A micro/nano-biomimetic coating on titanium orchestrates osteo/angio-genesis and osteoimmunomodulation for advanced osseointegration.

Metallic biomaterials are widely used in implants to strengthen, repair, or replace damaged bone tissue, and their material characteristics have direct influences on short- and long-term implant performance. Of these, titanium and its alloys are the most widely applied due to their superior corrosion resistance, biocompatibility, and mechanical properties, such as in joint replacements, dental implants, and spinal fusion cages. However, Ti and Ti alloys are bioinert materials that have difficulty in binding directly to bone tissue after implantation, due to a lack of osteoconductive and osteoinductive properties. Bacterial adhesion and colonisation at the implantation site may also lead to infection-associated complications. The surface of the titanium implant directly interfaces with blood, cells, and tissues in vivo, and the surface properties can have profound influences on protein- and cell-based interactions that then promote or impede osseointegration. Therefore, the material surface morphology, chemistry and antibacterial function are key parameters in implant design, and contribute to determining the long-term success of the implant. In this review, we systematically present the latest advances in surface modification techniques for orthopaedic implants, including mechanical, physical, chemical, and biological modification. We also analyse and compare different surface modification approaches, including drug loading, metallic element doping, and bionic coatings, as well as topographical modifications such as nanotubes, nanopores and nanowires. Finally, we present a critical analysis and future perspectives on the use of surface modifications to improve the osseointegration and antibacterial properties of orthopaedic implants.

/pdf/advances-in-implant-surface-modifications-to-improve-3ejicpqp1v.pdf

Advances in implant surface modifications to improve osseointegration

Type I collagen decorated nanoporous network on titanium implant surface promotes osseointegration through mediating immunomodulation, angiogenesis, and osteogenesis.

Advanced surface engineering of titanium materials for biomedical applications: From static modification to dynamic responsive regulation.

The interplay between hemostasis and immune response in biomaterial development for osteogenesis

Blood coagulation and inflammation are the earliest biological responses to implant surfaces. Implant nano-surfaces can significantly impact the osseointegration through the influence on the early phase of bone regeneration. However, the interplay between blood clot property and inflammatory reaction on nanosurfaces is rarely understood. Herein, titania nanotube arrays (TNAs) with different diameters are fabricated on titanium. In vitro evaluation with the whole blood indicates that TNA with a diameter of 15 nm (TNA 15) enables noteworthy platelet activation resulting in distinct clot features compared with that of pure Ti and TNA with a diameter of 120 nm (TNA 120). Further co-culture with macrophages on the clot or in the clot-conditioned medium shows that the clot on TNA 15 downregulates the inflammation and manipulates a favorable osteoimmunomodulatory environment for osteogenesis. In vivo studies further demonstrate that TNA 15 could downregulate the inflammation-related genes while upregulating growth metabolism-related genes in an early healing hematoma. Additionally, TNA 15 promotes de novo bone formation with improved extending of osteocyte dendrites, demonstrating the desired osseointegration. These findings indicate that surface nano-dimensions can significantly influence clot formation and appropriate clot features can manipulate a favorable osteoimmunomodulatory environment for bone regeneration and osseointegration.

Targeting Early Healing Phase with Titania Nanotube Arrays on Tunable Diameters to Accelerate Bone Regeneration and Osseointegration

Implant surfaces with a nanoscaled pattern can dominate the blood coagulation process resulting in a defined clot structure and its degradation behavior, which in turn influence cellular response and the early phase of osseointegration. Long non-coding (Lnc) RNAs are known to regulate many biological processes in the skeletal system; however, the link between the LncRNA derived from the cells within the clot and osseointegration has not been investigated to date. Hence, the sequence analysis of LncRNAs expressed within the clot formed on titania nanotube arrays (TNAs) with distinct nano-scaled diameters (TNA 15 of 15 nm, TNA 60 of 60 nm, TNA 120 of 120 nm) on titanium surfaces was profiled for the first time. LncRNA LOC103346307, LOC103352121, LOC108175175, LOC103348180, LOC108176660, and LOC108176465 were identified as the pivotal players in the early formed clot on the nano-scaled surfaces. Further bioinformatic prediction results were used to generate co-expression networks of LncRNAs and mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that distinct nano-scaled surfaces could regulate the biological functions of target mRNAs in the clot. LOC103346307, LOC108175175, and LOC108176660 upregulated mRNAs related to cell metabolism and Wnt, TGF-beta, and VEGF signaling pathways in TNA 15 compared with P-Ti, TNA 60, and TNA 120, respectively, whereas LOC103352121, LOC103348180, and LOC108176465 downregulated mRNAs related to bone resorption and inflammation through negatively regulating osteoclast differentiation, TNF, and NF-kappa signaling pathways. The results indicated that surface nano-scaled characteristics can significantly influence the clot-derived LncRNAs expression profile, which affects osseointegration through multiple signaling pathways of the targeted mRNAs, thus paving a way for better interpreting the link between the properties of a blood clot formed on the nano-surface and de novo bone formation.

https://www.mdpi.com/2079-4991/11/3/674/pdf

Correlation between LncRNA Profiles in the Blood Clot Formed on Nano-Scaled Implant Surfaces and Osseointegration.

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A micro/nano-biomimetic coating on titanium orchestrates osteo/angio-genesis and osteoimmunomodulation for advanced osseointegration.

Targeting Early Healing Phase with Titania Nanotube Arrays on Tunable Diameters to Accelerate Bone Regeneration and Osseointegration

Correlation between LncRNA Profiles in the Blood Clot Formed on Nano-Scaled Implant Surfaces and Osseointegration.