Multifunctional Surface with Enhanced Angiogenesis for Improving Long-Term Osteogenic Fixation of Poly(ether ether ketone) Implants

Abstract

Poly(ether ether ketone) (PEEK) is a biocompatible polymer, but the lack of angiogenesis makes the long-term osteogenic fixation of PEEK implants challenging, which has hampered their wider application in orthopedics. Herein, we develop a multifunctional micro-/nanostructured surface presenting hydroxyapatite (HA) nanoflowers and nickel hydroxide (Ni(OH) 2 ) nanoparticles on PEEK implants (sPEEK-Ni-HA) to tackle the problem. The results show that the reasonable release of Ni 2+ from sPEEK-Ni-HA significantly facilitates the migration, tube formation, and angiogenic gene expression of human umbilical vein endothelial cells (HUVECs). In addition to angiogenesis, the sPEEK-Ni-HA displays enhanced cytocompatibility and osteogenicity in terms of cell proliferation, spreading, alkaline phosphatase activity, matrix mineralization, and osteogenesis-related gene secretion, exceeding pure and other multifunctional sPEEK samples. Importantly, in vivo evaluations employing a rabbit femoral condyle implantation model confirm that such dual decoration of Ni elements and HA nanoflowers boosts bone remodeling/osseointegration, which dramatically promotes the in vivo osteogenic fixation of implants. Therefore, this work not only sheds light on the significance of angiogenesis on the osteogenic fixation of an implant but also presents a facile strategy to empower bioinert PEEK with a well-orchestrated feature of angiogenesis and osteogenesis.

<p>Impacts of a Nano-Laponite Ceramic on Surface Performance, Apatite Mineralization, Cell Response, and Osseointegration of a Polyimide-Based Biocomposite</p>

“…38 Surface characteristics (eg, chemical composition, roughness, hydrophilicity, and ion release) of biomaterials greatly influence osteoblast responses (adhesion, proliferation, and osteogenic differentiation) and NB formation around the implants, both in vitro and in vivo. 39,40 In the present study, compared with PI and LPC20, LPC40 containing higher LC content with improved surface properties (eg, roughness and hydrophilicity) not only stimulated osteoblast responses in vitro but also promoted NB formation in vivo. Previous studies have revealed that dissolution products containing Si, Mg, and Li ions from bioactive ceramics/glasses stimulated osteoblast proliferation and osteogenic differentiation.…”

Bioinspired Modifications of PEEK Implants for Bone Tissue Engineering

“…Subsequent studies attempted to develop bioactive PEEK composites by adding HA, nHA, or ion-substituted HA to PEEK (Wong et al, 2009;Deng et al, 2015b;Liu et al, 2016;Ma and Guo, 2019;Bastan, 2020;Dong et al, 2020). For instance, the addition of strontium-containing HA not only improved the bending modulus of PEEK, it also enhanced apatite formation in SBF and cell-mediated mineralization in vitro (Wong et al, 2009).…”

Simultaneous Regeneration of Bone and Nerves Through Materials and Architectural Design: Are We There Yet?

“…For example, introduction of HAp nanoflowers and nickel hydroxide nanoparticles into a polyether ether ketone scaffold enables reasonable release of Ni 2+ and Ca 2+ for simultaneous bone regeneration and angiogenesis ( Figure 12C). [328] Scaffolds with Structural and Functional Heterogeneity: Such a design establishes different structural and functional niches within a scaffold to provide cues that cater for the demands of bone and nerve regeneration within the respective regions. As an analogous example, simultaneous osteogenesis and angiogenesis has been contemplated using a dual-modular design that provides pockets for bone regeneration (module I: mesoporous bioactive glass with hierarchical porous structures and osteogenic rhBMP-2) and blood vessel regeneration (module II: gelatin methacryloyl hydrogel columns and angiogenic VEGF) ( Figure 12E).…”

“…For example, introduction of HAp nanoflowers and nickel hydroxide nanoparticles into a polyether ether ketone scaffold enables reasonable release of Ni 2+ and Ca 2+ for simultaneous bone regeneration and angiogenesis (Figure 12C). [ 328 ]…”