Localized Combination Therapy Using Collagen–Hydroxyapatite Bone Grafts for Simultaneous Bone Cancer Inhibition and Tissue Regeneration

Abstract

The global burden of cancer continues to grow, with bone cancer—though rare—posing serious challenges in terms of treatment and post-surgical reconstruction. Autologous bone grafting remains the gold standard, yet limitations such as donor site morbidity drive the search for alternative solutions. Tissue engineering, combining biomaterials and therapeutic agents, offers promising avenues. This study focuses on the development of multifunctional scaffolds based on collagen and hydroxyapatite obtained by the freeze-drying technique and incorporating both synthetic (doxorubicin) and natural (caffeic acid) compounds for osteosarcoma treatment. These scaffolds aim to combine tumor inhibition with bone regeneration, addressing the dual need for local drug delivery and structural repair in bone cancer therapy. The characterization of these composite materials revealed that a spongious structure with interconnected pores and a homogeneous pore distribution, with pore sizes between 20 and 250 μm suitable for osteoblasts infiltration. The Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis-differential scanning calorimetry (TG-DSC) and X-ray diffraction (XRD) analyses confirmed the formation of hydroxyapatite inside the collagen matrix. LDH and XTT assays confirmed that the antitumoral scaffolds possess great potential for osteosarcoma treatment, showing that after 3 days of culturing, the extracts containing doxorubicin-7A, both alone and in combination with caffeic acid-9A, significantly reduced the viability of cell lines to below 7% and 20%, respectively.