The natural repair process is characterized by the recruitment of progenitor cells to the site of injury, induction of these cells to expand, and finally directing cell fate to restore tissue function. A biomaterial strategy that mimics and/or boosts this natural repair process has potential to be a successful approach for bone defect healing. A hybrid scaffold compartments. In vitro 2D cell migration, cell proliferation and osteogenic differentiation assays were first performed to screen various growth factors. These assays indicated the strong potential of PDGF-ab as a chemoattractant and mitogen for osteoprogenitors, while BMP-2 showed the strongest mineralization potential of the tested factors. The alginate composition and cryogelation temperature were subsequently optimized to obtain cryogels with aligned pores to promote cell infiltration, and tailored release kinetics. PDGF-ab was incorporated into the collagen gel component, as this led to its rapid release from the scaffold, in order to recruit host stem cells to the scaffold and induce their proliferation. BMP-2 was incorporated into the alginate cryogel component, as that led to a delayed release, in order to trigger the recruited mesenchymal stem cells to differentiate down the osteogenic lineage. In vitro cell culture experiments with rat mesenchymal stem cells and preliminary subcutaneous implantation tests confirmed colonization of the scaffold with cells within 7 days. BMP-2 release was confirmed to promote the osteogenic differentiation of cells in the scaffold at the three week time point in vitro. This functionalized hybrid scaffold is expected to ultimately enhance the different stages of tissue repair in bone healing, from cell recruitment to specific stem cell differentiation.
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