A novel tantalum scaffold promoting osteoporotic osseointegration by controlled immune regulation

Abstract

Implant failure due to osteoporosis remains a significant clinical challenge that requires further investigation and resolution. The immunomodulatory properties of bone implant materials are of great significance for the regulation of bone immune microenvironment to promote osteogenesis. This study aims to utilize 3D printing technology to develop a personalized porous tantalum-based MZIF-8-PDA@PTa scaffold and to achieve uniform control of melatonin (MT) and ZIF-8 nano-drug controlled delivery system through polydopamine coating, as well as investigate the effects of osteoporosis on bone regeneration and osseointegration. The MZIF-8-PDA@ PTa scaffold displayed favorable biocompatibility, biodegradability, and mechanical properties, thereby providing an optimal microenvironment for new bone formation. Additionally, the findings indicated that the MZIF-8-PDA@PTa scaffold was capable of recruiting and stimulating M2 macrophage polarization, inhibiting inflammation, and promoting the proliferation and differentiation of bone marrow mesenchymal stem cells. Scaffolds were implanted into the distal femurs of ovariectomized (OVX) rats to ultimately promote bone regeneration and osseointegration in an osteoporotic environment. Moreover, transcriptome sequencing revealed that the MZIF-8-PDA@PTa scaffold was able to promote osteogenic differentiation and mineralization via the P38-MAPK signaling pathway in BMSC cells. Taken together, the MZIF-8-PDA@PTa scaffold enhances bone regeneration and osseointegration in osteoporotic environments through the modulation of macrophage M2 polarization. Consequently, this study offers an alternative approach to creating biomaterials suitable for individuals with osteoporosis.

Keywords

Immunomodulation / Macrophage polarization / Melatonin / Osteogenesis / Tantalum

Funding

This work was supported by the Health Industry Clinical Research Project of Shanghai Health Commission (Grant No. 20224Y0393), the Science and Technology Development Fund of Shanghai Pudong New Area (Grant No. PKJ2023-Y09), the Pudong New Area health talent training program (Grant No. 2025PDWSYCQN-06), the Outstanding Leaders Training Program of Pudong Hospital affiliated to Fudan University (Grant No. LX202201, YJRCJJ201908, YJ2023-11), the Project of Key Medical Specialty and Treatment Center of Pudong Hospital of Fudan University (Grant No. Tszb2023-05), the New Quality Clinical Specialty Program of High-end Medical Disciplinary Construction in Shanghai Pudong New Area (2024-PWXZ-14), the Program of Key Medicine of Shanghai Municipal Health Commission (2024ZDXK0031), the joint research project of Pudong Health Committee of Shanghai (Grant No. PW2021D-08), the Health science and technology project of Shanghai Pudong New Area Health Commission(PW2022A-48), and the Project of Key Medical Specialty and Treatment Center of Pudong Hospital of Fudan University (Zdxk2020-02, Zdzk2021-01).

Conflict of interest

The authors declare they have no competing interests.

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