Schematic illustration of the immunomodulatory multicellular scaffolds based on manganese silicate (MS) nanoparticles for integrated tendon-to-bone regeneration. [IMAGE: DU LIN AND WU CHENGTIE]

According to a study published in Science Advances, a research group led by Professor Wu Chengtie from the Shanghai Institute of Ceramics of the Chinese Academy of Sciences has developed a multicellular scaffold based on inorganic bioceramics to achieve immunomodulation and integrated regeneration in tendon-to-bone injuries, i.e., injuries occurring at the tendon-to-bone interface.

Restriction of motor activity due to loss of natural structure is a major cause of decreased life quality in patients suffering from tendon-to-bone injuries. Conventional biomaterials for their treatment of tendon-to-bone injuries focus on enhancing the regenerative capacity of tendon or bone tissues to promote the restoration of natural structure. However, due to the neglect of the immune environment at the interface and the lack of multi-tissue regenerative function, satisfactory results are still difficult to achieve.

The osteogenic differentiation of BMSCs and tenogenic differentiation of TSPCs encapsulated in the multicellular scaffolds. [IMAGE: DU LIN AND WU CHENGTIE]

To counter this problem, the researchers combined manganese silicate (MS) nanoparticles with tendon/bone-related cells to construct an immunomodulatory multicellular scaffold using layered cell distribution to achieve integrated tendon-to-bone regeneration.

According to the researchers, integrating biomimetic cell distribution and MS nanoparticles allowed the multicellular scaffolds to simultaneously induce tenogenic differentiation of tendon stem/progenitor cells in the upper layers and osteogenic differentiation of bone marrow mesenchymal stem cells in the lower layers.

The multicellular scaffolds based on MS nanoparticles achieved immunomodulation and induced functional restoration in rat RCT. [IMAGE: DU LIN AND WU CHENGTIE]

Furthermore, rabbit and rat rotator cuff tears treated with the immunomodulatory multicellular scaffolds were simultaneously able to achieve immunomodulation, restoration of interfacial microstructure, and functional recovery.

In addition, the role of immunomodulatory processes in the specific differentiation of scaffolds was confirmed by implanting the multicellular scaffolds containing MS nanoparticles into a macrophage-depleted rat model.

The immunomodulatory mechanism of multicellular scaffolds based on MS nanoparticles. [IMAGE: DU LIN AND WU CHENGTIE]

The result of the co-culture model with macrophages showed that MS nanoparticles enhanced the specific differentiation of multicellular scaffolds via regulation of macrophages, which was mainly attributed to the secretion of PGE2 factor in macrophages induced by Mn ions.

This research shows that these multicellular scaffolds based on inorganic biomaterials offer a new concept for achieving immunomodulation and integrated regeneration of tendon-to-bone and other soft/hard tissue interfaces.

For more information, please contact:

Professor Wu Chengtie

E-mail: chengtiewu@mail.sic.ac.cn

Shanghai Institute of Ceramics,

Chinese Academy of Sciences

Source: Shanghai Institute of Ceramics,

Chinese Academy of Sciences