
biofilm formation. Since sutures under different of hydrophilic β-lactam antibiotics, thus con-
host/environments can initiate SSI, the use of ferring intrinsic resistance towards antibiotics44.
appropriate sutures for surgical procedures plays Acquired antibiotic resistance, on the other hand,
an important role in preventing SSI31. occurs when microbes attain resistance to antibi-
otics previously susceptible due to mutations in
Common Microorganisms the drug targets, changes of cellular physiology
Associated with SSI or adoption of foreign genes encoding antibiotic
Wound contamination and insufficient disinfec- resistance via horizontal gene transfer43. Bac-
tion prior to surgical closure are the main reasons teria exhibit adaptive antibiotic resistance in a
for SSI. Local microflora or environmental contam- reversible, temporal manner in response to the
inants are frequently associated with the initiation alteration of environmental stress in the presence
of SSIs. Staphylococcus aureus, Staphylococcus of antibiotics45, and as a result of metabolic alter-
epidermidis, Escherichia coli, Pseudomonas aeru- ations and changes on gene/protein expression
ginosa, Acinetobacter species and Enterococcus profiles44,46.
species are common organisms isolated from pa- The antibiotics used for the treatment of staph-
tients with SSI35,36. S. aureus, which is present on ylococcal SSI depend on the location and depth of
the skin or anterior nares of almost 80% healthy the infection site, adequate removal of damaged
individuals, represents the most predominant organ- tissue or foreign object from surgical wound,
ism in causing SSIs during surgical intervention35-37. and the occurrence of MRSA SSI47. Commonly
The microbiological profiles of SSI vary with employed antimicrobial treatment for methicil-
the type and site of surgical manipulations. S. lin-sensitive S. aureus (MSSA) SSI are first-gen-
aureus is more likely to be implicated among pa- eration cephalosporins and antistaphylococcal
tients undergoing cardiac, neurosurgery, breast, penicillins47,48, while for MRSA SSI, the con-
and orthopedic surgeries, as well as patients ventional antibiotic employed is vancomycin47,49.
receiving grafts, prostheses, or implants, while Although vancomycin-containing antibiotic pro-
infections caused by Gram-negative bacilli are phylaxis has resulted in decreased SSI rates50,
more frequently associated with patients receiv- the use of vancomycin alone has been associated
ing appendectomy, colorectal, urologic, obstetric with a higher risk of MSSA in MRSA-negative
and gynecologic procedures2. Strict compliances patients51. Hence, routine administration of van-
to infection control measures including decol- comycin antibiotic prophylaxis in MRSA-neg-
onization of S. aureus prior to surgery, good ative patients is not recommended52. According
hygienic practice of healthcare professionals and to published guidelines, supportive data are still
patients, as well as the usage of proper antiseptics required for local and topical antibiotic therapy
for disinfection are recommended to reduce the including antibiotic irrigations, antimicrobial-im-
rate of SSIs effectively38-40. pregnated dressings, and wound sealants, in re-
ducing SSI risk52,53.
Antimicrobial Resistance and SSIs Since the emergence of MRSA, the proportion
The injudicious use of antibiotics has been of SSIs due to the superbug has increased from
identified as a cause for the emergence of an- 9.2% to 63.5%54, depending on postoperative

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 Surgical site infection and development of antimicrobial sutures: a review

antibiotic policy and surveillance programs at Biofilms on implanted medical devices (e.g.,
various clinical settings. Limited choices of drug catheters, implants and surgical sutures) are dif-
are available for the treatment of MRSA infec- ficult to be eradicated with the administration of
tions. Multidrug-resistant (MDR) strains of E. systemic antibiotics69. Surgical intervention is
coli and P. aeruginosa are also frequently report- essential for the management of infected tissues
ed in SSI2,55,56. About 68.6% of bacteria isolated and implanted medical devices70-72. As biofilm-as-
from orthopedic-related SSIs were resistant to sociated infections are one of the main factors be-
cefuroxime a major teaching hospital in China26. hind the onset of recurrent and chronic infections,
A systematic review of 41 studies published special care and appropriate strategies should be
between 1994 and 2016 on multi-drug resistant instituted for the prevention and eradication of
HAI among ICU patients in South East Asia re- the infections70,73.
vealed the predominance of MRSA (23 studies)56, Staphylococcus aureus displays a high capaci-
vancomycin-resistant enterococci (VRE), extend- ty to colonize new surfaces and is recognized as
ed-spectrum β-lactamase (ESBL)–producing or- a major cause of biofilm-associated infections in
ganisms, MDR A. baumannii, MDR P. aerugino- medical devices32,74. Begun et al75 showed that S.
sa, and MDR Klebsiella pneumoniae57,58. aureus strains producing excessive biofilm killed
SSIs caused by MDR bacteria often result in Caenorhabditis elegans worms quicker than the
longer hospital stays, higher rates of readmissions strains with less biofilm production, suggesting
and mortality, increased financial cost and treat- that staphylococcal biofilm is an important viru-
ment complexity53,57,59. Due to the use of more ex- lence factor. Biofilm formation, a process involv-
tensive drug regimens and aggressive treatment ing bacterial adherence, accumulation, matura-
strategies, it has been estimated that an additional tion, and dispersion, is determined by quorum
hospitalization cost of between USD 10,000 and sensing and various genetic factors. The density
USD 40,000 would be required for treating MDR of biofilm is determined by bacterial species,
bacterial infections60-62. High incidences of SSIs availability of nutrients, and surface charges of
caused by MDR bacteria have been reported to the cells76. The emergence of antibiotic resistance
pose a serious threat to patients and the health- in clinical settings worldwide has led to limited
care system63. options for the treatment of S. aureus biofilm-as-
sociated infections. As conventional approaches
Biofilm-Associated Infections target bacterial viability, selection for resistant
Biofilm is a multi-layered structure of mi- subpopulations frequently occurs in clinical set-
crobial communities embedded in extracellular tings. On the other hand, suppression of S. au-
polymeric matrixes which are composed of poly- reus virulence presumably exerts less selective
saccharides, extracellular DNA, protein, lipid, pressure for antibiotic resistance74, and thus, may
and other biopolymers64-66. The microbial com- serve as a promising approach for combating S.
munities in the biofilm show higher resistance aureus biofilm-associated infection77-79.
(up to 1000-fold) to antimicrobial therapy in
comparison to the planktonic counterparts67. Sev- Antimicrobial Sutures
eral mechanisms have been associated with the Several organizations have recommended the
increased antimicrobial resistance of biofilm-em- use of antimicrobial-coated sutures as a preven-
bedded bacteria, as shown in Figure 1. These tive measure against SSI80-82. The Centers for
include (i) inefficient antimicrobial infiltration Disease Control and Prevention (CDC) and WHO
through biofilm matrix, (ii) altered physiological guidelines on reducing the risk of SSI provide
responses of microbes to heterogeneous environ- recommendations on the use of triclosan-coated
ment of biofilm, (iii) emergence of persister or sutures, regardless of the type of the surgery11,53.
dormant cells, and (iv) the presence of polymicro- The National Institute for Health and Care Ex-
bial communities in a biofilm (i.e., co-infection of cellence (NICE) stated that the overall evidence
bacteria and fungi), which impede the selection favored triclosan-coated sutures over standard
of appropriate antimicrobial therapy for MDR sutures; and a clear benefit has been shown by the
bacteria68. Additionally, as biofilms can host dif- triclosan-coated sutures in pediatric surgery83.
ferent species of bacteria in close contact with The triclosan-coated suture is also recommended
each other, this may facilitate the dissemination by the American College of Surgeons & Surgical
of genes encoding drug resistance or plasmid ex- Infection Society (ACS/SIS) for wound closure in
change in the microbial communities68. clean and clean-contaminated abdominal cases52.

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 R.A.H.W. Chua, S.K. Lim, C.F. Chee, S.P. Chin, L.V. Kiew, K.S. Sim, S.T. Tay

A series of clinical studies and meta-analy- sutures based on the feature of absorption into the
ses80-82,84 indicated the superior efficacy of tri- body. Absorbable sutures are made of polydioxa-
closan-coated sutures to prevent SSI in compari- none, polyglycolic acid (PGA), monocryl polymer,
son to non-antimicrobial sutures. However, there and polylactic acid, while non-absorbable sutures
have been conflicting opinions on the use of tri- are made of nylon, polyester, and polypropylene
closan-coated sutures to reduce SSI risk and more (PP) etc. Poly (lactic-co-glycolic acid) (PLGA)88,
evidence on the benefits of using triclosan-coated polyvinyl alcohol (PVA) and poly-L-lactic acid
suture for the dressings of different wounds are (PLLA) are increasingly used in the manufactur-
required to draw a firm conclusion85. As the ing of modern sutures. Table II summarizes the
impact of antiseptic-impregnated sutures on the characteristics (antimicrobial compounds, suture
development of resistance to antiseptics is not materials and technique) of antimicrobial sutures
clear, the Society for Healthcare Epidemiology of that have been reported from 1990-2020, besides
America/Infectious Diseases Society of Ameri- triclosan-coated sutures.
ca (SHEA/IDSA) guidelines do not recommend The approaches used for incorporation of anti-
antiseptic-impregnated sutures for routine use as microbial compounds on sutures (as illustrated in
a strategy to prevent SSI86. Meanwhile, the Asia Figure 2) include (i) dip-coating, whereby sutures
Pacific Society of Infection Control (APSIC) rec- are dipped in a solution containing the antimicro-
ommends the use of antimicrobial-coated sutures bial agents and the polymeric coating agents (i.e.,
in settings with high SSI rates in clean surgeries9. PLGA, PVA, and PLLA) for a predefined period
Table I shows antimicrobial sutures that have for physical adsorption onto the sutures, (ii) sur-
been marketed for medical and veterinary use. face modification and compound immobilization;
Braided polyglactin 910 coated with triclosan (Vic- whereby the suture surface is modified either by
ryl Plus) was the first antimicrobial suture to re- plasma treatment, radiation, or chemical grafting
ceive approval for clinical use by the US Food and for introduction of a functional group to facilitate
Drug Administration (US FDA). To date, other tri- antimicrobial immobilization via formation of co-
closan-coated sutures, i.e., monofilament poligle- valent bonding, and (iii) blending and compound-
caprone (Monocryl Plus), monofilament polydiox- ing, whereby antimicrobial agents are blended
anone (PDS Plus) and multifilament polyglactin with suture materials followed by synthesis of
910 (Petcryl Plus) are commercially available. Sev- the antimicrobial suture. In this approach, elec-
eral types of chlorhexidine-based sutures have also trospinning technique has been used to produce
been marketed for veterinary use (Table I). very thin fibers (micro or nano scales)89. Amongst
these methods, dip-coating approach is the most
Antimicrobial Agents and common method for incorporation of bioactive
Suturing Technology molecules onto suture as it is less expensive and
The physical, biological, and handling char- technically less demanding compared to other
acteristics of sutures are essential to facilitate drug-elution/fabrication methods and does not
wound healing87. There are two types of synthetic affect the mechanical properties of sutures89,90.

Table I. Antimicrobial sutures that have been commercialized.

Suture type Brand name Properties Manufacturer

Medical use
Triclosan-based VICRYL Plus Multifilament, absorbable polyglactin 910 Ethicon Inc.
suture MONOCRYL Plus Monofilament, absorbable poliglecaprone
PDS Plus Monofilament, absorbable polydioxanone
Petcryl Plus Multifilament, absorbable polyglactin 910 Futura Surgicare Pvt Ltd
Chlorhexidine- Trisorb Plus Multifilament, absorbable poly(glycolic acid) SamYang
based suture Neosorb Plus Multifilament, absorbable poly(glycolic Biopharmaceuticals
co-lactic acid) (90:10) Corp
Monosorb Plus Monofilament, absorbable polydioxanone
Veterinary use
Chlorhexidine- Mono-Dox Plus Monofilament, absorbable polydioxanone CP Medical Inc.
based suture Visorb Plus Multifilament, absorbable poly(glycolic acid)
Monoswift Plus Monofilament, absorbable poly(glycolide-
co-caprolactone) 25

832
 Surgical site infection and development of antimicrobial sutures: a review

Table II. A summary of the studies conducted on the development of antimicrobial sutures (1990-2020).

Antimicrobial Main suturing Type of suture

sutures technology investigated Ref.

Antiseptics-based sutures
Chlorhexidine and octenidine Dip-coating Braided, absorbable PGA acid suture 73
(Gunze PGA)
Iodine Dip-coating Nylon fibers (Modipon (India) Ltd., 109
Modinagar-India)
2,5-dimethoxy-2,5-dihydro- Cross-linking Raw silk from Bombyx mori 110
furan (DMDF)–-iodine (Safia Silk Industries, Kolkata)
Octenidine hydrochloride, Dip-coating Synthetic absorbable PGA suture 111
chlorhexidine dipalmitate, (PGA Resorba)
chlorhexidine dilaurate
Octenidine Dip-coating PGA suture (PGA Resorba, USP 1.0), 112
Vicryl and Vicryl Plus (Ethicon)
Povidone-iodine, chlorhexidine Dip-coating Braided nylon, non-braided nylon, silk, 114
and Vicryl (Ethicon, USP 3-0) sutures
Chlorhexidine-functionalized Dip-coating Silk, polyester, and copolymer of glycolide 120
polyelectrolyte films and L-lactide sutures
Chlorhexidine and poly Dip-coating Monofilament sutures of polyglycolide-b- 121
(hexamethylene biguanide) poly(glycolide-co-trimethylene
(PHMB) carbonate-co-ε-caprolactone)-
b-polyglycolide suture (Monosyn)
Chlorhexidine Blending PCL monofilament 122
K21 Dip-coating Chromic gut, polyester suture, silk, 128
and nylon suture
Natural product-based sutures
Chitosan Dip-coating B. mori silk filaments 90
Aloe vera gel and silver (Ag) Plasma Poly (ethylene terephthalate) 91
functionalisation (PET, Reliance Industries Ltd. India)
Grapefruit seed extract Dip-coating PLGA synthetic absorbable braided suture 129
(Meta Biomed Co., Ltd.)
Aloe vera gel Dip-coating Braided, nonabsorbable silk sutures 130
(1.5 metric, size 4-0)
Aloe vera ethanolic extract Dip-coating Silk sutures (USP 3-0) 131
and ciprofloxacin
Chitosan Dip-coating Cotton yarn 133
Chlorinated high molecular Coating by PGA suture (Jinhuan Medical Products, 134
weight chitosan (N-halamine) layer-by-layer China)
assembly
Hydrolyzed chitosan, Dip-coating Multifilament polyethylene terephthalate 135
turmeric, and clove oil (PET; linear densities 540) and
polyamide (nylon 6) (1260 denier) threads
Totarol Spray coating Monofilament suture (Resonlon®, 75 cm 136
USP 3/0) and the multifilament sutures
(Ethibond Excel, 75 cm, USP 3-0)
Eugenol Dip-coating Cotton-sutures (Techno 3-0/30 mm, São Paulo, Brazil) 137
Chitosan and ethanolic Dip-coating Silk filament (20 denier, Sarvodhya 138
extracts of C. dactylon Sangam, Coimbatore)
Trans-resveratrol and rifampicin Dip-coating Braided, non-absorbable, nylon sutures (USP 0) 139

Continued

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 R.A.H.W. Chua, S.K. Lim, C.F. Chee, S.P. Chin, L.V. Kiew, K.S. Sim, S.T. Tay

Table II (Continued). A summary of the studies conducted on the development of antimicrobial sutures (1990-2020).

Antimicrobial Main suturing Type of suture

sutures technology investigated Ref.

Nanoparticle-based sutures
Sodium alginate-Ag nanoparticles Dip-coating Supramid polyamide sutures 140
(ref SD208000, Serag-Wiessner)
Sodium alginate-Ag nanoparticles Dip-coating Surgical gut plain suture (Ethicon Inc.) 141
Ag nanoparticles encapsulated Dip-coating Multifilament PGA sutures (Aesculap AG) 142
in hyperbranched polylysine
Ag nanoparticles (synthesized Dip-coating Catgut suture (Atramat, USP 3-0) 143
using hot water extract of
H. inuloides)
Bio-silver nanoparticles Dip-coating Nonabsorbable silk sutures) 144
(AgNP) (Dogsan, Turkey, USP 3-0
Bio-silver nanoparticles Dip-coating Nonabsorbable silk sutures (Doğsan, 145
(AgNP)-propolis Istanbul, Turkey, USP 4-0)
Zinc oxide nanoparticles Dip-coating Degummed silk fibers 146
Curcumin PEGylated gold Dip-coating TRUGLYDE FAST absorbable PGA suture 147
nanoparticles
Silver nanoparticles conjugated Dip-coating Multifilament, braided and absorbable 148
with trans-cinnamic acid and PGA sutures (DAMACRYL, USP 3-0)
povidone–iodine

Antibiotic-based sutures
Gentamicin and silver (Ag) Blending PCL suture 149
Sulfamethoxazole Dip-coating Silk suture (Jiangsu Medical Supplies Co., Ltd.) 150
Ciprofloxacin-PCL/PGA Dip-padding PLA suture (Zhejiang Gaoxin Company, 151
Jiaxing, China)
Levofloxacin Electrospinning PCL suture 152

Kanamycin, gentamicin, Graft polymerization PCA and PP twisted suture 153
monomycin, and doxycycline
Tetracycline hydrochloride Radiation grafting PP suture 154
Tetracycline hydrochloride, Plasma PP suture 155
chitosan, and silver nanoparticles, functionalization
Vancomycin Covalent PP monofilament suture 156
immobilization

Other antimicrobial-based sutures

Spider silk protein linked with Dip-coating Non-absorbable, multifilament silk sutures 157
human neutrophil defensin- (USP 3-0; Perma-Hand, Ethicon, USA)
1(HNP1)
Poly[(aminoethyl methacrylate)- Dip-coating Vicryl Plus sutures (VCP259, Ethicon Inc) 158
co-(butyl methacrylate)]
(PAMBM)
Poly(N-methylvinylimidazolium) Surface PP monofilaments (Atramat suture threads) 159
iodide functionalization
Poly(2-methacryloyloxyethyl Dip-coating Absorbable polyglactin sutures (KRAYON 160
phosphorylcholine (MPC)- Plus, KEISEI Medical Industrial Ltd.,
co-n-butyl methacrylate) (PMB) Tokyo, Japan)

Silver (Ag), nanoparticle (NP), polycaprolactone (PCL), polyglycolic acid (PGA), polypropylene (PP), poly-L-lactic acid
(PLLA), polycaproamide (PCA).

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 Surgical site infection and development of antimicrobial sutures: a review

Figure 2. A variety of novel sutures have been developed with antiseptics, nanoparticles, antibiotics, and biotechnological
products using techniques including (i) dip-coating, (ii) surface modification and (iii) blending and compounding, to provide
antimicrobial effects and improve the wound healing properties of sutures. a, A multifilament suture (scanning electron
microscopy, ×250 magnification). b, The antimicrobial effect of a suture can be determined by a zone of inhibition assay. The
clear zone surrounding suture on an agar plate lawn with bacterial culture indicates growth inhibition by an antimicrobial
suture. c, Use of antimicrobial sutures and good suturing techniques can minimize the risk of surgical site infection.

Although the delivery of many bioactive mol- Antiseptic-Based Sutures

ecules via sutures can be facilitated using melt Triclosan (5-chloro-2-(2,4-dichlorophenoxy)
spinning, electrospinning, and radiation, the me- phenol) is one of the antiseptics used in the early
chanical properties of sutures may be affected stage of antimicrobial suture development. It is a
during fabrication. Currently, plasma functional- broad-spectrum, non-cationic, lipid-soluble chlo-
ization of the suture and subsequent conjugation rinated phenoxyphenol compound used in the
with bioactive molecules are recognized as an formulation of personal care products including
effective strategy as both the mechanical and hand soap, toothpaste, antiperspirants shower gel,
infection prevention features are not likely to be dishwashing liquid and toothpaste92-95. It is also
affected during the fabrication process91. used as a topical decontamination agent for hos-
A variety of antimicrobial compounds including pital patients colonized with MRSA96. Triclosan
antiseptics, natural products, antibiotics, nanoparti- exhibits antibacterial activity against various
cles, and biotechnological products have been ap- Gram-positive and Gram-negative bacteria, as
plied for the development of antimicrobial sutures well as some antifungal, anti-mycobacterial and
(Table II). The evaluation of antimicrobial activities antiparasitic activities95,97. It interferes with bac-
of sutures is often performed using zone of inhibi- terial fatty acid formation through direct binding
tion (ZOI) assays against both Gram-positive and to the FabI protein (enoyl-acyl carrier protein
Gram-negative bacteria (Figure 2). Antimicrobi- reductase) and displays bacteriostatic activity at
al activities are confirmed when inhibition zones low concentrations (0.025 to 1.000 mg/ml), and
are observed surrounding sutures on agar plates bactericidal at high concentrations (7.5 to 8.0 mg/
lawn with SSI organisms. Additionally, bacterial ml)95,98-101. Several studies102-104 have reported the
adherence assays are performed to determine the development of triclosan resistance in bacteria
effectiveness of antimicrobial suture in resisting because of the high usage of triclosan in person-
bacterial adherence and colonization. A review of al and healthcare products. Triclosan resistance
the development of antimicrobial sutures over the is frequently reported in S. aureus100. Bacterial
last 30 years (1990-2020) is provided in Table II. strains with triclosan minimum inhibitory con-

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 R.A.H.W. Chua, S.K. Lim, C.F. Chee, S.P. Chin, L.V. Kiew, K.S. Sim, S.T. Tay

centrations (MICs) between 0.025 and 1 mg/ml lipin, causes interference on the bilayer structure,
have been found resistant to multiple antibiot- and cytoplasmic leakage123. The cationic surfac-
ics105,106. Pseudomonas aeruginosa is inherently tant has a broad-spectrum activity against MDR
resistant to triclosan due to the presence of the bacteria125. A study by Obermeier et al112 reported
FabV gene (encoding an isozyme of FabI pro- high biocompatibility, slow drug release and an-
tein)99,107. Hence, triclosan-coated surgical sutures timicrobial effect for up to 9 days of octenidine
are not suitable for surgical procedures associated (11, 22 and 33 mg/cm) coatings on sutures using
with P. aeruginosa infections. palmitic acid.
Iodine and povidone-iodine (PVP-I) are A series of antimicrobial sutures coated ei-
broad-spectrum antiseptics that act by oxidation ther with chlorhexidine or octenidine on PGA
of the reactive moieties on bacterial membranes sutures using laurate or palmitate as drug carri-
and inactivation of bacterial enzymes in the ers exhibited excellent antimicrobial activities111.
respiratory electron transport system108. Iodine Obermeier et al73 reported higher inhibition (1.7
has been incorporated either alone or with other log reduction) of S. aureus adherence on sutures
antiseptics onto sutures to produce promising coated with chlorhexidine/laurate, in comparison
antimicrobial results109. In a study by Francis to Vicryl Plus sutures112. Recently, K21, a new
et al110, radio-opaque antimicrobial sutures were class of quaternary ammonium silane (SiQAS)
developed by stepwise 2,5-dimethoxy-2,5-dihy- disinfectant126,127 has been introduced as a coating
dro-furan (DMDF)–iodine cross-linking reaction agent for different sutures. K21-coated sutures
for fabrication of silk fibers. The sutures inhibit- demonstrated dose-dependent inhibitory activi-
ed S. aureus and E. coli and were non-cytotoxic ty against oral microorganisms (Porphyromonas
against 3T3-fibroblast cells. gingivalis and Enterococcus faecalis)128.
Chlorhexidine is an oral antiseptic with prov-
en safety and efficacy that has been used for Natural Product-Based Sutures
the development of antimicrobial sutures73,111,112. Natural products including plant extracts have
Chlorhexidine exhibits broad-spectrum bacte- been recognized as a potential source of antimi-
ricidal activity against S. epidermidis, MRSA, crobial coatings on sutures. Various natural prod-
methicillin-resistant S. epidermidis (MRSE) and ucts including grapefruit seed extract, aloe vera,
E. coli113-118 through interaction with the phos- chitosan, turmeric, clove oil, and eugenol have
phate moieties of bacterial membrane119. Walker been explored for coating on sutures (Table II).
et al114 demonstrated antimicrobial activities of Lee et al129 showed the feasibility of incorporat-
nylon, silk and polyglactin (Vicryl) sutures coat- ing grapefruit seed extracts on sutures for wound
ed with chlorhexidine against S. aureus, MRSA healing applications. Ghafoor et al130 investigated
and S. epidermidis. Sutures functionalized with the efficacy of aloe vera-based antimicrobial su-
chlorhexidine, poly(ethyleneimine), poly(sodi- ture against bacteria (E. coli and P. aeruginosa)
um-4-styrene sulfonate), poly(allylamine hydro- and filamentous fungi (Aspergillus flavus and As-
chloride), poly(L-glutamic acid), and poly(L-ly- pergillus tubingensis). In their study, aloe vera gel
sine) were demonstrated to inhibit E. coli up to was incorporated with PVA using a dip-coating
7 days120. The inhibition against S. epidermidis approach. Silk sutures coated with 5% aloe vera/
and E. coli has been shown by monofilament PVA demonstrated the best inhibition against
sutures coated with a combination of chlorhexi- target organisms and reduced bacterial colony
dine, lactide, trimethylene, carbonate, and poly- counts at the incision sites of Balb/c mice.
hexamethylene biguanide (PHMB)121. Scaffaro In another approach undertaken by Ravishan-
et al122 explored a novel coating method by in- kar et al131, silk suture was dipped in an ethanolic
corporating chlorhexidine diacetate (CHX) onto extract of aloe vera, dried, and challenged with
polycaprolactone (PCL) monofilament suture via E. coli (ATCC 25922) using ZOI assays. The
a single-step approach during melt processing. suture demonstrated inhibitory activity to E. coli
Antimicrobial activities against E. coli, Micro- but did not outperform suture pre-treated with
coccus luteus and Bacillus subtilis strains were ciprofloxacin. A new approach of antimicrobial
observed at a low CHX concentration without polyethylene terephthalate (PET) suture devel-
affecting the tensile properties of the sutures. opment using plasma functionalization followed
Octenidine is an antiseptic that has been identi- by immobilization of aloe vera and silver (Ag)
fied as a replacement compound for triclosan123,124. has been recently described by Anjum et al91.
The compound interacts with membrane cardio- The antimicrobial sutures demonstrated superior

836
 Surgical site infection and development of antimicrobial sutures: a review

bacteriostatic and bactericidal activities against ing Ag nanoparticles onto polyamide sutures.
E. coli and S. aureus and improved the wound Taking the advantage of the negative charges of
healing process of Swiss albino mice. Ag nanoparticle binding to the cationic PDAD-
Chitosan is a natural antimicrobial agent well MAC, Ag nanoparticles were rapidly adsorbed
recognized for its low toxicity, biodegradability, to pre-coated PDADMAC layer on sutures. The
and biocompatibility. It binds to bacterial te- resulting suture showed a 76.82% reduction in S.
ichoic acids, and disrupts cell morphology and aureus colony counts. In a study conducted by
division132. Chitosan-coated surgical sutures have Augustine and Rajarathinam et al141, surgical gut
been reported to exhibit good antimicrobial ac- plain suture coated with Ag nanoparticles and
tivity and prevent bacterial adherence90,133. The sodium alginate demonstrated inhibition against
amino group of chitosan can be functionalized S. aureus and E. coli for up to 72 hours. A hy-
with other antimicrobial agents to enhance its perbranched-polylysine-based PGA suture was
antimicrobial property. Umair et al134 developed developed by Ho et al142 to ensure long-term re-
novel N-halamine-based antibacterial sutures lease of Ag nanoparticles. The coating agent was
by coating PGA suture with chitosan-poly-sodi- made up of a hydrophilic core (polylysine) and a
um-p-styrenesulfonate (PSS) via a layer-by-layer hydrophobic shell (stearoyl/palmitoyl chloride or
assembly technique to attain a linear relation- glycidyl hexadecyl ether) and encapsulated with
ship between the number of layers and chlorine at least 10 mg/cm of Ag nanoparticles. The suture
(released by N-halamine for its antimicrobial reduced more than 99.5 % of bacterial adherence
activity) loadings. Nine layers of chlorinated high in comparison to the uncoated control and exhib-
molecular weight chitosan were found to give the ited a stable release of Ag ions for up to 30 days.
most potent antibacterial effects, killing E. coli Biogenic Ag nanoparticles have attracted con-
and S. aureus within 15 minutes of contact. siderable attention as antimicrobial agents, large-
In a study by Masood et al135, multifilament ly due to their safety and high biocompatibility,
nonabsorbable PET and polyamide (Nylon 6) as compared to synthetic nanoparticles. Biogenic
sutures coated with varying ratios of hydrolyzed Ag nanoparticles are made from plant extracts or
chitosan, clove oil and turmeric, and corn starch biological materials, thus bypassing the need for
showed inhibition against S. aureus and improved reducing agents such as hydrazine, dimethylfor-
tensile and knot strength. Reinbold et al136 in- mamide, and sodium borohydride. Guadarrama
corporated totarol ((4bS,8aS)-4b,8,8-trimethyl-1- Reyes et al143 reported the use of a medicinal plant
propan-2-yl-5,6,7,8a,9,10-hexahydrophenanthren- (Heterotheca inuloides) extract to circumvent
2-ol), a plant-derived diterpenoid and PLGA the harmful effect of chemical-based reducing
onto non-absorbable monofilament and multifil- agents. After immersion in the nanoparticle solu-
ament sutures. The totarol/PLGA-coated sutures tion, Ag nanoparticle-based catgut suture threads
showed inhibition against S. aureus for over 15 showed inhibitory activities against S. aureus and
days without causing cytotoxicity to L929 mu- E. coli. Using a similar approach, Baygar et al144
rine fibroblast cells. Cotton sutures coated with reported the synthesis of Ag nanoparticles using
eugenol (4-allyl-2-methoxyphenol), an aromatic Streptomyces sp. AU2 cell-free extract as a reduc-
constituent of clove, have been demonstrated to ing agent. The resulting silk sutures demonstrat-
prevent Streptococcus mutans adherence137. Ad- ed inhibitory activities against Candida albicans,
ditionally, silk suture coated with chitosan and E. coli and S. aureus with minimal cytotoxicity
Cynodon dactylon, a herbal drug, also demon- towards 3T3 fibroblasts.
strated inhibition against S. aureus and E. coli138. Antimicrobial sutures have been developed by
Recently, a polymerized β-cyclodextrin-based coating propolis extract with Ag nanoparticles on
coating of trans-resveratrol (a plant antimicrobi- silk sutures145. Besides Ag nanoparticles, zinc ox-
al) and rifampicin has been reported to show 24- ide (ZnO) nanoparticles have also been explored
day long antimicrobial effects towards S. aureus for coating on silk suture146. The nanoparticles,
and 14-day long anti-inflammatory effects139. synthesized using honey as a bio-reductant, were
incubated with silk sutures for adsorption. The
Nanoparticle-Based Sutures sutures demonstrated inhibition against S. aureus
The potential application of nanoparticles (MTCC 6908) for up to 6 days. By conjugating
against infectious agents is well recognized in curcumin with PEGylated-gold nanoparticles, the
the medical field. Dubas et al140 were amongst solubility and metabolic stability of curcumin for
the first to use a layer-by-layer approach for coat- coating on PGA sutures have been improved147. A

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 R.A.H.W. Chua, S.K. Lim, C.F. Chee, S.P. Chin, L.V. Kiew, K.S. Sim, S.T. Tay

recent publication148 showed the use of hybrid ma- described by García-Vargas et al156 using grafting
terials (based on synergistic antimicrobial action followed by covalent immobilization of vancomy-
of biosynthesized silver nanoparticles, natural cin on polypropylene (PP) monofilament sutures
compounds, and antiseptic) as promising mate- pre-irradiated using a (60)Co γ-source. The result-
rials for the development of nanoparticle-based ing suture showed a reduced number of S. aureus
antimicrobial sutures. colonizing the suture.

Antibiotic-Based Sutures Other Antimicrobial-Based Sutures

Bacterial colonization is less likely to occur Biotechnological products such as synthetic
on suture in the presence of antibiotics (Table peptides and recombinant proteins have been
II). The development of antibiotic-based sutures explored for the development of antimicrobial
is dependent on the biocompatibility, retention sutures. The coating of silk suture with a chime-
of antibiotic activity, and the target organisms. ric recombinant protein consisting of spider silk
Sustained co-delivery of gentamicin and silver on protein and alpha-defensin using dip-coating ap-
PCL sutures using blending approach has been proach was reported by Franco et al157. The anti-
described149. Pre-treatment of braided-silk sutures microbial suture showed a reduction in the viabil-
with 0.1N sodium hydroxide solution, followed by ity, adherence, and biofilm formation of MRSA
coating of sulfamethoxazole trimethoprim using and E. coli, and high bio- and hemocompatibility.
PCL produced a longer duration (5 days) of anti- Amphiphilic polymers have been investigated
microbial activities against S. aureus and E. coli, for development of antimicrobial suture. Poly
in comparison to the untreated suture (4 days)150. [(aminoethyl methacrylate)-co-(butylmethacry-
Liu et al151 reported synergistic effects generated late)] (PAMBM)-coated suture demonstrated a
by PGA and PCL after incorporation with cipro- higher reduction in bacterial viability as com-
floxacin. Using a rat model of bacterial keratitis, pared to the triclosan-coated (Vicryl Plus) su-
Parikh et al152 reported the development of nanofi- tures158. Technological-wise, a novel method for
ber-based sutures loaded with a variety of drugs, grafting of bacteriostatic polymer, polyvinylim-
including levofloxacin for the prevention of rat idazole (PNVIm), onto PP suture has been de-
ocular infection. scribed by López-Saucedo et al159. In that study,
A method to introduce ion-exchange properties suture exposed to gamma-ray treatment followed
to polycaproamide (PCA) and PP fibers has been by acrylic monomers formed 2-hydroxyethyl
described for the development of antimicrobial methacrylate (HEMA) or N-isopropylacrylamide
sutures153. Methacrylic acid-grafted PCA and sul- (NIPAAm) brushes for grafting of methyl iodide
fonated styrene-grafted PP sutures facilitated the and methylimidazolium iodide which were inhib-
adsorption of antibiotics including kanamycin, itory to S. aureus and E. coli. In a recent study160,
gentamicin, monomycin, and doxycycline, result- polyglactin sutures coated with poly (2-methac-
ing in long-term in vivo antimicrobial efficacy (45 ryloyloxyethyl phosphorylcholine (MPC)-co-n-
and 78 days on gentamicin-immobilized PCA and butyl methacrylate) (PMB) were reported to ex-
PP sutures, respectively) and good shelf-life for hibit significant inhibition against adhesion and
storage (more than 3 years). A radiation grafting biofilm formation of MRSA and MSSA.
approach described by Gupta et al154 was used to
immobilize tetracycline hydrochloride onto PP Conclusions and Future Perspectives
suture. The suture surface was first activated us- In line with the current advances in human
ing radiation followed by grafting of acrylonitrile and veterinary medicine, there has been an in-
to introduce extra carboxyl groups for immo- creasing demand for surgical sutures for various
bilization of tetracycline. The resulting sutures procedures and wound management. This review
demonstrated antimicrobial activity against E. presents a summary of a variety of novel antimi-
coli and S. aureus with drug release duration of crobial sutures that have been developed over the
4 to 5 days, and anti-infective activity in albino last three decades. The enthusiasm of scientific
rats. Additionally, graft polymerization of acrylic research and innovation has led to the discovery
acid via plasma-induction followed by chitosan of novel antimicrobial compounds, new formula-
binding for immobilization of tetracycline hydro- tions, and improvements in suturing technology.
chloride and Ag nanoparticles showed promising Achieving a zero SSI rate is the goal for all
in vitro and in vivo antimicrobial and drug release healthcare providers. An ideal surgical suture
properties155. A new approach has been recently should be non-toxic, does not cause host inflam-

838
 Surgical site infection and development of antimicrobial sutures: a review

matory response, and at the same time, is able to Impact of surgical site infection after colorectal
minimize the risk of SSIs. Together with good surgery on hospital stay and medical expenditure
in Japan. Surg Today 2012; 42: 639-645.
aseptic technique and compliance to infection
7) Tuon FF, Cieslinski J, Ono AFM, Goto FL,
control practice in the healthcare facilities, an- Machinski JM, Mantovani LK, Kosop LR, Namba
timicrobial sutures would be able to deliver the MS, Rocha JL. Microbiological profile and sus-
best possible effects for wound care. Since the ceptibility pattern of surgical site infections relat-
beginning of COVID-19 pandemic, cessation of ed to orthopaedic trauma. Int Orthop 2019; 43:
non-urgent surgical procedures has been recom- 1309-1313.
mended to minimize healthcare provider-to-pa- 8) WHO. Report on the burden of endemic health
tient contact. Hence, the use of absorbable sutures care-associated infection worldwide. Geneva:
World Health Organization, 2011. 9241501502.
with antimicrobial property may be an option to
9) Ling ML, Apisarnthanarak A, Abbas A, Morikane
reduce unnecessary patients’ visits to healthcare K, Lee KY, Warrier A, Yamada K. APSIC guide-
facilities. As there is no “one size fits all” su- lines for the prevention of surgical site infections.
ture, future development of antimicrobial suture Antimicrob Resist Infect Control 2019; 8: 174.
should be tailored to the needs and assessment 10) Tae BS, Park JH, Kim JK, Ku JH, Kwak C,
of SSI risk factors in each individual patient. Kim HH, Jeong CW. Comparison of intraop-
Concomitantly, urgent actions are required to erative handling and wound healing between
(NEOSORB plus) and coated polyglactin 910
find the best effective solution to tackle antibiotic suture (NEOSORB): a prospective, single-blind,
resistance. randomized controlled trial. BMC Surg 2018;
18: 45.
11) World Health Organization. Global guidelines for
Conflict of Interest the prevention of surgical site infection. World
The Authors declare that they have no conflict of interests. Health Organization; 2018.
12) Lee KY, Coleman K, Paech D, Norris S, Tan JT.
The epidemiology and cost of surgical site in-
fections in Korea: a systematic review. J Korean
Acknowledgements Surg Soc 2011; 81: 295-307.
This study is funded by IIRG 003C-19FNW and ST029-
13) Morikane K, Honda H, Yamagishi T, Suzuki S,
2020 provided by Universiti Malaya, Malaysia.
Aminaka M. Factors associated with surgical site
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