Quantifying the effect of pore size and surface treatment on epidermal incorporation into percutaneously implanted sphere-templated porous biomaterials in mice - PubMed (original) (raw)

Quantifying the effect of pore size and surface treatment on epidermal incorporation into percutaneously implanted sphere-templated porous biomaterials in mice

Robert A Underwood et al. J Biomed Mater Res A. 2011.

Abstract

The sinus between skin and a percutaneous medical device is often a portal for infection. Epidermal integration into an optimized porous biomaterial could seal this sinus. In this study, we measured epithelial ingrowth into rods of sphere-templated porous poly(2-hydroxyethyl methacrylate) implanted percutaneously in mice. The rods contained spherical 20-, 40-, or 60-μm pores with and without surface modification. Epithelial migration was measured 3, 7, and 14 days post-implantation utilizing immunohistochemistry for pankeratins and image analysis. Our global results showed average keratinocyte migration distances of 81 ± 16.85 μm (SD). Migration was shorter through 20-μm pores (69.32 ± 21.73) compared with 40 and 60 μm (87.04 ± 13.38 μm and 86.63 ± 8.31 μm, respectively). Migration was unaffected by 1,1' carbonyldiimidazole surface modification without considering factors of pore size and healing duration. Epithelial integration occurred quickly showing an average migration distance of 74.13 ± 12.54 μm after 3 days without significant progression over time. These data show that the epidermis closes the sinus within 3 days, migrates into the biomaterial (an average of 11% of total rod diameter), and stops. This process forms an integrated epithelial collar without evidence of marsupialization or permigration.

Copyright © 2011 Wiley Periodicals, Inc.

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Figures

Figure 1

Figure 1

A) Mouse implantation model showing two porous cylindrical rods (arrows) using a through and through method creating four sites of epidermal/biomaterial contact. B) Illustration depicting a longitudinal view through one implant. Each implant was bisected perpendicular to the long rod axis of the implant and serially crossectioned starting from the interior region. Sectioning progressed through the region of epidermal incorporation and ended toward the exit site. C) Representative photomicrograph within the region of epidermal incorporation, as indicated by a red border (1B), after immunohistochemical labeling for keratin showing the circular crossection of a rod with 40μm pores and surrounding cutaneous tissue, 7 days post-implantation. The epidermis migrates a distance down along the rod prior to the region of incorporation. Thus, in crossection, the epidermal incorporation is not contiguous, nor does it always appear closest to the outer epidermis that bridges dorsally over the implant. Epidermis adjacent to the rod appears as a separate island until becoming contiguous toward the exit site.

Figure 2

Figure 2

A, B, C) This partial sequence of photomicrographs, spaced at 96μm intervals in the Z-direction, demonstrates epithelial incorporation into the 40μm pores of poly(HEMA) 7 days after implantation. D) Analyzed photomicrograph shows radial lines emanating from the centroid (central arrow) of the biomaterial (green mask), the contours outlining the keratin stain and intersects between radial lines and contours nearest the centroid (red dots). E) Same micrograph as D, showing how the Euclidean distance map assigned pixel values to each intersect according to its distance from the biomaterial’s edge (red arrow). Using image calibration, the pixel values were converted to microns (embedded table).

Figure 3

Figure 3

A) Charted data comparing the average migration distance grouped into 20, 40 and 60μm pores sizes regardless of material treatment or healing time. B) Distribution of migration distances for 20, 40 and 60μm pore sizes (midline indicates global average and arrows indicate positions of the migrating fronts for each pore size). C) Charted data comparing the average migration distance of poly(HEMA) and CDI modified poly(HEMA) regardless of pore size or healing time. D) Distribution of migration distances for poly(HEMA) and CDI (midline indicates global average and arrows indicate positions of the migrating fronts for each material). E) Charted data comparing the average migration distance of 3, 7 and 14 days of healing time regardless of pore size and material treatment. F) Distribution of migration distances for 3, 7 and 14 days of healing time (midline indicates overall average and arrows indicate positions of the averaged 2.5% furthest distances, or maximal front, for each healing time). Error bars represent standard error. P-values less than 0.05 are considered significant.

Figure 4

Figure 4

Chart 1) Line chart compares the effect on migration distance that 20, 40 or 60μm pore sizes exhibit over time. Chart 2) Line chart shows the effect that poly(HEMA) or CDI modified poly(HEMA) material has comparing rods with 20, 40 or 60μm pore sizes. Chart 3) Line chart shows the effect on migration distance of poly(HEMA) and CDI modified poly(HEMA) over time. Chart 4) Line chart shows the effect on migration distance of healing time of 3, 7 and 14 days comparing poly(HEMA) and CDI modified poly(HEMA). Chart 5) Line chart shows the effect on migration distance of pore size/material combinations over time. Chart 6) Line chart shows the effect on migration distance of pore size/time combinations comparing poly(HEMA) and CDI modified poly(HEMA). Error bars depict standard error and P values less than 0.05 are indicated by arrows.

Figure 5

Figure 5

Stereo pair representing the 3D reconstruction of analyzed micrographs through the region of epithelial incorporation as viewed from the ventral aspect. Green depicts the contours surrounding keratin stain within the porous biomaterial. Keratin stain contours (hair follicles and epidermis) outside the biomaterial are depicted in orange. Red dots depict the intersection between radial lines and keratinocyte stain contours and represent the epithelial migrating front. Radial lines within the biomaterial are represented in blue while radial lines outside the biomaterial are magenta.

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References

    1. Safdar N, Kluger DM, Maki DG. A review of risk factors for catheter-related bloodstream infection caused by percutaneously inserted, noncuffed central venous catheters: implications for preventive strategies. Medicine (Baltimore) 2002;81(6):466–479. - PubMed
    1. Fleckman P, Olerud JE. Models for the histologic study of the skin interface with percutaneous biomaterials. Biomed Mater. 2008;3(3):034006. - PMC - PubMed
    1. Fukano Y, Knowles NG, Usui ML, Underwood RA, Hauch KD, Marshall AJ, Ratner BD, Giachelli C, Carter WG, Fleckman P, et al. Characterization of an in vitro model for evaluating the interface between skin and percutaneous biomaterials. Wound Repair Regen. 2006;14(4):484–491. - PubMed
    1. Fukano Y, Usui ML, Underwood RA, Isenhath S, Marshall AJ, Hauch KD, Ratner BD, Olerud JE, Fleckman P. Epidermal and dermal integration into sphere-templated porous poly(2-hydroxyethyl methacrylate) implants in mice. J Biomed Mater Res A. 94(4):1172–1186. - PMC - PubMed
    1. Isenhath SN, Fukano Y, Usui ML, Underwood RA, Irvin CA, Marshall AJ, Hauch KD, Ratner BD, Fleckman P, Olerud JE. A mouse model to evaluate the interface between skin and a percutaneous device. J Biomed Mater Res A. 2007;83(4):915–922. - PubMed

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