Purpose: While the benefits of percutaneous devices are increasingly realized throughout the medical world, high infection rates limit their widespread use. The failure of epidermal cells to adhere to, and integrate with, the device surface establishes a chronic wound healing process at the percutaneous interface, resulting in epidermal downgrowth. Thus, identifying interface surface materials capable of promoting rapid and permanent epidermal cell adhesion would be of significance for avoiding epidermal down-growth and attendant infection. Our previous in vitro experiments revealed that heat-treated fluoridated apatites, such as fluorohydroxyapatite (FHA) and fluorapatite (FA), promote surface adhesion and differentiation of keratinocytes. This study tested the efficacy of these coatings in promoting soft tissue stabilization and wound healing at the skin-device interface in a swine model.
Methods: All heat-treated apatites were synthesized in-house. Devices consisted of a subdermal barrier and percutaneous post and were manufactured at Thortex Inc. (Portland, OR). Subdermal barriers were then coated at N2 Biomedical using heat-treated HA, FHA, FA, or commercial HA. Using an approved IACUC protocol, fifteen Yucatan miniature pigs (female; aged 3-4 months) underwent surgeries, with each animal receiving 6 devices: 1) HA sintered at 1150°C, 2) FHA sintered at 1150°C, 3) FHA sintered at 1250°C, 4) FA sintered at 1150°C, 5) commercial HA, and 6) uncoated (control). Five animals were sacrificed at each pre-selected time point: 4, 8, or 16-weeks post-surgery. At necropsy, devices and adjacent soft tissues were harvested, embedded in poly(methyl methacrylate), sectioned, polished, and stained with H&E for histological analyses.
Results: The devices were well tolerated and no adverse tissue reactions or infections were observed. Analysis of the skin-device interface revealed significant growth of subcutaneous adipose tissue over time. This hypertrophic subcutaneous fat prevented the measurable development of epithelial downgrowth that would normally be observed with percutaneous devices. In addition, the H&E stained samples were used to measure the relative degree of granulation tissue areas at the interface. At 16-weeks post-surgery, FA sintered at 1150°C had significantly less (p<0.05) granulation tissue than any of the tested device types.
Conclusion: In this time series study, the data revealed that there were no differences in downgrowth or GT area in the 4- and 8-week groups. This finding was expected, since these periods rest within the course of normal wound healing. However, the GT data from the 16-week group showed that the devices coated with FA sintered at 1150°C resulted in a smaller GT tissue area. Thus, it was concluded that FA sintered at 1150°C may provide an ideal coating for preventing downgrowth and improving interface healing. This finding warrants further investigation.