Tag Archive | Journal of Orthopaedic Research

Disrupting “Quorum Sensing” Could Help Fight Biofilms

Biofilm for OBuzzThis post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson. 

A biofilm is a complex combination of extracellular carbohydrates, proteins, lipids, and one or more species of bacteria that may adhere to an orthopaedic implant and surrounding tissue (see related OrthoBuzz post). Staphylococci bacteria are believed to account for more than 50% of all biofilm infections of medical devices.

Researchers recently summarized what we know about the biofilm formation process.1 In the attachment phase, free-floating bacteria attach to a prosthetic surface via proteins. Extracellular DNA from autolysis add to the mix. Then begins the irreversible attachment phase, during which the initial bacteria are incarcerated while more free-floating bacteria are added. During this phase, autoinducers are expressed, which serve as inter- and intrabacterial signals.

In the presence of an adequate quorum of bacteria, the maturation phase begins, during which the bacterial population cohesively shifts from replication to expression of virulence factors such as secretion systems, toxins, or biofilm formation. A mature biofilm is immune-resistant, although bacterial replication decreases. In the dispersal phase bacteria become planktonic again, potentially available to repeat the process.

Once a biofilm has formed, antibiotic administration becomes problematic because of the toxicity of the high doses needed to treat biofilm colonies. An underlying challenge with pharmacologic intervention is the variety of quorum-sensing communication pathways between bacterial species. The authors suggest that a future biofilm-fighting strategy may be to force bacteria into biofilm-forming behavior before they reach the necessary critical density to become virulent, although this notion remains unexplored. Researchers are investigating other possible strategies to disrupt the quorum-sensing communication among bacteria that enable them to behave as a “social” group.

Reference

  1. Mooney JA, Pridgen EM, Manasherob R, Suh G, Blackwell HE, Barron AE, Bollyky PL, Goodman SB, Amanatullah DF. Periprosthetic bacterial biofilm and quorum sensing. J Orthop Res. 2018 Sep;36(9):2331-2339. doi: 10.1002/jor.24019. Epub 2018 May 24.

When Is a Fracture Good to Go?

Fracture Callus for OBuzzThis post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson. 

Determining when a fracture has healed enough for functional use can be difficult. The Radiographic Union Score for Tibia fractures (RUST) assesses fracture healing on a continuous scale from 4 to 12 points. Based on an evaluation of anteroposterior and lateral radiographs, RUST accounts for callus without visible fracture line (3 points), callus with visible fracture line (2 points), or absence of any callus (1 point) for each of four cortices. The modified RUST (mRUST) score subdivides the second parameter into two categories (callus present and bridging callus), creating a score ranging from 4 to 16 points. This tool has demonstrated high intraclass correlation coefficients (ICCs). However, until now, the correlation of these scores to mechanical properties of healed bone had not been demonstrated.

Cooke et al.1 evaluated both scores against the physical properties of bone healing by using a model of  closed, stabilized femur fractures in 8- to 12-week-old male mice. Control mice received a normal diet and an experimental group received a phosphate-restricted diet. The physical properties of bone healing were determined with micro-computed tomography (µCT) and torsion testing on postoperative days 14, 21, 35, and 42. There were 10 to 16 mice in each group at any given time-point.

RUST scores from five raters were determined from anteroposterior and lateral radiographic views constructed from the µCT scans. ICCs were 0.71 (mRUST) and 0.63 (RUST). Both RUST scores were positively correlated with callus bone mineral density, bone volume fraction, callus strength, and rigidity. Radiographically healed calluses with an mRUST score of ≥13 and a RUST score of ≥10 had excellent relationships to structural and biomechanical metrics.

Mechanical properties revealed the effects of delayed healing due to phosphate dietary restrictions at later time points, but no such distinctions were found in the RUST scores. Both the RUST and mRUST scores have high correlation to physical properties of bone healing, but this tool may not be reliable for detecting poor bone quality due to nutrient deficiencies.

Reference

  1. Cooke ME, Hussein AI, Lybrand KE, Wulff A, Simmons E, Choi JH, Litrenta J, Ricci WM, Nascone JW, O’Toole RV, Morgan EF, Gerstenfeld LC, Tornetta P 3rd. Correlation between RUST assessments of fracture healing to structural and biomechanical properties. J Orthop Res. 2018 Mar;36(3):945-953. doi: 10.1002/jor.23710. Epub 2017 Sep 20. PMID: 28833572 PMCID: PMC5823715 DOI: 10.1002/jor.23710