Curcumin-Microsphere/IR820 Hybrid Bifunctional Hydrogels for In Situ Osteosarcoma Chemo-co-Thermal Therapy and Bone Reconstruction

Abstract

Conventional biomaterial-mediated osteosarcoma therapy mainly focuses on its antitumor effect yet often fails to overcome the problem of post-treatment bone tissue defect repair. Simultaneously, minimally invasive drug delivery methods are becoming spotlights for normal tissue preservation. Herein, an injectable curcumin-microsphere/IR820 coloaded hybrid methylcellulose hydrogel (Cur-MP/IR820 gel) platform was designed for osteosarcoma therapy and bone regeneration. In vitro, the K7M2wt osteosarcoma cells were eradicated by hyperthermia and curcumin. Later, the sustained release of curcumin promoted alkaline phosphatase expression and calcium deposition of bone mesenchymal stem cells. In vivo, this hybrid hydrogel could reach tumor site via injection and turned into hydrogel due to heat sensitivity. Under the irradiation of an 808 nm laser, localized hyperthermia (∼51 °C) generated in 5 min to ablate the tumor. Meanwhile, the thermal-accelerated curcumin release and thermal-increased cell membrane permeability led to tumor cell apoptosis. Tumors in photothermal-co-chemotherapy group were successfully restrained from day 2 after treatment. After that, bone reconstruction was promoted because of sustained released curcumin. The chemo-co-thermal efficacy and osteogenic capacity of Cur-MP/IR820 hydrogel suggest a promising approach to the treatment of osteosarcoma and provide provoking inspiration for treating bone tumors and repairing bone tissue.

A Review on the Design of Hydrogels With Different Stiffness and Their Effects on Tissue Repair

“…The three elements of tissue engineering include scaffold materials, cytokines, and stem cells. As one of the scaffold materials, hydrogel plays an important role in tissue engineering because of its high water content, hydrophilicity, simulation of extracellular matrix environment ( Abdollahiyan et al, 2020a ; Liao et al, 2021a ; Liao et al, 2021b ; Tan et al, 2021a ), good biocompatibility, and the ability to control drug release ( Gao et al, 2016 ; Huang et al, 2017 ; Tan et al, 2021b ). It is a hydrophilic three-dimensional (3D) polymer network formed by physical or chemical crosslinking.…”

Traditional Chinese Medicine Compound-Loaded Materials in Bone Regeneration

“…The curcumin microsphere/IR820 coloaded hybrid methylcellulose hydrogel induced more tumor cell apoptosis due to localized hyperthermia-accelerated curcumin release and promoted osteogenic differentiation, as shown by ALP and ARS staining and a microplate reader at days 7 and 14. The curcumin-loaded hydrogel with chemo-co-thermal efficacy and thermal-accelerated curcumin release efficiently eliminated osteosarcoma and promoted tibial bone defect regeneration according to micro-CT analysis, H&E staining, and Masson staining (Tan et al, 2021).…”

Effect of Micro-/Nanoparticle Hybrid Hydrogel Platform on the Treatment of Articular Cartilage-Related Diseases

“…Accordingly, the micro-/nanoparticle hybrid hydrogel platform is suitable for biomedicine and tissue engineering. Currently, it is popular with research on drug delivery [39,85,98], tumors [99][100][101][102], tissue repair and regeneration [103], and wound healing [94]. Obviously, the hybrid system is promising and effective in the treatment of diseases.…”

“…Therefore, some relevant studies that focused on bone defect repair can be highlighted. Bowen tan's team designed an injectable curcumin-microsphere/IR820 coloaded hybrid methylcellulose hydrogel (Cur-MP/IR820 gel) platform, which solved the problem of bone defects caused by osteosarcoma by promoting bone reconstruction [100]. Additionally, as a soft tissue, articular capsules can also be damaged.…”