Comparison of the Influence of 45S5 and Cu-Containing 45S5 Bioactive Glass (BG) on the Biological Properties of Novel Polyhydroxyalkanoate (PHA)/BG Composites

Polyhydroxyalkanoates (PHAs), due to their biodegradable and biocompatible nature and their ability to be formed in complex structures, are excellent candidates for fabricating scaffolds used in tissue engineering. By introducing inorganic compounds, such as bioactive glasses (BGs), the bioactive properties of PHAs can be further improved. In addition to their outstanding bioactivity, BGs can be additionally doped with biological ions, which in turn extend the functionality of the BG-PHA composite. Here, different PHAs were combined with 45S5 BG, which was additionally doped with copper in order to introduce antibacterial and angiogenic properties. The resulting composite was used to produce scaffolds by the salt leaching technique. By performing indirect cell biology tests using stromal cells, a dose-depending effect of the dissolution products released from the BG-PHA scaffolds could be found. In low concentrations, no toxic effect was found. Moreover, in higher concentrations, a minor reduction of cell viability combined with a major increase in VEGF release was measured. This result indicates that the fabricated composite scaffolds are suitable candidates for applications in soft and hard tissue engineering. However, more in-depth studies are necessary to fully understand the release kinetics and the resulting long-term effects of the BG-PHA composites

Highly Porous Polymer-Derived Bioceramics Based on a Complex Hardystonite Solid Solution

Highly porous bioceramics, based on a complex hardystonite solid solution, were developed from silicone resins and micro-sized oxide fillers fired in air at 950 °C. Besides CaO, SrO, MgO, and ZnO precursors, and the commercial embedded silicone resins, calcium borate was essential in providing the liquid phase upon firing and favouring the formation of an unprecedented hardystonite solid solution, corresponding to the formula (Ca0.70Sr0.30)2(Zn0.72Mg0.15Si0.13) (Si0.85B0.15)2O7. Silicone-filler mixtures could be used in the form of thick pastes for direct ink writing of reticulated scaffolds or for direct foaming. The latter shaping option benefited from the use of hydrated calcium borate, which underwent dehydration, with water vapour release, at a low temperature (420 °C). Both scaffolds and foams confirmed the already-obtained phase assemblage, after firing, and exhibited remarkable strength-to-density ratios. Finally, preliminary cell tests excluded any cytotoxicity that could be derived from the formation of a boro-silicate glassy phase

The effect of borate bioactive glass on the printability of methylcellulose-manuka honey hydrogels

Abstract 3D printing offers the possibility to generate complex and individualized constructs (scaffolds) for applications in tissue engineering. This is viable by using suitable inks based on advanced biomaterials. Methylcellulose (MC), a highly biocompatible biomaterial, can be combined with manuka honey (H) to fabricate a thermo-sensitive hydrogel. Besides providing favorable biological effects, H can also be used as a natural cross-linking agent. Furthermore, the addition of bioactive glass (BG) to the ink could improve its mechanical and bioactive properties. In this study, a composite based on MC as matrix incorporating H and particulate borate BG as filler, was investigated as ink for 3D printing. Besides the improvement of the inks’ printability owing to the addition of BG, the printed scaffolds exhibited suitable swelling behavior and mechanical properties. Moreover, cell biology tests demonstrated the potential of the composite for biofabrication and applications in tissue engineering, which should be further explored

Manuka honey and bioactive glass impart methylcellulose foams with antibacterial effects for wound-healing applications

Wound dressings able to deliver topically bioactive molecules represent a new generation of wound-regeneration therapies. In this article, foams based on methylcellulose cross-linked with Manuka honey were used as a platform to deliver borate bioactive glass particles doped additionally with copper. Borate bioactive glasses are of great interest in wound-healing applications due to a combination of favorable features, such as angiogenic and antibacterial properties. The multifunctional composite providing the dual effect of the bioactive glass and Manuka honey was produced by freeze-drying, and the resulting foams exhibit suitable morphology characterized by high porosity. Moreover, the performed tests showed improved wettability and mechanical performance with the addition of bioactive glass particles. Dissolution studies using simulated body fluid and cell biology tests using relevant skin cells further proved the excellent bioactivity and positive effects of the foams on cell proliferation and migration. Most interestingly, by the dual release of Manuka honey and ions from the copper-doped bioactive glass, an antibacterial effect against E. coli and S. aureus was achieved. Therefore, the multifunctional foams showed promising outcomes as potential wound dressings for the treatment of infected wounds

New insights into the nature of semi-soft elasticity and “mechanical-Fréedericksz transitions” in liquid crystal elastomers

The mechanical properties of an all-acrylate Liquid Crystal Elastomer (LCE) with a glass transition of 14±1°C are reported. The highly nonlinear load curve has a characteristic shape associated with semi-soft elasticity (SSE). Conversely, measurements of the director orientation throughout tensile loading instead indicate a “mechanical-Fréedericksz” transition (MFT). Values of the step length anisotropy, r, are independently calculated from the theories of SSE (r= 3.2±0.4), MFT (9.3<r<30.0) and thermally-induced length change (r=3.8±0.5). From simultaneously recorded polarising microscopy textures, the consequences of the above discrepancies are considered. Further, a mechanically-induced negative order parameter is observed. Results show the tensile load curve shape cannot solely be used to determine the underlying physics. Consequently, the LCE properties cannot be fully described by theories of SSE or MFTs alone. This suggests that the theory of LCEs is not yet complete. The conclusions suggest that both the LC order parameter and r must be functions of the mechanical deformation

Micrometer-Scale Porous Buckling Shell Actuators Based on Liquid Crystal Networks

Micrometer‐scale liquid crystal network (LCN) actuators have potential for application areas like biomedical systems, soft robotics, and microfluidics. To fully harness their power, a diversification in production methods is called for, targeting unconventional shapes and complex actuation modes. Crucial for controlling LCN actuation is the combination of macroscopic shape and molecular‐scale alignment in the ground state, the latter becoming particularly challenging when the desired shape is more complex than a flat sheet. Here, one‐step processing of an LCN precursor material in a glass capillary microfluidic set‐up to mold it into thin shells is used, which are stretched by osmosis to reach a diameter of a few hundred micrometers and thickness on the order of a micrometer, before they are UV crosslinked into an LCN. The shells exhibit radial alignment of the director field and the surface is porous, with pore size that is tunable via the osmosis time. The LCN shells actuate reversibly upon heating and cooling. The decrease in order parameter upon heating induces a reduction in thickness and expansion of surface area of the shells that triggers continuous buckling in multiple locations. Such buckling porous shells are interesting as soft cargo carriers with capacity for autonomous cargo release

Results of arthroscopic SLAP-Repair in 2890 consecutive patients

Diese retrospektive Studie analysierte 70 Patienten (Durchschnittsalter 34 Jahre) nach endoskopischer Refixierung von SLAP-Typ-II und Typ-IV Läsionen nach einem durchschnittlichen Follow-up von 34 Monaten. Von 71 SLAP-Läsionen wurden 17 in DASS-Technik (double anchor single suture) und 54 in SADS-Technik (single anchor double suture) refixiert. Ziel dieser Arbeit war der Vergleich der beiden Techniken an Hand der postoperativ erzielten Schulterfunktion. Als Zielvariable wurde der Constant Score verwendet. 30 Patienten erschienen persönlich zur Nachuntersuchung, 40 Patienten wurden anhand eines für die Selbsterhebung des Constant Scores validierten Bogens erfasst. In der postoperativen Schulterfunktion zeigte sich keine signifikanter Unterschied (p > 0,05) bei Vergleich der Operationstechniken. Es konnte die klinische Gleichwertigkeit der SADS-Technik mit der DASS-Technik gezeigt werden. Für alle Patienten konnte eine signifikante (p 0,05) in the comparison of the both repairs in the postoperative constant score. We could show the clinical equivalence of the SADS repair to the DASS repair. All patients showed a significant (p < 0,01) improvement in the constant score. Preoperative Constant-Score of 34,9 points improved to 84,46 points. We could achieve good clinical results for SLAP-II and SLAP-IV-Repair. The SADS repair and DASS repair resulted in equivalent clinical outcome

Entwicklung multifunktionaler Wundauflagen unter Verwendung neu gestalteter ionendotierter bioaktiver Borosilikat- und Boratgläser

The development of novel, multifunctional wound dressings is essential in the goal of achieving new therapies able to increase the quality of the treatment of patients suffering from insufficient wound healing, especially in the case of chronic and infected wounds. Based on the high social, economic and personal impact of skin wounds, ideal wound dressings able to actively protect the wounded skin and promote the healing process are in demand. Among other properties, modern wound dressings should be easy to produce (cost-effective) and should combine antibacterial with angiogenic properties in addition of being mechanically robust and pliable for easy application. Wound dressings, which can be used to deliver topically drugs or molecules, are of great interest as they can face the challenges leading to an effective wound healing process. Bioactive glasses (BGs) are a class of non-crystalline, inorganic materials able to release biologically active ions during implantation in the human body, which can induce specific cell responses such as accelerating haemostasis and angiogenesis. Research on BGs has mainly focused on their use in the field of bone replacing devices and bone tissue engineering. However, an increasing amount of studies is reporting promising results on the use of BGs in the regeneration of soft tissues and in wound healing. By designing new BG compositions with the capability to release ions that induce specific biological reactions, the applications of BGs are being further expanded in soft tissue repair. In this context, BGs have shown great potential for wound healing applications especially when BG compositions incorporating biologically active ions have been considered. Therefore, in the first part of this study, copper and/or zinc containing borosilicate and borate BGs were designed for wound healing applications. Copper was chosen to impart angiogenic properties and zinc to introduce antibacterial effects. The fabricated BGs were chemically and physically characterized and they showed excellent dissolution properties which were investigated by dissolution experiments carried out in simulated body fluid, lactic acid and TRIS solutions. Most importantly, especially the series of borate BGs containing copper and/or zinc showed promising results in an antibacterial study and were additionally tested in contact with immune cells. It was found that by using different compositions and concentrations of BGs, immune reactions can be actively (depending on the final application) dampened or induced,which can be achieved by the controlled release of therapeutic ions, in the present case, Zn and Cu. In order to be useful for applications in wound dressings, BGs must be applied in desired shapes having flexible and pliable characteristics and suitable pore structure. Therefore, in the second part of this thesis, BGs in particulate form (particle size range of 5-20 μm) were combined with methylcellulose (MC) crosslinked with Manuka honey (MH) to achieve flexible and mechanically stable structures. Due to its great biocompatibility and thermosensitive behaviour, MC was chosen, while MH was selected as an innovative cross-linker. Besides providing crosslinking potential, which could be proven in this work by Fourier transform infrared spectroscopy (FTIR), MH was also chosen due to its favourable effects such as promoting epithelialization and antibacterial activity. By using three different fabrication methods, namely freeze drying, electrospinning and 3D printing, different types of wound dressings composed of MC and MH doped with BG particles were fabricated. Freeze dried MC-MH foams containing Cu-doped borate BG particles showed a high porosity (around 95%) and improved wettability. Moreover, the foams showed suitable mechanical properties (compressive strength: ~40 kPa) while acellular in vitro dissolution tests in simulated body fluid indicated the bioactivity of the composite foams. Most importantly, cell biology tests using fibroblasts, keratinocytes and endothelial cells indicated the material biocompatibility and the foams showed superior antibacterial effects against both E. coli and S. aureus bacteria. By additionally combining MC-MH and BG particles with the polymer poly(ɛ-caprolactone) (PCL), which is well-known as a biocompatible and biodegradable polyester, composite fibre mats were fabricated by electrospinning. PCL-MH blend fibre mats containing BG particles (particle size of 5-20 μm) were composed of nanofibers in the range of 100-300 nm and showed a contact angle of around 45°, which is favourable to promote cell attachment due to the hydrophilic character of the surface. Although the ultimate tensile strength of the fibres was slightly reduced by the addition of MH and BG (from around 5 to 3 MPa), the tensile strain was not affected (in the range of 50%). In accordance with the freeze-dried foams, cell biology tests using fibroblasts and keratinocytes indicated the biocompatibility of the electrospun fibre mats. However, tests using E. coli and S. aureus showed no antibacterial efficiency of the fibre mats, indicating the need of further optimization by e.g. increasing the amount of MH and BG. By using phosphate buffer saline as solvent, MC-MH inks containing BG particles (particle size range of 5-20 μm) were successfully produced and used for 3D printing. Mechanical characterization of the 3D printed MC-MH scaffolds showed that the mechanical properties can be tuned by adding different amounts of BG particles into the ink. Moreover, the degradation properties of the resulting printed BG containing MC-MH scaffolds wereimproved in comparison to the too fast dissolving MC-MH scaffolds without the addition of BG. Cell biology tests using fibroblasts further showed the biocompatibility of the MC-MH-BG scaffolds, which indicates that MC-MH-BG inks are innovative for 3D printing and they should be further investigated for their use in the field of biofabrication of personalized wound dressings. In summary, the use of ion-doped borate and borosilicate BGs is a promising strategy in the development of novel wound dressings that offer several therapeutic effects such as being antibacterial and angiogenic. In this thesis, BG particles were for the first time combined with MH and MC in different types of devices by using different fabrication methods, demonstrating the versatile nature of these material combinations. The successful application of MH as natural crosslinker in combination with ion-doped BGs, enable the fabrication of different wound dressings offering various advantages. Whereas freeze dried wound dressings are especially interesting in the treatment of infected, deep wounds, electrospun fibre mats are important for superficial wounds. Inks based on MC-MH in combination with BGs demonstrated an attractive biomaterial platform for 3D printing as they open a new field for further research focusing on biofabrication. Overall, the results obtained in this thesis showed the great potential of ion-doped BGs in combination with MC and MH for the fabrication of antibiotic-free wound dressings capable of preventing infections and with extra functionality to promote wound regeneration