Fabrication of Pentoxifylline-Loaded Hydroxyapatite/Alginate Scaffold for Bone Tissue Engineering

Background: Hydroxyapatite (HAP), as a common biomaterial in bone tissue engineering, can be fabricated in combination with other osteogenic agents. Pentoxifylline (PTX) is demonstrated to have positive roles in bone defect healing. Since local administration can diminish the systemic side effects of the drug, the objectives of the current in vitro study were to find the effects of PTX on the osteoblast functions for tissue engineering applications. Methods: a HAP scaffold was fabricated by casting the HAP slurry within polyurethane foam. The scaffold was enriched with 5 mg/mL PTX. Alginate (Alg) was used as drug carrier to regulate the PTX releasing rate. MG-63 osteosarcoma cells were cultured on 3D scaffolds and 2D Alg films in the presence or absence of PTX. Results: PTX did not affect the cell viability, attachment and phenotype. Also, the ultrastructure of the scaffolds was not modified by PTX enrichment. Alizarin red S staining showed that PTX has no effect on calcium deposition. Besides, Raman confocal microscopy demonstrated an increase in the organic matrix formation including proline, valine and phenylalanine deposition (represented collagen). Although PTX increased the total protein secretion, it led to a decrease in the alkaline phosphatase activity and vascular endothelial growth factor (VEGF) content. PTX reduced the hydration and degradation rates and it was released mainly at the first 24 hours of incubation. Conclusion: Based on our in vitro study, application of engineered PTX-loaded HAP scaffold in bone regeneration can act on behalf of organic matrix production, but not angiogenesis and mineralization.