Enhanced Healing of Rat Calvarial Defects with MSCs Loaded on BMP-2 Releasing Chitosan/Alginate/Hydroxyapatite Scaffolds
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{"title"=>"Enhanced healing of rat calvarial defects with MSCs loaded on BMP-2 releasing chitosan/alginate/hydroxyapatite scaffolds", "type"=>"journal", "authors"=>[{"first_name"=>"Xiaoning", "last_name"=>"He", "scopus_author_id"=>"55551342500"}, {"first_name"=>"Yang", "last_name"=>"Liu", "scopus_author_id"=>"57196311516"}, {"first_name"=>"Xue", "last_name"=>"Yuan", "scopus_author_id"=>"55571801300"}, {"first_name"=>"Li", "last_name"=>"Lu", "scopus_author_id"=>"7403963267"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84905403206", "sgr"=>"84905403206", "doi"=>"10.1371/journal.pone.0104061", "pui"=>"373686030", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic) 1932-6203 (Linking)", "pmid"=>"25084008"}, "id"=>"6c628935-e797-3578-bfbb-120b91fd64c0", "abstract"=>"In this study, we designed a chitosan/alginate/hydroxyapatite scaffold as a carrier for recombinant BMP-2 (CAH/B2), and evaluated the release kinetics of BMP-2. We evaluated the effect of the CAH/B2 scaffold on the viability and differentiation of bone marrow mesenchymal stem cells (MSCs) by scanning electron microscopy, MTS, ALP assay, alizarin-red staining and qRT-PCR. Moreover, MSCs were seeded on scaffolds and used in a 8 mm rat calvarial defect model. New bone formation was assessed by radiology, hematoxylin and eosin staining 12 weeks postoperatively. We found the release kinetics of BMP-2 from the CAH/B2 scaffold were delayed compared with those from collagen gel, which is widely used for BMP-2 delivery. The BMP-2 released from the scaffold increased MSC differentiation and did not show any cytotoxicity. MSCs exhibited greater ALP activity as well as stronger calcium mineral deposition, and the bone-related markers Col1α, osteopontin, and osteocalcin were upregulated. Analysis of in vivo bone formation showed that the CAH/B2 scaffold induced more bone formation than other groups. This study demonstrates that CAH/B2 scaffolds might be useful for delivering osteogenic BMP-2 protein and present a promising bone regeneration strategy.", "link"=>"http://www.mendeley.com/research/enhanced-healing-rat-calvarial-defects-mscs-loaded-bmp2-releasing-chitosanalginatehydroxyapatite-sca", "reader_count"=>41, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>8, "Student > Master"=>10, "Other"=>1, "Student > Bachelor"=>6}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>8, "Student > Master"=>10, "Other"=>1, "Student > Bachelor"=>6}, "reader_count_by_subject_area"=>{"Engineering"=>3, "Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>8, "Materials Science"=>2, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>15, "Physics and Astronomy"=>1, "Chemistry"=>3}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>3}, "Materials Science"=>{"Materials Science"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>15}, "Chemistry"=>{"Chemistry"=>3}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Malaysia"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1618122"], "description"=>"<p><b>A.</b> SEM view of CAH/B2 scaffold at a magnification of 100×, <b>B.</b> SEM view of CAH/B2 scaffold at a magnification of 200×. SEM analysis showed that micro-pores were generated in the CAH scaffold, the average pore diameter in the scaffold being 100–110 µm. <b>C.</b> In vitro release behavior of BMP-2 from the CAH scaffold. Col/B2 served as a control. The release velocity of BMP-2 was delayed in the CAH/B2 group compared with release from Col/B2. The cumulative BMP-2 released from the CAH/B2 and the Col/B2 groups almost reached a plateau at 21 and 14 days, respectively. <b>D.</b> SEM view of MSCs cultured on a CAH/B2 scaffold at a magnification of 100×.</p>", "links"=>[], "tags"=>["biotechnology", "Bioengineering", "Tissue engineering", "biomaterials", "cell biology", "Cellular types", "Animal cells", "Bone marrow cells", "Bone marrow stem cells"], "article_id"=>1124352, "categories"=>["Biological Sciences"], "users"=>["Xiaoning He", "Yang Liu", "Xue Yuan", "Li Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0104061.g002", "stats"=>{"downloads"=>3, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Physicochemical_properties_of_CAH_B2_scaffolds_/1124352", "title"=>"Physicochemical properties of CAH/B2 scaffolds.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-08-01 02:45:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1618125"], "description"=>"<p>Coronal sections through the midlines of defects are shown. (A–E): lower magnification, Bar = 1 mm, yellow arrow: new bone formed; (A′–E′): higher magnification, Bar = 0.25 mm. (A, A′): Blank; (B, B′): CAH; (C, C′): CAH+M; (D, D′): CAH/B2+M. (E, E′)Col/B2+M. Blue arrow: new bone, Yellow arrow: host bone, *:interface between new bone and host bone.</p>", "links"=>[], "tags"=>["biotechnology", "Bioengineering", "Tissue engineering", "biomaterials", "cell biology", "Cellular types", "Animal cells", "Bone marrow cells", "Bone marrow stem cells"], "article_id"=>1124355, "categories"=>["Biological Sciences"], "users"=>["Xiaoning He", "Yang Liu", "Xue Yuan", "Li Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0104061.g005", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histology_analysis_/1124355", "title"=>"Histology analysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-08-01 02:45:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1618124"], "description"=>"<p>A. Image of calvarial bone from the LUNAR PIXImus system, 12 weeks after surgery. The areas of bone regeneration were labeled in different colors. A black area circled with a blue line (*) is a low density area. The dark gray area between inside blue line and inside yellow line (#) is an area of thin bone, the area between two yellow lines(▵) is considered an area of normal bone density, and the density in this area is close to that of normal bone tissue. B. Quantitative analysis of bone density. N =  6, *p<0.05:CAH/B2+M versus four other groups. • p<0.05: CAH+M versus CAH or blank. ♦p<0.05: CAH versus blank. C. Quantitative analysis of bone area in implanted region showed a significantly larger bone area within the CAH/B2+M group when compared with the other four groups. BV, bone area in the implant; TV, total implant area. N = 6, *p<0.05:CAH/B2+M versus four other groups. •p<0.05: CAH+M versus CAH or blank. ♦p<0.05: CAH versus blank.</p>", "links"=>[], "tags"=>["biotechnology", "Bioengineering", "Tissue engineering", "biomaterials", "cell biology", "Cellular types", "Animal cells", "Bone marrow cells", "Bone marrow stem cells", "scaffolds", "regeneration", "critical-sized", "calvarial", "defect"], "article_id"=>1124354, "categories"=>["Biological Sciences"], "users"=>["Xiaoning He", "Yang Liu", "Xue Yuan", "Li Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0104061.g004", "stats"=>{"downloads"=>2, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CAH_B2_scaffolds_enhance_bone_regeneration_in_the_rat_critical_sized_calvarial_defect_model_/1124354", "title"=>"CAH/B2 scaffolds enhance bone regeneration in the rat critical-sized calvarial defect model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-08-01 02:45:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1618126"], "description"=>"<p>Primer sequences of osteogenic markers.</p>", "links"=>[], "tags"=>["biotechnology", "Bioengineering", "Tissue engineering", "biomaterials", "cell biology", "Cellular types", "Animal cells", "Bone marrow cells", "Bone marrow stem cells", "sequences", "osteogenic"], "article_id"=>1124356, "categories"=>["Biological Sciences"], "users"=>["Xiaoning He", "Yang Liu", "Xue Yuan", "Li Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0104061.t001", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Primer_sequences_of_osteogenic_markers_/1124356", "title"=>"Primer sequences of osteogenic markers.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-08-01 02:45:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1618123"], "description"=>"<p><b>A.</b> MTS assay of MSCs cultured with CAH and CAH/B2 scaffolds. The cells were also cultured in plates as a control. Data represent the mean+SD of n = 5 samples. No statistically significant differences were seen between groups. <b>B.</b> Effects of CAH/B2 on in vitro ALP activity. ALP activity in the CAH/B2 group was higher than in the CAH group. One-way analyses of variance suggest that there are significant differences among three groups. The significant post hoc test results are identified by symbol *. N = 5. P<0.001: CAH vs. CAH/B2. <b>C.</b> The level of calcium deposition in 3-week cultures was evaluated by AR-S. The values indicated are means ± SD, (n = 5) p<0.005 as compared with that deposition in the CAH group. <b>D.</b> qRT-PCR analysis of osteoblast marker genes, showing that MSCs cultured on a CAH/B2 scaffold exhibited increased Col I, OCN and OPN gene expression. Data represent the mean + SD of n = 5 samples. P<0.05.</p>", "links"=>[], "tags"=>["biotechnology", "Bioengineering", "Tissue engineering", "biomaterials", "cell biology", "Cellular types", "Animal cells", "Bone marrow cells", "Bone marrow stem cells", "scaffold", "osteoblastic"], "article_id"=>1124353, "categories"=>["Biological Sciences"], "users"=>["Xiaoning He", "Yang Liu", "Xue Yuan", "Li Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0104061.g003", "stats"=>{"downloads"=>2, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Biocompatibility_and_effects_of_the_CAH_B2_scaffold_on_osteoblastic_differentiation_/1124353", "title"=>"Biocompatibility and effects of the CAH/B2 scaffold on osteoblastic differentiation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-08-01 02:45:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/1618121"], "description"=>"<p><b>A.</b> EDX analysis of CAH specimen. B. XRD pattern of CAH specimen.</p>", "links"=>[], "tags"=>["biotechnology", "Bioengineering", "Tissue engineering", "biomaterials", "cell biology", "Cellular types", "Animal cells", "Bone marrow cells", "Bone marrow stem cells"], "article_id"=>1124351, "categories"=>["Biological Sciences"], "users"=>["Xiaoning He", "Yang Liu", "Xue Yuan", "Li Lu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0104061.g001", "stats"=>{"downloads"=>2, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characterization_of_CAH_B2_scaffolds_/1124351", "title"=>"Characterization of CAH/B2 scaffolds.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-08-01 02:45:31"}

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