Paper of the week: In vivo analysis of a first-in-class tri-alkyl norspermidine-biaryl antibiotic in an active release coating to reduce the risk of implant-related infection. Williams DL, Epperson RT, Ashton NN, Taylor NB, Kawaguchi B, Olsen RE, Haussener TJ, Sebahar PR, Allyn G, Looper RE. Acta Biomater. 2019 Jan 31. pii: S1742-7061(19)30077-7. doi: 10.1016/j.actbio.2019.01.055.
Summary and Editorial by Sreeram Penna
This study in a sheep model of joint space infection was conducted to assess antibacterial properties of compound CZ-01127 as the active release agent in a silicone (Si)-based implant coating to prevent periprosthetic joint infection. Researchers also studied the impact of silicone-based coating and compound CZ-01127 on bone ingrowth and integration. Bone ingrowth was studied using implanting simulated total joint replacement device with regions of porous-coated titanium and adjacent silicone polymer with and without CZ-01127. To understand ability of CZ-01127 to reduce bioburden total joint replacement devices with a silicon-based coating with the above compound was used and compared against controls without compound. And sheep were inoculated with bacteria (MRSA) during implantation procedure after that sheep was monitored to assess outcome, especially infection.
Results of the study show that the CZ-01127 coating reduced bioburden near the total joint replacement device. It also appeared to provide some protection to the joint space and synovium. However joint space ultimately succumbed and was susceptible to infection following bacterial challenge. Bone ingrowth assessment showed that both Titanium and Silicone coated surfaces had decent osseointegration at 24 weeks post procedure. Coating with CZ-01127 resulted in initial bone resorption followed by regrowth, remodeling, and recovery by 8 weeks.
Implant-related infection is associated with significant morbidity and mortality.[1] To prevent this costly complication various methods are actively researched one of this is the development of active release coatings to implants that reduce bioburden and inhibit biofilm production.[2] Antibiotics are considered as compounds for active release. However, researchers in this study identified concerns using antibiotics as it is noted that these coatings loose activity over time and there is concern over the development of antibiotic resistance due to subminimum inhibitory concentrations reached at the site of implants. They suggested using novel substances which reduce the risk of resistance. Researchers identified CZ compounds as they have broad-spectrum activity against planktonic and biofilm bacteria.[3–5] This study assesses the use of newer compound CZ-01127 with silicone polymer to create an effective active release implant to combat implant-related infection.
References
[1] Parvizi J, Zmistowski B, Adeli B. Periprosthetic joint infection: treatment options. Orthopedics 2010;33:659. doi:10.3928/01477447-20100722-42.
[2] Hetrick EM, Schoenfisch MH. Reducing implant-related infections: active release strategies. Chem Soc Rev 2006;35:780–9. doi:10.1039/b515219b.
[3] Haussener TJ, Sebahar PR, Reddy HRK, Williams DL, Looper RE. A practical synthesis of N-alkyl- and N,N′-dialkyl-polyamines This work is dedicated to the memory of our dear colleague and friend Mr. Charles Edward Price. Tetrahedron Letters 2016;57:2845–8. doi:10.1016/j.tetlet.2016.05.034.
[4] Looper R, Williams D, Jeyapalina S, Haussener T, Sebahar PR, Reddy HK. Compositions comprising a biocidal polyamine. US8853278B1, 2014.
[5] Williams D, Looper R, Jeyapalina S, Haussener T, Sebahar PR, Reddy HK. Methods of use for compositions comprising a biocidal polyamine. US9034927B2, 2015.