Guiding Fibroblast Activation Using an RGD-Mutated Heparin Binding II Fragment of Fibronectin for Gingival Titanium Integration.

The formation of a biological seal around the neck of titanium (Ti) implants is critical for ensuring integration at the gingival site and for preventing bacterial colonization that may lead to periimplantitis. This process is guided by activated fibroblasts, named myofibroblasts, which secrete extracellular matrix (ECM) proteins and ECM-degrading enzymes resolving the wound. However, in some cases Ti is not able to attract and activate fibroblasts to a sufficient extent, which may compromise the success of the implant. Fibronectin (FN) is an ECM component found in wounds that is able to guide soft tissue healing through the adhesion of cells and attraction of growth factors (GFs). However, clinical use of FN functionalized Ti implants is problematic because FN is difficult to obtain, and is sensitive to degradation. Herein, we aim at functionalizing Ti with a modified recombinant Heparin Binding II (HBII) domain of FN, mutated to include an RGD sequence in order to promote fibroblast adhesion and GF attraction. The HBII-RGD domain is able to stimulate fibroblast adhesion, spreading, proliferation, migration and activation to a greater extent than the native HBII, reaching values closer to those of full-length FN suggesting that it might induce the formation of a biological sealing. This article is protected by copyright. All rights reserved.