Bacterial cellulose membrane functionalized with hydroxiapatite and anti-bone morphogenetic protein 2: A promising material for bone regeneration

Bone tissue engineering seeks to adequately restore functions related to physical and biological properties, aiming at a repair process similar to natural bone. The use of compatible biopolymers, such as bacterial cellulose (BC), as well as having interesting mechanical characteristics, presents a s...

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Veröffentlicht in:PloS one 2019-08, Vol.14 (8), p.e0221286
Hauptverfasser: Coelho, Fernanda, Cavicchioli, Maurício, Specian, Sybele Saska, Scarel-Caminaga, Raquel Mantuaneli, Penteado, Letícia de Aquino, Medeiros, Alexandra Ivo de, Ribeiro, Sidney José de Lima, Capote, Ticiana Sidorenko de Oliveira
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container_start_page e0221286
container_title PloS one
container_volume 14
creator Coelho, Fernanda
Cavicchioli, Maurício
Specian, Sybele Saska
Scarel-Caminaga, Raquel Mantuaneli
Penteado, Letícia de Aquino
Medeiros, Alexandra Ivo de
Ribeiro, Sidney José de Lima
Capote, Ticiana Sidorenko de Oliveira
description Bone tissue engineering seeks to adequately restore functions related to physical and biological properties, aiming at a repair process similar to natural bone. The use of compatible biopolymers, such as bacterial cellulose (BC), as well as having interesting mechanical characteristics, presents a slow in vivo degradation rate, and the ability to be chemically modified. To promote better bioactivity towards BC, we synthesized an innovative BC membrane associated to hydroxyapatite (HA) and anti-bone morphogenetic protein antibody (anti-BMP-2) (BC-HA-anti-BMP-2). We present the physical-chemical, biological and toxicological characterization of BC-HA-anti-BMP-2. Presence of BC and HA components in the membranes was confirmed by SEM-EDS and FTIR assays. No toxic potential was found in MC3T3-E1 cells by cytotoxicity assays (XTT Assay and Clonogenic Survival), genotoxicity (Comet Assay) and mutagenicity (Cytokinesis-blocked micronucleus Test). The in vitro release kinetics of anti-BMP-2 antibodies detected gradually reducing antibody levels, reducing approximately 70% in 7 days and 90% in 14 days. BC-HA-anti-BMP-2 increased SPP1, BGLAP, VEGF, ALPL, RUNX2 and TNFRSF11B expression, genes involved in bone repair and also increased mineralization nodules and phosphatase alcalin (ALP) activity levels. In conclusion, we developed BC-HA-anti-BMP-2 as an innovative and promising biomaterial with interesting physical-chemical and biological properties which may be a good alternative to treatment with commercial BMP-2 protein.
doi_str_mv 10.1371/journal.pone.0221286
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BC-HA-anti-BMP-2 increased SPP1, BGLAP, VEGF, ALPL, RUNX2 and TNFRSF11B expression, genes involved in bone repair and also increased mineralization nodules and phosphatase alcalin (ALP) activity levels. 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drug effects</topic><topic>Cell Line</topic><topic>Cell survival</topic><topic>Cellulose</topic><topic>Cellulose - chemistry</topic><topic>Cellulose - pharmacology</topic><topic>Chemistry</topic><topic>Comet assay</topic><topic>Cytokinesis</topic><topic>Cytotoxicity</topic><topic>Damage detection</topic><topic>Dentistry</topic><topic>Durapatite - chemistry</topic><topic>Durapatite - pharmacology</topic><topic>Endothelial growth factors</topic><topic>Engineering and Technology</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genotoxicity</topic><topic>Gluconacetobacter xylinus - chemistry</topic><topic>Health aspects</topic><topic>Hydroxyapatite</topic><topic>Hydroxyapatites</topic><topic>In vitro methods and tests</topic><topic>In vivo methods and tests</topic><topic>Inorganic chemistry</topic><topic>Kinetics</topic><topic>Materials</topic><topic>Materials Testing</topic><topic>Mechanical properties</topic><topic>Medical research</topic><topic>Medicine and Health Sciences</topic><topic>Membranes</topic><topic>Methods</topic><topic>Mice</topic><topic>Mineralization</topic><topic>Morphology</topic><topic>Mutagenicity</topic><topic>Nanocomposites</topic><topic>Nodules</topic><topic>Organic chemistry</topic><topic>Osteoblasts</topic><topic>Osteogenesis - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Coelho, Fernanda</au><au>Cavicchioli, Maurício</au><au>Specian, Sybele Saska</au><au>Scarel-Caminaga, Raquel Mantuaneli</au><au>Penteado, Letícia de Aquino</au><au>Medeiros, Alexandra Ivo de</au><au>Ribeiro, Sidney José de Lima</au><au>Capote, Ticiana Sidorenko de Oliveira</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bacterial cellulose membrane functionalized with hydroxiapatite and anti-bone morphogenetic protein 2: A promising material for bone regeneration</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-08-19</date><risdate>2019</risdate><volume>14</volume><issue>8</issue><spage>e0221286</spage><pages>e0221286-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Bone tissue engineering seeks to adequately restore functions related to physical and biological properties, aiming at a repair process similar to natural bone. The use of compatible biopolymers, such as bacterial cellulose (BC), as well as having interesting mechanical characteristics, presents a slow in vivo degradation rate, and the ability to be chemically modified. To promote better bioactivity towards BC, we synthesized an innovative BC membrane associated to hydroxyapatite (HA) and anti-bone morphogenetic protein antibody (anti-BMP-2) (BC-HA-anti-BMP-2). We present the physical-chemical, biological and toxicological characterization of BC-HA-anti-BMP-2. Presence of BC and HA components in the membranes was confirmed by SEM-EDS and FTIR assays. No toxic potential was found in MC3T3-E1 cells by cytotoxicity assays (XTT Assay and Clonogenic Survival), genotoxicity (Comet Assay) and mutagenicity (Cytokinesis-blocked micronucleus Test). The in vitro release kinetics of anti-BMP-2 antibodies detected gradually reducing antibody levels, reducing approximately 70% in 7 days and 90% in 14 days. BC-HA-anti-BMP-2 increased SPP1, BGLAP, VEGF, ALPL, RUNX2 and TNFRSF11B expression, genes involved in bone repair and also increased mineralization nodules and phosphatase alcalin (ALP) activity levels. In conclusion, we developed BC-HA-anti-BMP-2 as an innovative and promising biomaterial with interesting physical-chemical and biological properties which may be a good alternative to treatment with commercial BMP-2 protein.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31425530</pmid><doi>10.1371/journal.pone.0221286</doi><tpages>e0221286</tpages><orcidid>https://orcid.org/0000-0001-5794-4174</orcidid><oa>free_for_read</oa></addata></record>
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subjects Animals
Anti-antibodies
Antibodies
Antibodies, Immobilized - immunology
Antibodies, Immobilized - pharmacology
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal - pharmacology
Bacterial proteins
Bioassays
Biocompatibility
Biodegradation
Biological activity
Biological products
Biological properties
Biology and Life Sciences
Biomaterials
Biomedical materials
Biopolymers
Bone growth
Bone healing
Bone morphogenetic protein 2
Bone Morphogenetic Protein 2 - immunology
Bone Morphogenetic Protein 2 - metabolism
Bone morphogenetic proteins
Bone regeneration
Bone Regeneration - drug effects
Bone Substitutes - chemistry
Bone Substitutes - pharmacology
Bones
Calcium phosphates
Cbfa-1 protein
Cell adhesion & migration
Cell Differentiation - drug effects
Cell Line
Cell survival
Cellulose
Cellulose - chemistry
Cellulose - pharmacology
Chemistry
Comet assay
Cytokinesis
Cytotoxicity
Damage detection
Dentistry
Durapatite - chemistry
Durapatite - pharmacology
Endothelial growth factors
Engineering and Technology
Gene expression
Genes
Genotoxicity
Gluconacetobacter xylinus - chemistry
Health aspects
Hydroxyapatite
Hydroxyapatites
In vitro methods and tests
In vivo methods and tests
Inorganic chemistry
Kinetics
Materials
Materials Testing
Mechanical properties
Medical research
Medicine and Health Sciences
Membranes
Methods
Mice
Mineralization
Morphology
Mutagenicity
Nanocomposites
Nodules
Organic chemistry
Osteoblasts
Osteogenesis - drug effects
Osteoprotegerin
Peptides
Pharmaceutical sciences
Phosphatases
Physical Sciences
Polymers
Polysaccharides
Proteins
Regeneration
Regeneration (physiology)
Repair
Signal transduction
Signal Transduction - drug effects
Stem cells
Surgical implants
Testing
Tissue engineering
Tissue Engineering - methods
Toxicity
Toxicology
Trauma
Vascular endothelial growth factor
title Bacterial cellulose membrane functionalized with hydroxiapatite and anti-bone morphogenetic protein 2: A promising material for bone regeneration
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