In vitro cell response on CP-Ti surfaces functionalized with TGF-β1 inhibitory peptides

Abstract

Osseointegration of implants is conversely related to the generation of a fibrous tissue capsule around the implant by the host environment. Although TGF-β1 plays many roles in regeneration processes, it is the cytokine to be mostly associated to the production of fibrotic tissue and thus, its inhibition has demonstrated to be beneficial to prevent several fibrotic reactions. Surface biofunctionalization enables the immobilization of biologically active molecules on an implant surface to tailor the biological response of the host. Here, we studied in vitro biological effects of biofunctionalized CP-Ti surfaces with a TGF-β1 inhibitor peptide, P144. A reliable biofunctionalization process that tethers P144 peptides to commercially pure titanium was developed. Differentiation of human mesenchymal stem cells, osteoblasts and fibroblasts on P144-functionalized and control surfaces was assessed at the gene expression and protein production levels. Results showed that P144-functionalized surfaces reduced expression and production of fibrotic differentiation markers and increased osteoblastic differentiation markers. Therefore, biofunctionalization of surfaces with TGF-β1 inhibitor peptides are an alternative promising strategy for inducing osseointegration around medical devices and implants.

Biofunctionalization with a TGFβ-1 Inhibitor Peptide in the Osseointegration of Synthetic Bone Grafts: An In Vivo Study in Beagle Dogs

“…Furthermore, TGF-β1 has been related to cellular processes for wound healing as well as for the regulation of inflammatory processes [21]. That fact led our group to explore the biofunctionalization of titanium dental implants with TGF-β1 inhibitor peptides, which resulted in accelerating the osteoprogenitor cell differentiation in vitro [30].…”

“…The positive effects of biofunctionalization on the osseointegration of synthetic bone graft could be not only immediate but also in the medium or long term, thanks to trabecular apposition and lamellar remodeling, as described by Martino et al [72] and Biguetti et al [73]. Our TGF-β1 inhibitory peptides have proven to be able to adhere to Cp-Ti surfaces and keep their bioactivity [67] by evoking an in vitro cell response with a reduction of fibroblast differentiation and an increase of osteoblastic markers [30].…”

“…A TGF-β1 inhibitor peptide, P144, blocks the interaction of TGF-β1 with its receptor, thus altering its interaction with different cell types [27,28,29]. An increase of osteoblast and osteoprogenitor cell differentiation was observed as the in vitro results of P144 biofunctionalization of a CP-Ti surface [30]. Previous in vitro studies in MC3T3-E1 stem cells showed improvement of the quality of interfacial interactions during the healing process [31].…”

Bioactive Glass and Silicate-Based Ceramic Coatings on Metallic Implants: Open Challenge or Outdated Topic?

“…Subtractive treatments include grinding, polishing, blasting, acid-etching and laser texturing, whereas additive surface treatments mainly consist in coating depositions by means of different methods, such as plasma-spraying or electrophoretic deposition. Finally, biofunctionalization of surfaces with peptides, growth factors or drugs, has been proposed as an alternative promising strategy for improving the implant osseointegration [54,55,56].…”

Crestal bone changes around early vs. conventionally loaded implants with a multi‐phosphonate coated surface: A randomized pilot clinical trial

“…To this end, numerous strategies are being used, framed in the field of biomimetics. These include modifications of the physical-chemical features of the implant surface (Padial-Molina et al, 2011), addition of proteins with biological bone actions (Cirera et al, 2020;Sevilla et al, 2018), drugs such as melatonin (Galindo Moreno et al, 2016), adsorption of ions with certain cellular targets (Ellingsen et al, 2004), or the use chemical molecules with action on calcium and phosphate metabolism (Rupérez et al, 2016).…”