Enhancement of peri-implant bone osteogenic activity induced by a peptidomimetic functionalization of titanium

Ravanetti, Francesca; Gazza, Ferdinando; D’Arrigo, D.; Graiani, Gallia; Zamuner, Annj; Zedda, Marco; Manfredi, Edoardo; Dettin, Monica; Cacchioli, Antonio

doi:10.1016/j.aanat.2018.01.011

Cited by 6 publications

(6 citation statements)

References 35 publications

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“…Ref. [ 36 ]). In the context of BMP-2-functionalised Ti6Al4V, Kashigawi and colleagues [ 33 ] modified this growth factor with a peptide motif (RKLPDA) known to bond electrostatically to Ti6Al4V [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Development of a facile fluorophosphonate-functionalised titanium surface for potential orthopaedic applications

Shiel

Ayre

Blom

et al. 2020

Journal of Orthopaedic Translation

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s Background Aseptic loosening of total joint replacements (TJRs) continues to be the main cause of implant failures. The socioeconomic impact of surgical revisions is hugely significant; in the United Kingdom alone, it is estimated that £137 m is spent annually on revision arthroplasties. Enhancing the longevity of titanium implants will help reduce the incidence and overall cost of failed devices. Methods In realising the development of a superior titanium technology, we exploited the natural affinity of titanium for phosphonic acids and developed a facile means of coating the metal with (3S)1-fluoro-3-hydroxy-4-(oleoyloxy)butyl-1-phosphonate (FHBP), a phosphatase-resistant analogue of lysophosphatidic acid (LPA). Importantly LPA and selected LPA analogues like FHBP synergistically cooperate with calcitriol to promote human osteoblast formation and maturation. Results Herein, we provide evidence that simply immersing titanium in aqueous solutions of FHBP afforded a surface that was superior to unmodified metal at enhancing osteoblast maturation. Importantly, FHBP-functionalised titanium remained stable to 2 years of ambient storage, resisted ∼35 kGy of gamma irradiation and survived implantation into a bone substitute (Sawbone™) and irrigation. Conclusion The facile step we have taken to modify titanium and the robustness of the final surface finish are appealing properties that are likely to attract the attention of implant manufacturers in the future. The translational potential of this article We have generated a functionalised titanium (Ti) surface by simply immersing Ti in aqueous solutions of a bioactive lipid. As a facile procedure it will have greater appeal to implant manufacturers compared to onerous and costly developmental processes.

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Section: Discussionmentioning

confidence: 99%

Development of a facile fluorophosphonate-functionalised titanium surface for potential orthopaedic applications

Shiel

Ayre

Blom

et al. 2020

Journal of Orthopaedic Translation

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“…Although in vivo experiment reported a short time (∼15 d) for adhesive peptides to carry out the endosseous biological activity [21], in the present research study we decided to extend the in vivo experimental time (∼45-60 d) to maximize scaffold mineralization. Indeed, it has been reported that, to obtain a good degree of mineralization in the subcutaneous area time ranging from weeks to months is required [44].…”

Section: In Vivo Assaysmentioning

confidence: 99%

“…The importance to assure a stable and stereooriented peptide anchoring on the scaffold [17][18][19], was taken into consideration [16,20,21].…”

Section: Introductionmentioning

confidence: 99%

Biofunctionalization of bioactive ceramic scaffolds to increase the cell response for bone regeneration

Zamuner¹,

Brun²,

Ciccimarra³

et al. 2021

Biomed. Mater.

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Biofunctionalization was investigated for polymers and metals considering their scarce integration ability. On the contrary few studies dealt with ceramic biofunctionalization because the bioactive and bioresorbable surfaces of ceramics are able to positively interact with biological environment. In this study the cell-response improvement on biofunctionalized wollastonite and diopside-based scaffolds was demonstrated. The ceramics were first obtained by heat treatment of a silicone embedding reactive oxide fillers and then biofunctionalized with adhesive peptides mapped on vitronectin. The most promising in vitro results, in terms of h-osteoblast proliferation and bone-related gene expression, were reached anchoring selectively a peptide stable toward proteolytic degradation induced by serum-enriched medium. In in vivo assays the anchoring of this protease-stable adhesive peptide was combined with self-assembling peptides, for increasing cell viability and angiogenesis. The results demonstrated external and internal cell colonization of biofunctionalized scaffolds with formation of new blood vessels (neoangiogenesis) and stimulation of ectopic mineralization.

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“…With the aim to confer stability to the HVP peptide, the retro-inverted analog DHVP and its dimeric sequence D2HVP were designed and synthesized. Moreover, we investigated the ability of DHVP and D2HVP to maintain bioactivities comparable to those of native sequences including the analysis of cytotoxicity and resistance to proteolytic degradation [16,29]. Previous results demonstrated that the dimeric analog D2HVP is able to greatly increase cell adhesion, proliferation, gene expression, and mineralization in vitro when compared both to shorter HVP and DHVP peptides [16,30]: this improved bioactivity of the dimeric peptide in respect to DHVP could be inferred to increased ionic interactions with cellular GAGs or to a greater distance of the bioactive sequence from the implant surface (the first nine amino acids acting as a spacer), resulting in a better exposure of the adhesive sequence to the osteoblasts.…”

Section: Introductionmentioning

confidence: 99%

Selective Grafting of Protease-Resistant Adhesive Peptides on Titanium Surfaces

et al. 2022

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In orthopedic, dental, and maxillofacial fields, joint prostheses, plates, and screws are widely used in the treatment of problems related to bone tissue. However, the use of these prosthetic systems is not free from complications: the fibrotic encapsulation of endosseous implants often prevents optimal integration of the prostheses with the surrounding bone. To overcome these issues, biomimetic titanium implants have been developed where synthetic peptides have been selectively grafted on titanium surfaces via Schiff base formation. We used the retro-inverted sequence (DHVPX) from [351–359] human Vitronectin and its dimer (D2HVP). Both protease-resistant peptides showed increased human osteoblast adhesion and proliferation, an augmented number of focal adhesions, and cellular spreading with respect to the control. D2HVP-grafted samples significantly enhance Secreted Phosphoprotein 1, Integrin Binding Sialoprotein, and Vitronectin gene expression vs. control. An estimation of peptide surface density was determined by Two-photon microscopy analysis on a silanized glass model surface labeled with a fluorescent analog.

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Enhancement of peri-implant bone osteogenic activity induced by a peptidomimetic functionalization of titanium

Cited by 6 publications

References 35 publications

Development of a facile fluorophosphonate-functionalised titanium surface for potential orthopaedic applications

Development of a facile fluorophosphonate-functionalised titanium surface for potential orthopaedic applications

Biofunctionalization of bioactive ceramic scaffolds to increase the cell response for bone regeneration

Selective Grafting of Protease-Resistant Adhesive Peptides on Titanium Surfaces

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