Comparative osteoconductivity of bone void fillers with antibiotics in a critical size bone defect model

Abstract

The study aimed to evaluate the comparative osteoconductivity of three commercially available bone void fillers containing gentamicin with respect to new bone, growth, host tissue response and resorption of the implant material. Defects were created in the cancellous bone of the distal femur and proximal tibia of 12-skeletally mature sheep and filled with three commercially available bone void fillers containing gentamicin (Stimulan-G, Cerament-G, Herafill-G). Peripheral blood was taken pre-operatively and at the time of implantation, as well as at intermittent timepoints following surgery to determine systemic gentamicin levels (5-,15- and 30- minutes, 1, 2, 3, 6, 12, 24, 48- and 72-hours, 3-, 6- and 12-weeks). Decalcified, embedded samples were stained with haematoxylin and eosin (H&E) and used to assess the host tissue response and the formation of new bone in the presence of test implant materials. No adverse reactions were noted at harvest at any time points for any cancellous implantation sites with the various implant materials. Comparative microCT analysis of the Stimulan-G, Cerament-G and Herafill-G test materials revealed a similar increase in bone surface area and volume between animals implanted with Stimulan-G or Cerament-G test materials. Animals implanted with Herafill-G test materials demonstrated the lowest increases in bone volume and surface area of the test materials tested, at levels similar to the negative control sites. By 12-weeks, Stimulan-G defects were completely closed with mature bone and bone marrow whilst the Cerament-G material was still present after 12 weeks by histological examination. In conclusion, this study demonstrated differences in the bone regenerative capacity of a range of bone void fillers in an in vivo setting.

Ceramic composite with gentamicin decreases persistent infection and increases bone formation in a rat model of debrided osteomyelitis

“…No animals treated with CERAMENT G (CG) had any detectable infection so a similar comparison could not be drawn within this group. Both CERAMENT Bone Void Filler and CERAMENT G have been previously shown to facilitate new bone growth when utilized in uninfected environments, but literature which directly compared the two compounds in the absence of infection is not available (Nilsson et al, 2004;Oliver et al, 2020). To our knowledge there is no published literature detailing the relationship between persistent infec- tion and decreased bone growth when bone graft substitutes are used in osteomyelitic environments.…”

“…The advantages of using CERAMENT as a drug delivery device are that it forms a paste that can be injected into bone defects, completely filling the cavity and excluding any dead space, which obliterates any areas that may harbor residual bacteria or small fragments of biofilm (Ferguson et al, 2017;McNally et al, 2016). Other commercially available ceramic formulations with impregnated antibiotics include Herafill-G ® (calcium sulfate and calcium carbonate) and OSTEOSET ® (calcium sulfate with tobramycin) (Oliver et al, 2020) but are non-injectable and therefore may be less ideal for eradication of infection. In addition, the biodegradability of the product allows single-stage surgery and has previously been demonstrated to be highly efficient for treatment of chronic bone infections when combined with debridement and systemic antimicrobials in clinical studies (McNally et al, 2016;Niazi et al, 2019;Oliver et al, 2020).…”

“…Other commercially available ceramic formulations with impregnated antibiotics include Herafill-G ® (calcium sulfate and calcium carbonate) and OSTEOSET ® (calcium sulfate with tobramycin) (Oliver et al, 2020) but are non-injectable and therefore may be less ideal for eradication of infection. In addition, the biodegradability of the product allows single-stage surgery and has previously been demonstrated to be highly efficient for treatment of chronic bone infections when combined with debridement and systemic antimicrobials in clinical studies (McNally et al, 2016;Niazi et al, 2019;Oliver et al, 2020). While CERAMENT G has shown overall effectiveness in humans, our study represents the first evaluation of CERA-MENT G in a small animal model of debrided osteomyelitis and thus is useful in quantifying the ability of this compound to eradicate infection as well as facilitate new bone growth.…”

Innovations in orthopaedic trauma: Top advancements of the past two decades and predictions for the next two

“…In this situation an osteoconductive matrix must be provided, in addition to the osteogenic and osteoinductive elements. Bone void fillers such as CERAMENT (BONE SUPPORT AB, Ideon Science Park, Sweden) provide useful adjunct when structural graft is not required [56]. These biodegradable calcium based synthetic materials provide an excellent osteoconductive scaffold for the migration of MSCs, promote ingrowth of blood vessels, and can stimulate new bone formation at a rate similar to autogenous bone [57], [58].…”

Microstructure design for bone void filler

“…The calcium sulfate bone void fillers had been successfully used to treat trauma at femur or tibia, osteomyelitis at humerus, and enchondroma at phalanx 1–7 . Apart from calcium sulfate, other ingredients, such as calcium phosphates, calcium carbonate, or their composites, 6,8–10 had also been used as bone void filler. The absorption rate of calcium phosphates, such as hydroxyapatite or tricalcium phosphate, is much slower than that of calcium sulfate 11,12 .…”