Fracture-related infection (FRI) remains a major concern in orthopaedic trauma. Functionalizing implants with antibacterial coatings are a promising strategy in mitigating FRI. Numerous implant coatings have been reported but the preventive and therapeutic effects vary. This systematic review aimed to provide a comprehensive overview of current implant coating strategies to prevent and treat FRI in animal fracture and bone defect models. A literature search was performed in three databases: PubMed, Web of Science and Embase, with predetermined keywords and criteria up to 28 February 2023. Preclinical studies on implant coatings in animal fracture or defect models that assessed antibacterial and bone healing effects were included. A total of 14 studies were included in this systematic review, seven of which used fracture models and seven used defect models. Passive coatings with bacteria adhesion resistance were investigated in two studies. Active coatings with bactericidal effects were investigated in 12 studies, four of which used metal ions including Ag+ and Cu2+; five studies used antibiotics including chlorhexidine, tigecycline, vancomycin, and gentamicin sulfate; and the other three studies used natural antibacterial materials including chitosan, antimicrobial peptides, and lysostaphin. Overall, these implant coatings exhibited promising efficacy in antibacterial effects and bone formation. Antibacterial coating strategies reduced bacterial infections in animal models and favored bone healing in vivo. Future studies of implant coatings should focus on optimal biocompatibility, antibacterial effects against multi-drug resistant bacteria and polymicrobial infections, and osseointegration and osteogenesis promotion especially in osteoporotic bone by constructing multi-functional coatings for FRI therapy. The clinical treatment of FRI is complex and challenging. This review summarizes novel orthopaedic implant coating strategies applied to FRI in preclinical studies, and offers a perspective on the future development of orthopaedic implant coatings, which can potentially contribute to alternative strategies in clinical practice.
Within the field of biomaterials, the control of cell–surface interactions is generally addressed through surface chemistry modification. In this respect, Layer-by-Layer (LbL) coatings constitute promising versatile tools. Most cells are mechanosensitive, therefore the stiffness of their microenvironment should also be considered as a crucial parameter when designing polymer-based biomaterials. Here, we report on the combination of mechanics and surface chemistry of LbL-treated polydimethylsiloxane substrates of tunable stiffness to control cell behaviour. Biomimetic LbL films consist of poly-L-lysine (PLL) and chondroitin-4-sulfate (CSA). Stiffness, surface chemistry, wettability and topography of bare and LbL-treated polydimethylsiloxane were analysed. We demonstrated that cells adhered and grew up on all the substrates with significant promotive effects of PLL-terminated films and stiffer substrates. Pre-osteoblasts differentiation was enhanced onto PLL-terminated films irrespective of stiffness and onto CSA-terminated films in a mechanical dependent manner. These results open outlooks within the field of bone tissue engineering, as they demonstrate that osteoconductive surfaces can be obtained by combining uncrosslinked biomimetic LbL films and the intrinsic mechanical properties of the substrates, that is, without any commonly used, potentially cytotoxic chemical crosslinking.
Osteoporosis is characterized by the widespread deterioration of bone mass and microarchitecture. It poses an increasingly significant socioeconomic threat in light of the aging population. Emerging research highlights the crucial role played by crosstalk between bone cells and other components in the skeletal system, including immune cells, to maintain bone homeostasis. Despite articles introducing this novel field known as osteoimmunology, accumulating evidence has revealed that the role of the immune system in bone homeostasis extends beyond its previously recognized contributions. Therefore, we have performed a systematic review with the aim of synthesizing the existing literature on this particular topic, thereby offering readers a unified framework for immune-mediated bone regulation. A literature search was performed in PubMed, Embase and Web of Science. A total 16,021 results were found, and 150 articles were included following PRISMA guidelines. The involvement of the immune system in osteoporosis can be summarized into three primary aspects, providing a comprehensive overview for readers from diverse backgrounds: (1) the altered immune system in osteoporosis pathogenesis; (2) molecular pathways of immune system regulating bone homeostasis; and (3) current strategies targeting the immune system for therapeutic interventions. We found that the immune system not only responds to developmental changes through altered expression and differentiation but also mediates signals from other tissues to influence bone phenotype. We present a framework of osteoimmunology that can inform the development of new clinical strategies and biomaterials, highlighting immune cells as mediators of signals from other organs or tissues.