Metal-phenolic network biointerface-mediated cell regulation for bone tissue regeneration

Abstract

Bone tissue regeneration presents a significant challenge in clinical treatment due to inadequate coordination between implant materials and reparative cells at the biomaterial-bone interfaces. This gap underscores the necessity of enhancing interaction modulation between cells and biomaterials, which is a crucial focus in bone tissue engineering. Metal-polyphenolic networks (MPN) are novel inorganic-organic hybrid complexes that are formed through coordination interactions between phenolic ligands and metal ions. These networks provide a multifunctional platform for biomedical applications, with the potential for tailored design and modifications. Despite advances in understanding MPN and their role in bone tissue regeneration, a comprehensive overview of the related mechanisms is lacking. Here, we address this gap by focusing on MPN biointerface-mediated cellular regulatory mechanisms during bone regeneration. We begin by reviewing the natural healing processes of bone defects, followed by a detailed examination of MPN, including their constituents and distinctive characteristics. We then explore the regulatory influence of MPN biointerfaces on key cellular activities during bone regeneration. Additionally, we illustrate their primary applications in addressing inflammatory bone loss, regenerating critical-size bone defects, and enhancing implant-bone integration. In conclusion, this review elucidates how MPN-based interfaces facilitate effective bone tissue regeneration, advancing our understanding of material interface-mediated cellular control and the broader field of tissue engineering.

Keywords: Biointerface; Bone tissue regeneration; Immunoregulation; Metal-polyphenolic networks; Stem cells.

Graphical abstract

Scheme 1

Schematic illustration of the interface assembly, cell regulation, and bone regeneration applications of MPNs.

Fig. 1

Natural bone healing process at the cellular and molecular levels, including inflammatory response, callus formation, and bone remodeling.

Fig. 2

Material interface-mediated bone healing process, including immunoregulation, osteogenesis, and vascularization, influenced by physicochemical properties and surface modifications of these interfaces.

Fig. 3

Diversity and biologic activities of polyphenols and metal ions.

Fig. 4

Physicochemical properties of MPNs. (a) MPNs assembled at different surface substrates. Reproduced with permission from Ref. [30]. Copyright 2013 Science. (b) Mechanism of extensive adhesiveness. (c) Permeability of MPNs. Reproduced with permission from Ref. [158]. Copyright 2021 ACS Appl. Mater. Interfaces. (d) Catalysis ability of MPNs. Reproduced with permission from Ref. [161]. Copyright 2024 ACS Nano.

Fig. 5

Stimuli-responsiveness of MPNs. (a) pH-responsiveness of MPNs. Reproduced with permission from Ref. [157]. Copyright 2020 Chem. Mater. (b) GSH-responsiveness of MPNs. Reproduced with permission from Ref. [166]. Copyright 2023 Adv Healthcare Mater. (c) ROS-responsiveness of MPNs. Reproduced with permission from Ref. [167]. Copyright 2023 Adv Healthcare Mater. (d) Light-responsiveness of MPNs. Reproduced with permission from Ref. [168]. Copyright 2021 Adv. Mater.

Fig. 6

MPN biointerace-mediated cell regulation of macrophages, osteoblasts, and VECs. (a) Regulation of macrophage polarization by MPNs. Reproduced with permission from Ref. [79]. Copyright 2023 ACS Nano. (b) Regulation mechanisms of macrophage polarization by MPNs. (c) Promoting osteoblasts differentiation and inhibiting osteoclasts differentiation. Reproduced with permission from Ref. [177]. Copyright 2023 Biomaterials. (d) Regulation mechanisms of osteoblasts promotion and osteoclasts inhibition. (e) Promotion of VECs migration. Reproduced with permission from Ref. [182]. Copyright 2024 Adv Healthcare Mater. (f) Regulation mechanisms of promoting VECs angiogenesis.

Fig. 7

Fabrication of MPN composites loaded with BMP-2 and its application in treating periodontitis. Reproduced with permission from Ref. [194]. Copyright 2024 ACS Appl. Mater. Interfaces.

Fig. 8

Fabrication of MPN-coated BP and its application in critical bone defect regeneration. Reproduced with permission from Ref. [209]. Copyright 2023 Chem. Eng. J.

Fig. 9

Fabrication of MPN-coated Ti implants and its application in implant bone integration. Reproduced with permission from Ref. [173]. Copyright 2024 Adv. Sci.