Synergistic effects of bone surface mimic topography and chemistry on osteogenic stem cell differentiation and osteoimmunomodulation

The term "osteoimmunomodulation" refers to regulating immune responses to enhance bone healing. Osteoimmunology highlights the significant role of immune cells in bone repair. Conventional bone repair approaches often neglect the immune response, causing discrepancies between in vitro and in vivo environments. A suitable osteo-immune environment is crucial for successful bone regeneration. Surface and bulk properties like surface charge, porosity, pore size, wettability, bioactive ion release, and surface topography significantly affect cell behavior on biomaterials. These features influence cell adhesion, proliferation, stem cell differentiation, and immune cell behavior, including macrophage polarization. This thesis explored how the topographical and chemical characteristics of bone surfaces affect cellular behavior, specifically promoting osteogenic differentiation and enhancing osteoimmunomodulation. Model Poly-L-Lactic Acid (PLA) membranes were produced to mimic natural bone surface properties through soft lithography technique. To enhance biomimicry, BSM PLA membranes were modified with collagen type I (Col-I) and hydroxyapatite (HA). The effect of these membranes on the osteogenic differentiation of adipose-derived mesenchymal stem cells (ADMSC) and on osteoimmunomodulation using RAW 264.7 macrophage cells was examined. HA-deposited BSM PLA membranes promoted osteogenic differentiation in ADMSC and stimulated sequential M1 and M2 macrophage polarizations in RAW264.7 macrophage cells. These results lay the groundwork for future biomaterials research by demonstrating the capability of HA-deposited BSM PLA membranes to promote osteogenic differentiation and stimulate the osteoimmune response.