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International Journal of Bioprinting                                  Proteins-loaded 3D-printed PEEK cage




            However, some of the PEEK substrates were damaged due   5. Conclusion
            to surgical forces applied during the procedure.
                                                               In  this  study, we  designed  and fabricated  a  3D-printed
            4. Discussion                                      PEEK intervertebral fusion device via FDM. To improve
                                                               its fusion effect, we sequentially sulfonated the structure,
            Intervertebral disc degeneration (IDD) refers to a group   loaded it with BMP2, and grafted SP on the structure.
            of conditions that involve the gradual breakdown or   After the fusion device is implanted, SP is initially released,
            deterioration of structures in the lumbar spine.  It is   recruiting MSCs to the implant surface from surrounding
                                                     32
            often associated with aging and wear and tear on the   tissues. As the Gel/Chi multilayer films degrade, BMP2
            spine. 1,2,33  IDD can affect various components of the   is gradually released, further promoting osteogenic
            spine, leading to symptoms such as pain, stiffness, and   differentiation of MSCs. The in vivo results revealed that
            limited mobility.  In severe cases, surgical interventions,   S-P-BMP2/LBL and S-P-BMP2/LBL-SP exhibited superior
                         34
            such  as  discectomy,  spinal  fusion,  and  artificial  disc   fusion effects, particularly attributable to the strategy
            replacement, may be considered. 6,35  Spinal fusion with   of recruiting MSCs before osteogenic differentiation.
            an interbody cage is a commonly adopted clinical   This work presents a novel approach for designing and
            procedure. Currently, most interbody cages are made of   preparing PEEK intervertebral fusion devices with
            Ti alloy or PEEK.                                  excellent fusion effects.
               Polyetheretherketone (PEEK) is known for its excellent
            mechanical, thermal, and chemical properties, making   Acknowledgments
            it suitable for various applications across medical and   None.
            other industries. 36,37  However, PEEK interbody cages
            face limitations in processability, bioinertness, and   Funding
            radiolucency.  Hence, FDM 3D printing is a feasible
                      38
            method for fabricating PEEK interbody cages with   This work was supported by the Sichuan Provincial
            complex geometries.                                Department of Science and Technology (grant number:
                            39
                                                               2023ZYD0072).
               As  displayed  in  Figure  3B,  3D-printed  PEEK  cages
            exhibit a prominent rough striped surface structure   Conflict of interest
            attributed to the melting and cooling time. The rough
            surface of PEEK is beneficial for the stability of implanted   The authors declare no conflicts of interest.
            cages. To accelerate the fusion of PEEK cages, BMP2
            and SP were incorporated into the structure. BMP2 was   Author contributions
            loaded into the porous network structures formed from   Conceptualization: Feng Zheng, Haibin Lin
            sulfonation, and the structure was then sealed with Gel/Chi   Methodology: Feng Zheng, Haibin Lin
            multilayer films. SP is a peptide with a chain of 11 amino   Formal analysis: Xiaoqiang Gao, Sheng Chai
            acid residues, serving as a chemoattractant and activator   Investigation: Xiaoqiang Gao, Sheng Chai
            for macrophages, lymphocytes, and stem cells. 26,40  SP is   Project administration: Feng Zheng, Haibin Lin
            capable of restoring the cellular potential of senescent stem   Supervision: Huan Liu
            cells by possibly modulating the expression of paracrine   Visualization: Feng Zheng, Huan Liu
            factors from MSCs, which could accelerate MSC‐mediated   Writing - Original Draft: Feng Zheng, Xiaoqiang Gao,
            tissue repair. 41,42  
                                                                  Sheng Chai
               To retain the bioactivity of SP, we grafted SP on the   Writing - Review & Editing: Huan Liu
            outermost Chi layer via Schiff base reaction. All groups   All authors read and approved the final manuscript.
            reported good cytoactivity, except for the sulfonation
            group. When the modified PEEK cage is implanted    Ethics approval and consent to participate
            into  the  body,  SP  would  be  released  first  to  recruit   All animal experiments were approved by the Experimental
            MSCs to the implant (Figure 4). Subsequently, BMP2   Animal Ethics Committee of Southwest Medical University
            is released slowly (Figure 4A) to promote osteogenic   (20230228-013).
            differentiation of MSCs (Figures 5 and 6). Results from
            micro-CT and the push-out test validated the fusion   Consent for publication
            effects of BMP2-loaded PEEK cages, particularly in the
            S-P-BMP2/LBL-SP group.                             Not applicable.



            Volume 10 Issue 5 (2024)                       304                                doi: 10.36922/ijb.3574
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