A polyglutamic acid/tannic acid-based nano drug delivery system: Antibacterial, immunoregulation and sustained therapeutic strategies for oral ulcers.

Oral ulcers are a common inflammatory mucosal ulcer, and the moist and dynamic environment in the oral cavity makes topical pharmacological treatment of oral ulcers challenging. Herein, oral ulcer tissue adhesion nanoparticles were prepared by using esterification reaction between polyglutamic acid and tannic acid, and at the same time doxycycline hydrochloride was loaded into the nanoparticles. The obtained slow drug release effect of the drug-loaded nanoparticles reduced the toxicity of the drug, and by penetrating into the fine crevice region of the wound tissue and adhering to it, they could in-situ release the carried drug more effectively and thus have shown significant antibacterial effects. In addition, tannic acid in the system conferred adhesion, antioxidant and immune regulation activities to the nanocarriers. A rat oral ulcer model based on fluorescent labeling was established to investigate the retention of nanoparticles at the ulcer, and the results showed that the retention rate of drug-loaded nanoparticles at the ulcer was 17 times higher than that of pure drug. Due to the antibacterial and immune regulation effects of the drug-loaded nanoparticles, the healing of oral ulcer wounds was greatly accelerated. Such application of doxycycline hydrochloride loaded polyglutamic acid/tannic acid nanoparticles is a novel and effective treatment strategy for oral ulcer.

A Nature-Inspired Versatile Bio-Adhesive.

The application of most hydrogel bio-adhesives is greatly limited due to their high swelling, low underwater adhesion, and single function. Herein, a spatial multi-level physical-chemical and bio-inspired in-situ bonding strategy is proposed, to develop a multifunctional hydrogel bio-glue using polyglutamic acid (PGA), tyramine hydrochloride (TYR), and tannic acid (TA) as precursors and 4-(4,6-dimethoxytriazine-2-yl) -4-methylmorpholine hydrochloride(DMTMM) as condensation agent, which is used for tissue adhesion, hemostasis and repair. By introducing TYR and TA into the PGA chain, it is demonstrated that not only can the strong adhesion of bio-glue to the surface of various fresh tissues and wet materials be realized through the synergistic effect of spatial multi-level physical and chemical bonding, but also this glue can be endowed with the functions of anti-oxidation and hemostasis. The excellent performance of such bio-glue in the repair of the wound, liver, and cartilage is achieved, showing a great potential in clinical application for such bio-glue. This study will open up a brand-new avenue for the development of multifunctional hydrogel biological adhesive.

A bionic composite hydrogel with dual regulatory functions for the osteochondral repair.

Due to the avascular nature of cartilage, it is difficult to heal and regenerate spontaneously after injury. At present, tissue engineering has become a promising strategy for repairing damaged cartilage, but the use of seed cells and growth factors is limited. In addition, the importance of mechanical compatibility of scaffold materials is often ignored. In this study, osteochondral scaffold was designed as a bilayer structure with a dense γ-Polyglutamic acid/carboxymethyl chitosan/bacterial cellulose (PGA/CMCS/BC) hydrogel cartilage layer and a porous nano HA-containing PGA/CMCS/BC hydrogel osteogenic layer. In addition, bioactive ions were introduced into the hydrogel scaffold to adjust the mechanical and swelling properties of the material to match the mechanical properties of natural articular cartilage. At the same time, based on the structural characteristics of bone and cartilage, magnesium and copper ions were introduced into the double-layer hydrogel scaffold, respectively, to prepare the cartilage layer and the bone layer, which endowed the material with excellent antibacterial properties and achieved the purpose of the integrated repair of bone and cartilage. The results showed that, after adding magnesium ions, the tensile breaking strength of material was increased from 0.66 MPa to 1.37 MPa，the corresponding compression modulus of the material (strain 0-12%) increased from 0.15 MPa to 0.58 MPa whilst the maximum mass swelling rate decreased from 155% to 75%. The results of in vivo experiments show that the group with bioactive ions had a much better effect on the repair of osteochondral defects, compared with group without bioactive ions, demonstrating such double ion regulation strategy is a very practical strategy for the treatment of osteochondral defects.

Piezoelectric Effect of Antibacterial Biomimetic Hydrogel Promotes Osteochondral Defect Repair.

The lack of vascular tissue and the low metabolism and biological activity of mature chondrocytes lead to the low regeneration ability of articular cartilage. People try to solve this problem through various methods, but the effect is not very ideal. Inspired by the piezoelectric effect of collagen in cartilage tissue, this work focused on the design of a biomimetic hydrogel by introducing piezoelectric materials and silver nanowires into hydrogel to endow them with piezoelectric and antibacterial properties to promote tissue regeneration. Additionally, the mechanical and swelling properties of the material were adjusted to match natural articular cartilage. Based on bionic principles, a double-layer piezoelectric hydrogel was prepared and applied for the repair of osteochondral defects. An enhanced repair effect of osteochondral defects has been seen, which has demonstrated potential values for future application in bionics principle- and piezoelectric effect-based osteochondral tissue engineering. Furthermore, piezoelectric effect-induced degradation was observed. These results fully indicated the positive effect of the piezoelectric effect on promoting the regeneration of osteochondral tissue and in vivo degradation of materials.

A single integrated osteochondral in situ composite scaffold with a multi-layered functional structure.

This work focuses on the optimization design of a functional biomimetic scaffold for the repair of osteochondral defects and includes the study of single integrated osteochondral tissue engineering scaffolds with a multi-layered functional structure. Rabbit model experiments were used to evaluate the repair of osteochondral defects. The results revealed that good integration was achieved both at the interfaces between the scaffold material and the host tissue and between the newly formed subchondral bone and cartilage. The highest total histological score of 24.2 (based on the modified O'Driscoll scoring system at 12 weeks post-operation) was achieved for osteochondral repair. The completely repaired cylindrical full-thickness defects for the rabbit animal model reached 5 mm in diameter. The thickness of the regenerated cartilage was almost in line with that of the surrounding normal cartilage, the number and arrangement of cells in the superficial area of cartilage were very close to those of normal hyaline cartilage, and there were clear cartilage lacunas in the regenerated cartilage. The hybrid-use of growth factors and LIPUS stimulation exhibited good potential in enhancing vascularization and the formation of new bone and cartilage, providing better conditions for the overall osteochondral repair.