IMPLANTS ELICITING A FOREIGN BODY REACTION

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Must all implants elicit a foreign body reaction? The traditional view is "yes", with a specific cellular and humoral chain of events leading to eventual encapsulation or extrusion. The hypothesis of this proposal is that in each biologic environment the final and permanent stage of the implant-tissue interaction is determined by the intensity, the cellular and extracellular characteristics, and the duration of the initial inflammatory response. And, a more extensive understanding of the initial stage of the response to an implant will allow one to predict, and eventually to control, the ultimate tissue reaction. It is generally considered that a better understanding of the tissue-materials interaction is vital to the development of new materials, implants, and devices. Few investigators with a background in pathology have developed an interest in this area and only a few innovative in-vivo model systems have been proposed to address these questions. The aims of this program are to: 1) Employ four chemically well-characterized polymers. Two of these materials are bioresorbable polyesters derived from Krebs cycle decarboxylic acids with varying bioresorption rates. Two are biodurable materials, polyethylene as a primary reference material, obtained from the NHLBI, and polyethylene terephthalate, purified for subcutaneous implantation. 2) Implant these materials in animals. Two methods of implantation are proposed. The first is a paired subcutaneous implantation in mice. The second (a more innovative method) is parenteral (via tail vein or portal vein) injection of a colloidal suspension with localization in the pulmonary or hepatic parenchyma, respectively. 3) Evaluate the biologic reception of these materials. Standard light and electron microscopy, histochemistry, and morphometry will be employed, as well as the application of new quantative immunofluorescent methods. The analysis protocols as modified and established will have wider application in the field of tissue-materials interaction. 4) Analyze and correlate the biologic reception data. Analysis will be performed to identify features of value in predicting the "outcome" of the tissue material interaction. The third aim, "Analyze the biologic reception of these materials" is the essential concentration of this program. It is in this area that the special expertise gained through anatomic pathologic traning be applied in career development toward addressing the specific (and general) problems in tissue-material interaction analysis.