A Bioglass-Based Antibiotic (Vancomycin) Releasing Bone Void Filling Putty to Treat Osteomyelitis and Aid Bone Healing

Abstract

While the infection rate after primary total joint replacements (TJR) sits at 1–2%, for trauma-related surgery, it can be as high as 3.6 to 21.2% based on the type of trauma; the risk of reinfection after revision surgery is even higher. Current treatments with antibiotic-releasing PMMA-based bone cement/ beads and/or systemic antibiotic after surgical debridement do not provide effective treatment due to fluctuating antibiotic levels at the site of infection, leading to insufficient local antibiotic concentration. In addition, non-biodegradable PMMA does not support bone regrowth in the debrided void spaces and often must be removed in an additional surgery. Here, we report a bioactive glass or bioglass (BG) substrate-based biodegradable, easy to fabricate “press fitting” antibiotic-releasing bone void filling (ABVF-BG) putty to provide effective local antibiotic release at the site of infection along with support for bone regeneration. The ABVF-BG putty formulation had homogenously distributed BG particles, a porous structure, and showed putty-like ease of handling. Furthermore, the ABVF-BG putty demonstrated in vitro antibacterial activity for up to 6 weeks. Finally, the ABVF-BG putty was biodegradable in vivo and showed 100% bacterial eradication (as shown by bacterial cell counts) in the treatment group, which received ABVF-BG putty, compared to the infection control group, where all the rats had a high bacterial load (4.63 × 106 ± 7.9 × 105 CFU/gram bone) and sustained osteomyelitis. The ABVF-BG putty also supported bone growth in the void space as indicated by a combination of histology, µCT, and X-ray imaging. The potential for simultaneous infection treatment and bone healing using the developed BG-based ABVF-BG putty is promising as an alternative treatment option for osteomyelitis.

Antimicrobial Biomaterials for the Healing of Infected Bone Tissue: A Systematic Review of Microtomographic Data on Experimental Animal Models

“…The characteristics of all included studies are presented in Table 1 . All the ten included studies [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ] were in vivo animal studies published in the English language, between 2014 and 2021. Regarding the selection of the animal model, only one study used a large animal, female sheep [ 17 ].…”

“…Regarding the selection of the animal model, only one study used a large animal, female sheep [ 17 ]. Small animal models were predominant and included five studies with rats [ 18 , 21 , 22 , 25 , 26 ] and four studies with rabbits [ 19 , 20 , 23 , 24 ]. Among the rabbit models, three studies used male rabbits [ 19 , 23 , 24 ], and one study used female rabbits [ 20 ]; while regarding the use of the rat model, three studies used male rats [ 21 , 22 , 25 ], one study used both male and female animals [ 26 ].…”

Bone Healing Materials in the Treatment of Recalcitrant Nonunions and Bone Defects

“…Biomaterials are very important in scaffold-based bone tissue engineering. Therefore, numerous biomaterials have been developed to prepare bone tissue engineering scaffolds, including biometals (titanium (Ti) [ 16 ], iron (Fe) [ 17 , 18 ], magnesium (Mg) [ 19 , 20 ], zinc (Zn) [ 21 ]), bioceramics (hydroxyapatite (HA)) [ 22 , 23 ], tricalcium phosphate (TCP) [ 24 ], biopolymers (collagen [ 25 ], polylactic acid (PLA) [ 26 ], polycaprolactone (PCL) [ 27 ]), and biocomposites (HA/MONs@miR-34a composite coating, Bioglass (BG)-based ABVF-BG (antibiotic-releasing bone void filling) putty) [ 28 , 29 ].…”

Role of Implantable Drug Delivery Devices with Dual Platform Capabilities in the Prevention and Treatment of Bacterial Osteomyelitis

“…The main benefits of bioactive glasses include bioactivity, osteoconductive and osteoinductive properties, biodegradation [ 152 , 166 ], load bearing capabilities [ 163 ], and the ability to create a local environment that is hostile to microbial growth [ 113 , 163 ]. In fact, bioactive glass is said to produce higher quantity and quality of bone when compared with synthetic HA [ 167 ] and newer hybrid materials have tailorable degradation, which is attractive [ 168 ]. Bioactive glasses have become a focus of investigations for drug delivery within the last one to two decades [ 166 , 169 , 170 ] because of their strong regenerative qualities, reported biocompatibility [ 171 ], and the initial experimental use of bioactive glasses in the treatment of chronic osteomyelitis [ 172 ].…”

“…Bioactive glasses have become a focus of investigations for drug delivery within the last one to two decades [ 166 , 169 , 170 ] because of their strong regenerative qualities, reported biocompatibility [ 171 ], and the initial experimental use of bioactive glasses in the treatment of chronic osteomyelitis [ 172 ]. Hasan et al [ 167 ] created a biodegradable, bioactive glass-based antibiotic-releasing putty designed to be press-fitted into bone defects to provide support for bone growth while delivering antimicrobials (vancomycin) for 4–6 weeks to combat bacterial osteomyelitis. This material demonstrated vancomycin elution above the MIC of S. aureus for over 6 weeks in vitro, and as a putty, is attractive to surgeons because it can be formed into various dimensions [ 168 ].…”