Controlled Release of Small Molecules from Elastomers for Reducing Epidermal Downgrowth in Percutaneous Devices

The elevated infection rise associated with indwelling devices can compromise the performance of percutaneous devices and increase the risk of complications. High infection rates are associated with both the high bacterial load on the skin and epidermal downgrowth at the interface of the indwelling material. Here, we propose a drug-eluting material that promotes local dermal regeneration to reduce epidermal downgrowth. Mesoporous elastomeric matrices composed of naturally occurring monomers were prepared by a combination of photo- and thermal-crosslinking. Elastomeric devices loaded with conjugated linoleic acids (CLA), a class of small molecules that promote local anti-inflammatory responses, can deliver these compounds for 7 d (D = 3.94 × 10^-9 cm²/s, 95% CI [3.12 × 10^-9, 4.61 × 10^-9]). In a mouse model, CLA-eluting elastomeric matrices increase the M2 population (5.0 × 10³ ± 1.4 × 10³ cells/cm²), compared to blank devices (3.8 × 10³ ± 2.2 × 10³ cells/cm²), and also reduce skin contraction (98.9 ± 6.4%), compared to blank devices (70.9 ± 9.3%) at 7 d. Dermal downgrowth is also attenuated at 14 d (60.4 ± 32.4 μm) compared to blank devices (171.7 ± 93.8 μm). CLA-eluting elastomers are therefore a viable strategy to reduce epidermal downgrowth in percutaneous devices.