Di-Silvio, Luciana; (1995) A novel application of two biomaterials for the delivery of growth hormone and its effect on osteoblasts. Doctoral thesis (Ph.D.), University College London (United Kingdom).

Text A novel application of two bio.pdf Download (34MB)

Abstract

Hormonal stimulation of osteoblasts can provide better focal integration of orthopaedic implants. In this study both direct and indirect actions of growth hormone on primary human osteoblasts have been demonstrated. Growth hormone significantly increased cell proliferation and alkaline phosphatase activity and stimulated the synthesis of Insulin-like Growth Factor-I and the release of Insulin Growth Factor-binding protein 3. A drug delivery system releasing biologically active growth hormone targeted to osteoblasts could be used to improve tissue repair in orthopaedics. Two biomaterials have been successfully developed for this novel application. The first is based on natural biodegradable, biocompatible gelatin, in the form of microspheres, where the amount of growth hormone released was significantly increased following ultrasound treatment. The second, a non-degradable polymer based on polyethylmethacrylate and tetrahydrofurfurylmethacrylate (PEM/THFMA) showed an initial rapid release followed by a prolonged sustained release of growth hormone. The preparation method used, significantly affected the amount of growth hormone released. Varying the ratio of PEMA/HFMA and gelling it with hydroxyethylmethacrylate changed the profiles and increased the amount of growth hormone released, exposure to various temperatures did not affect the amount or bioactivity of the GH released. The initial rapid release of growth hormone locally from both systems is desirable post- operatively to stimulate osteogenic cells at the polymer interface and accelerate repair during the critical early wound healing period, whilst the subsequent slow release would enhance osteoid deposition and bone mineral formation. Both systems have advantages, the choice is dependent on the intended site of use. The microspheres are biodegradable and the GH released can be increased in a physiological manner depending on clinical requirements. The PEM/THFMA can be used where stability is required and can absorb tissue fluids and growth factors from the bone matrix, marrow and synovial fluid, thereby creating an optimal environment for rapid bone remodelling. This study has demonstrated a level of control for GH delivery in both systems and has confirmed that targeted osteoblasts respond to GH. Numerous clinical applications could benefit from these controlled systems, for example, enhancing the fixation of total joint prostheses, bone defects in non-union fractures, and in pathological conditions where local growth promoting effects would be beneficial.

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