This study proposes to systematically study the capacity of bioactive factors to induce cartilage and bone repair in experimentally formatted configurations introduced into in vivo model systems which have been shown previously to be suitable test systems for attempting to understand selected aspects of skeletal repair. The proposed studies are based on isolation and characterization of an adult long bone derived inductive factor. The development of controlled delivery release vehicles for in vivo implantation will utilize chemical bonding and/or physical entrapments of active components with a variety of inert biocompatible implant devices. In addition, a population of non-skeletal fibroblasts capable of """"""""transporting"""""""" soluble inductive activity be utilized as an implant vehicle. Initial screening of bioactive factor vehicle complexes will be performed by ectopic intramuscular implantation. The formation of cartilage and/or bone will be evaluated by roentgenographic, quantitative histologic, and biochemical techniques. Regeneration of stable well-integrated cartilage and/or bone tissue within a selected skeletal wound site is the ultimate object of our experimental efforts. The pre-screening procedures, as described above, will enhance the potential success of this most relevant test system. The most efficient, active vehicle will be studied in in vivo orthotopic sites, including iliac crest and femoral diaphyseal defect models for bony repair, and articular cartilage defects. In addition, factors from teeth and mandibles will be studied for repair characteristics in this skeletal tissue and compared to the results obtained from long bone derived factors. The ultimate outcome of these repaired sites will be evaluated by quantitative histology, ratiographic techniques, quantitative biochemistry, and mechanical testing, using torsional testing for bone and confined compression creep for cartilage. The overall goal of this proposal is therefore, to develop practical techniques which utilize bioactive factors in the repair of both cartilaginous and bony defects with ultimate application to clinical problems.
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| Lazarus, H M; Haynesworth, S E; Gerson, S L et al. (1995) Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use. Bone Marrow Transplant 16:557-64 |
