Local FK506 delivery induces osteogenesis in rat bone defect and rabbit spine fusion models.

Autor: Andraca Harrer J; Atlanta VA Medical Center, 1670 Clairmont Rd, Decatur, GA 30033, USA; Department of Orthopaedics, Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Dr NW, Atlanta, GA 30332, USA; Department of Bioengineering, Knight Campus for Accelerating Scientific Impact, University of Oregon 1505 Franklin Blvd, Eugene, OR 97403, USA., Fulton TM; Atlanta VA Medical Center, 1670 Clairmont Rd, Decatur, GA 30033, USA; Department of Orthopaedics, Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA., Sangadala S; Atlanta VA Medical Center, 1670 Clairmont Rd, Decatur, GA 30033, USA; Department of Orthopaedics, Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA., Kaiser JM; Atlanta VA Medical Center, 1670 Clairmont Rd, Decatur, GA 30033, USA; Department of Orthopaedics, Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA., Devereaux EJ; Department of Orthopaedics, Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA., Oliver C; Atlanta VA Medical Center, 1670 Clairmont Rd, Decatur, GA 30033, USA., Presciutti SM; Atlanta VA Medical Center, 1670 Clairmont Rd, Decatur, GA 30033, USA; Department of Orthopaedics, Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA., Boden SD; Department of Orthopaedics, Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA., Willett NJ; Atlanta VA Medical Center, 1670 Clairmont Rd, Decatur, GA 30033, USA; Department of Orthopaedics, Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Dr NW, Atlanta, GA 30332, USA; Department of Bioengineering, Knight Campus for Accelerating Scientific Impact, University of Oregon 1505 Franklin Blvd, Eugene, OR 97403, USA. Electronic address: nwillett@uoregon.edu.
Jazyk: angličtina
Zdroj: Bone [Bone] 2024 Oct; Vol. 187, pp. 117195. Date of Electronic Publication: 2024 Jul 11.
DOI: 10.1016/j.bone.2024.117195
Abstrakt: Bone grafting procedures are commonly used for the repair, regeneration, and fusion of bones in a wide range of orthopaedic surgeries, including large bone defects and spine fusion procedures. Autografts are the clinical gold standard, though recombinant human bone morphogenetic proteins (rhBMPs) are often used, particularly in difficult clinical situations. However, treatment with rhBMPs can have off-target effects and increase surgical costs, adding to patients' already high economic and mental burden. Recent studies have identified that FDA-approved immunosuppressant drug, FK506 (Tacrolimus), can also activate the BMP pathway by binding to its inhibitors. This study tested the hypothesis that FK506, as a standalone treatment, could induce osteogenic differentiation of human mesenchymal stromal cells (hMSCs), as well as functional bone formation in a rat segmental bone defect model and rabbit spinal fusion model. FK506 enhanced osteogenic differentiation and mineralization of hMSCs in vitro. Standalone treatment with FK506 delivered on a collagen sponge produced consistent bone bridging of a critically sized rat femoral defect with functional mechanical properties comparable to naïve bone. In a rabbit single level posterolateral spine fusion model, treatment with FK506 delivered on a collagen sponge successfully fused the L5-L6 vertebrae at rates comparable to rhBMP-2 treatment. These data demonstrate the ability of FK506 to induce bone formation in human cells and two challenging in vivo models, and indicate FK506 can be utilized to treat a variety of spine disorders.
Competing Interests: Declaration of competing interest Unrelated to this research, Scott D. Boden has previously received compensation for consulting work for Medtronic Sofamor Danek (Minneapolis, MN, USA) and for intellectual property. Emory University and some authors may receive future royalties for improved cellular responsiveness to BMP. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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