ENGINEERING THE TISSUE WHICH ENCAPSULATES SUBCUTANEOUS IMPLANTS .1. DIFFUSION PROPERTIES

This report uses normal rat subcutis as a reference point to provide a quantitative analysis of small analyte transport through the tissue w hich encapsulates implants. Polyvinyl alcohol (PVA) with 60- and 350-m u m mean pore size (PVA-60, PVA-350), nonporous PVA (PVA-skin), and st ainless-steel cage (SS) specimens were implanted in the subcutis of Sp rague-Dawley rats for 4 weeks to elicit a range of capsular wound-heal ing tissues. Histologic examination showed that the capsular tissue wh ich formed around PVA-skin and SS specimens was densely fibrous and av ascular. That forming around PVA-60 and PVA-350 was less densely fibro us and more vascular. The fibrous content of capsular tissue and subcu tis was determined from eosin-stained histologic sections. Dual-chambe r diffusion measurements of sodium fluorescein (M-w 376 g/mol) through capsular tissue and normal rat subcutis were used to quantitatively c ompare the effective diffusion coefficients of small analytes on the o rder of glucose. The two most fibrous capsular tissues exhibited diffu sion coefficients that were statistically (p < 0.05) less than that de termined for rat subcutis by 50 and 25% for PVA-skin and SS, respectiv ely. The diffusion coefficients of the less dense capsular tissue whic h formed around the porous implants were not statistically different f rom subcutis. The experimentally measured diffusion coefficients of th e two most fibrous capsular tissues were closely predicted by a simple two-component diffusion model consisting of an aqueous interstitium w ith an array of impenetrable bodies equal in volume fraction to the fi brous content of the tissue. This model overestimates the diffusion co efficients measured for the least fibrous tissues. Using the diffusion coefficient measured for the PVA-skin capsular tissue, a finite diffe rence model predicts that a 200-mu m-thick capsular layer would increa se from 5 to 20 min the time required for subcutaneously implanted sen sor to detect 95% of the blood analyte concentration This study sugges ts that the fibrous capsule forming around a subcutaneously implanted smooth-surface sensor imposes a significant diffusion barrier to small analytes such as glucose, thus increasing the lag time of the sensor by as much as threefold. A corollary observation is that a sensor with a porous surface which allows tissue ingrowth may be more responsive to blood analyte fluctuations as a result of its a more vascular and l ess fibrous encapsulation tissue. (C) 1997 John Wiley & Sons, Inc.