A personalized biomimetic dual-drug delivery system via controlled release of PTH1-34 and simvastatin for in situ osteoporotic bone regeneration

Tongtong Xu; Shang Gao; Nan Yang; Qi Zhao; Yutong Zhang; Tieshu Li; Zhihui Liu; Bing Han

doi:10.3389/fbioe.2024.1355019

A personalized biomimetic dual-drug delivery system via controlled release of PTH_1-34 and simvastatin for in situ osteoporotic bone regeneration

Front Bioeng Biotechnol. 2024 Jan 31:12:1355019. doi: 10.3389/fbioe.2024.1355019. eCollection 2024.

Authors

Tongtong Xu^{1

2}, Shang Gao³, Nan Yang¹, Qi Zhao^{1

2}, Yutong Zhang⁴, Tieshu Li⁴, Zhihui Liu¹, Bing Han⁴

Affiliations

¹ Department of Prosthodontics, Hospital of Stomatology, Jilin University, Changchun, China.
² Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Jilin University, Changchun, Jilin, China.
³ Department of Stomatology, Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China.
⁴ School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin, China.

Abstract

Patients with osteoporosis often encounter clinical challenges of poor healing after bone transplantation due to their diminished bone formation capacity. The use of bone substitutes containing bioactive factors that increase the number and differentiation of osteoblasts is a strategy to improve poor bone healing. In this study, we developed an in situ dual-drug delivery system containing the bone growth factors PTH_1-34 and simvastatin to increase the number and differentiation of osteoblasts for osteoporotic bone regeneration. Our system exhibited ideal physical properties similar to those of natural bone and allowed for customizations in shape through a 3D-printed scaffold and GelMA. The composite system regulated the sustained release of PTH_1-34 and simvastatin, and exhibited good biocompatibility. Cell studies revealed that the composite system reduced osteoblast death, and promoted expression of osteoblast differentiation markers. Additionally, by radiographic analysis and histological observation, the dual-drug composite system demonstrated promising bone regeneration outcomes in an osteoporotic skull defect model. In summary, this composite delivery system, comprising dual-drug administration, holds considerable potential for bone repair and may serve as a safe and efficacious therapeutic approach for addressing bone defects in patients with osteoporosis.

Keywords: PTH1-34; bone regeneration; drug delivery system; osteoporosis; simvastatin.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Jilin Province Development and Reform Commission (Grant No. 2023C043-3); Science and Technology Department of Jilin Province (Grant No. 20230204076YY and 20220401102YY); Changchun Science and Technology Bureau (Grant No. 21ZGY01).