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. 2024 Feb 12;9(8):8985-8994.
doi: 10.1021/acsomega.3c07232. eCollection 2024 Feb 27.

Engineering a Hybrid Ti6Al4V-Based System for Responsive and Consistent Osteogenesis

Affiliations

Engineering a Hybrid Ti6Al4V-Based System for Responsive and Consistent Osteogenesis

Francisca Melo-Fonseca et al. ACS Omega. .

Abstract

As the aging population increases worldwide, the incidence of musculoskeletal diseases and the need for orthopedic implants also arise. One of the most desirable goals in orthopedic reconstructive therapies is de novo bone formation. Yet, reproducible, long-lasting, and cost-effective strategies for implants that strongly induce osteogenesis are still in need. Nanoengineered titanium substrates (and their alloys) are among the most used materials in orthopedic implants. Although having high biocompatibility, titanium alloys hold a low bioactivity profile. The osteogenic capacity and osseointegration of Ti-based implantable systems are limited, as they critically depend on the body-substrate interactions defined by blood proteins adsorbed into implant surfaces that ultimately lead to the recruitment, proliferation, and differentiation of mesenchymal stem cells (MSCs) to comply bone formation and regeneration. In this work, a hybrid Ti6Al4V system combining micro- and nanoscale modifications induced by hydrothermal treatment followed by functionalization with a bioactive compound (fibronectin derived from human plasma) is proposed, aiming for bioactivity improvement. An evaluation of the biological activity and cellular responses in vitro with respect to bone regeneration indicated that the integration of morphological and chemical modifications into Ti6Al4V surfaces induces the osteogenic differentiation of MSCs to improve bone regeneration by an enhancement of mineral matrix formation that accelerates the osseointegration process. Overall, this hybrid system has numerous competitive advantages over more complex treatments, including reproducibility, low production cost, and potential for improved long-term maintenance of the implant.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Detailed Description of the Groups
Figure 1
Figure 1
Conventional implants result in bone resorption, compromising their success implantation outcomes. On the other hand, implants with a modified surface present unique features capable of improving the surface properties of the implant, resulting in the activation of cellular response and long-term maintenance. The programming and responsiveness of bone cells are expected to increase the longevity of the implant, which would improve the patient’s quality of life and reduce healthcare cost burdens by minimizing the need for revision surgeries.
Figure 2
Figure 2
(a) Mineralization values (absorbance read at 550 nm) from 0 to 21 days are shown in a scatter plot, in which the mean of each group is displayed by a cross. (b) Mineralization is displayed for both Ti–O and Ti–OC (left) and both Ti–H and Ti–HC (right) as the mean ± standard error of the mean, and kinetics is displayed on the top of each line (A.U./day, ×103).
Figure 3
Figure 3
(a) Biogenesis of osteoblasts. MSCs are programmed to commit and differentiate into osteoblasts, which express specific osteoblastic markers (highlighted in red), some of which are responsible for extracellular matrix mineralization, consisting of collagen, calcium, and phosphorus. (b) Expression of osteogenic markers during osteogenic differentiation. Values are reported as the mean ± standard error of the mean.
Figure 4
Figure 4
Fibronectin coating reduces variability in mineralization and when combined with hydrothermal treatment, it upregulates the expression of the gene associated with osteogenic differentiation. (a) Variability (standard deviation) in mineralization at different time points of bone marrow-derived human mesenchymal stem cells (MSCs) seeded on Ti6Al4V subjected to different treatments. (b) Relative gene expression levels of hallmarks of osteogenic differentiation in MSCs seeded on Ti6Al4V subjected to different treatments. Gene expression data are presented as fold changes at day 21 relative to the expression level on day 0.

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References

    1. Kraus V. B.; Blanco F. J.; Englund M.; Karsdal M. A.; Lohmander L. S. Call for Standardized Definitions of Osteoarthritis and Risk Stratification for Clinical Trials and Clinical Use. Osteoarthritis Cartilage 2015, 23 (8), 1233–1241. 10.1016/j.joca.2015.03.036. - DOI - PMC - PubMed
    1. Katz J. N.; Arant K. R.; Loeser R. F. Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review. JAMA, J. Am. Med. Assoc. 2021, 325 (6), 568–578. 10.1001/jama.2020.22171. - DOI - PMC - PubMed
    1. Hunter D. J.; Bierma-Zeinstra S. Osteoarthritis. Lancet 2019, 393 (10182), 1745–1759. 10.1016/S0140-6736(19)30417-9. - DOI - PubMed
    1. Apostu D.; Lucaciu O.; Berce C.; Lucaciu D.; Cosma D. Current Methods of Preventing Aseptic Loosening and Improving Osseointegration of Titanium Implants in Cementless Total Hip Arthroplasty: A Review. J. Int. Med. Res. 2018, 46 (6), 2104–2119. 10.1177/0300060517732697. - DOI - PMC - PubMed
    1. Gao X.; Fraulob M.; Haïat G. Biomechanical Behaviours of the Bone-Implant Interface: A Review. J. R. Soc. Interface 2019, 16 (156), 2019025910.1098/rsif.2019.0259. - DOI - PMC - PubMed

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