2. Academic Validation
  3. Fn-HMGB1 Adsorption Behavior Initiates Early Immune Recognition and Subsequent Osteoinduction of Biomaterials

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

  • Adv Healthc Mater. 2023 Aug 21;e2301808. doi: 10.1002/adhm.202301808.
Qin Zhao 1 2,  Zifan Zhao 3,  Jing Zhang 1 2,  Yueqi Ni 1 2,  Simin Ouyang 1 2,  Haoning Qi 1 2,  Yiqian Yu 1 2,  Richard J Miron 4,  Hua Tang 5 6,  Yufeng Zhang 1 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430079, China.
  • 2 Medical Research Institute, School of Medicine, Wuhan University, Wuhan, 430071, China.
  • 3 Center of Digital Dentistry, Faculty of Prosthodontics, Peking University School and Hospital of Stomatology; National Center of Stomatology; National Engineerœing Research Center of Oral Biomaterials and Digital Medical Devices; Beijing Key Laboratory of Digital Stomatology; Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, National Clinical Research Center for Oral Diseases, Beijing, 100081, China.
  • 4 Department of Periodontology, University of Bern, Bern, 300392, Switzerland.
  • 5 Department of Rheumatology and Autoimmunology, Shandong Provincial Key Laboratory for Rheumatic Disease and Translational Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250000, China.
  • 6 Institute of Infection and Immunity, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, China.
PMID: 37602504 DOI: 10.1002/adhm.202301808
Abstract

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, the early immune recognition and subsequent osteoinduction of biphasic calcium phosphate (BCP) after implantation to the protein adsorption behavior is attributed. By liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis, the biomaterial-related molecular patterns (BAMPs) formed after BCP implantation are mapped, dominated by the highly expressed extracellular matrix protein fibronectin (Fn) and the high mobility group box 1 (HMGB1). Molecular dynamics simulations show that Fn has the ability to bind more readily to the BCP surface than HMGB1. The preferential binding of Fn provides a higher adsorption energy for HMGB1. Furthermore, multiple hydrogen bonding sites between HMGB1 and Fn are demonstrated using a molecular docking approach. Ultimately, 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 is obstructed. This study introduces a mechanism for early immune recognition of implant Materials based on protein adsorption, providing perspectives for future design and application of tissue engineering Materials.

Keywords

biomaterial-associated molecular patterns; fibronectin; immune recognition; osteoinduction; protein adsorptions.

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