Titanium implants in orthopedic applications can fail due to infection and impaired integration into the host. Most research efforts that facilitate osseointegration of the implant have not considered infection, and vice versa. Moreover, most infection control measures involve the use of conventional antibiotics which contributes to the global epidemic of antimicrobial resistance. Nitric oxide (NO) is a promising alternative to antibiotics, and while researchers have investigated NO releasing coatings, there are few reports on the function/robustness or the mechanism of NO release. Our comprehensive mechanistic study has allowed us to design, characterize, and optimize NO releasing coatings to achieve maximum antimicrobial efficacy toward bacteria with minimum cytotoxicity to human primary osteoblasts in vitro. As the antibiotic era is coming to an end and the future of infection control continues to demand new alternatives, the coatings described herein represent a promising therapeutic strategy for use in orthopedic surgeries.

Wound Healing Skin disorders or injuries can weaken its barrier function, making a wound vulnerable to bacterial infection. Bacteria secrete proteases that disrupt the barrier integrity, delaying wound healing. In article 2202472, Robert Deller, Man Li, Rachel Williams, Raechelle D'Sa, and colleagues describe the potential of nitric oxide‐releasing peptide hydrogels to prevent loss of barrier function from bacterial secreted proteases in order to improve infected wound healing.

The skin serves as a crucial barrier against environmental insults and invading pathogens. However, traumatic injury or skin disorder can compromise this barrier function, leasing to bacterial colonization and infection of the wound with microorganisms such as Staphylococcus aureus, which are normally present on healthy skin. The secretion of bacterial proteases such as V8 protease from S. aureus can disturb the equilibrium between extracellular matrix degradation and deposition during wound healing resulting in loss of barrier integrity. We report the feasibility of a nitric oxide (NO) releasing poly‐ε‐lysine (pεK) hydrogel to prevent loss of barrier function caused by V8 proteases. The fabrication and characterization of the pεK hydrogel and NO releasing properties in biologically relevant media are reported. The NO‐releasing pεK hydrogel have demonstrated bactericidal activity against a clinical isolate of S. aureus in complex physiological media and concurrently reduce the catalytic activity of secreted V8 protease. Moreover, pεK hydrogels are cytocompatible with keratinocytes and dermal fibroblasts. In contrast, Penicillin G loaded pεK hydrogels showed excellent antimicrobial efficacy but did not affect V8 catalytic activity. This demonstrates that NO‐releasing pεK hydrogels hold potential as an effective treatment for infected wounds reducing the microbial burden and inactivating bacterial secreted proteases.