Abstract
In spite of advances in Total Joint Replacements (TJR), infection remains a major concern and a primary causative factor for revision surgery. Current clinical standards treat these osteomyelitis infections with antibiotic-laden poly(methyl methacrylate) (PMMA)-based cement, which has several disadvantages, including inadequate local drug release kinetics, antibiotic leaching for a prolonged period and additional surgical interventions to remove it, etc. Moreover, not all antibiotics (e.g., rifampicin, a potent antibiofilm antibiotic) are compatible with PMMA. For this reason, treatment of TJR-associated infections and related complications remains a significant concern. The objective of this study was to develop a polymer-controlled dual antibiotic-releasing bone void filler (ABVF) with an underlying osseointegrating substrate to treat TJR implant-associated biofilm infections. An ABVF putty was designed to provide sustained vancomycin and rifampicin antibiotic release for 6 weeks while concurrently providing an osseointegrating support for regrowth of lost bone. The reported ABVF showed efficient antibacterial and antibiofilm activity both in vitro and in a rat infection model where the ABVF both showed complete bacterial elimination and supported bone growth. Furthermore, in an in vivo k-wire-based biofilm infection model, the ABVF putty was also able to eliminate the biofilm infection while supporting osseointegration. The retrieved k-wire implants were also free from biofilm and bacterial burden. The ABVF putty delivering combination antibiotics demonstrated that it can be a viable treatment option for implant-related osteomyelitis and may lead to retention of the hardware while enabling single-stage surgery.
Highlights
Total Joint Replacements (TJR), including Total Knee Replacements (TKR) and Total Hip Replacements (THR), are arguably one of the most successful surgical interventions to improve quality of life, there is a growing trend in the number of secondary or revision surgeries being done in the United States, according to the American Academy of Orthopedic Surgeons (AAOS)
More than a million people undergo Total Joint Replacements (TJR) each year in the United States currently; with projections of more than 4 million procedures a year by 2030 [1,2,3], of which, an estimated 365,000 will be secondary or revision procedures [2]. These numbers do not necessarily reflect a failure in the TJR procedure as much they are an indication of (1) surgical intervention at an earlier age [4,5] often necessitating a revision surgery later in life as the TJR implants materials wear out and (2) rising obesity leading to osteoarthritis; osteoarthritis is reported to account for >90% of Total Knee Replacements (TKR) procedures, and (3) infection
The current study evaluated the in vitro kinetics of dual vancomycin and rifampicin release from a developed press-fitting antibiotic-releasing bone void filler (ABVF) putty and the in vitro antibacterial and anti-biofilm activity of the released combination
Summary
Total Joint Replacements (TJR), including Total Knee Replacements (TKR) and Total Hip Replacements (THR), are arguably one of the most successful surgical interventions to improve quality of life, there is a growing trend in the number of secondary or revision surgeries being done in the United States, according to the American Academy of Orthopedic Surgeons (AAOS). More than a million people undergo Total Joint Replacements (TJR) each year in the United States currently; with projections of more than 4 million procedures a year by 2030 [1,2,3], of which, an estimated 365,000 will be secondary or revision procedures [2] These numbers do not necessarily reflect a failure in the TJR procedure as much they are an indication of (1) surgical intervention at an earlier age [4,5] often necessitating a revision surgery later in life as the TJR implants materials wear out and (2) rising obesity leading to osteoarthritis; osteoarthritis is reported to account for >90% of Total Knee Replacements (TKR) procedures, and (3) infection. Non-infected revision TJR has a modestly increased infection risk of 5.4% [10]
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