Cellular Crosstalk Analysis of Periostin and Platelet-derived Growth Factor Subunit A Protein between Periosteum-Derived Progenitor Cells and Adipose-Derived Stem Cells during Bone Healing Process Utilizing Folding Paper-Based Bone Microenvironment Model

Abstract

Periosteum-derived progenitor cells (PDPCs) are incredibly promising for bone healing, playing an essential role in the osteogenic process. Adipose-derived stem cells (ADSCs), which are naturally close to periosteum tissue, release multiple growth factors that support bone healing. The periosteum-bone tissue microenvironments were constructed to study cellular crosstalk in the bone healing process by co-culturing PDPCs and ADSCs. Three-dimensional folding paper-based models were employed to mimic the bone healing microenvironment. Various paper-based substrates were utilized to conduct both monoculture and co-culture of PDPCs and ADSCs, with the addition of IL-6 as an inflammatory signal to simulate and induce the bone healing process. Growth factors like periostin and platelet-derived growth factor subunit A were directly analyzed using a paper-based immunoassay. Cellular crosstalk was studied by examining protein expression on the paper substrate through paper ELISA. Then a verification method was used to ensure the cell's interactions, by blocking the cell's interaction with its respective protein. Ths result showed that co-culture between PDPCs and ADSCs has higher osteogenic capability than monoculture itself and the blocking protein does influence the cell's interaction. Thus, this paper-based approach offers a promising way to study cellular interactions in a 3D co-culture environment, which could potentially lead to more effective bone regeneration therapies.