Engineering the transport properties of tissue-encapsulating long term subcutaneous implants

s a consequence of the foreign body response, nondegradable implants are often encapsulated in a densely packed, avascular tissue or "fibrous capsule". It has often been thought that fibrous capsules hinder the transport of blood-borne molecules to sensors, immunisolated cell systems, and other implants which require good communication with plasma. Little quantitative work, however, has been done to either confirm or dispute this. The general aim of this work has been to quantify the transport properties of capsular tissue and to determine how implant porosity can be used to engineer those properties. More specifically, diffusion coefficients were measured through the fibrous capsules around differently pore sized implants to determine their diffusion properties. Permeability and density of vessels within tissue surrounding differently pore sized implants were measured to determine their plasma-tissue exchange properties. Finally, a novel method to visualize in vivo transport was used to quantify a tissue response time constant, a measure of how quickly the analyte levels in tissue surrounding the different implants followed a change in plasma concentration. The principal findings of this work are as follows: The effective diffusion coefficients of low molecular weight analytes through the tightly packed capsular tissue which formed around nonporous polyvinyl alcohol (PVA) implants was approximately one half that through surrounding subcutis. The diffusion coefficients through the sparser tissue surrounding porous implants which allowed substantial fibrovascular ingrowth was similar to that through subcutis. Microvascular density within 100...