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Three-dimensional kagome structures in a PCL/HA-based hydrogel scaffold to lead slow BMP-2 release for effective bone regeneration

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Abstract

Osteoconductive function is remarkably low in bone disease in the absence of bone tissue surrounding the grafting site, or if the bone tissue is in poor condition. Thus, an effective bone graft in terms of both osteoconductivity and osteoinductivity is required for clinical therapy. Recently, the three-dimensional (3D) kagome structure has been shown to be advantageous for bone tissue regeneration due to its mechanical properties. In this study, a polycaprolactone (PCL) kagome-structure scaffold containing a hyaluronic acid (HA)-based hydrogel was fabricated using a 3D printing technique. The retention capacity of the hydrogel in the scaffold was assessed in vivo with a rat calvaria subcutaneous model for 3 weeks, and the results were compared with those obtained with conventional 3D-printed PCL grid-structure scaffolds containing HA-based hydrogel and bulk-type HA-based hydrogel. The retained hydrogel in the kagome-structure scaffold was further evaluated by in vivo imaging system analysis. To further reinforce the osteoinductivity of the kagome-structure scaffold, a PCL kagome-structure scaffold with bone morphogenetic protein-2 (BMP-2) containing HA hydrogel was fabricated and implanted in a calvarial defect model of rabbits for 16 weeks. The bone regeneration characteristics were evaluated with hematoxylin and eosin (H&E), Masson’s trichrome staining, and micro-CT image analysis.

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Acknowledgements

This research was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), the Ministry of Health & Welfare, Republic of Korea (Grant Number: HI14C2143), and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MIST) (NRF-2021R1A2C2009665). We thank the Laboratory of Animal Research core facility at the ConveRgence mEDIcine research cenTer (CREDIT), Asan Medical Center for support and instrumentation.

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  1. Se-Hwan Lee and Kang-Gon Lee have contributed equally to this work.

Authors and Affiliations

  1. McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, 36th Street and Hamilton Walk, Philadelphia, PA, 19104, USA

    Se-Hwan Lee & Su-** Heo

  2. Department of Biomedical Sciences, College of Medicine, Korea University, 73, Goryeodae-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea

    Kang-Gon Lee, Jaeyeon Lee & Yongdoo Park

  3. Medical Device Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI hub), 80, Cheombok-ro, Dong-gu, Daegu, 41061, Republic of Korea

    Yong Sang Cho

  4. Department of Mechanical Engineering, College of Engineering, Wonkwang University, 460, Iksan-daero, Iksan, 54538, Republic of Korea

    Min-Soo Ghim

  5. Biomedical Engineering Research Center, Asan Institute for Life Sciences, Asan Medical Center, 88, Olympic-ro, Songpa-gu, Seoul, 05505, Republic of Korea

    Soo** Kim & Bu-Kyu Lee

  6. Department of Mechanical Design Engineering, College of Engineering, Wonkwang University, 460, Iksan-daero, Iksan, 54538, Republic of Korea

    Young-Sam Cho

  7. MECHABIO Group, Wonkwang University, 460, Iksan-daero, Iksan, 54538, Republic of Korea

    Young-Sam Cho

  8. Department of Oral and Maxillofacial Surgery, Asan Institute for Life Sciences, Asan Medical Center, 88, Olympic-ro, Songpa-gu, Seoul, 05505, Republic of Korea

    Bu-Kyu Lee

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  1. Se-Hwan Lee
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Contributions

SHL, KGL, JL, YP, YSC, and BKL contributed to conceptualization; SHL, KGL, and JL contributed to writing-original draft preparation and visualization; JL and KGL contributed to synthesis of HA-hydrogel system; SHL, YSC, and MSG contributed to 3D printing; KGL and SK contributed to animal experiment; SHL, KGL, and JL contributed to analysis of experimental results; SHL, KGL, SJH, YP, YSC, and BKL contributed to review and editing; and YP, YSC, and BKL contributed to supervision and funding acquisition. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Yongdoo Park, Young-Sam Cho or Bu-Kyu Lee.

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IACUC approve numbers: 2017-12-002 and 2017-12-068. All institutional and national guidelines for the care and use of laboratory animals were followed.

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Lee, SH., Lee, KG., Lee, J. et al. Three-dimensional kagome structures in a PCL/HA-based hydrogel scaffold to lead slow BMP-2 release for effective bone regeneration. Bio-des. Manuf. 6, 12–25 (2023). https://doi.org/10.1007/s42242-022-00219-x

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