Tunable Calcium Phosphate Cement Formulations for Predictable Local Release of Doxycycline

20 Pages Posted: 2 Dec 2022

See all articles by qian liu

qian liu

Huazhong University of Science and Technology - Department of Stomatology

Irene Lodoso-Torrecilla

Radboud University Nijmegen - Department of Dentistry – Regenerative Biomaterials

Raquel Klein Gunnewiek

Radboud University Nijmegen - Department of Dentistry – Regenerative Biomaterials

Harry R. Harhangi

Radboud University Nijmegen - Department of Medical Microbiology

Antonios G. Mikos

Rice University - Department of Bioengineering

Laura van Niftrik

Radboud University Nijmegen - Department of Medical Microbiology

John A. Jansen

Radboud University Nijmegen - Department of Dentistry – Regenerative Biomaterials

Lili Chen

Huazhong University of Science and Technology - Department of Stomatology

Jeroen J.J.P. van den Beucken

Radboud University Nijmegen - Department of Dentistry – Regenerative Biomaterials

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Abstract

Osteomyelitis is a bacterial infection, which leads to bone loss. Local treatment is focused on elimination of bacteria, which is preferable for simultaneous management of the bone defect after sequestrectomy and bone reconstruction in one-stage treatment of osteomyelitis. Calcium phosphate cements (CPCs) have attracted increased attention as bone substitute material because of their injectability and in situ self-setting properties, which allow for minimally invasive surgical procedures and local drug delivery. We herein established a system to achieve different release profiles of the antibiotic drug doxycycline from CPC by finetuning their formulation. These CPC formulations were generated via facile addition of hydrolytically degrading PLGA particles, varying doses of doxycycline, and addition of the lubricant CMC. The CPC formulations exhibited appropriate handling properties in terms of injectability and setting time. Furthermore, doxycycline release profiles showed an adequate burst release followed by a cumulative release of up to 100% over a period of 8 weeks. Importantly, the released doxycycline retained its antibacterial activity against Staphylococcus aureus, the major pathogen causing osteomyelitis. Using an in vivo implantation model, antibacterial efficacy was demonstrated by a rapid decrease of inoculated S. aureus at the CPC surface and within surrounding tissues. Our data show the versatility of the CPC system toward local antibacterial therapy, extending its application beyond bone substitution.

Keywords: Calcium phosphate cement, Doxycycline, osteomyelitis, anti-bacterial property, Drug release

Suggested Citation

liu, qian and Lodoso-Torrecilla, Irene and Gunnewiek, Raquel Klein and Harhangi, Harry R. and Mikos, Antonios G. and van Niftrik, Laura and Jansen, John A. and Chen, Lili and van den Beucken, Jeroen J.J.P., Tunable Calcium Phosphate Cement Formulations for Predictable Local Release of Doxycycline. Available at SSRN: https://ssrn.com/abstract=4291451 or http://dx.doi.org/10.2139/ssrn.4291451

Qian Liu

Huazhong University of Science and Technology - Department of Stomatology ( email )

Irene Lodoso-Torrecilla

Radboud University Nijmegen - Department of Dentistry – Regenerative Biomaterials ( email )

Raquel Klein Gunnewiek

Radboud University Nijmegen - Department of Dentistry – Regenerative Biomaterials ( email )

Harry R. Harhangi

Radboud University Nijmegen - Department of Medical Microbiology ( email )

Antonios G. Mikos

Rice University - Department of Bioengineering ( email )

6500 Main Street
Houston, TX 77030
United States

Laura Van Niftrik

Radboud University Nijmegen - Department of Medical Microbiology ( email )

John A. Jansen

Radboud University Nijmegen - Department of Dentistry – Regenerative Biomaterials ( email )

Lili Chen

Huazhong University of Science and Technology - Department of Stomatology ( email )

China

Jeroen J.J.P. Van den Beucken (Contact Author)

Radboud University Nijmegen - Department of Dentistry – Regenerative Biomaterials ( email )

Nijmegen
Netherlands

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