Role of Phosphorus-Containing Molecules on the Formation of Nano-Sized Calcium Phosphate for Bone Therapy

Yingying Jiang; Yali Tao; Yutong Chen; Xu Xue; Gangyi Ding; Sicheng Wang; Guodong Liu; Mengmeng Li; Jiacan Su

doi:10.3389/fbioe.2022.875531

Role of Phosphorus-Containing Molecules on the Formation of Nano-Sized Calcium Phosphate for Bone Therapy

Front Bioeng Biotechnol. 2022 Jun 22:10:875531. doi: 10.3389/fbioe.2022.875531. eCollection 2022.

Authors

Yingying Jiang^{1

2}, Yali Tao¹, Yutong Chen¹, Xu Xue¹, Gangyi Ding¹, Sicheng Wang^{1

3}, Guodong Liu⁴, Mengmeng Li¹, Jiacan Su^{1

5}

Affiliations

¹ Institute of Translational Medicine, Shanghai University, Shanghai, China.
² Department of Orthopedic, Spinal Pain Research Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
³ Department of Orthopedics Trauma, Shanghai Zhongye Hospital, Shanghai, China.
⁴ Wound Care Center, Daping Hospital, Army Medical Center of PLA, Chongqing, China.
⁵ Department of Trauma Orthopedics, Changhai Hospital, Naval Medical University, Shanghai, China.

Abstract

Calcium phosphate (CaP) is the principal inorganic constituent of bone and teeth in vertebrates and has various applications in biomedical areas. Among various types of CaPs, amorphous calcium phosphate (ACP) is considered to have superior bioactivity and biodegradability. With regard to the instability of ACP, the phosphorus-containing molecules are usually adopted to solve this issue, but the specific roles of the molecules in the formation of nano-sized CaP have not been clearly clarified yet. Herein, alendronate, cyclophosphamide, zoledronate, and foscarnet are selected as the model molecules, and theoretical calculations were performed to elucidate the interaction between calcium ions and different model molecules. Subsequently, CaPs were prepared with the addition of the phosphorus-containing molecules. It is found that cyclophosphamide has limited influence on the generation of CaPs due to their weak interaction. During the co-precipitation process of Ca²⁺ and PO₄ ^3-, the competitive relation among alendronate, zoledronate, and foscarnet plays critical roles in the produced inorganic-organic complex. Moreover, the biocompatibility of CaPs was also systematically evaluated. The DFT calculation provides a convincing strategy for predicting the structure of CaPs with various additives. This work is promising for designing CaP-based multifunctional drug delivery systems and tissue engineering materials.

Keywords: bone therapy; calcium phosphate; drug delivery; nanocomposites; phosphorus-containing molecules.