Engineering the tissue which encapsulates subcutaneous implants. I. Diffusion properties

Abstract

This report uses normal rat subcutis as a reference point to provide a quantitative analysis of small analyte transport through the tissue which encapsulates implants. Polyvinyl alcohol (PVA) with 60-and 350-m mean pore size (PVA-60, PVA-350), nonporous PVA (PVA-skin), and stainless-steel cage (SS) specimens were implanted in the subcutis of Sprague-Dawley rats for 4 weeks to elicit a range of capsular wound-healing tissues. Histologic examination showed that the capsular tissue which formed around PVAskin and SS specimens was densely fibrous and avascular. That forming around PVA-60 and PVA-350 was less densely fibrous and more vascular. The fibrous content of capsular tissue and subcutis was determined from eosin-stained histologic sections. Dual-chamber diffusion measurements of sodium fluorescein (M w 376 g/mol) through capsular tissue and normal rat subcutis were used to quantitatively compare the effective diffusion coefficients of small analytes on the order of glucose. The two most fibrous capsular tissues exhibited diffusion coefficients that were statistically (p < 0.05) less than that determined for rat subcutis by 50 and 25% for PVA-skin and SS, respectively. The diffusion coefficients of the less dense capsular tissue which formed around the porous implants were not statistically different from subcutis. The experimentally measured diffusion coef-ficients of the two most fibrous capsular tissues were closely predicted by a simple two-component diffusion model consisting of an aqueous interstitium with an array of impenetrable bodies equal in volume fraction to the fibrous content of the tissue. This model overestimates the diffusion coefficients measured for the least fibrous tissues. Using the diffusion coefficient measured for the PVA-skin capsular tissue, a finite difference model predicts that a 200-m-thick capsular layer would increase from 5 to 20 min the time required for subcutaneously implanted sensor to detect 95% of the blood analyte concentration. This study suggests 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 less fibrous encapsulation tissue.

Species and Density of Implant Surface Chemistry Affect the Extent of Foreign Body Reactions

“…11,13,19,20,[56][57][58] The collagenous capsule acts as a barrier to the diffusion of drugs and also blocks the supply of nutrients to the encapsulated cells in cell delivery systems. 11,[18][19][20]59 By diminishing biomaterial-mediated fibrotic reactions and accompanied collagenous diffusion barrier formation, the drug release properties, life-span and sensor sensitivity could be significantly enhanced. 11,[18][19][20]23,57,58,60 Surface chemical properties of implant materials have been shown to affect protein adsorption and acute cellular responses.…”

“…Many recent evidences have supported that dense avascular fibrotic tissues serve as diffusion barrier for the released drugs to enter into circulation and for blood components and nutrition from the tissue fluid to interact with implanted sensor. 11,[18][19][20] The enormity of this complication is underlined by previous studies which have found that even low molecular weight substances cannot cross the barrier. [21][22][23][24] Therefore, it is generally accepted that, by reducing implant-mediated fibrotic tissue, the life span, function, and efficacy of drug releasing devices, sensors, and tissue engineering scaffolds could be substantially improved.…”

Non-invasive method to detect the changes of glucose concentration in whole blood using photometric technique

“…The functional loss can be due to the histological changes like inflammatory reaction, fibrous encapsulation that takes place on the tissues around the implants. The fibrous encapsulation restricts the diffusion transportation of glucose to the sensor and thus reducing sensitivity [16][17][18] . The stability of glucose sensor was tested by Rebrin et al and reported instability in measurement and loss of sensitivity.…”

Blood Glucose Self-Monitoring with a Long-Term Subconjunctival Glucose Sensor

“…Several attempts to overcome FBR are discussed in the literature, e.g., specially designed surface architectures and biocompatible or drug-eluting surface coatings. [28][29][30][31][32][33][34][35] This article provides in vivo data from a clinical trial of the EyeSense subconjunctival glucose monitoring system (SGMS) with a biocompatible surface coating, designed to minimize protein-surface interaction, to prolong the duration of action of the system.…”