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Porous polymer scaffolds are essential materials for tissue engineering because they can be easily processed to deliver stem cells or bioactive factors. However, scaffolds made of synthetic polymers normally lack a bioactive cell-material interface and undergo a burst release of growth factors, which may hinder their further application in tissue engineering. In this paper, a metal-phenolic network (MPN) was interfacially constructed on the pore surface of a porous poly(DL-lactide) (PPLA) scaffold. Based on the molecular gating property of the MPN supramolecular structure, the PPLA@MPN scaffold achieved the sustained release of the loaded molecules. In addition, the MPN coating provided a bioactive interface, thus encouraging the migration and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The PPLA@MPN scaffolds exhibited enhanced bone regeneration in a rat femoral defect model in vivo compared to PPLA, which is ascribed to the combined effect of sustained bone morphogenetic protein-2 (BMP-2) release and the osteogenic ability of MPN. This nanodressing technique provides a viable and straightforward strategy for enhancing the performance of porous polymer scaffolds in bone tissue engineering.

Maintaining the stemness of the transplanted stem cell spheroids in an inflammatory microenvironment is challenging but important in regenerative medicine. Direct delivery of stem cells to repair periodontal defects may yield suboptimal effects due to the complexity of the periodontal inflammatory environment. Herein, stem cell spheroid is encapsulated by interfacial assembly of metal-phenolic network (MPN) nanofilm to form a stem cell microsphere capsule. Specifically, periodontal ligament stem cells (PDLSCs) spheroid was coated with FeIII/tannic acid coordination network to obtain spheroid@[FeIII-TA] microcapsules. The formed biodegradable MPN biointerface acted as a cytoprotective barrier and exhibited antioxidative, antibacterial and anti-inflammatory activities, effectively remodeling the inflammatory microenvironment and maintaining the stemness of PDLSCs. The stem cell microencapsulation proposed in this study can be applied to multiple stem cells with various functional metal ion/polyphenol coordination, providing a simple yet efficient delivery strategy for stem cell stemness maintenance in an inflammatory environment toward a better therapeutic outcome.

Treating bacterial biofilm infections on implanted materials remains challenging in clinical practice, as bacteria can be resistant by weakening the host defense from immune cells like macrophages. Herein, a metal-piezoelectric hetero-nanostructure with mechanical energy-driven antimicrobial property is in situ constructed on the Ti implant. Under ultrasonic irradiation, the formed piezotronic Ti (piezoTi) can promote the generation of reactive oxygen species (ROS) by facilitating local charge transfer at the surface, thus leading to piezodynamic killing of Staphylococcus aureus (S. aureus) while downregulating biofilm-forming genes. In addition, the stimulated macrophages on piezoTi display potent phagocytosis and anti-bacterial activity through the activation of PI3K-AKT and MAPK pathway. As a demonstration, one-time ultrasound irradiation of piezoTi pillar implanted in an osteomyelitis model efficiently eliminates the S. aureus biofilm infection and rescues the implant with enhanced osteointegration. By the synergistic effect of ultrasound-driven piezodynamic therapy and immuno-regulation, the proposed piezoelectric nanostructured surface can endow Ti implants with highly efficient antibacterial performance in an antibiotic-free, noninvasive, and on-demand manner.