Fn-HMGB1 Adsorption Behavior Initiates Early Immune Recognition and Subsequent Osteoinduction of Biomaterials.

Implantable biomaterials are widely used in bone tissue engineering, but little is still known about how they initiate early immune recognition and the initial dynamics. Herein, we attribute the early immune recognition and subsequent osteoinduction of biphasic calcium phosphate (BCP) after implantation to the protein adsorption behavior. By liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis, we mapped the biomaterial related molecular patterns (BAMPs) formed after BCP implantation. Dominanted by the highly expressed extracellular matrix protein fibronectin (Fn) and the high mobility group box 1 (HMGB1). Then molecular dynamics (MD) simulations showed that Fn has the ability to bind more readily to the BCP surface than HMGB1. The preferential binding of Fn provided a higher adsorption energy for HMGB1. Furthermore, multiple hydrogen bonding sites between HMGB1 and Fn were demonstrated using a molecular docking approach. Ultimately, we obstructed the formation of BAMPs through HMGB1 antagonist glycyrrhizic acid (GA), resulting in impaired immune recognition of myeloid differentiation factor 88 (MYD88) mediated dendritic cells (DCs) and macrophages (Mφs), as well as failed osteoinduction processes. This study introduces a mechanism for early immune recognition of implant materials based on proteins adsorption, providing perspectives for future design and application of tissue engineering materials. This article is protected by copyright. All rights reserved.