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E-cadherin mediated cell-biomaterial interaction reduces migration of keratinocytes in-vitro

Dehli, J., Karlsson, C., Bizelli-Silveira, C., Jiang, Xingyu, Kraft, D., Foss, M.
Colloids and surfaces 2019 v.180 pp. 326-333
adherens junctions, adhesion, cadherins, calcium, cell movement, cell proliferation, colloids, enzyme-linked immunosorbent assay, fibroblasts, fibronectins, human cell lines, interphase, keratinocytes, pathogens, titanium
Percutaneous devices suffer from imperfect sealing of the epidermis-implant interphase, the so-called three-phase junction, allowing invading pathogens access to colonize the implant at the tissue interface and potentially cause an infection. In skin, one of the key components of the epidermal barrier is the E-cadherin mediated adherens junctions. We investigated the response of a human keratinocyte cell line (HaCaT) to a titanium substrate functionalized with the extracellular domain of E-cadherin fused to an Fc domain. Polydopamine was used as a binding layer to attach the E-cadherin to the titanium surface in two ways: 1) by attaching protein A to the polydopamine followed by E-cadherin (aligned orientation) or 2) by direct attachment of the E-cadherin to the polydopamine (random orientation). The E-cadherin surface functionalization was stable for up to two months as determined by ELISA. HaCaTs did attach to the surface irrespective of E-cadherin orientation. However, decreased cell proliferation and increased cell size was observed for cells on aligned E-cadherin surfaces as compared to a positive control coated with fibronectin. The adhesion of the HaCaTs to the surface with aligned E-cadherin was more sensitive to cell media Ca2+ depletion. A confluent layer of HaCaTs was almost immobile on the aligned E-cadherin surface, as compared to a surface coated with fibronectin, whereas cell migration was also observed on randomly oriented E-cadherin. The E-cadherin coated surfaces were non-adhesive for primary human dermal fibroblasts, a cell type not expressing E-cadherin. These results show the potential of using E-cadherin as a functional surface at the three-phase junction of percutaneous implants to ensure epidermal attachment, limit epidermal downgrowth and prevent fibroblast adhesion.