Aaron Schindeler

Covalent biofunctionalization of implant surfaces using anti microbial agents is a promising approach to reducing bone infection and implant failure. Radical‐rich, ion‐assisted plasma polymerized (IPP) coatings enable surface covalent biofunctionalization in a simple manner; but until now, they are limited to only 2D surfaces. Here a new technology is demonstrated to create homogenous IPP coatings on 3D materials using a rotating, conductive cage that is negatively biased while immersed in RF plasma. Evidence is provided that under controlled energetic ion bombardment, this technology enables the formation of highly robust and homogenous radical‐rich coatings on 3D objects for subsequent covalent attachment of antimicrobial agents. To functionally apply this technology, the broad‐spectrum antimicrobial CSA‐90 is attached to the surfaces, where it retained potent antibacterial activity against Staphylococcus aureus . CSA‐90 covalent functionalization of stainless‐steel pins used in a murine model of orthopedic infection revealed the highly promising potential of this coating system to reduce S. aureus infection‐related bone loss. This study takes the previous research on plasma‐based covalent functionalization of 2D surfaces a step further, with important implications for ushering in a new dimension in the biofunctionalization of 3D structures for applications in bone implants and beyond.

Senolytics are a category of drugs that reduce the impact of cellular senescence, an effect associated with a range of chronic and age‐related diseases. Since the discovery of the first senolytics in 2015, the number of known senolytic agents has grown dramatically. This review discusses the broad categories of known senolytics—kinase inhibitors, Bcl‐2 family protein inhibitors, naturally occurring polyphenols, heat shock protein inhibitors, BET family protein inhibitors, P53 stabilizers, repurposed anti‐cancer drugs, cardiac steroids, PPAR‐alpha agonists, and antibiotics. The approaches used to screen for new senolytics are articulated including a range of methods to induce senescence, different target cell types, various senolytic assays, and markers. The choice of methods can greatly influence the outcomes of a screen, with high‐quality screens featuring robust systems, adequate controls, and extensive validation in alternate assays. Recent advances in single‐cell analysis and computational methods for senolytic identification are also discussed. There is significant potential for further drug discovery, but this will require additional research into drug targets and mechanisms of actions and their subsequent rigorous evaluation in pre‐clinical models and human trials.