Stem cell-seeded hybrid nanocomposite for chest wall repair in a murine model

Introduction:

Resection of the thoracic wall is a common procedure in case of invasion by malignant tumors. Usually, Gore-Tex® is used to replace the defect, however, this material is inert and not degradable. Novel biodegradable materials are nowadays available that stimulate and modulate the regeneration process. Moreoever, stem cell seeding can be decisive for graft integration.

Materials and Methods:

A biodegradable bi-layered hybrid nanocomposite material developed, based on poly-lactic-co-glycolic acid and amorphous calcium phosphate nanoparticles (PLGA/aCaP) and pure PLGA. Mechanical properties under dry (day 0) and wet conditions (day 14) were assessed. Electrospun meshes were seeded with murine adipose-derived stem cells (ASCs of C57BL/6). In a mouse model (C57BL/LY5.1), ASC-seeded hybrid scaffolds were implanted as a chest wall graft in order to study biointegration and cell-interactions. After 4 and 8 weeks, implant integration towards the skin and the lung, cell infiltration into the bi-layered material, inflammatory responses, neo-vascularization, fibrosis and ECM components (collagen I and fibronectin) were determined in six different graft zones.

Results:

The bi-layered nanocomposite had an ultimate stress of 6 MPa after 2 weeks in DMEM, significantly higher than for the pure PLGA/aCaP. In vivo, grafts were integrated with cellular infiltration through the graft. From newly formed extracellular matrix (ECM), collagen I increased from 4 to 8 weeks, for both, the ASC-seeded and the cell-free scaffolds, while fibronectin was comparable at 4 and 8 weeks for both scaffolds. Higher numbers of macrophages and lymphocytes were found in ASC-seeded scaffolds compared to cell-free ones. Cell-free scaffolds were more vascularized than ASC-seeded ones at 8 weeks post-operation.

Conclusion:

Hybrid scaffolds with PLGA and PLGA/aCaP are superior in terms of mechanical stability than pure PLGA/aCaP. Murine ASCs from C57BL/6 evoked a mild inflammatory response in C57BL/LY5.1 mice when seeded onto the hybrid scaffold. The bi-layered scaffold was stably integrated and vascularized and thus offers a viable option to the gold standard Goretex®.