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Effect of 3D Printing Temperature on Bioactivity of Bone Morphogenetic Protein-2 Released from Polymeric Constructs

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Abstract

Growth factors such as bone morphogenetic protein-2 (BMP-2) are potent tools for tissue engineering. Three-dimensional (3D) printing offers a potential strategy for delivery of BMP-2 from polymeric constructs; however, these biomolecules are sensitive to inactivation by the elevated temperatures commonly employed during extrusion-based 3D printing. Therefore, we aimed to correlate printing temperature to the bioactivity of BMP-2 released from 3D printed constructs composed of a model polymer, poly(propylene fumarate). Following encapsulation of BMP-2 in poly(dl-lactic-co-glycolic acid) particles, growth factor-loaded fibers were fabricated at three different printing temperatures. Resulting constructs underwent 28 days of aqueous degradation for collection of released BMP-2. Supernatants were then assayed for the presence of bioactive BMP-2 using a cellular assay for alkaline phosphatase activity. Cumulative release profiles indicated that BMP-2 released from constructs that were 3D printed at physiologic and intermediate temperatures exhibited comparable total amounts of bioactive BMP-2 release as those encapsulated in non-printed particulate delivery vehicles. Meanwhile, the elevated printing temperature of 90 °C resulted in a decreased amount of total bioactive BMP-2 release from the fibers. These findings elucidate the effects of elevated printing temperatures on BMP-2 bioactivity during extrusion-based 3D printing, and enlighten polymeric material selection for 3D printing with growth factors.

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Acknowledgments

This work was supported by the National Institutes of Health (Grant P41 EB023833). G.L.K. is supported by the Robert and Janice McNair Foundation MD/PhD Student Scholar Program. M.D. is supported by a Rubicon postdoctoral fellowship from the Dutch Research Council (NWO; Project No. 019.182EN.004). The authors gratefully acknowledge Anthony J. Melchiorri and Yu Seon Kim for their guidance on polymer synthesis, and Luis Diaz-Gomez for his input on 3D printing.

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Authors and Affiliations

  1. Department of Bioengineering, Rice University, Houston, TX, USA

    Gerry L. Koons, Mani Diba, Letitia K. Chim & Antonios G. Mikos

  2. Center for Engineering Complex Tissues, Houston, TX, USA

    Gerry L. Koons & Antonios G. Mikos

  3. Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA

    Gerry L. Koons

  4. Department of Biochemistry and Cell Biology, Rice University, Houston, TX, USA

    Panayiotis D. Kontoyiannis

  5. Department of Statistics, Rice University, Houston, TX, USA

    David W. Scott

  6. BioScience Research Collaborative, Department of Bioengineering, Rice University, MS-142, 6500 Main Street, Houston, TX, 77030, USA

    Antonios G. Mikos

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  1. Gerry L. Koons
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Correspondence to Antonios G. Mikos.

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Koons, G.L., Kontoyiannis, P.D., Diba, M. et al. Effect of 3D Printing Temperature on Bioactivity of Bone Morphogenetic Protein-2 Released from Polymeric Constructs. Ann Biomed Eng 49, 2114–2125 (2021). https://doi.org/10.1007/s10439-021-02736-9

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