Host defense peptide-mimicking peptide polymer-based antibacterial hydrogel enables efficient healing of MRSA-infected wounds

Wound infections are a compelling health issue caused by the invasion and proliferation of pathogens in wound sites.Antibioticloaded hydrogels are widely used to achieve anti-infectious wound healing.However,due to the quick emergence of drugresistant bacteria,such as methicillin-resistant Staphylococcus aureus(MRSA),wound infection has been a formidable challenge to human health.To address MRSA-infected wounds,an antibacterial peptide polymer-loaded hyaluronic acid(HA)hydrogel(Gel-HA@P)is prepared.The peptide polymer is designed to mimic host defense peptides as the antibiotic alternative showing potent antibacterial activity,low susceptibility to drug resistance and good stability against proteolysis.HA is biocompatible and biodegradable hydrogel substrate as a primary constituent of the extracellular matrix and suitable for cell migration and wound healing.Gel-HA@P shows potent activity against MRSA in vitro and in vivo,low toxicity during the treatment and promotes the wound healing in vivo.This design has proven to be an effective and antibiotic-free strategy to enable the healing of MRSA-infected wounds.

Biofilm-inspired adhesive and antibacterial hydrogel with tough tissue integration performance for sealing hemostasis and wound healing

Uncontrolled bleeding and infection can cause significant increases in mortalities.Hydrogel sealants have attracted extensive attention for their ability to control bleeding.However,because interfacial water is a formidable barrier to strong surface bonding,a challenge remains in finding a product that offers robust tissue adhesion combined with anti-infection properties.Inspired by the strong adhesive mechanism of biofilm and mussels,we report a novel dual bionic adhesive hydrogel(DBAH)based on chitosan grafted with methacrylate(CS-MA),dopamine(DA),and N-hydroxymethyl acrylamide(NMA)via a facile radical polymerization process.CS-MA and DA were simultaneously included in the adhesive polymer for imitating the two key adhesive components:polysaccharide intercellular adhesin(PIA)of staphylococci biofilm and 3,4-dihydroxy-L-phenylalanine(Dopa)of mussel foot protein,respectively.DBAH presented strong adhesion at 34 kPa even upon three cycles of full immersion in water and was able to withstand up to 168 mm Hg blood pressure,which is significantly higher than the 60–160 mm Hg measured in most clinical settings.Most importantly,these hydrogels presented outstanding hemostatic capability under wet and dynamic in vivo movements while displaying excellent antibacterial properties and biocompatibility.Therefore,DBAH represents a promising class of biomaterials for high-efficiency hemostasis and wound healing.

Recent advances in polymeric biomaterials-based gene delivery for cartilage repair

Untreated articular cartilage damage normally results in osteoarthritis and even disability that affects millions of people.However,both the existing surgical treatment and tissue engineering approaches are unable to regenerate the original structures of articular cartilage durably,and new strategies for integrative cartilage repair are needed.Gene therapy provides local production of therapeutic factors,especially guided by biomaterials can minimize the diffusion and loss of the genes or gene complexes,achieve accurate spatiotemporally release of gene products,thus provideing long-term treatment for cartilage repair.The widespread application of gene therapy requires the development of safe and effective gene delivery vectors and supportive gene-activated matrices.Among them,polymeric biomaterials are particularly attractive due to their tunable physiochemical properties,as well as excellent adaptive performance.This paper reviews the recent advances in polymeric biomaterial-guided gene delivery for cartilage repair,with an emphasis on the important role of polymeric biomaterials in delivery systems.

Opportunities and challenges for the development of polymer-based biomaterials and medical devices

Biomaterials and medical devices are broadly used in the diagnosis,treatment,repair,replacement or enhancing functions of human tissues or organs.Although the living conditions of human beings have been steadily improved in most parts of the world,the incidence of major human’s diseases is still rapidly growing mainly because of the growth and aging of population.The compound annual growth rate of biomaterials and medical devices is projected to maintain around 10%in the next 10 years;and the global market sale of biomaterials and medical devices is estimated to reach$400 billion in 2020.In particular,the annual consumption of polymeric biomaterials is tremendous,more than 8000 kilotons.The compound annual growth rate of polymeric biomaterials and medical devices will be up to 15-30%.As a result,it is critical to address some widespread concerns that are associated with the biosafety of the polymer-based biomaterials and medical devices.Our group has been actively worked in this direction for the past two decades.In this review,some key research results will be highlighted.

Electrostatic assembly functionalization of poly(γ-glutamic acid)for biomedical antibacterial applications

Poly(γ-glutamic acid)(γ-PGA)has been found widespread applications in biomedical field because of its excellent water solubility,biocompatibility,and bioactivity.Herein,a water-insoluble γ-PGA antibacterial compound is facilely fabricated via one-pot electrostatic assembly of γ-PGA with cationic ethyl lauroyl arginate(ELA).The functionalized γ-PGA compound(γ-PGA-ELA)ethanol solution can facilely produce colorless and transparent coatings on various inorganic,metal,and polymeric substrates,especially for the lumen of slender catheters(length up to 2 m,and inner diameter down to 1 mm).The functionalized γ-PGA coating presents remarkable antibacterial efficacy in vitro and in vivo.In addition,the γ-PGA compound is used as antibacterial additives of polyolefin via melting extrusion,and the asprepared antibacterial polyolefin demonstrates advantageous antibacterial efficacy.More importantly,the functionalized γ-PGA coating exhibit good hemocompatibility,low cytotoxicity,and satisfactory histocompatibility.The as-proposed γ-PGA compound has a great potential to serve as a safe and multifunctional antibacterial candidate to combat biomedical devices-related infections.

Biocompatible hierarchical zwitterionic polymer brushes with bacterial phosphatase activated antibacterial activity

Hierarchical polymer brushes have been considered as an effective and promising method for preventing implant-associated infections via multiple antibacterial mechanisms.Herein,a bacterial phosphatase re-sponsive surface with hierarchical zwitterionic structures was developed for timely dealing with the poly-meric implant-associated bacterial infection.The hierarchical polymeric architecture was subtly realized on model polypropylene(PP)substrate by sequential photo living grafting of poly(2-(dimethylamino)ethyl methacrylate(PDMAEMA)bottom layer and zwitterionic poly(sulfobetaine methacrylate)(PSBMA)upper layer,followed by the conversion of the PDMAEMA into the zwitterionic structure via succes-sive quaternization and phosphorylation reactions.Owing to shielding the bottom polycations,the hi-erarchical zwitterionic polymer brushes guaranteed the surface with the optimal biocompatibility under the normal physiological environment.Once bacteria are invaded,the surface bactericidal activity of the bottom layer can be rapidly and automatically activated owing to the transition triggered by bacterial phosphatase from zwitterion to polycation.Additionally,ameliorated by the upper layer,the hierarchical surface showed obvious adhesion resistance to dead bacterial cells and notably migrated the cytotoxic-ity of exposed polycation after completion of the bactericidal task.As a proof-of-principle demonstration,this self-adaptive hierarchical surface with sensitive bacterial responsiveness and biocompatibility showed great potential in combating hernia mesh-related infection.This work provides a promising and universal strategy for the on-demand prevention of medical device-associated infections.