Solid Free‐Form Fabrication of Tissue‐Engineering Scaffolds with a Poly(lactic‐co‐glycolic acid) Grafted Hyaluronic Acid Conjugate Encapsulating an Intact Bone Morphogenetic Protein–2/Poly(ethylene glycol) Complex |
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Authors: | Jung Kyu Park Jin‐Hyung Shim Kyung Shin Kang Junseok Yeom Ho Sang Jung Jong Young Kim Keum Hong Lee Tae‐Ho Kim Shin‐Yoon Kim Dong‐Woo Cho Sei Kwang Hahn |
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Affiliation: | 1. Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), San 31, Hyoja‐dong, Nam‐gu, Pohang, Kyungbuk 790‐784, Korea;2. Department of Mechanical Engineering and/or Division of Integrative Biosciences and Biotechnology, POSTECH, Korea;3. Department of Mechanical Engineering, Andong National University, 388 Songchun‐dong, Andong, Kyungbuk 760‐749, Korea;4. Kyungpook National University Hospital, Kyungpook National University, 101 Dongin‐dong 2 Ga, Jung‐gu, Daegu, 700‐422, Korea;5. Department of Medicine, School of Medicine, Kyungpook National University, 101 Dongin‐dong 2 Ga, Jung‐gu, Daegu, 700‐422, Korea |
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Abstract: | Despite wide applications of bone morphogenetic protein–2 (BMP‐2), there are few methods to incorporate BPM‐2 within polymeric scaffolds while maintaining biological activity. Solid free‐form fabrication (SFF) of tissue‐engineering scaffold is successfully carried out with poly(lactic‐co‐glycolic acid) grafted hyaluronic acid (HA‐PLGA) encapsulating intact BMP‐2/poly(ethylene glycol) (PEG) complex. HA‐PLGA conjugate is synthesized in dimethyl sulfoxide (DMSO) by the conjugation reaction of adipic acid dihydrazide modified HA (HA‐ADH) and PLGA activated with N,N′‐dicyclohexylcarbodiimide (DCC) and N‐hydroxysuccinimide (NHS). BMP‐2 is complexed with PEG, which is encapsulated within the PLGA domain of the HA‐PLGA conjugate by SFF to prepare tissue‐engineering scaffolds. In vitro release tests confirm the sustained release of intact BMP‐2 from the scaffolds for up to a month. After confirmation of the enhanced osteoblast cell growth, and high gene‐expression levels of alkaline phosphatase (ALP), osteocalcin (OC), and osterix (OSX) in the cells, the HA‐PLGA/PEG/BMP‐2 scaffolds are implanted into calvarial bone defects of Sprague Dawley (SD) rats. Microcomputed tomography (μCT) and histological analyses with Masson's trichrome, and hematoxylin and eosin (H&E) staining reveal effective bone regeneration on the scaffolds of HA‐PLGA/PEG/BMP‐2 blends. |
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Keywords: | conjugates solid free‐form fabrication bone regeneration tissue engineering scaffolds |
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