A biomimetic PEKK implant was developed to promote osteoporotic bone regeneration and delay adjacent bone loss.

Osteoinductivity of a biomaterial scaffold can notably enhance the bone healing performance. In this study, we developed a biomimetic and hierarchically porous polyetherketoneketone (PEKK) scaffold with unique osteoinductivity using a combined surface treatment strategy of a sulfonated process and a nano bone-like apatite deposition. In a beagle intramuscular model, the scaffold induced bone formation ectopically after 12-week implantation. The better bone healing ability of the scaffold than the original PEKK was also confirmed in orthotopic sites. After culturing with bone marrow–derived mesenchymal stem cells (BMSCs), the scaffold induced osteogenic differentiation of BMSCs, and the new bone formation could be mainly depending on cell signaling through adenylate cyclase 9, which activates the cyclic adenosine monophosphate/protein kinase A signaling cascade pathways. The current work reports a new osteoinductive synthetic polymeric scaffold with its detailed molecular mechanism of action for bone repair and regeneration.

Weak osteogenic activity affects the long-term fixation and lifespan of titanium (Ti) implants. Surface modification along with a built-in porous structure is a highly considerable approach to improve the osteoinduction and osseointegration capacity of Ti. Herein, the osteoinduction and osteogenic activities of electrochemically deposited (ED) nanoplate-like, nanorod-like and nanoneedle-like hydroxyapatite (HA) coatings (named EDHA-P, EDHA-R, and EDHA-N, respectively) were evaluated in vitro and in vivo by comparison with those of acid/alkali (AA) treatment. The results revealed that the apatite forming ability of all nanostructured EDHA coatings was excellent, and only 12 h of soaking in SBF was needed to induce a complete layer of apatite. More serum proteins adsorbed on EDHA-P than others. In cellular experiments, different from those on EDHA-R and EDHA-N, the cells on EDHA-P presented a polygonal shape with lamellipodia extension, and thus exhibited a relatively larger spreading area. Furthermore, EDHA-P was more favorable for the enhancement of the proliferation and ALP activity of BMSCs, and the up-regulation of OPN gene expression. Based on the good biological performance in vitro, EDHA-P was selected to further evaluate its osteoinduction and osteogenic activities in vivo by comparison with AA treatment. Interestingly, a greater ability of ectopic osteoinduction was observed in the EDHA-P group compared to that in the AA group. At the osseous site, EDHA-P promoted more bone on/ingrowth, and had a higher area percentage of newly formed bone in the bone–implant interface and inner pores of the implants than in the AA group. Thus, a nanoplate-like HA coating has good potential in improving the osteoinductivity and osteogenic activity of porous Ti implants in clinical applications.

The bio-inertness and inferior osseointegration of polyetheretherketone (PEEK) affect its long-term lifetime in clinical applications, and appropriate surface modification is an effective way to enhance osseointegration of PEEK implants. In the present study, a strategy of combining sulfonation with alkali treatment was proposed to endow PEEK with rapid apatite deposition and thus enhanced bioactivity. After 3 min of sulfonation with 98% H₂SO₄, the sample (PEEK-S-3) showed an optimized surface microporous network and obviously improved hydrophilicity. Its contact angle reduced from the original 106 ± 2.3° to 88 ± 4.0°. After a further 24 h of NaOH treatment on PEEK-S-3, Na element was introduced into the obtained sample (PEEK-Na-24), which had a similar surface morphology and chemical structure with PEEK-S-3 and had a further reduced contact angle (77.9 ± 2.9°). The in vitro bioactivity tests showed that after only 3 days of immersion in simulated body fluid (SBF), PEEK-Na-24 was fully covered with a layer of uniform bone-like apatite. The apatite deposition sharply decreased the contact angle of the sample (PEEK-HA) to 16.6 ± 2.6° and increased its surface roughness to 1.05 ± 0.27 μm, leading to the enhanced adsorption of serum proteins on PEEK-HA. The in vitro cell culture indicated that all the three surface-modified samples (PEEK-S-3, PEEK-Na-24 and PEEK-HA) could promote the adhesion, spreading, proliferation and osteoblastic differentiation of MC3T3-E1 pre-osteoblasts, and PEEK-HA presented the best effect. Thus, the surface bioactive PEEK resulting from the optimized surface modification, i.e. combination of sulfonation, alkali treatment and biomimetic apatite deposition, could have good potential in clinical application.

The control of the inflammatory response induced by the implantation of foreign biomaterials is fundamental in determining tissue healing. It has been shown that the activation of specific macrophage pathways upon contact with a biomaterial can lead either to a chronic inflammation preventing a physiological tissue repair or to an improved tissue healing. In the case of bone repair, calcium phosphate cements with good osteoconductivity properties have been successfully applied in bone defect filling and repair, but poor handling properties, insufficient viscous flow and unmatched degradation rate are still problems that remain unsolved. In this study, a strontium-doped hydroxyapatite (HA) gel was modified by integrating branched poly(epsilon-lysine) dendrons with third-generation branches exposing phosphoserine (SrHA/G3-K PS). The interaction of this material with macrophages was investigated in vitro, focusing on the secretion and gene expression of specific pro-inflammatory cytokines. Our results showed that the addition of strontium and G3-K PS to HA sol–gel could down-regulate the gene expression of inflammatory factors such as IL-1β, TNF-α and MCP-1, while increasing the gene expression of IL-6, a cytokine known for its osteogenic effect. These results were further confirmed by ELISA test of the respective protein concentrations. When exposed to supernatants of macrophage culture in the presence of strontium and G3-K PS, osteoblast viability was promoted with elevated osteogenic gene markers, in terms of OPG, ALP, OCN and COL-I. In vivo implantation experiments using an osteoporotic rat model with bone defect further confirmed that the addition of G3-K PS to HA could dramatically promote new bone regeneration. Although the introduction of strontium improved the degradation properties of the injectable materials, no positive effect on promoting in vivo bone regeneration was observed.

Polyetheretherketone (PEEK) has been widely used in the fields of orthopedics and trauma, but weak osteointegration and bacterial infection affect its long-term stability and repair effects. Surface modification is an effective way to improve the osteogenic and antibacterial activity of PEEK implants. In the present study, a layer of acrylic acid (AA) polymer coating loaded with zinc ions (Zn²⁺) was constructed on the surface of PEEK (PEEK-AA-Zn) using a strategy of combining plasma-induced graft polymerization with a chemical immersion technique. Successful construction of the AA coating remarkably enhanced the hydrophilicity of PEEK, and effectively loaded and released Zn²⁺. In vitro cell culture using MC3T3-E1 preosteoblasts showed that the Zn²⁺ released from PEEK-AA-Zn promoted cell proliferation and elevated gene expression levels of alkaline phosphatase (ALP), osteocalcin (OCN) and bone sialoprotein (BSP). Antibacterial tests revealed that PEEK-AA-Zn efficiently inhibited the proliferation of Staphylococcus aureus (S. aureus). These results suggest that the combined method of graft polymerization and ion incorporation endows PEEK with excellent osteogenic and antibacterial activity, which provides a wide range of possibilities for developing PEEK implants with multifunctional properties for bone tissue repair.