Poly(γ-glutamic acid)/silica hybrids with calcium incorporated in the silica network by use of a calcium alkoxide precursor.

Current materials used for bone regeneration are usually bioactive ceramics or glasses. Although they bond to bone, they are brittle. There is a need for new materials that can combine bioactivity with toughness and controlled biodegradation. Sol-gel hybrids have the potential to do this through their nanoscale interpenetrating networks (IPN) of inorganic and organic components. Poly(γ-glutamic acid) (γ-PGA) was introduced into the sol-gel process to produce a hybrid of γ-PGA and bioactive silica. Calcium is an important element for bone regeneration but calcium sources that are used traditionally in the sol-gel process, such as Ca salts, do not allow Ca incorporation into the silicate network during low-temperature processing. The hypothesis for this study was that using calcium methoxyethoxide (CME) as the Ca source would allow Ca incorporation into the silicate component of the hybrid at room temperature. The produced hybrids would have improved mechanical properties and controlled degradation compared with hybrids of calcium chloride (CaCl2 ), in which the Ca is not incorporated into the silicate network. Class II hybrids, with covalent bonds between the inorganic and organic species, were synthesised by using organosilane. Calcium incorporation in both the organic and inorganic IPNs of the hybrid was improved when CME was used. This was clearly observed by using FTIR and solid-state NMR spectroscopy, which showed ionic cross-linking of γ-PGA by Ca and a lower degree of condensation of the Si species compared with the hybrids made with CaCl2 as the Ca source. The ionic cross-linking of γ-PGA by Ca resulted in excellent compressive strength and reduced elastic modulus as measured by compressive testing and nanoindentation, respectively. All hybrids showed bioactivity as hydroxyapatite (HA) was formed after immersion in simulated body fluid (SBF).

High strength and strain alginate fibers by a novel wheel spinning technique for knitting stretchable and biocompatible wound-care materials.

Alginate fibrous materials have been applied as wound dressing to enhance wound healing due to its nontoxic, biodegradable, and hemostatic nature. Conventional nonwoven fabrication tactics, however, showed weakness in inflammation, degradation stability and mechanical properties. Herein, the wet-spun alginate fibers were prepared by a novel wheel spinning technique, then knitted into wound dressing. Benefiting from optimized wet spinning parameters and the agglomeration of alginate multimers, the fibers were endowed with elevated mechanical performances and biodegradability, which allowed for the feasibility of knitting wound-care materials. Using the new wheel spinning technique, high strength alginate fibers with 173 MPa were produced with breaking strain up to 18% and toughness of 16.16 MJ*m-3. Meanwhile, alginate fibers with high breaking strain reaching 35% were produced with tensile strength of 135 MPa and toughness of 37.47 MJ*m-3. The overall mechanical performances of these alginate fibers with high breaking strain are significantly higher (up to 2 times) than those published in the literature in term of toughness. In vitro degradation evaluation revealed that this wet spun fibrous dressing had good aqueous absorbency (50%) and sustained biodegradation properties. Furthermore, the consequent cell viability study also proved that this alginate knitted fabric is biocompatible for being applied as wound dressing.

Highly degradable porous melt-derived bioactive glass foam scaffolds for bone regeneration.

A challenge in using bioactive melt-derived glass in bone regeneration is to produce scaffolds with interconnected pores while maintaining the amorphous nature of the glass and its associated bioactivity. Here we introduce a method for creating porous melt-derived bioactive glass foam scaffolds with low silica content and report in vitro and preliminary in vivo data. The gel-cast foaming process was adapted, employing temperature controlled gelation of gelatin, rather than the in situ acrylic polymerisation used previously. To form a 3D construct from melt derived glasses, particles must be fused via thermal processing, termed sintering. The original Bioglass® 45S5 composition crystallises upon sintering, altering its bioactivity, due to the temperature difference between the glass transition temperature and the crystallisation onset being small. Here, we optimised and compared scaffolds from three glass compositions, ICIE16, PSrBG and 13-93, which were selected due to their widened sintering windows. Amorphous scaffolds with modal pore interconnect diameters between 100-150µm and porosities of 75% had compressive strengths of 3.4±0.3MPa, 8.4±0.8MPa and 15.3±1.8MPa, for ICIE16, PSrBG and 13-93 respectively. These porosities and compressive strength values are within the range of cancellous bone, and greater than previously reported foamed scaffolds. Dental pulp stem cells attached to the scaffold surfaces during in vitro culture and were viable. In vivo, the scaffolds were found to regenerate bone in a rabbit model according to X-ray micro tomography imaging. STATEMENT OF SIGNIFICANCE: This manuscript describes a new method for making scaffolds from bioactive glasses using highly bioactive glass compositions. The glass compositions have lower silica content that those that have been previously made into amorphous scaffolds and they have been designed to have similar network connectivity to that of the original (and commercially used) 45S5 Bioglass. The aim was to match Bioglass' bioactivity. The scaffolds retain the amorphous nature of bioactive glass while having an open pore structure and compressive strength similar to porous bone (the original 45S5 Bioglass crystallises during sintering, which can cause reduced bioactivity or instability). The new scaffolds showed unexpectedly rapid bone regeneration in a rabbit model.

Spherical bioactive glass particles and their interaction with human mesenchymal stem cells in vitro.

Sub-micron particles of bioactive glass (SMBGs) with composition 85 mol% SiO(2) and 15 mol% CaO were synthesised and characterised. Bioactivity was demonstrated by the formation of calcium apatite following 5 days immersion in simulated body fluid (SBF). The effect of a 24 h exposure of SMBGs (100 µg/ml, 150 µg/ml, 200 µg/ml) to human mesenchymal stem cells (hMSCs) on cell viability, metabolic activity and proliferation were determined using the LIVE/DEAD, MTT, total DNA and LDH assays after 1, 4 and 7 days of culture. None of the SMBG concentrations caused significant cytotoxicity at 1 and 4 days, but the doses of 150 and 200 µg/ml significantly decreased hMSC metabolic activity after 7 days of culture. Cell proliferation decreased as SMBG concentration increased; however none of the SMBGs tested had a significant effect on DNA quantity compared to the control. Confocal microscopy confirmed cellular uptake and localisation of the SMBGs in the hMSC cytoskeleton. Transmission electron microscopy revealed that the SMBGs localised inside the cell cytoplasm and cell endosomes. These findings are important for assessing the toxicity of sub-micron particles that may either be used as injectables for bone regeneration or generated by wear or degradation of bioactive glass scaffolds.