Use of contemporary biomaterials in chronic osteomyelitis treatment: Clinical lessons learned and literature review
First published: 24 October 2020
https://doi.org/10.1002/jor.24896
Chronic osteomyelitis has always been a therapeutic challenge for patient and surgeon due to the specific problems related with bone infection and bacterial biofilm eradication. Other than being the cause of infection or facilitating spread or persistence of infection, biomaterials are also becoming a tool in the treatment of infection.
Certain novel biomaterials have unique and ideal properties that render them perfectly suited to combat infection and are therefore used more and more in the treatment of chronic bone infections.
In case of infection treatment, there is still debate whether these properties should be focused on bone regeneration and/or their antimicrobial properties.
These properties will be of even greater importance with the challenge of emerging antimicrobial resistance.
This review highlights indications for use and specific material properties of some commonly used contemporary biomaterials for this indication as well as clinical experience and a literature overview.
INTRODUCTION
In orthopedic surgery and traumatology, bone infection is an underestimated and challenging condition for both the patient and the physician. Diagnosis can be difficult,1 treatment is often prolonged and cumbersome, sometimes involving multiple surgeries and can impose a significant financial burden on both the patient and the health system in general. Although tremendous progress has been made in the treatment of musculoskeletal infection over the years, studies have shown that elective surgery infection rates are not able to be reduced below 1–2% and failures of revision surgery remain as high as 33%.2, 3 The cost of treating bone infection is substantial and will increase as the absolute number of patients suffering from it keeps rising.4
Two specific entities of orthopedic infection can be identified: those infections that only involve bone (osteitis/osteomyelitis) and those affecting bone and an associated implant, like a joint replacement or some kind of osteosynthesis. Both entities are different in their approach, although overlap exists. To improve treatment outcomes, biomaterials have been used to help eradicate infection, fill bony defects and support remaining bone and/or implants. Some biomaterials function as antibiotic-delivery devices, such as gentamicin-loaded beads or spacers, as developed by Wahlig and Dingeldein in the 70s.5 Locally, they release high doses of antibiotics, far higher than the minimal inhibitory concentration (MIC) and higher than what can be achieved by parenteral administration of the same antibiotic, thereby eradicating an important part of the local bacterial load. These antibiotic-loaded bone cements have served well over time, although several concerns have been addressed like antibiotic elution levels becoming subtherapeutic, thereby possibly inducing antimicrobial resistance, the absence of standardized formulation protocols and the absence of validated assays to determine the minimum biofilm eradication concentration to predict efficacy of these antibiotic-loaded bone cements against specific microorganisms.6
Other materials have also been shown to have antibacterial properties and are used to coat the surface of an implant like nanoparticles, such as silver (Ag), magnesium (Mg), copper (Cu), and gold (Au) to prevent infection (by inhibiting the surface to be colonized by bacteria, who would than outrun host-cells in the race for the surface).7-9 This is the concept, first described by Gristina in 1987, whereby when any foreign material is introduced in the body, a “race” will occur between our own cells/immune system and the microorganisms.10, 11 If the implant is covered by human or eukaryotic cells first, it will be “shielded” and as such be more difficult to reach for microorganisms. Eventually, (osseo)integration of the implant in the surrounding tissues will occur. On the other hand, if microorganisms are first, the implant will be contaminated. As soon as bacteria or other microorganisms bond with the surface, they will form biofilm, rendering themselves much more resistant to the body's immune system. This is because our immune cells cannot easily penetrate this biofilm and because bacteria downregulate their metabolism so they do not duplicate as often (metabolically less active), compared to their planktonic (or free-floating) counterparts. The latter is also the reason why antibiotics are less effective for bacteria in biofilm, with MICs that can be 1000-fold higher.12, 13 So, in essence bacteriae cover themselves in a slime layer when adhering on an implant, but when looking closer, biofilm is much more complex and concepts like metabolism, growth rate, gene expression changes, or persistor cells have to be taken into account.
Coating technology and implant modification (for instance: biomaterials with empirical antimicrobial behavior) to combat biofilm formation and/or persistence still deal with several concerns and necessitate further research, but will become important future methods to deal with implant-related infection.14 Because of this, a separate working group was established at the 2018 International Consensus Meeting on Musculoskeletal Infection to provide insights on the biomaterial surface question.15
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There are multiple commercially available biodegradable biomaterials that are studied for treatment of chronic osteomyelitis in a one-stage fashion (Table 1).
These materials are generally based on antibiotic loaded calcium sulfates, calcium phosphates, or bioactive glasses.
| Product name | Composition | Antimicrobial mechanism | Antibiotic type | Level of evidencea |
|---|---|---|---|---|
| BonAlive® | S53P4 bioactive glass S53P4 (53% SiO2, 4% P2O5, 23% Na2O, and 20% CaO) | Release of surface ions causing increase of pH and osmotic pressure | None | 2b |
| Cerament G/V® | 60% calcium sulfate, 40% hydroxyapatite | Antibiotic loaded BGS | Gentamicin, vancomycin | 2b |
| Herafill-G® | Calcium sulfate and calcium carbonate | Antibiotic loaded BGS | Gentamicin | 3b |
| Osteoset-T® | ɑ-Hemihydrate calcium sulfate | Antibiotic loaded BGS | Tobramycin | 2b |
| Perossal® | Nano-crystalline hydroxyapatite (51.5%) and calcium sulfate (48.5%) | Antibiotic loaded BGS | Different types of antibiotics (surgeon's choice) | 2b |
| Stimulan® | Hemihydrate calcium sulfate | Antibiotic loaded BGS | Gentamicin, vancomycin, tobramycin | 2b |
- Abbreviations: BGS, bone graft substitute; CEBM, Centre of Evidence Based Medicine.
- a Level of evidence is based on best available methodological quality and is based on the CEBM criteria of the University of Oxford centre of evidence (2b, individual cohort study (including low quality RCT; e.g., <80% follow-up; 3b, individual case-control study).
