Antibacterial approaches in tissue engineering using metal ions and nanoparticles:From mechanisms to applications

Bacterial infection of implanted scaffolds may have fatal consequences and,in combination with the emergence of multidrug bacterial resistance,the development of advanced antibacterial biomaterials and constructs is of great interest.Since decades ago,metals and their ions had been used to minimize bacterial infection risk and,more recently,metal-based nanomaterials,with improved antimicrobial properties,have been advocated as a novel and tunable alternative.A comprehensive review is provided on how metal ions and ion nanoparticles have the potential to decrease or eliminate unwanted bacteria.Antibacterial mechanisms such as oxidative stress induction,ion release and disruption of biomolecules are currently well accepted.However,the exact antimicrobial mechanisms of the discussed metal compounds remain poorly understood.The combination of different metal ions and surface decorations of nanoparticles will lead to synergistic effects and improved microbial killing,and allow to mitigate potential side effects to the host.Starting with a general overview of antibacterial mechanisms,we subsequently focus on specific metal ions such as silver,zinc,copper,iron and gold,and outline their distinct modes of action.Finally,we discuss the use of these metal ions and nanoparticles in tissue engineering to prevent implant failure.

Design of functional biomaterials as substrates for corneal endothelium tissue engineering

Corneal endothelium defects are one of the leading causes of blindness worldwide.The actual treatment is transplantation,which requires the use of human cadaveric donors,but it faces several problems,such as global shortage of donors.Therefore,new alternatives are being developed and,among them,cell therapy has gained interest in the last years due to its promising results in tissue regeneration.Nevertheless,the direct administration of cells may sometimes have limited success due to the immune response,hence requiring the combination with extracellular mimicking materials.In this review,we present different methods to obtain corneal endothelial cells from diverse cell sources such as pluripotent or multipotent stem cells.Moreover,we discuss different substrates in order to allow a correct implantation as a cell sheet and to promote an enhanced cell behavior.For this reason,natural or synthetic matrixes that mimic the native environment have been developed.These matrixes have been optimized in terms of their physicochemical properties,such as stiffness,topography,composition and transparency.To further enhance the matrixes properties,these can be tuned by incorporating certain molecules that can be delivered in a sustained manner in order to enhance biological behavior.Finally,we elucidate future directions for corneal endothelial regeneration,such as 3D printing,in order to obtain patient-specific substrates.