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Extended Release Combination Antibiotic Therapy from a Bone Void Filling Putty for Treatment of Osteomyelitis
Raquib Hasan1, Kambri Schaner2, Meredith Schroeder3
1Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58102, USA.
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.
Insights
A novel antibiotic-eluting bone void filler (ABVF) effectively treats joint replacement infections. This dual-antibiotic putty supports bone growth and eliminates biofilm, potentially enabling single-stage surgeries.
Area of Science:
- Biomaterials Science
- Infectious Diseases
- Orthopedic Surgery
Background:
- Total Joint Replacement (TJR) infections are a major cause of revision surgery.
- Current treatments using antibiotic-laden poly(methyl methacrylate) (PMMA) cement have limitations, including poor drug release and incompatibility with certain antibiotics like rifampicin.
- Effective treatment for TJR-associated osteomyelitis and biofilm infections remains a significant clinical challenge.
Purpose of the Study:
- To develop a polymer-controlled dual antibiotic-releasing bone void filler (ABVF) with osseointegrating properties.
- To address limitations of current PMMA-based treatments for implant-associated infections.
- To provide a sustained release of vancomycin and rifampicin for combating biofilm infections and promoting bone regeneration.
Main Methods:
- Development of an ABVF putty designed for sustained release of vancomycin and rifampicin over 6 weeks.
- Evaluation of the ABVF's antibacterial and antibiofilm efficacy in vitro.
- Assessment of the ABVF's performance in a rat osteomyelitis model and a k-wire-based biofilm infection model in vivo.
- Investigation of the ABVF's ability to support bone regrowth and osseointegration.
Main Results:
- The ABVF demonstrated efficient in vitro antibacterial and antibiofilm activity.
- In vivo studies showed complete bacterial elimination and supported bone growth in a rat infection model.
- The ABVF putty successfully eliminated biofilm infection and promoted osseointegration in a k-wire model.
- Retrieved implants were free from biofilm and bacterial burden.
Conclusions:
- The dual-antibiotic ABVF putty is a viable treatment for implant-related osteomyelitis.
- This approach may allow for hardware retention and single-stage surgical intervention.
- The developed ABVF offers a promising solution for managing TJR-associated infections and promoting bone healing.
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