Biomaterials-Driven Sterile Inflammation

Abstract

Performance of the biomaterials used for regenerative medicine largely depends on biocompatibility; however, the biological mechanisms underlying biocompatibility of a biomaterial within the host system is poorly understood. In addition to the classical immune response against non-self-entities, the sterile inflammatory response could limit the compatibility of biological scaffolds. Whereas the immediate to short-term host response to a biomaterial implant have been characterized, the long-term progression of host-biomaterial relationship has not been described. This article explores the novel concept of biomaterials-driven sterile inflammation (BSI) in long-term biodegradable implants and throws light for possible explanation for the onset of BSI and the associated damage-associated molecular patterns. The understanding of BSI would advance the current strategies to improve biomaterial-host tissue integration and open novel translational avenues in biomaterials-based tissue regeneration. Impact statement Understanding the novel concept of biomaterials-driven sterile inflammation and associated damage-associated molecular patterns in long-term biodegradable implants would determine their success and improves the tissue engineering and regenerative strategies.

Keywords: DAMPs; biocompatibility; biomaterials; implant immunology; sterile inflammation.

FIG. 1.

Proposed BSI pathway: (A) DAMPs released from injured cells from the implant procedure adhere to the biomaterial surface immediately. Some DAMPs are recognized by immune cells and contribute to the acute inflammation. Others remain “dormant” owing to their orientation. (B) Chronic inflammation is characterized by the dominant presence of macrophages that can recognize DAMPs through PRR. Macrophages may also fuse to form FBGC. (C) The degradation of the biomaterial causes adhered DAMPs to be released into the microenvironment. BSI, biomaterials-driven sterile inflammation; DAMP, damage-associated molecular pattern; FBGCs, foreign body giant cells; PRR, pattern recognition receptor. Color images are available online.

FIG. 2.

Release of IL-1β and IL-18 by NLRP3 inflammasome activation: The production of mature IL-1β and IL-18 requires two signals. Signal 1: biomaterial degradation products cause local cell necrosis leading to the release of DAMPs. Recognition of DAMPs by TLR eventually leads to NF-κB-induced transcription of pro-IL-1β and pro-IL-18. Signal 2: Endocytosis of crystals has been shown to activate NLRP3 inflammasome pathway. We speculate that endocytosis of biomaterial debris can lead to similar activation. NF-κB, nuclear factor kappa B. Color images are available online.