Metal–phenolic networks acted as a novel bio-filler of a barrier membrane to improve guided bone regeneration via manipulating osteoimmunomodulation

Abstract

A guided bone tissue regeneration membrane (GBRM) is traditionally viewed as an inert physical barrier to isolate soft tissue from the bone defect area. However, as a “foreign body”, the implantation of a GBRM would inevitably modulate immune response and subsequently affect bone dynamics. Herein, we developed strontium ion (Sr²⁺)-based metal–phenolic network complexes (MPNs) as a novel type of bio-filler to manipulate the osteoimmunomodulation of the advanced GBRM. For controllable delivery of Sr²⁺ depending on the difference in affinity between phenolic ligands and Sr²⁺, tannic acid (TA), epigallocatechin gallate (EGCG), and epigallocatechin (EGC) were selected to chelate with Sr²⁺. The formed MPNs were incorporated into PCL nanofibrous membranes by blending electrospinning. Among them, TA/Sr based MPN particles displayed the most sustainable release profile of phenolic ligands and Sr²⁺. Further investigations demonstrated that Sr²⁺ could not only directly promote osteogenic differentiation of BMSCs, but also manipulate an anti-inflammatory osteoimmune microenvironment in a synergistic manner with TA, thus enhancing osteogenesis and inhibiting bone resorption. The rat alveolar bone defect model also confirmed that the TA/Sr nanoparticle modified membrane displayed better bone regeneration performance than the pure PCL membrane via inhibiting bone resorption. This work provides a new platform for controllable delivery of bioactive nutrient elements, and holds great promise for advancing multi-functional biocomposites.