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Polymers 2018, 10(6), 620; https://doi.org/10.3390/polym10060620

Gelatin/Nanohyroxyapatite Cryogel Embedded Poly(lactic-co-glycolic Acid)/Nanohydroxyapatite Microsphere Hybrid Scaffolds for Simultaneous Bone Regeneration and Load-Bearing

1
Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan
2
Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Keelung 20401, Taiwan
3
Department of Plastic and Reconstructive Surgery and Craniofacial Research Center, Chang Gung Memorial Hospital, Kwei-San, Taoyuan 33305, Taiwan
4
Research Center for Food and Cosmetic Safety, Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kwei-San, Taoyuan 33302, Taiwan
5
Department of Materials Engineering, Ming Chi University of Technology, Tai-Shan, New Taipei City 24301, Taiwan
These authors contributed equally to this paper.
*
Author to whom correspondence should be addressed.
Received: 14 May 2018 / Revised: 1 June 2018 / Accepted: 2 June 2018 / Published: 5 June 2018
(This article belongs to the Special Issue Polymer Scaffolds for Biomedical Application)
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Abstract

It is desirable to combine load-bearing and bone regeneration capabilities in a single bone tissue engineering scaffold. For this purpose, we developed a high strength hybrid scaffold using a sintered poly(lactic-co-glycolic acid) (PLGA)/nanohydroxyapatite (nHAP) microsphere cavity fitted with gelatin/nHAP cryogel disks in the center. Osteo-conductive/osteo-inductive nHAP was incorporated in 250–500 μm PLGA microspheres at 40% (w/w) as the base matrix for the high strength cavity-shaped microsphere scaffold, while 20% (w/w) nHAP was incorporated into gelatin cryogels as an embedded core for bone regeneration purposes. The physico-chemical properties of the microsphere, cryogel, and hybrid scaffolds were characterized in detail. The ultimate stress and Young’s modulus of the hybrid scaffold showed 25- and 21-fold increases from the cryogel scaffold. In vitro studies using rabbit bone marrow-derived stem cells (rBMSCs) in cryogel and hybrid scaffolds through DNA content, alkaline phosphatase activity, and mineral deposition by SEM/EDS, showed the prominence of both scaffolds in cell proliferation and osteogenic differentiation of rBMSCs in a normal medium. Calcium contents analysis, immunofluorescent staining of collagen I (COL I), and osteocalcin (OCN) and relative mRNA expression of COL I, OCN and osteopontin (OPN) confirmed in vitro differentiation of rBMSCs in the hybrid scaffold toward the bone lineage. From compression testing, the cell/hybrid scaffold construct showed a 1.93 times increase of Young’s modulus from day 14 to day 28, due to mineral deposition. The relative mRNA expression of osteogenic marker genes COL I, OCN, and OPN showed 5.5, 18.7, and 7.2 folds increase from day 14 to day 28, respectively, confirming bone regeneration. From animal studies, the rBMSCs-seeded hybrid constructs could repair mid-diaphyseal tibia defects in rabbits, as evaluated by micro-computed tomography (μ-CT) and histological analyses. The hybrid scaffold will be useful for bone regeneration in load-bearing areas. View Full-Text
Keywords: poly(lactic-co-glycolic acid); nanohydroxyapatite; cryogel; microsphere; hybrid scaffold; bone tissue engineering; gelatin poly(lactic-co-glycolic acid); nanohydroxyapatite; cryogel; microsphere; hybrid scaffold; bone tissue engineering; gelatin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Shalumon, K.T.; Kuo, C.-Y.; Wong, C.-B.; Chien, Y.-M.; Chen, H.-A.; Chen, J.-P. Gelatin/Nanohyroxyapatite Cryogel Embedded Poly(lactic-co-glycolic Acid)/Nanohydroxyapatite Microsphere Hybrid Scaffolds for Simultaneous Bone Regeneration and Load-Bearing. Polymers 2018, 10, 620.

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