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Applications of chitosan-based biomaterials: a focus on dependent antimicrobial properties

  • Corresponding author: Ya Liu, yaliu@ouc.edu.cn
  • Received Date: 2020-02-18
    Accepted Date: 2020-03-18
    Published online: 2020-06-12
  • Edited by Xin Yu.
  • Zhenwei Deng and Ting Wang contributed equally to this work.
  • Marine-derived chitosan has been widely examined for its use in developing biomedical materials. Not only is it non-toxic, biocompatible, and degradable, it has also shown unique antimicrobial properties. The antimicrobial properties of chitosan are restricted by neutral and physiological conditions because it is insoluble in water and its pKa values is 6.5. One solution to this problem is to graft chemically modified groups onto the backbone of chitosan. The aim of this paper is to review the mode of antimicrobial action of chitosan and chitosan derivatives. Using chitosan alone may not meet the demands of various applications. However, the introduction of additional polymers and antimicrobial agents is commonly used to enhance the antimicrobial potential of chitosan-based biomaterials. Chitosan-based composite biomaterials have been developed that allow diversified formulations to broaden applications, including nanoparticles, hydrogels, films, sponges, fibers, or even microspheres. These along with recent advances on chitosan-based composite biomaterials used for wound healing, food packaging, textile sector, 3D printing and dental materials, were reviewed in detail.
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  • Abdollahi M, Rezaei M, Farzi G (2012) Improvement of active chitosan film properties with rosemary essential oil for food packaging. Int J Food Sci Tech 47:847–853 doi: 10.1111/j.1365-2621.2011.02917.x
    Ali F, Khan SB, Kamal T, Anwar Y, Alamry KA, Asiri AM (2017) Anti-bacterial chitosan/zinc phthalocyanine fibers supported metallic and bimetallic nanoparticles for the removal of organic pollutants. Carbohydr Polym 173:676–689 doi: 10.1016/j.carbpol.2017.05.074
    Al-Naamani L, Dobretsov S, Dutta J (2016) Chitosan-zinc oxide nanoparticle composite coating for active food packaging applications. Innov Food Sci Emerg 38:231–237 doi: 10.1016/j.ifset.2016.10.010
    An J, Ji Z, Wang D, Luo Q, Li X (2014) Preparation and characterization of uniform-sized chitosan/silver microspheres with antibacterial activities. Mater Sci Eng C Mater Biol Appl 36:33–41 doi: 10.1016/j.msec.2013.11.037
    Anisha BS, Biswas R, Chennazhi KP, Jayakumar R (2013) Chitosan-hyaluronic acid/nano silver composite sponges for drug resistant bacteria infected diabetic wounds. Int J Biol Macromol 62:310–320 doi: 10.1016/j.ijbiomac.2013.09.011
    Appel EA, Forster RA, Rowland MJ, Scherman OA (2014) The control of cargo release from physically crosslinked hydrogels by crosslink dynamics. Biomaterials 35:9897–9903 doi: 10.1016/j.biomaterials.2014.08.001
    Arshad N, Zia KM, Jabeen F, Anjum MN, Akram N, Zuber M (2018) Synthesis, characterization of novel chitosan based water dispersible polyurethanes and their potential deployment as antibacterial textile finish. Int J Biol Macromol 111:485–492 doi: 10.1016/j.ijbiomac.2018.01.032
    Ashrafi A, Jokar M, Mohammadi Nafchi A (2018) Preparation and characterization of biocomposite film based on chitosan and kombucha tea as active food packaging. Int J Biol Macromol 108:444–454 doi: 10.1016/j.ijbiomac.2017.12.028
    Bakshi PS, Selvakumar D, Kadirvelu K, Kumar NS (2020) Chitosan as an environment friendly biomaterial - a review on recent modifications and applications. Int J Biol Macromol 150:1072–1083 doi: 10.1016/j.ijbiomac.2019.10.113
    Basha M, AbouSamra MM, Awad GA, Mansy SS (2018) A potential antibacterial wound dressing of cefadroxil chitosan nanoparticles in situ gel: fabrication, in vitro optimization and in vivo evaluation. Int J Pharm 544:129–140 doi: 10.1016/j.ijpharm.2018.04.021
    Berger J, Reist M, Mayer JM, Felt O, Peppas NA, Gurny R (2004) Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications. Eur J Pharm Biopharm 57:19–34 doi: 10.1016/S0939-6411(03)00161-9
    Bi L, Cao Z, Hu Y, Song Y, Yu L, Yang B, Mu JH, Huang ZS, Han YS (2011) Effects of different cross-linking conditions on the properties of genipin-cross-linked chitosan/collagen scaffolds for cartilage tissue engineering. J Mater Sci Mater Med 22:51–62 doi: 10.1007/s10856-010-4177-3
    Biao LH, Tan SN, Wang YL, Guo XM, Fu YJ, Xu FJ, Zu YG, Liu ZG (2017) Synthesis, characterization and antibacterial study on the chitosan-functionalized Ag nanoparticles. Mater Sci Eng C Mater Biol Appl 76:73–80 doi: 10.1016/j.msec.2017.02.154
    Bingjun Q, Jung J, Zhao Y (2015) Impact of acidity and metal ion on the antibacterial activity and mechanisms of beta- and alpha-chitosan. Appl Biochem Biotechnol 175:2972–2985 doi: 10.1007/s12010-014-1413-1
    Busscher HJ, Engels E, Dijkstra RJB (2008) Influence of a chitosan on oral bacterial adhesion and growth in vitro. Eur J Oral Sci 116:493–495 doi: 10.1111/j.1600-0722.2008.00568.x
    Carvalho IC, Medeiros Borsagli FGL, Mansur AAP, Caldeira CL, Haas DJ, Lage AP, Ciminelli VST, Mansur HS (2019) 3D sponges of chemically functionalized chitosan for potential environmental pollution remediation: biosorbents for anionic dye adsorption and 'antibiotic-free' antibacterial activity. Environ Technol. https://doi.org/10.1080/09593330.2019.1689302
    Colobatiu L, Gavan A, Mocan A, Bogdan C, Mirel S, Tomuta I (2019a) Development of bioactive compounds-loaded chitosan films by using a QbD approach—a novel and potential wound dressing material. React Funct Polym 138:46–54 doi: 10.1016/j.reactfunctpolym.2019.02.013
    Colobatiu L, Gavan A, Potarniche A-V, Rus V, Diaconeasa Z, Mocan A, Tomuta I, Mirel S, Mihaiu M (2019b) Evaluation of bioactive compounds-loaded chitosan films as a novel and potential diabetic wound dressing material. React Funct Polym 145:104369 doi: 10.1016/j.reactfunctpolym.2019.104369
    Costa EM, Silva S, Veiga M, Tavaria FK, Pintado MM (2018) Chitosan's biological activity upon skin-related microorganisms and its potential textile applications. World J Microbiol Biotechnol 34:93 doi: 10.1007/s11274-018-2471-2
    Decker EM, von Ohle C, Weiger R, Wiech I, Brecx M (2005) A synergistic chlorhexidine/chitosan combination for improved antiplaque strategies. J Periodontal Res 40:373–377 doi: 10.1111/j.1600-0765.2005.00817.x
    Divakar DD, Jastaniyah NT, Altamimi HG, Alnakhli YO, Muzaheed AAA, Haleem S (2018) Enhanced antimicrobial activity of naturally derived bioactive molecule chitosan conjugated silver nanoparticle against dental implant pathogens. Int J Biol Macromol 108:790–797 doi: 10.1016/j.ijbiomac.2017.10.166
    Dong F, Zhang J, Yu C, Li Q, Ren J, Wang G, Gu G, Guo Z (2014) Synthesis of amphiphilic aminated inulin via 'click chemistry' and evaluation for its antibacterial activity. Bioorg Med Chem Lett 24:4590–4593 doi: 10.1016/j.bmcl.2014.07.029
    Dutta PK, Tripathi S, Mehrotra GK, Dutta J (2009) Perspectives for chitosan based antimicrobial films in food applications. Food Chem 114:1173–1182 doi: 10.1016/j.foodchem.2008.11.047
    Fan L, Du Y, Zhang B, Yang J, Zhou J, Kennedy JF (2006) Preparation and properties of alginate/carboxymethyl chitosan blend fibers. Carbohyd Polym 65:447–452 doi: 10.1016/j.carbpol.2006.01.031
    Garrido-Maestu A, Ma Z, Paik SY, Chen N, Ko S, Tong Z, Jeong KC (2018) Engineering of chitosan-derived nanoparticles to enhance antimicrobial activity against foodborne pathogen Escherichia coli O157:H7. Carbohydr Polym 197:623–630 doi: 10.1016/j.carbpol.2018.06.046
    Gebler M, Schoot Uiterkamp AJM, Visser C (2014) A global sustainability perspective on 3D printing technologies. Energy Policy 74:158–167 doi: 10.1016/j.enpol.2014.08.033
    Geisberger G, Gyenge EB, Hinger D, Kach A, Maake C, Patzke GR (2013) Chitosan-thioglycolic acid as a versatile antimicrobial agent. Biomacromol 14:1010–1017 doi: 10.1021/bm3018593
    Goncalves IC, Magalhaes A, Fernandes M, Rodrigues IV, Reis CA, Martins MC (2013) Bacterial-binding chitosan microspheres for gastric infection treatment and prevention. Acta Biomater 9:9370–9378 doi: 10.1016/j.actbio.2013.07.034
    Hayashi Y, Ohara N, Ganno T, Yamaguchi K, Ishizaki T, Nakamura T, Sato M (2007) Chewing chitosan-containing gum effectively inhibits the growth of cariogenic bacteria. Arch Oral Biol 52:290–294 doi: 10.1016/j.archoralbio.2006.10.004
    Hernandez-Rangel A, Silva-Bermudez P, Espana-Sanchez BL, Luna-Hernandez E, Almaguer-Flores A, Ibarra C, Garcia-Perez VI, Velasquillo C, Luna-Barcenas G (2019) Fabrication and in vitro behavior of dual-function chitosan/silver nanocomposites for potential wound dressing applications. Mater Sci Eng C Mater Biol Appl 94:750–765 doi: 10.1016/j.msec.2018.10.012
    Hosseinnejad M, Jafari SM (2016) Evaluation of different factors affecting antimicrobial properties of chitosan. Int J Biol Macromol 85:467–475 doi: 10.1016/j.ijbiomac.2016.01.022
    Hu SH, Bi SC, Yan D, Zhou ZZ, Sun GH, Cheng XJ, Chen XG (2018) Preparation of composite hydroxybutyl chitosan sponge and its role in promoting wound healing. Carbohydr Polym 184:154–163 doi: 10.1016/j.carbpol.2017.12.033
    Hu HX, Ye BH, Lv YH, Zhang Q (2019) Preparing antibacterial and in-situ formable double crosslinking chitosan/hyaluronan composite hydrogels. Mater Lett 254:17–20 doi: 10.1016/j.matlet.2019.06.102
    Huang L, Zhu ZY, Wu DW, Gan WD, Zhu SS, Li WQ, Tian JH, Li LH, Zhou CR, Lu L (2019) Antibacterial poly (ethylene glycol) diacrylate/chitosan hydrogels enhance mechanical adhesiveness and promote skin regeneration. Carbohydr Polym 225:115110 doi: 10.1016/j.carbpol.2019.115110
    Jia Z, Shen D, Xu W (2001) Synthesis and antibacterial activities of quaternary ammonium salt of chitosan. Carbohydr Res 333:1–6 doi: 10.1016/S0008-6215(01)00112-4
    Kaya M, Seyyar O, Baran T, Turkes T (2014) Bat guano as new and attractive chitin and chitosan source. Front Zool 11:59 doi: 10.1186/s12983-014-0059-8
    Khoushab F, Yamabhai M (2010) Chitin research revisited. Mar Drugs 8:1988–2012 doi: 10.3390/md8071988
    Kim JH, Hong WS, Oh SW (2018) Effect of layer-by-layer antimicrobial edible coating of alginate and chitosan with grapefruit seed extract for shelf-life extension of shrimp (Litopenaeus vannamei) stored at 4 ℃. Int J Biol Macromol 120:1468–1473 doi: 10.1016/j.ijbiomac.2018.09.160
    Kong M, Chen XG, Liu CS, Liu CG, Meng XH, Yu LJ (2008) Antibacterial mechanism of chitosan microspheres in a solid dispersing system against E. coli. Colloid Surface B 65:197–202 doi: 10.1016/j.colsurfb.2008.04.003
    Kong M, Chen XG, Xing K, Park HJ (2010) Antimicrobial properties of chitosan and mode of action: a state of the art review. Int J Food Microbiol 144:51–63 doi: 10.1016/j.ijfoodmicro.2010.09.012
    Kritchenkov AS, Egorov AR, Kurasova MN, Volkova OV, Meledina TV, Lipkan NA, Tskhovrebov AG, Kurliuk AV, Shakola TV, Dysin AP, Egorov MY, Savicheva EA, Dos Santos WM (2019) Novel non-toxic high efficient antibacterial azido chitosan derivatives with potential application in food coatings. Food Chem 301:125247 doi: 10.1016/j.foodchem.2019.125247
    Li XF, Feng XQ, Yang S, Fu GQ, Wang TP, Su ZX (2010) Chitosan kills Escherichia coli through damage to be of cell membrane mechanism. Carbohydr Polym 79:493–499 doi: 10.1016/j.carbpol.2009.07.011
    Li D, Diao J, Zhang J, Liu J (2011) Fabrication of new chitosan-based composite sponge containing silver nanoparticles and its antibacterial properties for wound dressing. J Nanosci Nanotechnol 11:4733–4738 doi: 10.1166/jnn.2011.4179
    Li Q, Tan WQ, Zhang CL, Gu GD, Guo ZY (2016) Synthesis of water soluble chitosan derivatives with halogeno-1, 2, 3-triazole and their antifungal activity. Int J Biol Macromol 91:623–629 doi: 10.1016/j.ijbiomac.2016.06.006
    Li JJ, Wu XY, Shi QF, Li C, Chen XG (2019) Effects of hydroxybutyl chitosan on improving immunocompetence and antibacterial activities. Mater Sci Eng C 105:110086 doi: 10.1016/j.msec.2019.110086
    Lim S-H, Hudson SM (2004) Application of a fiber-reactive chitosan derivative to cotton fabric as an antimicrobial textile finish. Carbohydr Polym 56:227–234 doi: 10.1016/j.carbpol.2004.02.005
    Liu H, Gao CY (2009) Preparation and properties of ionically cross-linked chitosan nanoparticles. Polym Advan Technol 20:613–619 doi: 10.1002/pat.1306
    Liu XF, Guan YL, Yang DZ, Li Z, Yao KD (2001) Antibacterial action of chitosan and carboxymethylated chitosan. J Appl Polym Sci 79:1324–1335 doi: 10.1002/1097-4628(20010214)79:7<1324::AID-APP210>3.0.CO;2-L
    Liu Y, Ji PH, Lv HL, Qin Y, Deng LH (2017) Gentamicin modified chitosan film with improved antibacterial property and cell biocompatibility. Int J Biol Macromol 98:550–556 doi: 10.1016/j.ijbiomac.2017.01.121
    Luo Q, Han QQ, Wang Y, Zhang HM, Fei ZH, Wang YQ (2019) The thiolated chitosan: synthesis, gelling and antibacterial capability. Int J Biol Macromol 139:521–530 doi: 10.1016/j.ijbiomac.2019.08.001
    Ma GP, Yang DZ, Zhou YS, Xiao M, Kennedy JF, Nie J (2008) Preparation and characterization of water-soluble N-alkylated chitosan. Carbohydr Polym 74:121–126 doi: 10.1016/j.carbpol.2008.01.028
    Martins AF, Facchi SP, Follmann HD, Pereira AG, Rubira AF, Muniz EC (2014) Antimicrobial activity of chitosan derivatives containing N-quaternized moieties in its backbone: a review. Int J Mol Sci 15:20800–20832 doi: 10.3390/ijms151120800
    Min T, Zhu Z, Sun X, Yuan Z, Zha J, Wen Y (2020) Highly efficient antifogging and antibacterial food packaging film fabricated by novel quaternary ammonium chitosan composite. Food Chem 308:125682 doi: 10.1016/j.foodchem.2019.125682
    Moura MJ, Figueiredo MM, Gil MH (2007) Rheological study of genipin cross-linked chitosan hydrogels. Biomacromolecules 8: 3823–3829 doi: 10.1021/bm700762w
    Naseri-Nosar M, Ziora ZM (2018) Wound dressings from naturally-occurring polymers: a review on homopolysaccharide-based composites. Carbohydr Polym 189:379–398 doi: 10.1016/j.carbpol.2018.02.003
    Naz F, Zuber M, Mehmood Zia K, Salman M, Chakraborty J, Nath I, Verpoort F (2018) Synthesis and characterization of chitosan-based waterborne polyurethane for textile finishes. Carbohydr Polym 200:54–62 doi: 10.1016/j.carbpol.2018.07.076
    Nešović K, Janković A, Radetić T, Vukašinović-Sekulić M, Kojić V, Živković L, Perić-Grujić A, Rhee KY, Mišković-Stanković V (2019) Chitosan-based hydrogel wound dressings with electrochemically incorporated silver nanoparticles—In vitro study. Eur Polym J 121:109257 doi: 10.1016/j.eurpolymj.2019.109257
    Pan C, Qian J, Fan J, Guo H, Gou L, Yang H, Liang C (2019a) Preparation nanoparticle by ionic cross-linked emulsified chitosan and its antibacterial activity. Colloid Surf A 568:362–370 doi: 10.1016/j.colsurfa.2019.02.039
    Pan H, Zhao T, Xu LH, Shen Y, Wang LM, Ding Y (2020) Preparation of novel chitosan derivatives and applications in functional finishing of textiles. Int J Biol Macromol 153:971–976 doi: 10.1016/j.ijbiomac.2019.10.226
    Park S-C, Nah J-W, Park Y (2011) pH-dependent mode of antibacterial actions of low molecular weight water-soluble chitosan (LMWSC) against various pathogens. Macromol Res 19:853–860 doi: 10.1007/s13233-011-0812-1
    Patrulea V, Ostafe V, Borchard G, Jordan O (2015) Chitosan as a starting material for wound healing applications. Eur J Pharm Biopharm 97:417–426 doi: 10.1016/j.ejpb.2015.08.004
    Qi LF, Xu ZR, Jiang X, Hu CH, Zou XF (2004) Preparation and antibacterial activity of chitosan nanoparticles. Carbohydr Res 339:2693–2700 doi: 10.1016/j.carres.2004.09.007
    Qi GB, Zhang D, Liu FH, Qiao ZY, Wang H (2017) An "On-site transformation" strategy for treatment of bacterial infection. Adv Mater 29:1703461 doi: 10.1002/adma.201703461
    Qian JQ, Pan CL, Liang CH (2017) Antimicrobial activity of Fe-loaded chitosan nanoparticles. Eng Life Sci 17:629–634 doi: 10.1002/elsc.201600172
    Rahimi M, Ahmadi R, Samadi Kafil H, Shafiei-Irannejad V (2019) A novel bioactive quaternized chitosan and its silver-containing nanocomposites as a potent antimicrobial wound dressing: Structural and biological properties. Mater Sci Eng C 101:360–369 doi: 10.1016/j.msec.2019.03.092
    Rathinamoorthy R, Sasikala L (2019) In vivo—wound healing studies of Leptospermum scoparium honey loaded chitosan bioactive wound dressing. Wound Med 26:100162 doi: 10.1016/j.wndm.2019.100162
    Riaz A, Lei SC, Akhtar HMS, Wan P, Chen D, Jabbar S, Abid M, Hashim MM, Zeng XX (2018) Preparation and characterization of chitosan-based antimicrobial active food packaging film incorporated with apple peel polyphenols. Int J Biol Macromol 114:547–555 doi: 10.1016/j.ijbiomac.2018.03.126
    Sadeghi-Kiakhani M, Safapour S (2016) Improvement of dyeing and antimicrobial properties of nylon fabrics modified using chitosan-poly(propylene imine) dendreimer hybrid. J Ind Eng Chem 33:170–177 doi: 10.1016/j.jiec.2015.09.034
    Sarasam AR, Brown P, Khajotia SS, Dmytryk JJ, Madihally SV (2008) Antibacterial activity of chitosan-based matrices on oral pathogens. J Mater Sci Mater Med 19:1083–1090 doi: 10.1007/s10856-007-3072-z
    Sarhan WA, Azzazy HM, El-Sherbiny IM (2016) Honey/Chitosan nanofiber wound dressing enriched with Allium sativum and Cleome droserifolia: enhanced antimicrobial and wound healing activity. ACS Appl Mater Inter 8:6379–6390 doi: 10.1021/acsami.6b00739
    Sarwar A, Katas H, Zin NM (2014) Antibacterial effects of chitosan–tripolyphosphate nanoparticles: impact of particle size molecular weight. J Nanopart Res 16:2517 doi: 10.1007/s11051-014-2517-9
    Sasikala L, Durai B, Rathinamoorthy R (2013) Manuka honey loaded chitosan hydrogel films for wound dressing applications. Int J Pharm Tech Res 5:1774–1785 
    Shafei AE, Abou-Okeil A (2011) ZnO/carboxymethyl chitosan bionano-composite to impart antibacterial and UV protection for cotton fabric. Carbohydr Polym 83:920–925 doi: 10.1016/j.carbpol.2010.08.083
    Shahid I, Butola BS (2019) Recent advances in chitosan polysaccharide and its derivatives in antimicrobial modification of textile materials. Int J Biol Macromol 121:905–912 doi: 10.1016/j.ijbiomac.2018.10.102
    Shao W, Wu J, Wang S, Huang M, Liu X, Zhang R (2017) Construction of silver sulfadiazine loaded chitosan composite sponges as potential wound dressings. Carbohydr Polym 157:1963–1970 doi: 10.1016/j.carbpol.2016.11.087
    Simoes D, Miguel SP, Ribeiro MP, Coutinho P, Mendonca AG, Correia IJ (2018) Recent advances on antimicrobial wound dressing: a review. Eur J Pharm Biopharm 127:130–141 doi: 10.1016/j.ejpb.2018.02.022
    Souza CP, Almeida BC, Colwell RR, Rivera IN (2011) The importance of chitin in the marine environment. Mar Biotechnol (NY) 13:823–830 doi: 10.1007/s10126-011-9388-1
    Su ZW, Han QM, Zhang F, Meng XH, Liu BJ (2020) Preparation, characterization and antibacterial properties of 6-deoxy-6-arginine modified chitosan. Carbohydr Polym 230:115635 doi: 10.1016/j.carbpol.2019.115635
    Takala PN, Salmieri S, Vu KD, Lacroix M (2011) Effects of combined treatments of irradiation and antimicrobial coatings on reduction of food pathogens in broccoli florets. Radiat Phys and Chem 80:1414–1418 doi: 10.1016/j.radphyschem.2011.07.005
    Tanaka CB, Lopes DP, Kikuchi LNT, Moreira MS, Catalani LH, Braga RR, Kruzic JJ, Goncalves F (2020) Development of novel dental restorative composites with dibasic calcium phosphate loaded chitosan fillers. Dent Mater 36:551–559 doi: 10.1016/j.dental.2020.02.004
    Tang H, Zhang P, Kieft TL, Ryan SJ, Baker SM, Wiesmann WP, Rogelj S (2010) Antibacterial action of a novel functionalized chitosan-arginine against Gram-negative bacteria. Acta Biomater 6:2562–2571 doi: 10.1016/j.actbio.2010.01.002
    Thaya R, Vaseeharan B, Sivakamavalli J, Iswarya A, Govindarajan M, Alharbi NS, Kadaikunnan S, Al-Anbr MN, Khaled JM, Benelli G (2018) Synthesis of chitosan-alginate microspheres with high antimicrobial and antibiofilm activity against multi-drug resistant microbial pathogens. Microb Pathog 114:17–24 doi: 10.1016/j.micpath.2017.11.011
    Tripathi S, Mehrotra GK, Dutta PK (2009) Physicochemical and bioactivity of cross-linked chitosan-PVA film for food packaging applications. Int J Biol Macromol 45:372–376 doi: 10.1016/j.ijbiomac.2009.07.006
    Tripathi S, Mehrotra GK, Dutta PK (2010) Preparation and physicochemical evaluation of chitosan/poly(vinyl alcohol)/pectin ternary film for food-packaging applications. Carbohydr Polym 79:711–716 doi: 10.1016/j.carbpol.2009.09.029
    Tseng H-J, Hsu S-h, Wu M-W, Hsueh T-H, Tu P-C (2009) Nylon textiles grafted with chitosan by open air plasma and their antimicrobial effect. Fiber Polym 10:53–59 doi: 10.1007/s12221-009-0053-5
    Varun TK, Senani S, Jayapal N, Chikkerur J, Roy S, Tekulapally VB, Gautam M, Kumar N (2017) Extraction of chitosan and its oligomers from shrimp shell waste, their characterization and antimicrobial effect. Vet World 10:170–175 doi: 10.14202/vetworld.2017.170-175
    Wang QQ, Kong M, An Y, Liu Y, Li JJ, Zhou X, Feng C, Li J, Jiang SY, Cheng XJ, Chen XG (2013) Hydroxybutyl chitosan thermo-sensitive hydrogel: a potential drug delivery system. J Mater Sci 48:5614–5623 doi: 10.1007/s10853-013-7356-z
    Wang CX, Lv JC, Ren Y, Zhou QQ, Chen JY, Zhi T, Lu ZQ, Gao DW, Ma ZP, Jin LM (2016) Cotton fabric with plasma pretreatment and ZnO/Carboxymethyl chitosan composite finishing for durable UV resistance and antibacterial property. Carbohydr Polym 138:106–113 doi: 10.1016/j.carbpol.2015.11.046
    Wang HX, Qian J, Ding FY (2018a) Emerging chitosan-based films for food packaging applications. J Agric Food Chem 66:395–413 doi: 10.1021/acs.jafc.7b04528
    Wang J, Nor Hidayah Z, Razak SIA, Kadir MRA, Nayan NHM, Li Y, Amin KAM (2018b) Surface entrapment of chitosan on 3D printed polylactic acid scaffold and its biomimetic growth of hydroxyapatite. Compos Interfaces 26:465–478 
    Wang Y, Dang Q, Liu C, Yu D, Pu X, Wang Q, Gao H, Zhang B, Cha D (2018c) Selective adsorption toward Hg(Ⅱ) and inhibitory effect on bacterial growth occurring on thiosemicarbazide-functionalized chitosan microsphere surface. ACS Appl Mater Interfaces 10:40302–40316 doi: 10.1021/acsami.8b14893
    Won JS, Lee SJ, Park HH, Song KB, Min SC (2018) Edible coating using a chitosan-based colloid incorporating grapefruit seed extract for cherry tomato safety and preservation. J Food Sci 83:138–146 doi: 10.1111/1750-3841.14002
    Wu CS (2016) Modulation, functionality, and cytocompatibility of three-dimensional printing materials made from chitosan-based polysaccharide composites. Mater Sci Eng C 69:27–36 doi: 10.1016/j.msec.2016.06.062
    Wu TT, Wu CH, Fu SL, Wang LP, Yuan CH, Chen SG, Hu YQ (2017) Integration of lysozyme into chitosan nanoparticles for improving antibacterial activity. Carbohydr Polym 155:192–200 doi: 10.1016/j.carbpol.2016.08.076
    Wu TT, Huang JQ, Jiang YY, Hu YQ, Ye XQ, Liu DH, Chen JC (2018) Formation of hydrogels based on chitosan/alginate for the delivery of lysozyme and their antibacterial activity. Food Chem 240:361–369 doi: 10.1016/j.foodchem.2017.07.052
    Wu CH, Sun JS, Lu YZ, Wu TT, Pang J, Hu YQ (2019) In situ self-assembly chitosan/epsilon-polylysine bionanocomposite film with enhanced antimicrobial properties for food packaging. Int J Biol Macromol 132:385–392 doi: 10.1016/j.ijbiomac.2019.03.133
    Xia GX, Liu Y, Tian MP, Gao P, Bao ZX, Bai XY, Yu XP, Lang XQ, Hu SH, Chen XG (2017) Nanoparticles/thermosensitive hydrogel reinforced with chitin whiskers as a wound dressing for treating chronic wounds. J Mater Chem B 5:3172–3185 
    Xia GX, Zhai DQ, Sun Y, Hou L, Guo XF, Wang LX, Li ZJ, Wang F (2020) Preparation of a novel asymmetric wettable chitosan-based sponge and its role in promoting chronic wound healing. Carbohydr Polym 227:115296 doi: 10.1016/j.carbpol.2019.115296
    Xiong Y, Chen M, Warner RD, Fang ZX (2020) Incorporating nisin and grape seed extract in chitosan-gelatine edible coating and its effect on cold storage of fresh pork. Food Control 110:107018 doi: 10.1016/j.foodcont.2019.107018
    Xu T, Xin M, Li M, Huang H, Zhou S (2010) Synthesis, characteristic and antibacterial activity of N, N, N-trimethyl chitosan and its carboxymethyl derivatives. Carbohydr Polym 81:931–936 doi: 10.1016/j.carbpol.2010.04.008
    Xu QB, Zheng WS, Duan PP, Chen JN, Zhang YY, Fu FY, Diao HY, Liu XD (2019) One-pot fabrication of durable antibacterial cotton fabric coated with silver nanoparticles via carboxymethyl chitosan as a binder and stabilizer. Carbohydr Polym 204:42–49 doi: 10.1016/j.carbpol.2018.09.089
    Yang H, Wen XL, Guo SG, Chen MT, Jiang AM, Lai LS (2015) Physical, antioxidant and structural characterization of blend films based on hsian-tsao gum (HG) and casein (CAS). Carbohydr Polym 134:222–229 doi: 10.1016/j.carbpol.2015.07.021
    Yang Y, Chu L, Yang S, Zhang H, Qin L, Guillaume O, Eglin D, Richards RG, Tang T (2018) Dual-functional 3D-printed composite scaffold for inhibiting bacterial infection and promoting bone regeneration in infected bone defect models. Acta Biomater 79:265–275 doi: 10.1016/j.actbio.2018.08.015
    Ye WJ, Leung MF, Xin J, Kwong TL, Lee DKL, Li P (2005) Novel core-shell particles with poly(n-butyl acrylate) cores and chitosan shells as an antibacterial coating for textiles. Polymer 46:10538–10543 doi: 10.1016/j.polymer.2005.08.019
    Zahedi P, Rezaeian I, Ranaei-Siadat S-O, Jafari S-H, Supaphol P (2009) A review on wound dressings with an emphasis on electrospun nanofibrous polymeric bandages. Polym Advan Technol 21:77-95 
    Zhang WL, Jiang WB (2020) Antioxidant and antibacterial chitosan film with tea polyphenols-mediated green synthesis silver nanoparticle via a novel one-pot method. Int J Biol Macromol 155:1252–1261 doi: 10.1016/j.ijbiomac.2019.11.093
    Zhang XD, Xiao G, Wang YQ, Zhao Y, Su HJ, Tan TW (2017) Preparation of chitosan-TiO2 composite film with efficient antimicrobial activities under visible light for food packaging applications. Carbohydr Polym 169:101–107 doi: 10.1016/j.carbpol.2017.03.073
    Zheng L-Y, Zhu J-F (2003) Study on antimicrobial activity of chitosan with different molecular weights. Carbohyd Polym 54:527–530 doi: 10.1016/j.carbpol.2003.07.009
    Zhou ZZ, Yan D, Cheng XJ, Kong M, Liu Y, Feng C, Chen XG (2016) Biomaterials based on N, N, N-trimethyl chitosan fibers in wound dressing applications. Int J Biol Macromol 89:471–476 doi: 10.1016/j.ijbiomac.2016.02.036
    Zhu XY, Hou XL, Ma BM, Xu HL, Yang YQ (2019) Chitosan/gallnut tannins composite fiber with improved tensile, antibacterial and fluorescence properties. Carbohydr Polym 226:115311 doi: 10.1016/j.carbpol.2019.115311
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Applications of chitosan-based biomaterials: a focus on dependent antimicrobial properties

    Corresponding author: Ya Liu, yaliu@ouc.edu.cn
  • 1. College of Marine Life Science, Ocean University of China, Qingdao 266003, China
  • 2. Qingdao National Laboratory for Marine Science and Technology, Qingdao 266000, China

Abstract: Marine-derived chitosan has been widely examined for its use in developing biomedical materials. Not only is it non-toxic, biocompatible, and degradable, it has also shown unique antimicrobial properties. The antimicrobial properties of chitosan are restricted by neutral and physiological conditions because it is insoluble in water and its pKa values is 6.5. One solution to this problem is to graft chemically modified groups onto the backbone of chitosan. The aim of this paper is to review the mode of antimicrobial action of chitosan and chitosan derivatives. Using chitosan alone may not meet the demands of various applications. However, the introduction of additional polymers and antimicrobial agents is commonly used to enhance the antimicrobial potential of chitosan-based biomaterials. Chitosan-based composite biomaterials have been developed that allow diversified formulations to broaden applications, including nanoparticles, hydrogels, films, sponges, fibers, or even microspheres. These along with recent advances on chitosan-based composite biomaterials used for wound healing, food packaging, textile sector, 3D printing and dental materials, were reviewed in detail.

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Introduction
  • Chitosan (CS), a natural polysaccharide, is a deacetylated biopolymer from chitin. Chitin, the second most abundant polysaccharide on the planet (Park et al. 2011; Tang et al. 2010), is widely found in the animal and plant kingdoms, including yeast, green algae, insects and crustaceans. Chitin is also a component of the skeleton of crustaceans, the cell wall of fungi, and the cuticle of some insects. It also exists in exoskeletons, tendons, and the linings of excretory, respiratory, and digestive systems of arthropods, as well as the eyes of arthropods and cephalopods (Khoushab et al. 2010). Although its sources are extensive, the primary source of chitin is the ocean. The estimated annual output of chitin in the ocean is billions of tons (Souza et al. 2011). Commercially, chitin and chitosan are obtained from shellfish waste, such as crabs, crayfish, lobster, shrimps, prawn, krill, and cuttlefish (Kaya et al. 2014). The shellfish waste from shrimps and crabs contains 14–27% and 13–15% chitin or chitosan, respectively (Varun et al. 2017).

    CS is a high-molecular-weight linear polycationic heteropolysaccharide composed of copolymers of β-1, 4-linked d -glucosamine and N-acetyl-d -glucosamine (Park et al. 2011). Water-insoluble CS becomes soluble in acidic aqueous media (pH < 6), such as hydrochloric acid, phosphoric acid, and lactic acid (Moura et al. 2007). Its polycationic nature is attributed to the protonation of amino groups (pKa value: 6.3 ~ 6.5). The alkaline polysaccharide is hydrolyzed to produce oligomers using lysozyme in vivo, promoting the secretion of N-acetyl-d -glucosaminidase from macrophages, followed by the production of N-acetyl glucosamine (NAG), d -glucosamine, and substituted glucosamines (Bakshi et al. 2019). These products can be absorbed completely and easily in the body.

    CS has been used as an antimicrobial agent against fungi, yeast, algae, and bacteria. Its antimicrobial action is related to various intrinsic and extrinsic factors, such as degree of deacetylation (DD), molecular weight (Mw), concentration, pH, and target microorganism (Berger et al. 2004). Antibacterial activity is weakened with increased pH value and is higher against Gram-positive bacteria than Gram-negative bacteria, probably because of different cell wall structures (Bingjun et al. 2015; Park et al. 2011). The inhibition effect of CS is significantly correlated with both DD and concentration. The Mw and DD independently affect the antimicrobial activity of CS (Hosseinnejad et al. 2016).

    Properties of CS (i.e., it is non-toxic, has good biodegradability, biocompatible, and has antimicrobial activity) have made it attractive for food, biomedical, and pharmaceutical applications (Bi et al. 2011). However, its applications have been limited by its low solubility under neutral conditions and the weak positive charge of amino groups (Hosseinnejad et al. 2016). Recently, CS derivatives and CS-polymer complexes have been exploited. Functional groups, like C2-amino group, C3-primary and C6-secondary hydroxyl groups, provide opportunities for the synthesis of chemically modified CS (Martins et al. 2014). CS derivatives retain the original nature of CS and improve characteristics through the addition of these modified functional groups. Different structural modifications have also been implemented to improve the inherent antimicrobial activity of CS. One approach is to blend CS with natural or synthetic polymers in order to enhance its antimicrobial activity.

    CS is also easily processed into different functional forms, such as hydrogels, fibers, films, nanoparticles, sponges, and microspheres. These various functional forms prepared from CS and its derivatives have multipurpose applications in wound healing, food packaging, and textile sector. In this review, we will summarize recent advancements of the dependent antimicrobial properties of CS–based biomaterials from the following aspects: the key mechanisms of the antimicrobial action of CS and its derivatives, its different formulations, and applications of CS–based biomaterials related to antimicrobial activity.

Mechanisms of chitosan and its derivatives antimicrobial activity

    Inherent antimicrobial mechanisms of chitosan

  • The antimicrobial activity of CS is well-known against a range of microorganisms from fungi to bacteria. However, the exact antimicrobial mechanism has remained unclear. The antimicrobial activity of CS is likely mediated by one or more of four generally accepted mechanisms. The first mechanism is attributed to the electrostatic interaction between positively charged amino groups of CS and the negatively charged microbial cell membrane, causing changes in cell membrane permeability that result in the leakage of cell content (e.g., proteins and potassium ion) and microbial death (Dutta et al. 2009; Li et al. 2010). The second is based on lower molecular weight chitosan (LMWC), which influences the physiological processes of microorganisms (Bingjun et al. 2015; Dutta et al. 2009). CS could combine with negatively charged intracellular components, such as nucleic acids and proteins, after entering the cells, then disrupt the metabolism of microorganisms (Kong et al. 2008; Zheng et al. 2003). A third mechanism suggests that chelation occurs between CS and some trace transition metals, which are necessary for microbial growth, leading to the inhibition of growth processes (Kong et al. 2008; Sarwar et al. 2014). It is suggested that through the last mechanism a polymer membrane formed by CS can absorb on the cell surface, hindering the exchange of intracellular and extracellular nutrients or oxygen (Hosseinnejad et al. 2016; Zheng et al. 2003).

    As an antifungal agent, CS works against many filamentous fungi (e.g., Neurospora crassa) and yeast due to the permeabilization of the plasma membrane caused by the charge interaction, affecting the synthesis of nucleic acids and proteins. For bacteria, the electrostatic interaction was shown to promote the entrance of CS from the extracellular domain to the intracellular domain at pH 5.3 (below pKa). However, the chelation of CS with Mg2+ and Ca2+ in the cell wall held a dominant position as pH was above pKa, disrupting the integrity of the cell wall (Kong et al. 2010).

  • Antimicrobial mechanisms of chitosan derivatives

  • CS derivatives were obtained by chemical modification at the –NH2 groups or at the –OH groups. The grafted cationic moieties or other hydrophilic and hydrophobic groups not only improved the water solubility of CS, but also positively or negatively affected the antimicrobial capacity of CS (Fig. 1).

    Figure 1.  Schematic representation of CS and its derivatives (Red arrows indicate enhanced antimicrobial activity and blue arrows indicate reduced antimicrobial activity)

  • Chitosan derivatives with enhanced antimicrobial capacity

  • To enhance the antimicrobial activity of CS, the introduction of positively charged groups or protonated groups (e.g., quaternary ammonium, arginine, and carboxymethyl) was a common and effective modification method (Dong et al. 2014). Quaternized chitosan derivatives, a water-soluble polyelectrolyte, showed higher antibacterial activities against Escherichia coli and Staphylococcus aureus than that of CS alone (Jia et al. 2001). N, N, N-trimethyl chitosan (TMC) was a representative CS derivative with quaternary ammonium salt, which was synthesized by the reaction of amino groups on CS with methyl iodide in the presence of NaOH. TMC with positively charged N-atoms and its cationic moiety could interact with the negatively charged cell surface of bacteria. TMC exhibited a higher antibacterial activity caused by permanent quaternary moieties. Moreover, the antimicrobial activity of TMC was significantly affected by pH value. O-methyl free TMC was obtained by pretreating CS with formic acid and formaldehyde. O-methyl free TMC with a higher degree of trimethylation exhibited higher antibacterial activity at pH 7.2, demonstrating that the trimethylated amino group was involved in antibacterial activity. However, the antibacterial activity was inversely proportional to the degree of trimethylation at pH 5.5, due to the weakened antibacterial activity of trimethylated amino groups caused by the steric hindrance effect of more methyl groups than other quaternized amino groups. Moreover, the carboxy methylated modification reduced the activity of O-methyl free TMC (Xu et al. 2010).

    Arginine-containing guanidyl groups have been shown to react with CS to obtain arginine-functionalized chitosan. Guanidine carried a positive charge under neutral pH, owing to its high pKa value (12.48) (Su et al. 2019). Water-soluble arginine-functionalized chitosan strongly inhibited Pseudomonas fluorescens and E. coli growth at pH 7, resulting from its interaction with the cell membrane, leading to an increased membrane permeability and cell death (Tang et al. 2010). Generally, arginine was grafted onto the skeleton of CS by the reaction of its carboxyl group and C2 amino group of CS. Arginine was also shown to react with the C6 hydroxyl group of CS to synthesized 6-deoxy-6-arginine modified chitosan (DAC). The efficient antibacterial effects of DAC against E. coli and S. aureus were observed. This was presumed to be due to the introduction of cationic guanidine groups at 6-OH positions and the reservation of 2-NH2 positions (Su et al. 2019).

    Carboxy methylated chitosan (CMCS) was another water-soluble CS derivative, prepared by the addition of NaOH solution in a CS suspension in an isopropanol medium with the subsequent addition of monochloro acetic acid (Wang et al. 2016). The antibacterial activity of O-carboxy methylated chitosan (O-CM-chitosan) has been reported to be superior to CS. When –CH2COOH was introduced into –OH of CS, O-CM-chitosan was synthesized. Moreover, its –COOH groups may have reacted with the NH2 groups intra‐ or inter-molecularly and charged these NH2 groups (Liu et al. 2001). The low antifungal effects of CMCS against Candida albicans, Candida krusei, and Candida glabrata were observed by Luo et al. (2019).

    Thiolated chitosan was obtained by grafting coupling reagents bearing thiol functions on the amino groups of CS, including chitosan-cysteine conjugates, chitosan-thioglycolic acid conjugates, and chitosan-4-thio-butyl-amidine conjugates. Among them, LMWC-thioglycolic acid displayed superior antimicrobial activity in a study conducted by Geisberger et al. (2013). These authors showed a killing rate of 100% in Streptococcus sobrinus and a reduction of colony counts by 99.99% in Neisseria subflava and 99.97% in C. albicans at 30 min of incubation.

    Additionally, the introduction of antibacterial groups to the CS chain was another route to enrich antibacterial activity of CS. Azido compounds were efficient antibacterial agents and have strong toxicity. N-(3-azido-2-hydroxypropyl) chitosan was synthesized by the introduction of azido compound 1-azido-3-chloropropane-2-ol in the CS backbone. The azido chitosan derivatives showed excellent antibacterial effect due to the presence of organic azides, which could disrupt the integrity of bacterial cell membrane followed by the leakage of intracellular contents. Meanwhile, the toxicity of azido compounds was diminished (Kritchenkov et al. 2019). The CS derivative containing halogeno-1, 2, 3-triazole groups exhibited antifungal activities against Colletotrichum lagenarium (Pass) Ell.et halst, Fusarium oxysporum f.sp.niveum, and Fusarium oxysporum.sp.cucumebrium Owen, due to the antimicrobial functional groups of triazole (Li et al. 2016).

  • Chitosan derivatives with reduced antimicrobial capacity

  • The modification of some groups produced the opposite effect for antimicrobial activity. Hydroxy butyl chitosan (HBCS) was formed by the heterogeneous reaction of CS with 1, 2-butylene oxide (Wang et al. 2013). The antibacterial effects of HBCS against S. aureus and E. coli did not improve compared to CS, which may be attributed to the conjugation of hydroxybutyl groups that occurred in the hydroxyl and amino groups of CS, leading to the decrease of amino groups in HBCS polymers (Li et al. 2019). Using the Michael addition reaction, the amino groups of CS at the C2 position reacted with hydroxyethyl acryl to form N-Alkylated chitosan, resulting in decreased antimicrobial activity (Ma et al. 2008). Furthermore, N, O‐carboxymethylated chitosan was produced by the substitution of -CH2COOH groups with –NH2 groups and –OH groups. The antibacterial assessment showed reduced antimicrobial activity against E. coli (Liu et al. 2001).

  • Chitosan-based systems as antimicrobial agents

    Nanoparticles
  • CS-based nanoparticles have been widely used as drug delivery systems for proteins and nucleic acids (Fig. 2a) (Liu et al. 2009). As the antibacterial activity of CS has only been observed in acidic medium, CS-based nanoparticles with nano size and larger surface area were prepared to improve the antibacterial activity (Qi et al. 2004). The attraction between nanoparticles and microbial cell wall and the leakage of intracellular contents led to better antibacterial activity of CS-based nanoparticles compared to CS alone. CS nanoparticles (CS NPs) were prepared by ionic gelation using TPP as a cross-linking agent. The particle size and Mw were negatively correlated with the antibacterial activities of CS–TPP NPs against E. coli, Acinetobacter schindleri, and Pseudomonas aeruginosa (Pan et al. 2019a, b; Sarwar et al. 2014). In addition to TPP, sodium sulfate was used as another cross-linking agent to form CS NPs with LMWC at a final concentration of 0.4–0.6%, exhibiting considerable antimicrobial activity (Garrido-Maestu et al. 2018).

    Figure 2.  The different formulations of chitosan-based biomaterials and the structure of CS. Adapted from figures of a Liu et al. (2009); b Xia et al. (2017); c Zhang et al. (2019); d Hu et al. (2018); e Zhu et al. (2019); f Kong et al. (2008)

    The loading of metal ions in CS NPs was also a good strategy to improve its antibacterial activity. In this context, Qi et al. (2004) prepared CS NPs loaded with copper ions, inhibiting the growth of E. coli, S. choleraesuis, and S. typhimurium, and reaching an MBC values of 1 μg/ml and an MIC values of < 0.25 μg/ml. In another work, CS NPs loaded with Fe2+ or Fe3+ were produced and revealed that the nanoparticles had high inhibition ratios against E. coli, S. aureus, and C. albicans (Qian et al. 2017). Silver products were considered essential due to its strong inhibitory and bactericidal effects. Upon addition of silver product to CS, the chitosan-Ag nanoparticles had high bactericidal efficiency against both bacterial and fungi (Biao et al. 2017).

    The applications of antimicrobial peptides or proteins has been restricted due to its instability. The integration of lysozyme with CS NPs may be used to increase the antibacterial activity and improve the quality of lysozyme. Thus, lysozyme-loaded chitosan nanoparticles (CS-Lys-NPs) were developed and demonstrated a greater inhibition zone, lowering MIC and MBC compared to CS NPs (Wu et al. 2017). Wang's research group evaluated the efficacy of transformable polymer–peptide nanosystems with a CS backbone for the delivery of KLAK, a broad‐spectrum antimicrobial peptide (AMP). This nanosystem showed strong bactericidal activity of S. aureus in vitro, enhancing the accumulation and retention of AMPs in infectious sites, which is caused by the in situ morphological transformation (Qi et al. 2017).

  • Hydrogels
  • Hydrogels have aroused enormous interest for use in drug-delivery systems, cell carriers, and tissue engineering scaffolds due to their good mechanical properties, controlled release of drugs, and their similarity to soft extra cellular matrix (Appel et al. 2014). However, application of chitosan hydrogels has been restricted due to its weak flexibility. Various composite hydrogels have been established to broaden its application. Wu and colleagues reported that chitosan/sodium alginate (CS-ALG) hydrogels were utilized to deliver lysozyme and eliminate foodborne microorganisms. A 100% bacterial clearance rate of CS/ALG loaded with lysozyme was observed, which was attributed to the superposition effect stimulated by CS and lysozyme (Wu et al. 2018). Huang and colleagues (2019) designed a series of hydrogels based on poly (ethylene glycol) diacrylate (PEGDA) and CS or thiolated chitosan. The hydrogels had good antibacterial activity and their antibacterial rate against E. coli and S. aureus remained above 80% after incubation for 6, 12, 24 and 36 h. These investigators also demonstrated that double crosslinking hydrogels, based on maleilated chitosan (CS-MA) and hyaluronan, exhibited a much higher antibacterial efficiency against S. aureus than that of chemical cross-linked one, as the synergistic effect of CS-MA and CS (Hu et al. 2019). Xia et al. (2017) designed a chitin whisker/CMCS NPs/HBC composite hydrogel (CW/NPs/HBC-HG) loaded with linezolid as a wound dressing (Fig. 2b). The composite hydrogels had sustained antibacterial effects against E. coli and S. aureus that lasted for seven days.

    Silver nanoparticles (AgNPs) with potent antibacterial activity ability were often utilized as an additive in the development of antibacterial hydrogels (Rahimi et al. 2019). Nešović et al. (2019) designed biocompatible CS and poly (vinyl alcohol) (PVA) hydrogels with incorporated AgNPs as an antibacterial wound dressing. The release profile of Ag was characterized by an initial burst, effectively preventing bacterial infections, followed by a slow release to day 28 maintaining the sterile environment around wound surroundings for a longer period. After 1 h of incubation with hydrogels containing AgNPs, bacterial numbers of S. aureus and E. coli were significantly reduced, manifesting effective antibacterial activity of the hydrogels.

  • Film
  • CS with good film‐forming ability was extensively used as an active packaging material. CS-based films have been investigated for multiple functionalities, such as films prepared via many strategies like direct casting, coating, dipping, layer-by-layer assembly, and extrusion (Wang et al. 2018a, b, c). However, the mechanical property and antimicrobial activity of pure CS film has been shown to not be satisfactory for food packaging applications. CS can interact with inorganic nano-sized materials, such as TiO2 and AgNPs. Zhang et al. (2017) developed a CS-TiO2 composite film with efficient antibacterial activity, which had a bactericidal ratio of more than 90% for E. coli, S. aureus, C. albicans, and Aspergillus niger. The antimicrobial activity of the pure CS film was improved by the addition of TiO2 nano-powder. Moreover, the addition of natural active products could significantly enhance the performance of CS film. Zhang et al. (2019) prepared CS/tea polyphenols-silver nanoparticles (CS/TP-AgNPs) composite film and explored the antibacterial activity (Fig. 2c). The inhibition zone results showed that the nanocomposite film functionalized by TP-AgNPs had higher antibacterial activity against both E. coli and S. aureus than the CS film. Moreover, the Luna-Barcenas group synthesized CS-silver nanoparticles (CTS-AgNPs) film as an alternative dual-function (antibacterial and biocompatible) wound dressing (Hernandez-Rangel et al. 2019). CTS-AgNPs film exhibited significant antibacterial activity against E. coli, P. aeruginosa, and S. aureus, and moderated antibacterial activity against Staphylococcus epidermidi.

    Apart from adding the inorganic nano-sized materials, antibiotics have also been chemically conjugated on the CS chain as an antibacterial CS film. Liu et al. (2017) studied the antibacterial property of gentamicin-modified chitosan film (CS-GT). Gentamicin was shown to be an effective aminoglycoside antibiotic for most species including Gram-positive and Gram-negative aerobic bacteria. The lesser colony forming units of S. aureus and E. coli treated with CS-GT were observed compared to the pure CS film, indicating that the antibacterial efficiency of CS-GT was much higher than pure CS film.

  • Sponges
  • CS sponges have received a great deal of attention in the biomedical field due to their high porosity, high swelling capacity, good antibacterial activity, and high permeability. However, the usage of pure CS sponge as a wound healing dressing material is limited for their poor hydrophilicity and fewer surface amino groups (Patrulea et al. 2015). To address this, a composite sponge based on CS and hydrophilic HBC was synthesized (Fig. 2d). The composite sponge significantly increased the antibacterial ratio of S. aureus and E. coli compared to the HBC sponge and CS sponge. The CS content was proportional to the antibacterial effect (Hu et al. 2018). Water-soluble TMC had excellent antibacterial activity compared to CS as a result of the increased amino groups. Xia et al. (2020) prepared TMC NPs/CS composite sponge with asymmetric wettability surface. The TMC NPs/CS sponge could reduce the survival population of E. coli and S. aureus in vitro due to the introduced TMC NPs. Regarding the adsorption applications, CS and its derivatives have been widely investigated as a potential biosorbent for wastewater treatment to remove heavy metal ions and dyes. Carvalho et al. (2019) synthesized 3D porous sponges formed by CS polymers that were modified using 11-mercaptoundecanoic acid (MUA) as bio-adsorbents. The CHI-MUA porous sponges exhibited a significant antibacterial effect against P. aeruginosa, which was equivalent to conventional antibiotic drugs.

    The introduction of nano silver or silver sulfadiazine (AgSD) has been verified to be effective in improving the antibacterial ability of CS sponges (Li et al. 2011). Anisha et al. (2013) mixed CS, hyaluronic acid (HA), and nano silver (nAg) before freeze drying to obtain chitosan HA/nAg composite sponges. The nanocomposite sponges showed high antimicrobial activity against S. aureus, P. aeruginosa, E. coli, Klebsiella pneumonia, and methicillin-resistant Staphylococcus aureus (MRSA), which could be used for the treatment of diabetic foot ulcers. AgSD particles were added to the CS matrix to obtain CS/AgSD composite sponges, which also showed potential as a wound dressing because of its broad-spectrum antibacterial activity (Shao et al. 2017).

  • Fibers
  • CS fibers have been proposed as a safe wound dressing due to their intrinsic bacteriostatic activity and biodegradability. Unfortunately, for CS fibers, poor liquid absorbing capacity in the solid state limit its application as a wound dressing. Zhou et al. (2016) prepared TMC fiber and evaluated its potential as a wound dressing material. The TMC fiber had higher water absorption capability compared to CS fiber. The antibacterial activity of designed TMC fiber was higher than that of CS fibers and enhanced as the degree of quaternization of TMC. Fan et al. (2006) developed novel bicomponent fibers composed of alginate and CMCS. The fibers were treated with silver nitrate to enhance antibacterial ability. The bacterial reduction rate of obtained fibers was above 99.9%.

    Additionally, CS fibers could be used as an absorbent suture. Zhu et al. (2019) developed a CS/gallnut tannin (CS/GT) composite fiber (Fig. 2e). The bacterial reduction of S. aureus treated with fiber revealed that the antibacterial activity of CS/GT composite fiber was significantly higher than that of CS fiber, due to the addition of GT molecules. CS fibers have shown great potential in the field of polluted water treatment. After preparing CS/zinc phthalocyanine (ZnPc-CS) composite fibers by dispersing ZnPc in CS solution, Ali et al. (2017) loaded metal nanoparticles onto composite fibers by water-based in situ preparation process. These fibers not only had an inhibitory effect on a variety of pathogenic bacteria, such as E. coli, but also had the potential to reduce azo dyes in polluted water.

  • Microspheres
  • CS microspheres (CMs) have great potential in the fields of controlled drug release because of its excellent mucoadhesive and permeation enhancing effect. Using an inverse-emulsification cross-linking method, An et al. (2014) synthesized a type of CS/AgNPs microsphere (CAgM). Experiments using four typical Gram bacteria and fungi (i.e., E. coli, S. aureus, Rhizopus and Mucor) proved that CAgM not only has much higher antibacterial activity than original CS, but also has extensive antibacterial activity. The size of the microspheres was shown to affect its antibacterial activity, with smaller microspheres having high antibacterial activity. Kong et al. (2008) introduced oleoyl groups into the CS of the CMs, prepared using W/O emulsification in order to study the relationship between the degree of hydrophobicity of CMs and its antibacterial activity (Fig. 2f). Studies have shown that the antibacterial activity of CMs is directly proportional to its hydrophobic activity and concentration. Thaya et al. (2018) fabricated chitosan-alginate (CS/ALG) microspheres by ionic cross-linking method. The microspheres could effectively inhibit the growth of S. aureus, E. faecalis, P. aeruginosa, and P. vulgaris by decomposing bacterial biofilms.

    H. pylori attached to gastric cells is an important cause of gastric cancer. To remove H. pylori from gastric cells, Goncalves et al. (2013) developed genipin crosslinked chitosan microspheres. The microspheres could remove H. pylori which colonized the gastric mucosa effectively. Wang et al.(2018a, b, c) constructed TSC-PGMA-MACS microspheres from CS, malic acid (MA), glycidyl methacrylate (GMA), and thiosemicarbazide (TSC). The TSC-PGMA-MACS microspheres not only showed high antibacterial activity against E. coli and S. aureus, but also had high adsorption capacity, making them potentially useful for wastewater purification.

  • Applications of chitosan-based systems as antimicrobial agents

  • CS derived from chitin can be extracted from crab and shrimp shells. Recycling seafood processing waste is critical for environmental sustainability. The production of CS is a considerable way to relieve the continuing increase in seafood waste generation, which could be effectively used in biomedical research (Bakshi et al. 2019). As a promising biopolymer, CS is widely used in wound dressings, food packaging, textiles, 3D printing, and dental materials.

  • Wound dressing
  • A wound is defined as the damage of anatomical structure of normal skin, leading to the disruption of barrier function, hence increasing the risk of microbial infection (Zahedi et al. 2009). Wounded skin needs to be covered with a suitable dressing material to offer a favorable micro-environment for physiological reconstruction and to prevent bacterial infection (Naseri-Nosar et al. 2018). An ideal wound dressing should possess numerous properties, such as non-allergenic and non-toxic, facilitating gaseous exchange, absorbing wound exudate, and impermeable protection. CS medical dressings have been developed due to their biodegradability, non-toxicity, biocompatibility, and antimicrobial activity, all necessary to facilitate the wound healing process. Some commercial CS-based wound dressings are already available, such as HidroKi®, Axiostat®, Chitopack®, Tegasorb® and KytoCel® (Simoes et al. 2018).

    Wounds, based on healing tendency, are classified as chronic (e.g., infectious wound, artery ulcers, pressure ulcers, venous ulcers, and diabetic foot ulcers) or acute (e.g., laceration, surgical incision and burn). Wounds that do not heal within 12 weeks are defined as chronic. Colobatiu et al.(2019a, b) developed a CS film formulation loaded with bioactive compounds (i.e., an extract mixture of Plantago lanceolata, Tagetes patula, Symphytum officinale, Calendula officinalis, and Geum urbanum) and evaluated its feasibility as a functional wound dressing for diabetic wounds. The bioactive compounds-loaded CS film was found to have an effective inhibition effect of P. aeruginosa (inhibition zone of 12 mm). Based on a streptozotocin-induced diabetic rat model, the composite film formulation accelerated re-epithelialization and promoted the wound healing process compared to the blank film formulation. According to the effective antimicrobial activity of TMC NPs/CS sponge with asymmetric wettability surface (Fig. 3a, b), wound healing was facilitated and wound infection was controlled (Fig. 3c). Meanwhile, re-epithelialization and angiogenesis were observed in a chronic wound healing model (Xia et al. 2020).

    Figure 3.  a SEM images of CS sponges (A1: 0.5%; A2: 1.0%; A3: 2.0%). b Antibacterial activity of CS (Ⅰ), modified TMC NPs/CS (Ⅱ) and modified CS (Ⅲ) sponges against E. coli (B1, B3) and S. aureus (B2, B4). c Photographs of wounds in diabetic mice with bacterial infection (C1) and bacteria isolated from the mice wounds (C2). d SEM images of LCPHs (D1: LCPH0; D2: LCPH1; D3: LCPH2; D4: LCPH3). e Antibacterial results of survival S. aureus clones after contacting with LCPHs. f Appearance and g closure rate of wounds with control group (no dressing) and LCPHs on days 0, 5, 10 and 15.ac Adapted from figures of Xia et al. (2020); dg Adapted from figures of Zhang et al. (2019)

    The acute wound model was also studied. Sasikala et al. (2013) prepared a chitosan honey hydrogel film as a wound dressing. The chitosan honey films showed higher antibacterial activity against S. aureus and E. coli than that of blank chitosan film. The activity was found to increase with increased honey concentration demonstrated by increased inhibition zone. Rathinamoorthy et al. (2019) further studied the Leptospermum scoparium honey/CS wound dressing, which possessed a better wound healing efficacy in excision, incision, and burn wound models. The wound beds in excision, incision, and burn wound models were almost fully recovered on 18, 18, 21 days, respectively.

    The incorporation of natural extracts and antibiotics is commonly employed to accelerate wound healing and to prevent bacterial infection. Sarhan et al. (2016) loaded Cleome droserifolia (CE) and Allium sativum aqueous extract (AE) into nanofibers (HPCS) consisting of honey, PVA, and CS to construct antimicrobial wound dressing. The HPCS-AE/CE completely inhibited the growth of S. aureus and had mild antibacterial activity against MRSA. The wound closure rate of the HPCS-AE/CE treatment group was similar to AquacelAg, a commercial wound dressing. Zhang et al. (2019) utilized lignin–CS–PVA composite hydrogel (LCPH) as an excision wound dressing (Fig. 3d). LCPH without lignin could better inhibit bacteria growth than the LCPH-containing lignin (Fig. 3e). Complete healing without skin contraction was completed in 15 days in the LCPH treated group (Fig. 3f, g). Basha et al. (2018) developed in situ gel formed by CS NPs loaded with cefadroxil (CDX) (CDX-CSNPs) for promoting wound healing. The high bactericidal effect and significantly accelerated wound healing process were observed in CDX-CSNP1 in situ gel treatment group after 24 h of two full-thickness skin excision rounded wound model and S. aureus bacterial infection.

  • Food packaging
  • Eco-friendly food packaging materials have received considerable interest as an alternative to non-biodegradable petroleum-based polymers (Yang et al. 2015). CS with good biodegradability and antimicrobial activity has been employed to produce food packaging material. For example, an edible coating, which was a thin layer formed by edible material, was used to improve the quality of food products (Takala et al. 2011). Pork treated with the CS coating alone exhibited minimum pH changes and inhibition of microbial growth, when stored at 25 ℃ for 20 days. Incorporating gelatin into a CS coating further enhanced the preservative activity (Xiong et al. 2020). Polyethylene films coated with chitosan-ZnO nanocomposites completely inhibited the growth of S. enterica, E. coli, and S. aureus after 24 h incubation (Al-Naamani et al. 2016). Min et al. (2020) designed a food packaging composite coating based on quaternary ammonium salt modified chitosan (HACC) and PVA to achieve antifogging and antibacterial functions (Fig. 4a). The antibacterial ability of the HACC/PVA composite coating against E. coli, S. aureus, and Botrytis cinerea was increased when the HACC quality ratio increased (Fig. 4b). The composite coating effectively extended the shelf life of strawberries and retained their original color and flavor during the five days of storage at 25 ℃ (Fig. 4c). Additionally, grapefruit seed extract (GSE) can play a vital role in the formation of edible coatings. Won et al. (2018) reported a CS‐based coating containing GSE for the protection of cherry tomatoes. The effectively antimicrobial activity against Salmonella was observed in CS coating and GSE‐CS coating treatment groups. This effect was further enhanced in GSE‐CS‐coated cherry tomatoes during storage at 25 ℃. Moreover, the CS‐GSE coating had the advantage of biosecurity for lycopene concentration, color, and sensory properties of cherry tomatoes. Kim et al. (2018) investigated the influence of CS–alginate coating with GSE in the storage of shrimp (Litopenaeus vannamei) for 15 days at under 4 ℃. The coating could inhibit the growth of mesophilic and psychrotrophic bacteria and decrease the production of total volatile base nitrogen and melanosis during storage.

    Figure 4.  a SEM images of the surface (left) and cross-section (right) of quaternary ammonium salt modified chitosan (HACC) and poly (vinyl alcohol) (PVA) composite coating. b Inhibition rate of the composite coating against E. coli, S. aureus and Botrytis cinerea. c Photographs of strawberries treated with control (left) and 2% HACC/PVA composite coating (right) after storage for 1, 3, 5 days. d SEM surface image (D1) and cross-section image (D2) of pure CS film; SEM surface image (D3) and cross-section image (D4) of chitosan-TiO2 film. e Bactericidal ratios of the chitosan-TiO2 film against E. coli, S. aureus, C. albicans and A. niger for different times. f Preservation of red grape packed in different materials at 37 ℃ for six days: (F1) plastic wrap; (F2) pure CS film; (F3) chitosan-TiO2 film.ac Adapted from figures of Min et al. (2020); df Adapted from figures of Zhang et al. (2017)

    Aside from edible coating, researchers have used CS to construct bioactive film for food packaging materials. Wu et al. (2019) synthesized CS/ε-polylysine (ε-PL) bionanocomposite film using sodium tripolyphosphate (TPP) as a cross-linking agent. The bionanocomposite film showed decreased mechanical and barrier properties by increasing the ratio of ε-PL. However, the incorporation of ε-PL increased the antimicrobial efficacy of bionanocomposite film against E. coli and S. aureus, making it an excellent candidate for food packaging. CS/ PVA film has also been used for the design of antimicrobial film applied to tomatoes. Using glutaraldehyde as the cross-linker, the obtained CS-PVA film exhibited an inhibitory effect against pathogenic bacteria, such as E. coli, S. aureus, and Bacillus subtilis, demonstrated by an inhibitory zone of 1.5, 1.2 and 1.4 cm, respectively (Tripathi et al. 2009). Tripathi et al. (2010) added pectin to CS-PVA film. The ternary film was shown to inhibit growth of pathogenic bacteria including E. coli, S. aureus, Bacillus subtilis, Pseudomonas, and C. albicans, verified by the higher clear zone diameter values than the diameter of film strips. To better enhance the antimicrobial efficacy of CS film, TiO2 was added (Fig. 4d). The microbial growth of E. coli, S. aureus, C. albicans, and A. niger were inhibited by CS-TiO2 film with a 100% antimicrobial rate in 12 h (Fig. 4e). In a red grapes model, CS film and CS-TiO2 film effectively served as an active packaging material maintaining a bright red and smooth surface and extending the shelf-life for 15 days and 22 days, respectively (Fig. 4f) (Zhang et al. 2017). The CS film could be functionalized into different compounds including apple peel polyphenols (Riaz et al. 2018), kombucha tea (KT) (Ashrafi et al. 2018), and rosemary essential oil (Abdollahi et al. 2012). Ashrafi et al. (2018) also developed a film composed of CS and KT that could be used as a potential active packaging material. Agar diffusion test results showed high antimicrobial property of CS/KT film against E. coli and S. aureus. The minced beef packed with CS/KT film was preserved up to three days, and microbial growth changed from 5.36 to 2.11 log cfu/gr after storage for four days.

  • Textile sector
  • Textiles act as a protective barrier of skin against foreign threats, such as microbial colonization and infection. However, natural textiles, especially cellulose and protein fiber products, present appropriate growth conditions for pathogenic microorganisms. Numerous efforts have focused on the functionalization of textiles with antimicrobial capacity (Costa et al. 2018). Due to non-biodegradability and toxicity, some organic antibacterial agents can contribute to environmental pollution that adversely affect human health. Natural antimicrobial agents have drawn people's attention to the development of antibacterial textiles. CS has been explored and applied to textile materials due to its unique antimicrobial properties (Shahid ul et al. 2019).

    The application of direct coating of CS onto textiles is limited as it is only soluble in acidic aqueous solutions (Lim et al. 2004). To overcome this problem, Pan et al.(2019, 2020) synthesized a water-soluble CS derivative, O-acrylamidomethyl-N-[(2-hydroxy-3-dimethyldodecylammonium) propyl] chitosan chloride (NMA-HDCC), obtained by reacting CS with epoxy propyl dodecyl dimethyl quaternary ammonium salt and N-methylolacryl amide (NMA). The NMA-HDCC was held on cotton through chemical bonds formed by covalently binding with cellulose fabrics. The cotton fabrics treated with NMA-HDCC had durable antimicrobial properties against E. coli even after 30 consecutively repeated launderings, good dying properties using salt-free reactive dying and washing fastness. In addition, core–shell particles consisting of poly (n-butyl acrylate) (PBA) cores and CS shells were also formed to improve the drawbacks of CS. The PBA-CS particles were coated on the surface of cotton using a conventional pad-dry-cure method. The cotton treated with PBA-chitosan particles exhibited over 99% bacterial reduction of S. aureus (Ye et al. 2005).

    CS has some advantages to enhance the dispersion and stability of nanoparticles like Ag NPs and nano ZnO, which were carried out by the formation of various chemical bonds with heavy metals. But CS could not form covalent bonds with cotton fibers (Shafei and Abou-Okeil 2011). CMCS could react with the hydroxyl groups of cellulose due to the presence of carboxylic acid groups. Xu et al. (2019) immobilized Ag NPs onto the surface of cotton fabric through the reaction of carboxyl groups of CMCS and the hydroxyl groups of cellulose (Fig. 5a, b). The bacterial reduction activities of finished cotton fabric against both S. aureus and E. coli remained over 94% even after 50 washing cycles (Fig. 5c, d). In another work, ZnO/CMCS composite was introduced on the cotton fabric by pad-dry-cure. The modified cotton fabric obtained enhanced antibacterial activities against S. aureus and K. pneumoniae as the concentration of ZnO/CMCS composite increased (Wang et al. 2016).

    Figure 5.  a The prepared procedure of modified cotton fabric by CMC and Ag NP. b The optical and SEM images of the original cotton (B1, B4, B7) and the modified cotton fabric samples (B2, B5, B8, B3, B6, B9). c Antibacterial effects and d the durability results of the modified cotton fabric samples against E. coli (left) and S. aureus (right). Adapted from figures of Xu et al. (2019)

    Water dispersible polyurethanes (WDPUs) were widely used in the textile sector acting as breathable coating. Arshad et al. (2018) introduced CS into WDPUs backbone following a three-step synthesis process to improve the antibacterial activity of the finished textiles. The first pre-polymerization step was carried out by using polyethylene glycol (PEG) (Mn = 600), dimethylolpropionic acid (DMPA), and isophorone diisocyanate (IPDI). CS-WDPU treated printed and dyed poly-cotton fabric samples showed inhibition ability towards the growth of pathogenic bacteria (e.g., E. coli, B. subtilus, and S. aureus). The inhibition effect increased with the increasing concentration of CS. In another work, Naz et al. (2018) synthesized CS-based waterborne polyurethane (CS-WPU), which was carried out in two steps. The PU-prepolymers were formed through the reaction between hexamethylene diisocyanate (HDI), PEG (Mw = 6 kDa), and DMPA. The mechanical properties and antimicrobial activity of fabrics treated with CS-WPU both increased as the mole ratio of CS increased.

    Besides cotton fabric, nylon has also been modified by CS and its derivatives to improve the antimicrobial activity. The best antibacterial activity was observed in nylon modified with CS polymers or oligomers after air plasma pretreatment at 26 m/min for three times (Tseng et al. 2009). CS-poly (propylene imine) dendreimer hybrid (CS-PPI) was grafted onto Nylon 6 fabric surface. Optimal treatment condition was pH 4, 60 ℃, 6 h and 2.5 g/L CS-PPI. The CS-PPI treatment improved dye up-take of nylon and introduced additional antibacterial activity against E. coli and S. aureus (Sadeghi-Kiakhani et al. 2016).

  • 3D printing
  • Three-dimensional (3D) printing technology, which has been regarded as an important part of the third industrial revolution, has been widely used in biomedicine (e.g., as implantable devices and scaffold fabrication in tissue engineering) because of its excellent accuracy and reproducibility. Various materials, such as plastics, metals and ceramics, can be used as base materials for printing tissue engineering scaffolds (Gebler et al. 2014; Wang et al. 2018a, b, c). 3D printing strips with maleic anhydride-grafted polylactide (PLA-g-MA) and CS were fabricated; the incorporation of CS effectively enhanced the antibacterial activity of PLA-g-MA composites (Wu 2016).

    The treatment of bone defects, especially infected bone defects in orthopedics, still needs to be improved. 3D printing technology as a potential technology in the bone tissue engineering field is attracting increasing interest. 3D printing technology can make bioactive scaffolds that can be used as bone substitutes. The healing process of infected bone defects is closely related to the prevention of biofilm, and implanted bone engineering scaffolds, which may become a new source of infection (Yang et al. 2018). To repair bone defects and prevent bone infections, Yang et al. (2018) synthesized 3D-printed scaffolds using polylactide-co-glycolide (PLGA) and hydroxyapatite (HA) and grafted quaternized chitosan (hydroxypropyl trimethyl ammonium chloride chitosan, HACC) to the scaffolds to obtain PLGA/HA/HACC. The composite scaffold not only reduces bacterial adhesion and bacterial biofilm formation, but also has osteoconductive properties. Therefore, PLGA/HA/HACC has good clinical application potential.

  • Dental materials
  • As an effective antimicrobial agent, CS also plays an important role in the field of oral health. Caries and periodontal disease have always affected human health. The most important cause of these diseases is the supragingival dental plaque, which is formed by the accumulation of various bacteria. Saliva-coated enamel with Streptococcus sanguinis attached was treated with CS to simulate in vivo conditions. S. sanguinis was effectively suppressed (Busscher et al. 2008). Hayashi et al. (2007) conducted double-blind experiments to evaluate the inhibitory effect of chewing gum containing CS on oral bacteria and found that this gum could effectively control the growth of cariogenic bacteria. Sarasam et al. (2008) synthesized 2-D membranes and 3-D scaffolds using CS to study the antibacterial performance of chitosan-based matrices against a variety of oral bacteria. The results showed that CS showed bacteriostatic properties only after contacting the bacterial surface and bacteriostatic properties were different for different oral bacteria.

    Chlorhexidine (CHX), a well-known antiplaque agent, has been shown to have a good antibacterial effect on Streptococcus mutans. However, it has no effect against S. sanguinis. The combination of chitosan derivative and CHX has been shown to effectively improve the bacteriostatic efficiency (Decker et al. 2005). Plaque accumulation caused by S. mutans and Porphyromonas gingivalis has led to the failure of dental implants. To solve this problem, Divakar et al. (2018) combined Ag NPs and CS nanoparticles as a coating for titanium dental implants. The coating material inhibited bacterial adhesion and reduced bacterial biofilm formation. Tanaka et al. (2020) synthetized CS and CS/dibasic calcium phosphate anhydrous (DCPA) particles with the electrospray method and loaded them onto composite resins, a restorative dental composite. The CS and CS/DCPA particles could effectively improve the bacteriostatic activity without reducing other composite properties.

Perspectives and future
  • Chitosan has been widely used because of its unique and modifiable physical properties. One of its most important properties is its antimicrobial activity. Chitosan is insoluble in neutral aqueous solution, which is the major limiting factor for achieving its antimicrobial activity. Modifying chitosan makes the antimicrobial activity play a greater role in many applications. With the evidence base increasing about antimicrobial materials, researchers have focused on incorporating polymers and high-effect antimicrobials onto chitosan to overcome this limitation. The combination of organic chitosan or its derivatives and inorganic active substances also promotes the development of antimicrobial materials, which may considerably minimize the side effects of the antimicrobial agents. The composite materials will be extensively studied and used in different dosage forms and is one of the promising future research directions. Besides, the literature on mechanisms and affecting factors of the antimicrobial effect of chitosan is abundant. But the exact theory of action still needs to be improved and perfected.

Acknowledgements
  • This work was supported by the National Natural Science Foundation of China (Grant number 31500807); China Postdoctoral Science Foundation Special Funded Project (Grant number 2016T90651); Taishan Scholar Program, China.

Author contributions
  • YL and XC designed this review. ZD and TW wrote the article. All authors read and approved the final manuscript.

Compliance with ethical standards

    Conflict of interest

  • All the authors declare that they have no conflict of interest.

  • Animal and human rights statement

  • This article does not contain any studies with human participants or animals performed by any of the authors.

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