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2. Bioinspired Glycopeptide Hydrogel Reestablishing Bone Homeostasis through Mediating Osteoclasts and Osteogenesis in Periodontitis Treatment

Author

Zhao, Zhezhe, Wu, Chenxuan, Huangfu, Yini, Zhang, Yufeng, Zhang, Ju, Huang, Pingsheng, Dong, Anjie, Wang, Yonglan, Deng, Jiayin, Wang, Weiwei, and Feng, Zujian

Abstract

Irreversible alveolar bone resorption is one of the important clinical manifestations of periodontitis, which is initiated by a plaque biofilm and exacerbated by the imbalance of osteoclast activity and osteogenesis, affecting a patient’s masticatory function and resulting in a high recurrence rate of periodontitis. Herein, to reestablish bone homeostasis in periodontitis, a minocycline hydrochloride (MH)-loaded glycopeptide hydrogel (MH/GRWgel) is fabricated to mediate alveolar bone absorption through sequential antibacterial and RANKL-blocking activities. GRWgelshows an ECM-like fibrous and porous microstructure serving as a scaffold for cell proliferation and differentiation and holds the merits including injectability, self-healing properties, and good biocompatibility. After injection in situ, MH is released rapidly from the hydrogel in the early stage, demonstrating a potent antimicrobial effect to combat the biofilm in the deep periodontal pocket. Moreover, MH/GRWgelexhibits a high specific binding efficiency with RANKL to suppress osteoclast maturation by shielding the RANKL/RANK interaction and enhancing osteogenic differentiation, thereby synergistically regulating bone homeostasis. In the rat periodontitis model, MH/GRWgelsignificantly curtails periodontitis progression through antimicrobial activity, inhibition of alveolar bone resorption, and promotion of bone regeneration, which is superior to the treatment of a commercial gel. These findings suggest that MH/GRWgelwith superiority in regulating bone homeostasis provides a promising therapeutic strategy for periodontitis.

Published
2024
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4. Additional file 1 of A drug delivery system constructed by a fusion peptide capturing exosomes targets to titanium implants accurately resulting the enhancement of osseointegration peri-implant

Author

Li, Xuewen, Liu, Zihao, Xu, Shendan, Ma, Xinying, Zhao, Zhezhe, Hu, Han, Deng, Jiayin, Peng, Cheng, Wang, Yonglan, and Ma, Shiqing

Abstract

Additional file 1: Figure S1. Pseudo-3D views and the secondary structure prediction of PEP1–3. Figure S2. SEM imaged the surface topography of titanium surface. Figure S3. A) CLSM imaged the distribution of PEP1–3. B) CLSM colocalized DiRlabeled exosomes and FITC-labeled PEP of EXO-PEP1–3. C) the fluorescence intensity was quantitated. Figure S4. Representative ex vivo images of A) PEPs and B) EXO-PEPs in different organs and femurs. Figure S5. Flow cytometry for rhodamine-labeled PEP-exosome complexes to determine the quantity of PEP diafiltrated and un-diafiltrated. Figure S6. A) CCK-8 assay determined most optimum concentration of EXOpep. B) CCK-8 assay determined to the cytotoxicity of different bioactive molecules. C) CCK-8 assay determined to the proliferation of BMSCs cultured on the titanium discs incubated with different treatment after 1, 2, 3, 4, 5, 6 and 7 day culture periods (P < 0.05). D) AO/EB assay determined to the proliferation of BMSCs. E) CLSM determined to the morphology of BMSCs. red: phalloidin; blue, DAPI. Figure S7. A) Characterization and B) quantity analysis of exosome uptake by hBMSCs analyzed by representative confocal microscopic images. Figure S8. A 3D-printed titanium implant (2 mm in thickness，5 mm in lengthen, 4 mm in width) was used to replace the femur bone defection (2 mm in width，5 mm in lengthen, 4 mm in depth) on the rat. Figure S9. Measurement of serum Crea and BUN in rats injected PBS, EXO, EXOPEP and EXO-PEP (UF). Figure S10. The 3D reconstructed models and the section images of bone defect replaced by the implant in coronal, axial and sagittal view. Purple refers bone tissue, green refers titanium implant, yellow refers the contour of bone. Figure S11. Western blot analysis the expression of osteogenesis signal pathway.

Published
2023
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12. Evaluation of self-prepared absorbable hemostatic cellulose fibrils.

Author

Wang L, Tong J, Zhao Z, and Yang X

Subjects
Animals, Cellulose pharmacology, Hemostasis, Rats, Spleen, Hemostatics pharmacology
Abstract

To evaluate the effectiveness and safety of self-prepared absorbable hemostatic fibrils.A kind of absorbable hemostatic fibrils were prepared by self-developed patent technique. The physical form and molecular structure of the fibrils and a marketed product Surgicel were characterized by general observation and infrared spectroscopy; the carboxyl content, pH value and relative molecular mass of fibrils were determined by potentiometric titration method, pH meter and copper ethylenediamine method, respectively. The behavior of the fibrils and Surgicel in contact with blood was observed by inverted microscope, the cytotoxicity was evaluated by agarose diffusion cell assay . The external iliac artery hemorrhage model and the back muscle infiltration model in rats were established. The hemostatic effectiveness of the fibrils was investigated by hemostasis time and blood weight, and the degradation and biosafety of fibrils were investigated by observation photography, immune organ weighing, hematology and coagulation index measuring, and histopathological examination. The fibrils and Surgicel had similar molecular structures. Compared with the raw material regenerated cellulose, the typical carboxyl stretching vibration absorption peak of -COOH appeared near in both fibrils and Surgicel. The carboxyl content of the two materials was about 20%, and the pH value was about 3. The relative molecular mass of the fibers after oxidation was 4466±79, which was close to that of Surgicel(>0.05). After contacting with blood, the volume of fibrils and Surgicel expanded, and absorbed blood of dozens of times as their own weight. The results of agar diffusion test showed that the fibrils had no cytotoxicity. The results of animal experiments showed that the hemostasis completed within and there was no significant difference in blood weight and speed of hemostasis between two products (both >0.05). The fibrils could be degraded 1 week after being implanted to the bleeding sites of the muscle. There were no pathological effects on the appearance, body weight, food intake, immunological tissue thymus, spleen, lymph nodes, hematology and coagulation indexes of the rats, and no obvious abnormality found in the histopathological examination. The prepared absorbable hemostatic fibrils have excellent biological safety and effectiveness.

Published
2021
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