Structural Evolution of PCL during Melt Extrusion 3D Printing

Screw‐assisted material extrusion technique is developed for tissue engineering applications to produce scaffolds with well‐defined multiscale microstructural features and tailorable mechanical properties. In this study, in situ time‐resolved synchrotron diffraction is employed to probe extrusion‐based 3D printing of polycaprolactone (PCL) filaments. Time‐resolved X‐ray diffraction measurements reveals the progress of overall crystalline structural evolution of PCL during 3D printing. Particularly, in situ experimental observations provide strong evidence for the development of strong directionality of PCL crystals during the extrusion driven process. Results also show the evidence for the realization of anisotropic structural features through the melt extrusion‐based 3D printing, which is a key development toward mimicking the anisotropic properties and hierarchical structures of biological materials in nature, such as human tissues.     

Phosphate content affects structure and bioactivity of sol-gel silicate bioactive glasses

Bioactive glasses can heal bone defects and bond with bone through formation of hydroxyl carbonate apatite (HCA) surface layer. Sol-gel derived bioactive glasses are thought to have potential for improving bone regeneration rates over melt-derived compositions. The 58S sol-gel composition (60 mol% SiO₂, 36 mol% CaO, and 4 mol% P₂O₅) has appeared in commercial products. Here, hydroxyapatite (HA) was found to form within the 58S glass during sol-gel synthesis after thermal stabilization. The preformed HA may lead to rapid release of calcium orthophosphate, or nanocrystals of HA, on exposure to body fluid, rather than the release of separate the calcium and phosphate species. Increasing the P₂O₅ to CaO ratio in the glass composition reduced preformed HA formation, as observed by XRD and solid-state NMR. Instead, above 12 mol% phosphate, a phosphate glass network (polyphosphate) formed, creating co-networks of phosphate and silica. Nanopore diameter of the glass and rate of HCA layer formation in simulated body fluid (SBF) decreased when the phosphate content increased.     

Preparation of electrospun siloxane-poly(lactic acid)-vaterite hybrid fibrous membranes for guided bone regeneration

A nonwoven fabric scaffold for guided bone regeneration (GBR) consisting of siloxane-poly(lactic acid) (PLA)-vaterite hybrid material (SiPVH) was prepared by an electrospinning method. To improve the cellular compatibility of the fabric, the fibers were completely coated with hydroxyapatite (HA) by soaking in simulated body fluid. The HA-coated SiPVH nonwoven fabric contained large-sized spaces and showed the ability of releasing soluble silica and calcium species, which have previously been reported to stimulate osteogenic cells at the genetic level. A new type of GBR membrane was prepared by bonding SiPVH fabric with PLA nonwoven fabric with small-sized pores for preventing the intrusion of soft tissue. The resultant bi-layered membrane was expected to be effective not only for having an open structure for bone formation and a barrier to soft tissue, but also for enhancing bone growth by the release of ionic species.     

A comparative study of oxygen diffusion in tissue engineering scaffolds

Tissue engineering scaffolds are designed to support tissue self-healing within physiological environments by promoting the attachment, growth and differentiation of relevant cells. Newly formed tissue must be supplied with sufficient levels of oxygen to prevent necrosis. Oxygen diffusion is the major transport mechanism before vascularization is completed and oxygen is predominantly supplied via blood vessels. The present study compares different designs for scaffolds in the context of their oxygen diffusion ability. In all cases, oxygen diffusion is confined to the scaffold pores that are assumed to be completely occupied by newly formed tissue. The solid phase of the scaffolds acts as diffusion barrier that locally inhibits oxygen diffusion, i.e. no oxygen passes through the scaffold material. As a result, the oxygen diffusivity is determined by the scaffold porosity and pore architecture. Lattice Monte Carlo simulations are performed to compare the normalized oxygen diffusivities in scaffolds obtained by the foam replication (FR) method, robocasting and sol–gel foaming. Scaffolds made by the FR method were found to have the highest oxygen diffusivity due to their high porosity and interconnected pores. These structures enable the best oxygen supply for newly formed tissue among the scaffold types considered according to the present numerical predictions.     

Process‐Driven Microstructure Control in Melt‐Extrusion‐Based 3D Printing for Tailorable Mechanical Properties in a Polycaprolactone Filament

3D printing techniques are utilized to produce biomaterial scaffolds with porous architectures that enable cell attachment, biological factors, and appropriate mechanical strength. As the basic building block of a scaffold, the individual filaments should have sufficient mechanical properties, comprising high compressive loading, and fracture resistance to mimic the natural tissue organisation. In this contribution, process–structure–property relationships in melt extruded polycaprolactone filaments are investigated by considering crystalline features, tensile properties, and an array of processing parameters. The tensile properties of the filaments are improved significantly with relatively higher screw rotational speed and relatively lower processing temperature resulting in considerable increase in Young's modulus. The favorable properties are attributed to the increased crystal volume fraction and anisotropy. Thus, this study provides initial pathways for the potential control of mechanical properties of bioscaffolds via engineering crystalline structural features in printed filaments.     

Novel Chitosan-Silica Hybrid Hydrogels for Cell Encapsulation and Drug Delivery

Hydrogels constructed from naturally derived polymers provide an aqueous environment that encourages cell growth, however, mechanical properties are poor and degradation can be difficult to predict. Whilst, synthetic hydrogels exhibit some improved mechanical properties, these materials lack biochemical cues for cells growing and have limited biodegradation. To produce hydrogels that support 3D cell cultures to form tissue mimics, materials must exhibit appropriate biological and mechanical properties. In this study, novel organic-inorganic hybrid hydrogels based on chitosan and silica were prepared using the sol-gel technique. The chemical, physical and biological properties of the hydrogels were assessed. Statistical analysis was performed using One-Way ANOVAs and independent-sample t-tests. Fourier transform infrared spectroscopy showed characteristic absorption bands including amide II, Si-O and Si-O-Si confirming formation of hybrid networks. Oscillatory rheometry was used to characterise the sol to gel transition and viscoelastic behaviour of hydrogels. Furthermore, in vitro degradation revealed both chitosan and silica were released over 21 days. The hydrogels exhibited high loading efficiency as total protein loading was released in a week. There were significant differences between TC₂G and C₂G at all-time points (p < 0.05). The viability of osteoblasts seeded on, and encapsulated within, the hydrogels was >70% over 168 h culture and antimicrobial activity was demonstrated against Pseudomonas aeruginosa and Enterococcus faecalis. The hydrogels developed here offer alternatives for biopolymer hydrogels for biomedical use, including for application in drug/cell delivery and for bone tissue engineering.     

In situ 4D tomography image analysis framework to follow sintering within 3D-printed glass scaffolds

We propose a novel image analysis framework to automate analysis of X-ray microtomography images of sintering ceramics and glasses, using open-source toolkits and machine learning. Additive manufacturing (AM) of glasses and ceramics usually requires sintering of green bodies. Sintering causes shrinkage, which presents a challenge for controlling the metrology of the final architecture. Therefore, being able to monitor sintering in 3D over time (termed 4D) is important when developing new porous ceramics or glasses. Synchrotron X-ray tomographic imaging allows in situ, real-time capture of the sintering process at both micro and macro scales using a furnace rig, facilitating 4D quantitative analysis of the process. The proposed image analysis framework is capable of tracking and quantifying the densification of glass or ceramic particles within multiple volumes of interest (VOIs) along with structural changes over time using 4D image data. The framework is demonstrated by 4D quantitative analysis of bioactive glass ICIE16 within a 3D-printed scaffold. Here, densification of glass particles within 3 VOIs were tracked and quantified along with diameter change of struts and interstrut pore size over the 3D image series, delivering new insights on the sintering mechanism of ICIE16 bioactive glass particles in both micro and macro scales.     

Synthesis and dissolution behaviour of CaO/SrO-containing sol–gel-derived 58S glasses

The effect of the substitution of strontium for calcium in the tertiary the SiO₂–CaO–P₂O₅ sol–gel bioactive glass 58S (60SiO₂·36CaO·4P₂O₅, mol%) on its structure and its chemical durability on soaking in simulated body fluids was investigated. 58S was selected as a starting composition, and substitution for calcium was carried out from 0 to 100% with an increment of 25%. A novel phosphate source of diethylphosphatoethyltriethoxysilane, which consists of Si and P connected with ethylene group, was used in this work. XRD and FTIR showed that the gels obtained following drying at 130 °C had a typical sol–gel structure, where a continuous amorphous silica gel network and surface bound mineral salts of Ca(NO₃)₂ and Sr(NO₃)₂. Once the gels were heat stabilised to decompose nitrates and incorporate the cations into the network, samples containing Sr formed a strontium silicate crystalline phase. With increasing levels of Sr in the composition, the overall crystallinity of the glass–ceramic increased, while, at the maximum substitution of 100% SrO, macroscopic phase separation was observed, characterised by needle-like crystals of strontium apatite (Sr₅(PO₄)₃OH) and strontium silicate (Sr₂SiO₄) phases in addition to amorphous regions. Dissolution experiments in Tris-buffered solution showed Sr successfully released into the media even though it existed as a crystalline phase in the glass–ceramic. Further, the glass–ceramics induced nucleation and growth of carbonated hydroxyapatite (HA) on their surface suggesting potential bioactivity of the materials. At higher substitutions (75 and 100% SrO for CaO), HA nucleation was not found to occur this may have been due to low amount of phosphate released from the original glass–ceramic as a result of it being locked up in the strontium apatite phase.     

Neutron diffraction study of antibacterial bioactive calcium silicate sol-gel glasses containing silver

Bioactive sol-gel calcia-silica glasses can regenerate damaged or diseased bones due to their ability to stimulate bone growth. This capability is related to the formation of a hydroxyapatite layer on the glass surface, which bonds with bone, and the release of soluble silica and calcium ions in the body fluid which accelerates bone growth. The addition of silver ions imbues the glass with antibacterial properties due to the release of antibacterial Ag⁺ ion. The antibacterial activity is therefore closely dependent on the dissolution properties of the glasses which in turn are related to their atomic-level structure. Structural characterization of the glasses at the atomic level is therefore essential in order to investigate and control the antibacterial properties of the glass. We have used neutron diffraction to investigate the structure of silver-containing calcia-silica sol-gel bioactive glasses with different Ag₂O loading (0, 2, 4, 6 mol%). The presence of the silver had little effect on the host glass structure, although some silver metal nanoparticles were present. Results agreed with previous computer simulations.