Development Of Antimicrobial Polypropylene Mesh Materials For Hernia Repair: By Surface Modification With Cold Oxygen Plasma And ?-cyclodextrin

Hernia is a ?rupture of an organ? due to the weakness or defect of abdominal surrounding walls.The main reason of this defect is a higher intra-abdominal pressure that results in herniation at the weakest area of the abdominal wall.Synthetic meshes have been used with the objective of delivering long-term reinforcement to the damaged tissues of the abdominal hernia.Most widely used synthetic meshes are polyester(PET),polytetrafluoroethylene(e PTFE)and polypropylene(PP).However,among synthetic light weight PP meshes has been used as current ?gold standard? material for hernia repair.Nevertheless,the main drawback of these implants is that all synthetic devices favor infection due to the uneven topography of knitted meshes.Thus,mesh infection is a major problem of current PP knitted meshes and need to be cured in early stages of mesh implantation otherwise;secondary operation is imposed to remove infected mesh.The current method for mesh infection prevention after hernia repair is antibiotic prophylaxis.However,PP mesh is a hydrophobic material which do not absorb drug.Thus,mesh infection remains major complication of hernia repair.Therefore,use of antimicrobial mesh material with slow drug release could be better option to prevent infection after mesh implantation.Therefore,this study was focusing on preparation of antimicrobial PP meshes by incorporating antimicrobials that can be slowly released during early stage of mesh implantation.PP mesh surface was modified with ?-cyclodextrin(CD)and loaded with antimicrobial which could deliver slow release of drug for the mesh infection prevention.This,study has taken two necessary sequential approaches to prepare antimicrobial PP mesh materials with controlled release performances.However,before surface modification of PP meshes with CD,the PP surfaces were first functionalized with cold oxygen plasma to increase the surface roughness,hydrophilicity and interaction with CD and hexamethylene diisocyanate(HDI).In the first approach,surface activated PP meshes were coated with CD & HDI in one bath solution.Afterwards,antimicrobials(triclosan or levofloxacin HCL)were loaded into CD cavity for antibacterial properties.In the second approach,cold oxygen plasma treated PP mesh surfaces were first reacted with HDI and then with CD in two grafting steps(PP-HDI-CD).Afterwards,antibiotics(triclosan or levofloxacin HCL)were separately loaded into CD cavity for desired antibacterial functions.After cold oxygen plasma treatment surface roughness was increased for CD&DHI coating and PP-HDI-CD grafting.The CD&DHI was incorporated on the surfaces of oxygen plasma treated PP meshes and formed large spherical coated meshes with small hills and valleys.In the case of PP-HDI-CD grafted meshes a thin layer of HDI was observed and after CD grafting modified meshes shown thick and thin globules of CD on the surfaces of HDI treated PP meshes.All modified meshes coated and grafted loaded with antibiotics(triclosan or levofloxacin HCL)showed slightly swollen effect on the surfaces of modified meshes.Presence of different elements such as oxygen,nitrogen,chlorine and fluorine were observed on the surfaces of coated(CD&DHI)and grafted(PP-HDI-CD)PP meshes.Peaks of oxygen plasma,HDI and CD were also confirmed on modified coated(CD&DHI)and grafted(PP-HDICD)PP meshes.Moreover,it was observed that after plasma treatment and incorporation of CD,hydrophilicity of modified PP meshes dramatically increased.PP control showed an average contact angle of 139.36° and coated(CD&HDI)meshes demonstrated decreased(157%)of contact angle up to 54.2°.Although,coated(CD&HDI)meshes(54.2°)showed better surface wettability(6.27%)than grafted(PP-HDI-CD)meshes(57.6°).CD&HDI coated meshes incorporated with antimicrobials were analyzed for antibacterial properties using two different types of antimicrobials(triclosan and levofloxacin HCL)against Staphylococcus aureus and Escherichia coli.Thus,both antimicrobial loaded meshes demonstrated excellent inhibition zones and displayed sustained antimicrobial properties for seven days.However,inhibition zone diameter of triclosan was larger as compared to inhibition zone diameters of levofloxacin for all seven days.Moreover,PP meshes grafted(PP-HDI-CD)and loaded with antimicrobial displayed excellent sustained antibacterial properties.However,there was not much difference in the inhibition zone diameter of two antimicrobials(triclosan and levofloxacin HCL)but triclosan showed more slow and sustained antimicrobial properties for continuous 13 days as compared to levofloxacin HCL which demonstrated 10 days sustained antimicrobial properties against Staphylococcus aureus and Escherichia coli.Moreover,antibiotic kinetics release performances of coated(CD&HDI)meshes loaded with triclosan exhibited continuous drug release performance more than 48 hours.However,initially burst release properties were observed up to 6 hours.Afterwards,slow release was begin and after 36 hours more sustained drug release was displayed.However,HDI&CD coated but levofloxacin loaded meshes showed similar trend of drug release except that accumulative drug release of levofloxacin(90.26%)was slightly greater than triclosan(86.38%)after 48 hour.Moreover,PP meshes grafted(PP-HDI-CD)and loaded with triclosan demonstrated controlled release of antimicrobials.Thus,burst release of triclosan was also observed during first hour but later after 24 hours sustained drug release was continued up to 48 hour and accumulative drug release was only 62 % of the total drug.However,CD grafted(PP-HDI-CD)meshes loaded with levofloxacin showed slightly different drug release profile.Levofloxacin HCL was also burst released in the beginning but somewhat less stable accumulative drug release than triclosan.Thus,levofloxacin HCL accumulative drug release up to 48 hours was 77% in comparison of 62% of triclosan.These all results of drug release correlates with antimicrobial properties of coated(PP&HDI)and grafted(PP-CD-HDI)meshes.Initially,all samples demonstrated burst release of antibiotics which was due to the fact that un-complexed and surface adhered antibiotics were released during initial stage.Such release profile of drug could be beneficial for mesh infection prevention due to the reason that after mesh implantation initial time duration is considered as crucial for bacteria biofilm formation.However,CD grafted(PP-HDI-CD)and loaded with levofloxacin demonstrated excellent antibacterial properties for 10 days as well as showed suitable drug release profile.Thus,the yield product could be used for hernia mesh infection prevention.