Preparation and performance study of lithium‑zinc doped bio-glass/chitosan/polyacrylamide composite hydrogel loaded with doxorubicin hydrochloride

Osteosarcoma, a malignant tumor, often results in significant bone defects following surgical resection, accompanied by challenges of recurrence and metastasis. In this study, a mesoporous bio-glass doped with Li⁺ to promote angiogenesis and Zn²⁺ to provide antibacterial properties (Li/Zn-MBG) was synthesized as a carrier for the anticancer drug doxorubicin hydrochloride (DOX). The drug-loaded Li/Zn-MBG (Li/Zn-MBG@DOX) was then incorporated into a chitosan (CS)/polyacrylamide (PAM) dual-network hydrogel to form the Li/Zn-MBG@DOX/CS/PAM hydrogel. Results showed that the inclusion of Li⁺ and Zn²⁺ enhanced the mesoporous structure and dispersibility of MBG, resulting in more uniform particles (178.4 ± 7.1 nm), higher specific surface area (102.93 m²·g^-1), pore volume (0.26 cm³·g^-1), and pore diameter (9.62 nm). Moreover, the drug loading and encapsulation efficiencies were increased to 23.95 % and 95.80 %, respectively, with sustained DOX release over 14 days (24.30 ± 0.17 %). The Li/Zn-MBG@DOX/CS/PAM hydrogel exhibited a stable three-dimensional porous structure with uniform internal pores and demonstrated favorable mechanical properties, including a compressive strength of 762.00 ± 0.55 kPa and a swelling rate of 800-900 %. Cell experiments revealed that the composite hydrogel promoted the proliferation and differentiation of mouse bone marrow stromal stem cells (BMSCs) while inhibiting the proliferation and differentiation of human osteosarcoma cells (U2OS). In vivo studies showed that in mice with femoral defects treated with the Li/Zn-MBG@DOX/CS/PAM hydrogel, nearly all defects healed by week 12 with minimal inflammation. These findings suggest that the Li/Zn-MBG@DOX/CS/PAM composite hydrogel holds significant promise for the repair of bone defects following osteosarcoma surgery.