Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high.Staphylococcus aureusis responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity, mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including:Staphylococcalabscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network (OLCN) of cortical bone. In contrast,S. aureusintracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome againstS. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies (MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.

Mesenchymal stem cells (MSCs) were isolated from bone marrow of 18 adult New Zealand White rabbits. These cells were culture expanded, suspended in type I collagen gel, and implanted into a surgically induced defect in the donor s right patellar tendon. A cell-free collagen gel was implanted into an identical control defect in the left patellar tendon. Repair tissues were evaluated biomechanically (n = 13) and histomorphometrically (n = 5) at 4 weeks after surgery. Compared to their matched controls, the MSC-mediated repair tissue demonstrated significant increases of 26% (p < 0.001), 18% (p < 0. 01), and 33% (p < 0.02) in maximum stress, modulus, and strain energy density, respectively. Qualitatively, there appeared to be minor improvements in the histological appearance of some of the MSC- mediated repairs, including increased number of tenocytes and larger and more mature-looking collagen fiber bundles. Morphometrically, however, there were no significant left-right differences in nuclear aspect ratio (shape) or nuclear alignment (orientation). Therefore, delivering a large number of mesenchymal stem cells to a wound site can significantly improve its biomechanical properties by only 4 weeks but produce no visible improvement in its microstructure.