Decoding biomaterial-associated molecular patterns (BAMPs): influential players in bone graft-related foreign body reactions

Abstract

Bone grafts frequently induce immune-mediated foreign body reactions (FBR), which hinder their clinical performance and result in failure. Understanding biomaterial-associated molecular patterns (BAMPs), including physicochemical properties of biomaterial, adsorbed serum proteins, and danger signals, is crucial for improving bone graft outcomes. Recent studies have investigated the role of BAMPs in the induction and maintenance of FBR, thereby advancing the understanding of FBR kinetics, triggers, stages, and key contributors. This review outlines the stages of FBR, the components of BAMPs, and their roles in immune activation. It also discusses various bone grafting biomaterials, their physicochemical properties influencing protein adsorption and macrophage modulation, and the key mechanisms of protein adsorption on biomaterial surfaces. Recent advancements in surface modifications and immunomodulatory strategies to mitigate FBR are also discussed. Furthermore, the authors look forward to future studies that will focus on a comprehensive proteomic analysis of adsorbed serum proteins, a crucial component of BAMPs, to identify proteins that promote or limit inflammation. This understanding could facilitate the design of biomaterials that selectively adsorb beneficial proteins, thereby reducing the risk of FBR and enhancing bone regeneration.

Keywords: BAMPs; Bone grafts; FBR; Macrophages; Protein adsorption.

Figure 1. A tentative rendering of the various phases of FBR.

During the first phase of FBR, serum proteins quickly adsorb onto bone graft surfaces, triggering an acute inflammatory response characterized by neutrophils and M1 macrophages. Persistent M1 macrophages maintain chronic inflammation through Th1 responses, resulting in fibrosis and biomaterial failure. In contrast, the presence of M2 anti-inflammatory macrophages promotes angiogenesis and successful biomaterial integration through Th2 response. (Image created using Biorender.com).

Figure 2. BAMPs in bone grafting biomaterial.

Adsorbed serum proteins, danger signals, and the physicochemical properties of the biomaterial comprise the components of BAMPs. The properties of the biomaterial’s surface dictate the adsorbed proteome profile and subsequent immune cell interactions. Protein-protein interactions also occur during protein adsorption onto biomaterials. (Image created using Biorender.com).

Figure 3. Physicochemical properties modulating macrophage phenotypes.

The macrophage phenotypes are influenced by the physicochemical characteristics of bone graft biomaterials. The M1 phenotype is promoted by surface features such as hydrophobicity, porosity, cationic charges, and methyl functional groups. In contrast, M2 macrophages are encouraged by hydrophilicity, increased surface roughness, anionic charges, and carboxyl functional groups. The various cytokines, chemokines, and surface markers of M1 and M2 macrophages are also discussed. (Image created using Biorender.com).