Research On Bio-inspired Antibacterial Coating For Urinary Stent Associated Infection And Encrustation Prevention

Clinically,catheters and ureteral stents are used as treatments for urinary drainage,which significantly reduces the progression of urinary related diseases and the incidence of postoperative complications.However,catheter placement is often accompanied by a breach of the normal urinary defense barrier,which lead to infection.In particular,the long-term indwelling of catheter or stent in urinary system will inevitably produce encrustation,aggravate infection,and even cause hydronephrosis.These complications will increase the difficulty of catheter removal,eventually increase the patient’s pain and economic burden.At present,the main way to deal with infection and encrustation is to graft antibacterial coating on the surface of catheter,such as antibiotic drug release coating,silver ion release coating,antibacterial peptide graft coating and polymer anti-fouling composite coating.Grafted catheters with antibacterial coating have been proved to have certain antibacterial and anti-encrustation effects,but there are still few studies on their long-term effectiveness.However,due to the inert surface of the catheter material,the existing coating catheter has some shortcomings,such as relatively complex preparation process,potential biological toxicity,low preparation efficiency and easy peeling of the coating,which restrict its widespread application in clinical practice.Marine mussel species have excellent natural adhesion properties.It was found that the main adhesion structure in mussel was the amino acid polypeptide sequence containing catechol group.This research embarked from the mussel adhesion mechanism,grafted the antimicrobial peptide on the surface of catheter through the structure of catechol as molecular bridge grafting.Simulating mussel adhesion,two kinds of antibacterial peptide coating were designed:polydopamine antibacterial peptide coating and Mussel biomimetic polypeptide antibacterial peptide coating,which achieve the long anti-infection and incrustation performance in the urinary catheter surface.The details are as follows:1.Polydopamine antimicrobial peptide coatingDopamine is a common drug with a unique structure similar to that of mussel adhesion.Through its own oxidative polymerization,dopamine can be formed as a polymer coating（polydopamine coating）on the surface of a variety of materials based on multiple non-covalent,covalent and coordination interactions.In this paper,firstly,the polydopamine coating was constructed on the surface of polyurethane ureteral stent based on the characteristic of oxidative self-polymerization of dopamine.Meanwhile,the metal-phenol coordination effect of catecheol-Cu²⁺was used to increase the thickness of coating and the density of graft site.Subsequently,with the help of high density quinone bonds coated with polydopamine,the antimicrobial peptides with sulfhydryl were covalently combined to obtain urinary stents with broad spectrum antibacterial effect on the surface.Scanning electron microscopy（SEM）,atomic force microscopy（AFM）,X-ray photoelectron spectroscopy（XPS）and contact angle results all indicate that the antibacterial coating has been successfully grafted onto the surface of the stents.In vitro and in vivo anti-bacterial and anti-encrustation experiments showed good antibacterial and anti-encrustation properties.Cytotoxicity and cell proliferation experiments also showed that the coating owned the property of good biocompatibility.We also found that the antibacterial coating had stability of up to 8 weeks by simulating coating degradation.In conclusion,the antibacterial coating based on metal phenol polydopamine is expected to be an effective surface modification strategy to prevent infection and encrustation.2.Mussel biomimetic polypeptide antibacterial peptide coatingBy further analyzing the molecular adhesion mechanism of Marine mussels,we designed a polypeptide containing multiple catechol side amino acids,and used this as a graft bridge to achieve a highly biocompatible bionic antibacterial coating with specific graft sites.A biomimetic peptide with four catechol side groups and one dibenzo cyclooctyne（DBCO）modified end group was synthesized by solid phase peptide synthesis.Due to the multiple catechol groups,the peptide can stably bind to the polyurethane stent surface with the assistance of Cu²⁺coordination.At the same time,DBCO was used to react with antibacterial peptides containing azido groups through click chemical reaction.Under the precondition of less influence on the activity of antibacterial peptides,more efficient and more specific surface grafting of antibacterial peptides to obtain urinary stent with high antibacterial effect was realized.SEM and AFM analysis showed that the surface morphology of grafted stents changed significantly.XPS analysis showed that the content of elements on the surface of the stents were changed.Droplet contact Angle experiment showed that the hydrophilic property of grafted surface was significant improved.These results confirmed that the antimicrobial peptide coating has been successfully grafted onto the stent surface.In addition to excellent biocompatibility,the antibacterial polypeptide coating also demonstrates high antibacterial and anti-encrustation properties in vitro and in vivo experiments.In the experiment of anti-encrustation in rat bladder,its anti-encrustation ability was significantly improved compared with that of uncoated stent.Due to its good resistance to infection,inflammation in the tissue around the implant was also significantly reduced.The stability test of the coating showed that the coating still had excellent antibacterial properties after 6 weeks.We will optimize the molecular design and preparation conditions of this coating afterwards.Relevant research on this paper can provide reference for the development and application of long-term antibacterial and anti-encrustation indwelled stent.