Strategically Designed Bifunctional Polydopamine Enwrapping Polycaprolactone-Hydroxyapatite-Doxorubicin Composite Nanofibers for Osteosarcoma Treatment and Bone Regeneration.

Abstract

This study presents a new multifunctional nanofibrous drug delivery system to provide effective combination therapy with enormous potential for the treatment of osteosarcoma. We developed a composite nanofiber scaffold comprising poly(ε-caprolactone) (PCL) and hydroxyapatite (HAp)-loaded doxorubicin (DOX) coated with polydopamine (PDA) to combine cancer cell inhibition with bone tissue regeneration. DOX was conjugated with HAp and then mixed with a PCL solution to prepare a PCL/HAp-DOX (labeled PCLDH) nanofiber. Then, in situ polymerization of PDA on the PCLDH occurred to produce the PCLDH@PDA composite nanofiber. The morphology, XRD, FT-IR, wettability, photothermal characteristics, cumulative drug release, and in vitro bioactivities were evaluated. We found that the PDA coating not only enhanced the hydrophilic properties but also controlled drug release. The PCLDH@PDA composite scaffold significantly suppressed the proliferation of bone cancer cells initially and, consequently, improved the adhesion and proliferation of human mesenchymal stem cells (hMSCs). The PDA coating boosted the composite scaffold's bioactivity, as demonstrated through ALP activity, ARS assay, and biomineralization results. This strategy offers a promising dual-function scaffold to treat residual cancer and reconstruct defects after osteosarcoma surgery.