Osteosarcoma (OS) is the most common bone tumor in pediatrics. After resection, allografts or metal endoprostheses reconstruct bone voids, and systemic chemotherapy is used to prevent recurrence. This urges the development of novel treatment options for the regeneration of bone after excision. We utilized a previously developed biomimetic, biodegradable magnesium-doped hydroxyapatite/type I collagen composite material (MHA/Coll) to promote bone regeneration in the presence of chemotherapy. We also performed experiments to determine if human mesenchymal stem cells (hMSCs) seeded on MHA/Coll scaffold migrate less toward OS cells, suggesting that hMSCs will not contribute to tumor growth and therefore the potential of oncologic safety in vitro. Also, hMSCs seeded on MHA/Coll had increased expression of osteogenic genes (BGLAP, SPP1, ALP) compared to hMSCs in the 2D condition, even when exposed to chemotherapeutics. This is the first study to demonstrate that a highly osteogenic scaffold can potentially be oncologically safe because hMSCs on MHA/Coll tend to differentiate and lose the ability to migrate toward tumor cells. Therefore, hMSCs on MHA/Coll could potentially be utilized for bone regeneration after OS excision.