Bioactive and electrically conductive GelMA-BG-MWCNT nanocomposite hydrogel bone biomaterials

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Abstract

Natural bone is a complex organic-inorganic composite tissue that possesses endogenous electrically conductive properties in response to mechanical forces. Mimicking these unique properties collectively in a single synthetic biomaterial has so far remained a formidable task. In this study, we report a synthesis strategy that comprised gelatin methacryloyl (GelMA), sol-gel derived tertiary bioactive glass (BG), and uniformly dispersed multiwall carbon nanotubes (MWCNTs) to create nanocomposite hydrogels that mimic the organic-inorganic composition of bone. Using this strategy, biomaterials that are electrically conductive and possess electro-mechanical properties similar to endogenous bone were prepared without affecting their biocompatibility. Nanocomposite hydrogel biomaterials were biodegradable and promoted biomineralization, and supported multipotent mesenchymal progenitor cell (10T1/2) cell interactions and differentiation into an osteogenic lineage. To the best of our knowledge, this work presents the first study to functionally characterize suitable electro-mechanical responses in nanocomposite hydrogels, a key process that occurs in the natural bone to drive its repair and regeneration. Overall, the results demonstrated GelMA-BG-MWCNT nanocomposite hydrogels have the potential to become promising bioactive biomaterials for use in bone repair and regeneration.

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Brandon V Slaughter, Shahana S Khurshid, Omar Z Fisher … (2009)

Hydrogels, due to their unique biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics, have been the material of choice for many applications in regenerative medicine. They can serve as scaffolds that provide structural integrity to tissue constructs, control drug and protein delivery to tissues and cultures, and serve as adhesives or barriers between tissue and material surfaces. In this work, the properties of hydrogels that are important for tissue engineering applications and the inherent material design constraints and challenges are discussed. Recent research involving several different hydrogels polymerized from a variety of synthetic and natural monomers using typical and novel synthetic methods are highlighted. Finally, special attention is given to the microfabrication techniques that are currently resulting in important advances in the field.

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The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation.

Kazuhisa Nakashima, Xin Zhou, Gary A Kunkel … (2002)

We have identified a novel zinc finger-containing transcription factor, called Osterix (Osx), that is specifically expressed in all developing bones. In Osx null mice, no bone formation occurs. In endochondral skeletal elements of Osx null mice, mesenchymal cells, together with osteoclasts and blood vessels, invade the mineralized cartilage matrix. However, the mesenchymal cells do not deposit bone matrix. Similarly, cells in the periosteum and in the condensed mesenchyme of membranous skeletal elements cannot differentiate into osteoblasts. These cells do, however, express Runx2/Cbfa1, another transcription factor required for bone formation. In contrast, Osx is not expressed in Runx2/Cbfa1 null mice. Thus, Osx acts downstream of Runx2/Cbfa1. Because Osx null preosteoblasts express typical chondrocyte marker genes, we propose that Runx2/Cbfa1-expressing preosteoblasts are still bipotential cells.

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Review of bioactive glass: from Hench to hybrids.

Julian R. Jones (2013)

Bioactive glasses are reported to be able to stimulate more bone regeneration than other bioactive ceramics but they lag behind other bioactive ceramics in terms of commercial success. Bioactive glass has not yet reached its potential but research activity is growing. This paper reviews the current state of the art, starting with current products and moving onto recent developments. Larry Hench's 45S5 Bioglass® was the first artificial material that was found to form a chemical bond with bone, launching the field of bioactive ceramics. In vivo studies have shown that bioactive glasses bond with bone more rapidly than other bioceramics, and in vitro studies indicate that their osteogenic properties are due to their dissolution products stimulating osteoprogenitor cells at the genetic level. However, calcium phosphates such as tricalcium phosphate and synthetic hydroxyapatite are more widely used in the clinic. Some of the reasons are commercial, but others are due to the scientific limitations of the original Bioglass 45S5. An example is that it is difficult to produce porous bioactive glass templates (scaffolds) for bone regeneration from Bioglass 45S5 because it crystallizes during sintering. Recently, this has been overcome by understanding how the glass composition can be tailored to prevent crystallization. The sintering problems can also be avoided by synthesizing sol-gel glass, where the silica network is assembled at room temperature. Process developments in foaming, solid freeform fabrication and nanofibre spinning have now allowed the production of porous bioactive glass scaffolds from both melt- and sol-gel-derived glasses. An ideal scaffold for bone regeneration would share load with bone. Bioceramics cannot do this when the bone defect is subjected to cyclic loads, as they are brittle. To overcome this, bioactive glass polymer hybrids are being synthesized that have the potential to be tough, with congruent degradation of the bioactive inorganic and the polymer components. Key to this is creating nanoscale interpenetrating networks, the organic and inorganic components of which have covalent coupling between them, which involves careful control of the chemistry of the sol-gel process. Bioactive nanoparticles can also now be synthesized and their fate tracked as they are internalized in cells. This paper reviews the main developments in the field of bioactive glass and its variants, covering the importance of control of hierarchical structure, synthesis, processing and cellular response in the quest for new regenerative synthetic bone grafts. The paper takes the reader from Hench's Bioglass 45S5 to new hybrid materials that have tailorable mechanical properties and degradation rates. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.