Papers by Author: Jerome Guicheux

Abstract: The integration of drugs and devices is a growing force in the medical industry. The incorporation of pharmaceutical products not only promises to expand the therapeutic scope of device technology but to access combination products whose therapeutic value stem equally from both the structural attributes of the device and the intrinsic therapy of the drug. For example, the orthopedic industry is exploring drug-coated hip, knee and bone reconstruction implants capable of promoting healing as an added therapeutic benefit for device recipients. In this context, the drug is eluted locally, being targeted in a specific site of interest, thus offering a convenient strategy to avoid adverse effects commonly observed for systemic treatments of some diseases, as an additional benefit. In addition, these new technologies are generally well adapted to the development of minimally invasive surgery for their implantation. In this context, given the wide use of calcium phosphates (CaPs) and bisphosphonates (BPs) for the therapy of bone-related affections, there was great interest to investigate the chemistry taking place when combining the two systems since: (i) it could provide better insight in the mechanism of BP fixation on bones (ii) such combination could act as efficient BP delivery systems when implanted in bone defects.

Abstract: One type of potent aminobisphosphonate (Zoledronate) has been chemically associated onto b-tricalcium phosphate [b-TCP] and calcium deficients apatite [CDA]. Two different association modes have been observed, according to the nature of the Calcium Phosphate [CaP] support and/or the initial concentration of the Zoledronate solution. b-TCP appears to promote Zoledronate-containing crystals formation. On the other hand, at concentrations < 0.05 mol.L-1 CDA seems to undergo chemisorption of the drug through a surface adsorption process, due to PO3 for PO4 exchange, which is well described by Freundlich equations. At concentrations > 0.05 mol.L-1, crystalline needles of a Zoledronate complex form onto the CDA surface. The ability of CDA to release Zoledronate, resulting in the inhibition of osteoclastic activity, was shown using a specific in vitro bone resorption model.

Abstract: Bone invasion is common in case of Squamous Cell Carcinomas (SCC) of the upper aero-digestive tract. Radiotherapy is required in addition to large surgical tumor removal. This treatment usually generates irreversible injuries on the reparation properties of the tissues, especially on bone. The quality of life of patients undergoing major surgery and radiotherapy in maxillary and mandible areas is reduced, but could be improved by bone reconstruction. The aim of this study was to evaluate the bone reconstruction possibilities by Macroporous Biphasic Calcium-Phosphate (MBCPÔ). The MBCP substitute was evaluated as granules and associated to autologous bone marrow (BM) graft in irradiated areas, in an inbreeding rodent model. Radiation sequels were created on inferior members of half of the rats. 3 weeks later, 3-mm osseous defects were created on each animal. The inbreeding model allows BM to be grafted without graft-versus-host reaction. Defects were filled either with MBCP alone, BM alone or a mixture of MBCP and BM. Six weeks after implantation, animals were sacrificed: bone repair and ceramic degradation were evaluated by qualitative and quantitative study. Results showed that bioceramics were well osteointegrated. Filling the defects with BM alone showed a significant increased of newly-formed bone formation but only after irradiation, whereas filling defects with MBCP alone increased new-bone formation only without previous irradiation. Associating MBCP to BM provided the best new-bone formation rates after irradiation. Degradation of the ceramic was the most important in case of BM grafting. This study demonstrated that BM added to MBCP constitute an appropriate material to be considered in case of bone defect occurring in irradiated tissue, and could be foreseen for use after bone removal for oncologic obligations.