Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds.
ABSTRACT This paper provides an extensive overview of published studies on the development and applications of three-dimensional bone tissue engineering (TE) scaffolds with potential capability for the controlled delivery of therapeutic drugs. Typical drugs considered include gentamicin and other antibiotics generally used to combat osteomyelitis, as well as anti-inflammatory drugs and bisphosphonates, but delivery of growth factors is not covered in this review. In each case reviewed, special attention has been given to the technology used for controlling the release of the loaded drugs. The possibility of designing multifunctional three-dimensional bone TE scaffolds for the emerging field of bone TE therapeutics is discussed. A detailed summary of drugs included in three-dimensional scaffolds and the several approaches developed to combine bioceramics with various polymeric biomaterials in composites for drug-delivery systems is included. The main results presented in the literature are discussed and the remaining challenges in the field are summarized with suggestions for future research directions.
Article: State of the art and future directions of scaffold-based bone engineering from a biomaterials perspective.[show abstract] [hide abstract]
ABSTRACT: Scaffold-based bone tissue engineering aims to repair/regenerate bone defects. Such a treatment concept involves seeding autologous osteogenic cells throughout a biodegradable scaffold to create a scaffold-cell hybrid that may be called a tissue-engineered construct (TEC). A variety of materials and scaffolding fabrication techniques for bone tissue engineering have been investigated over the past two decades. This review aims to discuss the advances in bone engineering from a scaffold material point of view. In the first part the reader is introduced to the basic principles of bone engineering. The important properties of the biomaterials and the scaffold design in the making of tissue engineered bone constructs are discussed in detail, with special emphasis placed on the new material developments, namely composites made of synthetic polymers and calcium phosphates. Advantages and limitations of these materials are analysed along with various architectural parameters of scaffolds important for bone tissue engineering, e.g. porosity, pore size, interconnectivity and pore-wall microstructures.Journal of Tissue Engineering and Regenerative Medicine 1(4):245-60. · 3.28 Impact Factor
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ABSTRACT: Surgeons continually struggle to reduce orthopaedic infections, but no current treatment offers minimum side effects with maximum effectiveness. Antibiotics mixed in plaster of paris have been successful in treating large bony defects in patients with chronic osteomyelitis, and have the advantage of being well tolerated and absorbed by the body. Antibiotics impregnated in polymethylmethacrylate (PMMA) have offered local antibiotic delivery with some success. However, the effect of the antibiotic on the bone cement, the inconsistent elution of the antibiotic, and the need to remove the PMMA implant drives the need for a better system of antibiotic delivery. Polymers or copolymers of antibiotic-impregnated polylactic acid, polyglycolic acid or polyparadioxanone may provide an absorbable system for localized antibiotic delivery. Similar biodegradable systems used to treat small bone fractures have been successful with minimal side effects. In vitro studies have shown promising results of antibiotic elution from bioabsorbable microspheres and beads. Animal in vivo tests have shown that antibiotic impregnated polymers can successfully treat induced osteomyelitis in rabbits and dogs. These studies have provided consistent reproducible results, and now it is time to plan human trials to assess the efficacy of antibiotic microspheres implanted in infected bone and to plan in vivo and in vitro animal testing to investigate the feasibility of antibiotic-polymer-coated components.Clinical Orthopaedics and Related Research 09/2005; · 2.53 Impact Factor
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ABSTRACT: We investigated the use of an ofloxacin-impregnated bioabsorbable composite for the prevention of acute Staphylococcus aureus osteomyelitis. New Zealand White rabbits were anesthetized, the femur was exposed, and a cortical hole was drilled. Animals were randomly given drug-free composites or ofloxacin-impregnated composites; the composites were placed at the site of injury, and the incision was closed. One hour later, all animals were intravenously inoculated with 5 x 10(4) CFU of S. aureus and observed for 28 days. Bone culture data revealed that S. aureus was isolated from 3 of 12 rabbits in the ofloxacin composite group and 9 of 11 animals in the control group (P = 0.02). Radiographic evaluation revealed that the drug-free group had a significantly (P = 0.01) greater degree of radiographic evidence of infection than the group given ofloxacin composites. Although a limited number of histologic samples were available, these data also paralleled the radiographic and culture data. This study demonstrates the effectiveness of the implantable ofloxacin bioabsorbable composites to prevent the development of acute osteomyelitis.Antimicrobial Agents and Chemotherapy 05/1998; 42(4):840-2. · 4.84 Impact Factor