Designed peptide amphiphiles as scaffolds for tissue engineering.

Peptide amphiphiles (PAs) are peptide-based molecules that contain a peptide sequence as a head group covalently conjugated to a hydrophobic segment, such as lipid tails. They can self-assemble into well-ordered supramolecular nanostructures such as micelles, vesicles, twisted ribbons and nanofibers. In addition, the diversity of natural amino acids gives the possibility to produce PAs with different sequences. These properties along with their biocompatibility, biodegradability and a high resemblance to native extracellular matrix (ECM) have resulted in PAs being considered as ideal scaffold materials for tissue engineering (TE) applications. This review introduces the 20 natural canonical amino acids as building blocks followed by highlighting the three categories of PAs: amphiphilic peptides, lipidated peptide amphiphiles and supramolecular peptide amphiphile conjugates, as well as their design rules that dictate the peptide self-assembly process. Furthermore, 3D bio-fabrication strategies of PAs hydrogels are discussed and the recent advances of PA-based scaffolds in TE with the emphasis on bone, cartilage and neural tissue regeneration both in vitro and in vivo are considered. Finally, future prospects and challenges are discussed.

Additive Manufacturing of Polyhydroxyalkanoate-Based Blends Using Fused Deposition Modelling for the Development of Biomedical Devices.

In the last few decades Additive Manufacturing has advanced and is becoming important for biomedical applications. In this study we look at a variety of biomedical devices including, bone implants, tooth implants, osteochondral tissue repair patches, general tissue repair patches, nerve guidance conduits (NGCs) and coronary artery stents to which fused deposition modelling (FDM) can be applied. We have proposed CAD designs for these devices and employed a cost-effective 3D printer to fabricate proof-of-concept prototypes. We highlight issues with current CAD design and slicing and suggest optimisations of more complex designs targeted towards biomedical applications. We demonstrate the ability to print patient specific implants from real CT scans and reconstruct missing structures by means of mirroring and mesh mixing. A blend of Polyhydroxyalkanoates (PHAs), a family of biocompatible and bioresorbable natural polymers and Poly(L-lactic acid) (PLLA), a known bioresorbable medical polymer is used. Our characterisation of the PLA/PHA filament suggest that its tensile properties might be useful to applications such as stents, NGCs, and bone scaffolds. In addition to this, the proof-of-concept work for other applications shows that FDM is very useful for a large variety of other soft tissue applications, however other more elastomeric MCL-PHAs need to be used.

Silk Fibroin as a Functional Biomaterial for Tissue Engineering.

Tissue engineering (TE) is the approach to combine cells with scaffold materials and appropriate growth factors to regenerate or replace damaged or degenerated tissue or organs. The scaffold material as a template for tissue formation plays the most important role in TE. Among scaffold materials, silk fibroin (SF), a natural protein with outstanding mechanical properties, biodegradability, biocompatibility, and bioresorbability has attracted significant attention for TE applications. SF is commonly dissolved into an aqueous solution and can be easily reconstructed into different material formats, including films, mats, hydrogels, and sponges via various fabrication techniques. These include spin coating, electrospinning, freeze drying, physical, and chemical crosslinking techniques. Furthermore, to facilitate fabrication of more complex SF-based scaffolds with high precision techniques including micro-patterning and bio-printing have recently been explored. This review introduces the physicochemical and mechanical properties of SF and looks into a range of SF-based scaffolds that have been recently developed. The typical TE applications of SF-based scaffolds including bone, cartilage, ligament, tendon, skin, wound healing, and tympanic membrane, will be highlighted and discussed, followed by future prospects and challenges needing to be addressed.

Magnetic Alginate/Chitosan Nanoparticles for Targeted Delivery of Curcumin into Human Breast Cancer Cells.

Curcumin is a promising anti-cancer drug, but its applications in cancer therapy are limited, due to its poor solubility, short half-life and low bioavailability. In this study, curcumin loaded magnetic alginate/chitosan nanoparticles were fabricated to improve the bioavailability, uptake efficiency and cytotoxicity of curcumin to Human Caucasian Breast Adenocarcinoma cells (MDA-MB-231). Alginate and chitosan were deposited on Fe3O4 magnetic nanoparticles based on their electrostatic properties. The nanoparticle size ranged from 120⁻200 nm, within the optimum range for drug delivery. Controllable and sustained release of curcumin was obtained by altering the number of chitosan and alginate layers on the nanoparticles. Confocal fluorescence microscopy results showed that targeted delivery of curcumin with the aid of a magnetic field was achieved. The fluorescence-activated cell sorting (FACS) assay indicated that MDA-MB-231 cells treated with curcumin loaded nanoparticles had a 3⁻6 fold uptake efficiency to those treated with free curcumin. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay indicated that the curcumin loaded nanoparticles exhibited significantly higher cytotoxicity towards MDA-MB-231 cells than HDF cells. The sustained release profiles, enhanced uptake efficiency and cytotoxicity to cancer cells, as well as directed targeting make MACPs promising candidates for cancer therapy.

Catalytic Janus Colloids: Controlling Trajectories of Chemical Microswimmers.

Catalytic Janus colloids produce rapid motion in fluids by decomposing dissolved fuel. There is great potential to exploit these "autonomous chemical swimmers" in applications currently performed by diffusion limited passive colloids. Key application areas for colloids include transporting active ingredients for drug delivery, gathering analytes for medical diagnostics, and self-assembling into regular structures used for photonic materials and lithographic templating. For drug delivery and medical diagnostics, controlling colloidal motion is key in order to target therapies, and transport analytes through lab-on-a-chip devices. Here, the autonomous motion of catalytic Janus colloids can remove the current requirements to induce and control colloid motion using external fields, thereby reducing the technological complexity required for medical therapies and diagnostics. For materials applications exploiting colloidal self-assembly, the additional interactions introduced by catalytic activity and rapid motion are predicted to allow access to new reconfigurable and responsive structures. In order to realize these goals, it is vital to develop methods to control both individual colloidal paths and collective behavior in motile catalytic colloidal systems. However, catalytic Janus colloids' trajectories are randomized by Brownian effects, and so require new strategies in order to be harnessed for transport. This is achievable using a variety of different approaches. For example, self-assembly and control of catalyst geometry can introduce controlled amounts of rotary motion, or "spin" into chemical swimmer trajectories. Furthermore, rotary motion combined with gravity, produces well-defined orientated helical trajectories. In addition, when catalytic colloids interact with topographical features, such as edges and trenches, they are steered. This gives rise to a new approach for autonomous colloidal microfluidic transport that could be deployed in future lab-on-a-chip devices. Chemical gradients can also influence the motion of catalytic Janus colloids, for example, to cause collective accumulations at specific locations. However, at present, the predicted theoretical degree of control over this phenomenon has not been fully verified in experimental systems. Collective behavior control for chemical swimmers is also possible by exploiting the potential for the complex interactions in these systems to allow access to self-assembled, dynamic and reconfigurable ordered structures. Again, current experiments have not yet accessed the breadth of possible behavior. Consequently, continued efforts are required to understand and control these interaction mechanisms in real world systems. Ultimately, this will help realize the use of catalytic Janus colloids for tasks that require well-controlled motion and structural organization, enabling functions such as analyte capture and concentration, or targeted drug delivery.