by Keyword: Growth factors
Dhawan, U, Williams, JA, Windmill, JFC, Childs, P, Gonzalez-Garcia, C, Dalby, MJ, Salmeron-Sanchez, M, (2024). Engineered Surfaces That Promote Capture of Latent Proteins to Facilitate Integrin-Mediated Mechanical Activation of Growth Factors Advanced Materials , 2310789 
Conventional osteogenic platforms utilize active growth factors to repair bone defects that are extensive in size, but they can adversely affect patient health. Here, an unconventional osteogenic platform is reported that functions by promoting capture of inactive osteogenic growth factor molecules to the site of cell growth for subsequent integrin-mediated activation, using a recombinant fragment of latent transforming growth factor beta-binding protein-1 (rLTBP1). It is shown that rLTBP1 binds to the growth-factor- and integrin-binding domains of fibronectin on poly(ethyl acrylate) surfaces, which immobilizes rLTBP1 and promotes the binding of latency associated peptide (LAP), within which inactive transforming growth factor beta 1 (TGF-beta 1) is bound. rLTBP1 facilitates the interaction of LAP with integrin beta 1 and the subsequent mechanically driven release of TGF-beta 1 to stimulate canonical TGF-beta 1 signaling, activating osteogenic marker expression in vitro and complete regeneration of a critical-sized bone defect in vivo. An osteogenic platform that functions by capturing inactive growth factor molecules is engineered to overcome conventional challenges associated with the use of active growth factors. The platform triggers capture of inactive transforming growth factor beta-1 for its subsequent integrin-mediated activation which activates osteogenic downstream signaling in vitro and fully repairs critical-sized bone defect in vivo. image
JTD Keywords: Bone, Bone defect, Bone regeneration, Cell proliferation, Cells, Chemical activation, Defects, Differentiation, Fibronectin, Growth factor, Growth factors, Integrins, Latency associated peptides, Ltbp1, Osteogenic, Recombinant proteins, Release, Repair, Tgf-beta, Tgf-β1, Transforming growth factors
Heras-Parets, A, Ginebra, MP, Manero, JM, Guillem-Marti, J, (2023). Guiding Fibroblast Activation Using an RGD‐Mutated Heparin Binding II Fragment of Fibronectin for Gingival Titanium Integration Advanced Healthcare Materials 12, e2203307
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, functionalizing Ti with a modified recombinant heparin binding II (HBII) domain of FN, mutated to include an Arg-Gly-Asp (RGD) sequence for promoting both fibroblast adhesion and GF attraction, is aimed at. 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.© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.
JTD Keywords: alpha-4-beta-1, beta, cell-binding, collagen, extracellular-matrix, fibroblast activation, fibronectin, growth factors, integrins, metalloproteinases, myofibroblasts, proliferation, soft-tissue integration, titanium, Biological-activities, Fibroblast activation, Titanium