Incorporation of synthetic water-soluble curcumin polymeric drug within calcium phosphate cements for bone defect repairing

Ying Zhang; Hailiang Xu; Jing Wang; Xiaochen Fan; Fang Tian; Zhiyuan Wang; Botao Lu; Weidong Wu; Youjun Liu; Yixiang Ai; Xiaohui Wang; Lei Zhu; Shuaijun Jia; Dingjun Hao

doi:10.1016/j.mtbio.2023.100630

Incorporation of synthetic water-soluble curcumin polymeric drug within calcium phosphate cements for bone defect repairing

Mater Today Bio. 2023 Apr 7:20:100630. doi: 10.1016/j.mtbio.2023.100630. eCollection 2023 Jun.

Authors

Ying Zhang^{1

2}, Hailiang Xu^{1

2}, Jing Wang³, Xiaochen Fan⁴, Fang Tian^{1

2}, Zhiyuan Wang^{1

2}, Botao Lu^{1

2}, Weidong Wu^{1

2}, Youjun Liu^{1

2}, Yixiang Ai^{1

2}, Xiaohui Wang^{1

2}, Lei Zhu^{1

2}, Shuaijun Jia^{1

2}, Dingjun Hao^{1

2}

Affiliations

¹ Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.
² Shaanxi Key Laboratory of Spine Bionic Treatment, Xi'an, Shaanxi, China.
³ Science and Technology on Thermostructural Composite Materials Laboratory, Northwestern Polytechnical University, Xi'an, China.
⁴ Department of Chinese Medicine and Rehabilitation, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.

Abstract

Modified macroporous structures and active osteogenic substances are necessary to overcome the limited bone regeneration capacity and low degradability of self-curing calcium phosphate cement (CPC). Curcumin (CUR), which possesses strong osteogenic activity and poor aqueous solubility/bioavailability, esterifies the side chains in hyaluronic acid (HA) to form a water-soluble CUR-HA macromolecule. In this study, we incorporated the CUR-HA and glucose microparticles (GMPs) into the CPC powder to fabricate the CUR-HA/GMP/CPC composite, which not only retained the good injectability and mechanical strength of bone cements, but also significantly increased the cement porosity and sustained release property of CUR-HA in vitro. CUR-HA incorporation greatly improved the differentiation ability of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts by activating the RUNX family transcription factor 2/fibroblast growth factor 18 (RUNX2/FGF18) signaling pathway, increasing the expression of osteocalcin and enhancing the alkaline phosphatase activity. In addition, in vivo implantation of CUR-HA/GMP/CPC into femoral condyle defects dramatically accelerated the degradation rate of cement and boosted local vascularization and osteopontin protein expression, and consequently promoted rapid bone regeneration. Therefore, macroporous CPC based composite cement with CUR-HA shows a remarkable ability to repair bone defects and is a promising translational application of modified CPC in clinical practice.

Keywords: Bone defects; Calcium phosphate cement; Curcumin; Hyaluronic acid; Osteogenic activity.