Novel tubular composite matrix for bone repair.

Tissue engineering develops organ replacements to overcome the limitations associated with autografts and allografts. The work presented here details the development of biodegradable, porous, three-dimensional polymer-ceramic-sintered microsphere matrices to support bone regeneration. Poly(lactide-co-glycolide)/hydroxyapatite microspheres were formed using solvent evaporation technique. Individual microspheres were placed in a cylindrical mold and sintered at various temperatures. Scaffolds were characterized using scanning electron microscopy, mercury porosimetry, and mechanical testing in compression. After varying the temperature of sintering, a single temperature was selected and the time of sintering was varied. Mechanical testing indicated that as the sintering temperature or time was increased, the elastic modulus, compressive strength, maximum compressive load, and energy at failure significantly increased. Furthermore, increasing the sintering temperature or time resulted in a decreased porosity and the spherical morphology of the microspheres was lost as the microspheres blended together. To more closely mimic the bone marrow cavity observed in native bone tissue, tubular composite-sintered microsphere matrices were formed. These scaffolds demonstrated no statistically significant difference in compressive mechanical properties when compared with cylindrical composite-sintered microsphere matrices of the same dimension. One potential application for these scaffolds is bone regeneration.

Orthopaedic applications of gene therapy.

Current treatment modalities for musculoskeletal injuries due to disease or trauma often implement the use of tissue grafts, cell transplantations, and artificial scaffolding. These approaches may be augmented with the use of specific biological factors, which accelerate healthy tissue regeneration. Unfortunately, the short half-life and inherent instability of proteins requires the delivery of high doses or multiple doses of these molecules, neither of which is ideal for the patient or clinician. Gene therapy, as an alternative approach, has the potential to circumvent the existing limitations associated with protein delivery by producing a sustained release of the biologic agent at therapeutic levels. This is achieved by the direct transfer of the gene encoding the therapeutic agent to the cells of the afflicted tissue or by implanting cells that have been previously genetically modified in vitro. Using these methods, several laboratories have demonstrated the ability to deliver genes in vitro and in vivo resulting in accelerated and enhanced musculoskeletal tissue regeneration or inhibited disease progression. Many of these investigations, which involved bone, ligament, tendon, and cartilage, are covered in this review. Specifically, musculoskeletal tissue anatomy, factors relevant to musculoskeletal tissue regeneration, target cells, and in vivo and ex vivo gene therapy approaches for musculoskeletal regeneration are discussed. The experience and knowledge gained from these studies have affirmed gene therapy is a promising therapeutic strategy to combat musculoskeletal tissue repair and regeneration following disease or injury.