Promoting Stem Cell Mechanosensing and Osteogenesis by Hybrid Soft Fibers.

Bone regenerative biomaterials are essential in treating bone defects as they serve as extracellular matrix (ECM) mimics, creating a favorable environment for cell attachment, proliferation, and differentiation. However, the currently used bone regenerative biomaterials mostly exhibit high stiffness, which may lead to difficulties in degradation and thus increase the risk of foreign body ingestion. In this study, we prepared soft fibrous scaffolds modified with Zn-MOF-74 nanoparticles via electrostatic spinning. The soft fibers (only 1 kPa) permit remodeling under cellular adhesive force, optimizing the mechanical cues in the microenvironment to support cell adhesion and mechanosensing. In addition, the incorporation of Zn-MOF-74 nanoparticles enables the stable and sustained release of zinc ions, promoting stem cell mechanotransduction and osteogenic differentiation. Therefore, the hybrid soft fibers facilitate the regeneration of new bone in the rat femoral defect model, which provides a promising approach for regenerative medicine.

Multi-activity cobalt ferrite/MXene nanoenzymes for drug-free phototherapy in bacterial infection treatment.

Drug-free antibacterial strategies are of great significance for pathogenic bacterial infection treatment in clinical practice. Phototherapy with antibacterial function plays a vital role in mainstream germicidal research. However, phototherapy could lead to residual heat and excess reactive oxygen species (ROS), which are the main side-effects during antibacterial treatment. Unique CoFe2O4/MXene (CM) nanoenzymes, which were fabricated with electrostatic interactions, have been designed to conquer those challenges caused by side-effects of phototherapy in our research. The CM nanoenzymes possess many promising properties including photothermal and photodynamic induced phototherapy and mimic peroxidase (POD), glutathione oxidase (GSHOx), and catalase (CAT). Upon treatment with near-infrared (NIR) light, CM nanoenzymes can create a local high-temperature circumstance as well as raise bacterial membrane permeability. Furthermore, the photodynamic process and multi-enzyme-mimicking activities of CM enzymes boost the interbacterial ROS level. Herein, bacteria can hardly survive in synergistic phototherapy and multi-enzyme-mimicking catalytic therapy in vitro and in vivo. Meanwhile, the CM nanoenzymes exhibit excellent biocompatibility in vitro and in vivo. Overall, this research establishes a strong foundation for effectively employing nanoenzymes, leading to a new way to cure bacterial infections.

Spatiotemporal Management of the Osteoimmunomodulation of Fibrous Scaffolds by Loading a Novel Amphiphilic Nanomedicine.

Implanted bone scaffolds or their biodegradation products may disturb the sequential functions of distinct macrophage phenotypes and cause improper timing of macrophage activation, resulting in delayed or dysfunctional bone regeneration. Although spatiotemporal manipulation of the immune response has been recognized as a promising strategy to address this issue, developing satisfactory drug delivery systems with the function of proper timing control on the macrophage phenotype transformation from pro-inflammatory M1 to anti-inflammatory M2 phenotype still remains a challenge. Here, we propose an amphiphilic nanomedicine with dual anti-inflammatory functions and inflammation-responsive drug release properties to spatiotemporally manage the osteoimmunomodulation of the bone scaffold. The nanomedicine enables the modified scaffold to manipulate the immune response in a staged manner, not only avoiding the overinhibition of M1 macrophages in the initial phase but also facilitating its polarization to M2 phenotype, as well as exhibiting full-course inhibition on later biodegradation-induced inflammation. The described immunomodulatory manner attempts to conform to the principle of osteoimmunomodulation, consequently resulting in better in vivo osteogenesis compared with traditional drug delivery systems. We anticipate that this strategy might aid the development of advanced immunomodulatory bone biomaterials.