Osteoimmunity-Regulating biospun 3D silk scaffold for bone regeneration in critical-size defects

Silk-based biomaterials have received a great deal of attention in tissue engineering research for bone repair. Current silk-based materials are typically derived from silk protein solutions, but the limited solubility and solution stability of silk protein solution, coupled with problems such as high preparation cost and low productivity, which severely restrict the application of silk-based materials.

To address the challenges associated with the complex extraction process and inferior mechanical properties of silk protein or silk fiber-based materials in bone scaffold preparation, flat cocoon silk-based materials were developed to assess their potential for repairing large bone defects.

We converted the upper cluster mesh's three-dimensional structure into a two-dimensional flattened plate and controlled the thickness and area of the flattened silkworm cocoons by adjusting the number of mature silkworms and spitting time to match the needs of different sites and bone defect areas. After being hot-pressed, the flattened silkworm cocoons were mixed with PLA to form an excellent tissue engineering scaffold material with a highly porous structure.

The 3D FSC/PLA scaffold demonstrated superior mineralization, mechanical resilience, and biocompatibility. Notably, it promoted anti-inflammatory gene expression, suppressed inflammatory responses through M2 macrophage polarization, and enhanced bone formation and angiogenesis by modulating key pathways, including PI3K-AKT, Wnt, MAPK, and Notch.

By using silkworm larvae to directly create a scaffold, a three-dimensional matrix with properties similar to extracellular matrix and a gradient structure that closely resembles cortical bone was created. This process effectively modulates the immune balance for fibroin dissolution and regeneration. The targeted infiltration of PLA within the 3D silk matrix enabled precise control over porosity and degradation, fostering optimal cellular adhesion and proliferation. As an osteoimmunity-regulating scaffold, it holds significant promise for enhancing bone regeneration and offers a robust foundation for repairing large-scale bone defects.