ABSTRACT
There is a great need for an approach that can maintain sufficient local doses of antibiotics at osteomyelitic sites because the wound areas are almost impenetrable. The inaccessability of the diseased site is due to the decrease of the vasculature at the infected site, and also the site is surrounded by a thick, collageneous material, making access and therefore therapy more difficult. Osteomyelitis is a dramatic disease with a mortality of around 20% and a morbidity three times that amount. Secondary infection due to trauma or iatrogenic infection following orthopedic surgery where implants are used are the main causes of the disease in developed countries, whereas hematogenous osteomyelitis is still a problem in developing countries. Eighty-five percent of the people who are involved in traffic accidents have one or more fractures in their long bones, and at least 50% of them undergo a surgery related to that fracture. Open fractures caused by other events (accidents, old age, etc.) are also sources of infection. In addition there is the possibility of infection during surgeries such as total hip implantation. When metal implants are used (and at present there are practically no orthopedic implants of other materials), the risk of infection increases due to the adherence of bacteria to the metal. A systemic route of antibiotic administration is inefficient because only low levels of antibiotic reach the target site and persist there for a short duration. The use of nonresorbable controlled release systems containing antibiotics to prevent the establishment of the disease or to treat an already established disease by delivering the drug locally has been practiced for quite a number of years. Gentamicin-loaded polymethylmethacrylate (PMMA) [1-6] is the pioneer of these systems and is still in clinical use; however, it has its disadvantages. The nonresorbability and thus the need for removal upon depletion of the drug content
and the low rates of antibiotic release from these hydrophobic, acrylic beads are the major problems [7, 8]. A resorbable, controlled release implant would diminish the need for a second surgery and would also positively influence the outcome of fracture fixation. As alternatives to PMMA, biodegradable and biocompatible materials such as degradable polymers [9-15], bioceramics [16-22], polymer-ceramic composites [23], and, recently, calcium phosphate-gelatin composites [24] were developed. The major advantages of these implants are decreased morbidity due to one-stage surgery, osteoconductivity and/or osteoinductivity, steady and extended release providing longer and higher antimicrobial agent availability, and a wider selection of antibiotics including thermolabile ones that cannot be used with PMMA microspheres.
