Calcium phosphate complex of recombinant human thrombomodulin promote bone formation in interbody fusion.

Autor:	Lin CL; Department of Orthopedic Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No.138, Sheng Li Road, Tainan 704, Taiwan (R.O.C)., Chen YW; School of Pharmacy, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan 701, Taiwan (R.O.C)., Kuo CH; International Center for Wound Repair and Regeneration, National Cheng Kung University, No.1, University Road, Tainan 701, Taiwan (R.O.C)., Tu TY; Department of Biomedical Engineering, National Cheng Kung University, No.1, University Road, Tainan 701, Taiwan (R.O.C)., Wu HL; Department of Biochemistry and Molecular Biology, National Cheng Kung University, No.1, University Road, Tainan 701, Taiwan (R.O.C)., Tsai JC; School of Pharmacy, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan 701, Taiwan (R.O.C)., Shyong YJ; School of Pharmacy, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan 701, Taiwan (R.O.C).
Jazyk:	angličtina
Zdroj:	Biofabrication [Biofabrication] 2024 Oct 24; Vol. 17 (1). Date of Electronic Publication: 2024 Oct 24.
DOI:	10.1088/1758-5090/ad8035
Abstrakt:	Interbody fusion is an orthopedic surgical procedure to connect two adjacent vertebrae in patients suffering from spinal disc disease. The combination of synthetic bone grafts with protein-based drugs is an intriguing approach to stimulate interbody bone growth, specifically in patients exhibiting restricted bone progression. Recombinant human thrombomodulin (rhTM), a novel protein drug characterized by its superior stability and potency, shows promise in enhancing bone formation. A composite bone graft, termed CaP-rhTM, has been synthesized, combining calcium phosphate (CaP) microparticles as a delivery vehicle for rhTM to facilitate interbody fusion. In vitro studies have demonstrated that rhTM significantly promotes the proliferation and maturation of preosteoblasts at nanogram dosage, while exerting minimal impact on osteosarcoma cell growth. The expression levels of mature osteoblast markers, including osteocalcin, osteopontin, alkaline phosphatase, and calcium deposition were also enhanced by rhTM. In rat caudal disc model of interbody fusion, CaP-rhTM with 800 ng of drug dosage was implanted along with a polylactic acid cage, to ensure structural stability within the intervertebral space. Microcomputed tomography analyses revealed that from 8 to 24 weeks, CaP-rhTM substantially improves both bone volume and trabecular architecture, in addition to the textural integrity of bony endplate surfaces. Histological examination confirmed the formation of a continuous bone bridge connecting adjacent vertebrae. Furthermore, biomechanical assessment via three-point bending tests indicated an improved bone quality of the fused disc. This study has demostrated that rhTM exhibits considerable potential in promoting osteogenesis. The use of CaP-rhTM has also shown significant improvements in promoting interbody fusion. (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)
Databáze:	MEDLINE
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