Antibiotic-eluting resorbable bone-void filler evaluated in a large animal infection prevention model

Abstract

Periprosthetic infection in total knee arthroplasty is a difficult-to-treat complication. Current implant revision procedures use non-degradable, antibiotic-loaded bone cement for local antimicrobial delivery. As a permanent foreign body, antibiotic-loaded bone cement is susceptible to bacterial colonisation after antibiotic release. In this first step, of a multi-study approach, an infection prevention model assessed a resorbable, antibiotic-eluting bone-void filler for preventing infection in a large animal model. Four groups of sheep were utilised to monitor antibiotic-eluting bone-void filler-induced osteoconductivity, infection prevention, and implant resorption. Explanted bone and surrounding tissues were evaluated using quantitative microbiology, backscattered electron microscopy, bone mineral apposition, and Sanderson's staining at the 12-week endpoint. Control groups received commercially available bone-void filler, implanted into a surgically created defect on the right medial femoral condyle. Experimental groups received six antibiotic-eluting bone-void filler devices placed into identically sized defects. One control and one experimental group tested osteoconductivity. An additional control and experimental group were each inoculated with 5 × 10 5 colony forming units/mL Staphylococcus aureus during implant placement for bactericidal effects. Osteoconductivity was confirmed for both antibiotic-eluting bone-void filler and commercially available bone-void filler. The experimental group inoculated with S. aureus showed no detectable bacteria at the study's 12-week endpoint, while infection controls required euthanasia 6-11 d post-inoculation due to infection. This large animal study validated this antibiotic-eluting bone-void filler as osteoconductive, in situ degradable, and bactericidal. All groups, except the infection control, exhibited bone formation comparable to commercial filler ProOsteon ® 500R.

Choosing the right animal model for osteomyelitis research: Considerations and challenges

“…Large animal models, such as pigs and sheep, have also been established to replicate human osteomyelitis using sclerosing agents. In skeletally mature (2–4 years old) sheep, a defect with dimensions of 7 mm tall, 9 mm wide, and 7.5 mm deep was created in the medial face of the distal femoral condyle [ 195 , 196 ] ( Fig. 3 d).…”

Recent Advances in the Evaluation of Antimicrobial Materials for Resolution of Orthopedic Implant-Associated Infections In Vivo

“…, silicone nanotopography that can repel bacteria, , chitosan, hyaluronic acid, ,, etc. ), it is often necessary to incorporate antibiotics into polymeric materials to impart antimicrobial activity. ,,,− The rate of enzymatic/hydrolytic degradation of biodegradable polymers such as chitosan, ,, hyaluronic acid, , alginate, , poly­(lactic acid) derivatives ( e.g. , poly­[ l -lactic] acid, poly­[ d , l -lactide- co -lactide], poly­[ d - l -lactide]), − ,− polycaprolactone, ,, and poly­(lactic- co -glycolic acid) (PLGA) ,,,,, dictates the rate of antibiotic release from the implanted material and subsequent duration of antimicrobial activity.…”

“…In vivo models have been established to enable evaluation of the ability of antimicrobial biomaterials to prevent orthopedic implant-associated infections in a variety of species including mice, ,− ,− ,− rats, − ,− ,,,,− rabbits, ,,− ,,,,− sheep, ,,− and goats , (Table ). In these models, a metallic component is placed in either the tibia or femur and the prophylactic antimicrobial material is placed at the time of bacterial inoculation to enable evaluation of the ability of the material to prevent the development of implant-associated infection.…”

“…Throughout the duration of the study, the extent of infection can be monitored through the use of in vivo BLI in conjunction with luminescent bacteria ( e.g. , Xen strains). − ,,− The ability of the antimicrobial implant to prevent the infection can be determined via quantification of the bacteria remaining following euthanasia using CFU counts on the surface of the implant, and the morphology of bacterial biofilms can be analyzed using SEM. ,,,​− ,− ,,,,,,,,,,,− ,− Additionally, the concentration of antimicrobial agent ( e.g. , antibiotics or metallic ions) used to prevent infection can be evaluated through collection of blood and soft tissues surrounding the implanted antimicrobial material.…”

Vancomycin Elution Kinetics of Four Antibiotic Carriers Used in Orthopaedic Surgery: In Vitro Study over 42 Days

“…Currently, resorbable synthetic devices, such as calcium sulphate-, hydroxyapatite-, and tricalcium phosphate-based materials, and non-resorbable synthetic devices like polymethylmethacrylate (PMMA), are also frequently used in clinical practice [10][11][12][13]. Biodegradable synthetic bone fillers have been refined to act as antibiotic carriers and not only serve as a local scaffold [13][14][15][16][17]. On the other hand, the high primary mechanical stability and low costs of non-resorbable synthetic bone fillers can be seen as advantageous over resorbable ones [18].…”