Sulfated Chitosan-Modified CuS Nanocluster: A Versatile Nanoformulation for Simultaneous Antibacterial and Bone Regenerative Therapy in Periodontitis.

Periodontitis, a prevalent chronic inflammatory disease worldwide, is triggered by periodontopathogenic bacteria, resulting in the progressive destruction of periodontal tissue, particularly the alveolar bone. To effectively address periodontitis, this study proposed a nanoformulation known as CuS@MSN-SCS. This formulation involves coating citrate-grafted copper sulfide (CuS) nanoparticles with mesoporous silica (MSNs), followed by surface modification using amino groups and sulfated chitosan (SCS) through electrostatic interactions. The objective of this formulation is to achieve efficient bacteria removal by inducing ROS signaling pathways mediated by Cu2+ ions. Additionally, it aims to promote alveolar bone regeneration through Cu2+-induced pro-angiogenesis and SCS-mediated bone regeneration. As anticipated, by regulating the surface charges, the negatively charged CuS nanoparticles capped with sodium citrate were successfully coated with MSNs, and the subsequent introduction of amine groups using (3-aminopropyl)triethoxysilane was followed by the incorporation of SCS through electrostatic interactions, resulting in the formation of CuS@MSN-SCS. The developed nanoformulation was verified to not only significantly exacerbate the oxidative stress of Fusobacterium nucleatum, thereby suppressing bacteria growth and biofilm formation in vitro, but also effectively alleviate the inflammatory response and promote alveolar bone regeneration without evident biotoxicity in an in vivo rat periodontitis model. These findings contribute to the therapeutic effect on periodontitis. Overall, this study successfully developed a nanoformulation for combating bacteria and facilitating alveolar bone regeneration, demonstrating the promising potential for clinical treatment of periodontitis.

Modulation of T Cell Responses by Fucoidan to Inhibit Osteogenesis.

Fucoidan has sparked considerable interest in biomedical applications because of its inherent (bio)physicochemical characteristics, particularly immunomodulatory effects on macrophages, neutrophils, and natural killer cells. However, the effect of fucoidan on T cells and the following regulatory interaction on cellular function has not been reported. In this work, the effect of sterile fucoidan on the T-cell response and the subsequent modulation of osteogenesis is investigated. The physicochemical features of fucoidan treated by high-temperature autoclave sterilization are characterized by UV-visible spectroscopy, X-ray diffraction, Fourier transform infrared and nuclear magnetic resonance analysis. It is demonstrated that high-temperature autoclave treatment resulted in fucoidan depolymerization, with no change in its key bioactive groups. Further, sterile fucoidan promotes T cells proliferation and the proportion of differentiated T cells decreases with increasing concentration of fucoidan. In addition, the supernatant of T cells co-cultured with fucoidan greatly suppresses the osteogenic differentiation of MC3T3-E1 by downregulating the formation of alkaline phosphatase and calcium nodule compared with fucoidan. Therefore, our work offers new insight into the fucoidan-mediated T cell and osteoblast interplay.

Regulation of T Cell Responses by Nano-Hydroxyapatite to Mediate the Osteogenesis.

Nano-hydroxyapatite (nHA) has been widely applied as a tissue-engineering biomaterial and interacted with osteoblasts/stem cells to repair bone defects. In addition, T cells that coexist with osteoblasts/stem cells in the bone modulate the regulation of osteoimmunology by cytokine formation. However, the effects of nHA on T cells and the following regulatory interplay on osteogenic differentiation have been rarely examined. In this work, the physicochemical properties of needle-like nHA are characterized by field emission scanning electron microscopy, zeta potential, Fourier transform-infrared and X-ray diffraction. It is found that as the concentration of nHA increases, the proliferation of T cells gradually increases, and the proportion of apoptotic T cells decreases. The percentage of CD4+ T cells is higher than that of CD8+ T cells under the regulation of needle-like nHA. Furthermore, the supernatant of T cells co-cultured with nHA significantly inhibits the osteogenic differentiation of MC3T3-E1 by downregulating the formation of alkaline phosphatase and calcium nodule compared with the supernatant of nHA. Thus, our findings provide new insight into the nHA-mediated T cell and osteoblast interactions.

Preparation of triamcinolone acetonide-loaded chitosan/fucoidan hydrogel and its potential application as an oral mucosa patch.

Oral inflammatory diseases (OIDs) are among the most common lesions in the oral cavity, affecting the quality of human life and even causing oral cancer. However, most of the current oral mucosa patches still have some limitations, particularly instant, poor mechanical strength and conformability, low adhesion to tissue, and foreign body sensation. Herein, triamcinolone acetonide (TA)-loaded chitosan/fucoidan (CF) composite hydrogels were prepared via chemical crosslinking. The macro/microscopic morphologies and (bio)physicochemical properties of composite hydrogels were investigated. Incorporating fucoidan in chitosan hydrogels greatly enhanced their swelling behavior, mechanical strength, and adhesion properties. Further, the addition of TA in CF hydrogels improved their elastic feature, inhibited inflammatory response, and promoted the formation of mature and well-organized collagen fibers. The developed composite hydrogels displayed not only good antibacterial properties but also good cytocompatibility and histocompatibility. Thus, the designed hydrogels allow the development of oral mucosa patches as a potential treatment for OIDs.