Combating Implant Infections: Shifting Focus from Bacteria to Host

The widespread use of biomaterials to support or replace body parts is increasingly threatened by the risk of implant-associated infections. In the quest for finding novel anti-infective biomaterials, there generally has been a one-sided focus on biomaterials with direct antibacterial properties, which leads to excessive use of antibacterial agents, compromised host responses, and unpredictable effectiveness in vivo. This review sheds light on how host immunomodulation, rather than only targeting bacteria, can endow biomaterials with improved anti-infective properties. How antibacterial surface treatments are at risk to be undermined by biomaterial features that dysregulate the protection normally provided by critical immune cell subsets, namely, neutrophils and macrophages, is discussed. Accordingly, how the precise modification of biomaterial surface biophysical cues, or the incorporation of immunomodulatory drug delivery systems, can render biomaterials with the necessary immune-compatible and immune-protective properties to potentiate the host defense mechanisms is reviewed. Within this context, the protective role of host defense peptides, metallic particles, quorum sensing inhibitors, and therapeutic adjuvants is discussed. The highlighted immunomodulatory strategies may lay a foundation to develop anti-infective biomaterials, while mitigating the increasing threat of antibacterial drug resistance.