Ryan Dimmock

The limbal niche is an adult source of epithelial stem cells which regenerate the cornea epithelium. The architecture and biomechanical properties of the limbus have previously been demonstrated to change due to aging and disease. This study aims to non‐destructively and simultaneously quantify these limbal niche properties, along with their age‐related changes. A lab‐built vibrational optical coherence elastography (OCE) device consisting of a phase‐sensitive optical coherence tomography (OCT) with a vibrational stimulator has been used to collect structural images and the depth‐resolved elasticity of human corneoscleral tissues (aged 4–96 years old). The limbal palisades of Vogt (POV) were delineated well in OCT images which were validated by histology. The POVs have been spatially mapped with simultaneous elasticity measurements in cross‐sections, showing tissue stiffness distributions across the undulations. A significant influence of age on the dimensions of the POVs was explored. The elastic modulus within the limbal niches for the ≥65‐year‐old group was significantly higher than that of the <65‐year‐old group.

In the biomedical field, there is a demand for the development of novel approaches for the investigation of optical epithelial anatomical features with biomimetic materials. These materials are not only required to replicate structures but also enable dynamic modelling for disease states such as limbal stem cell deficiency and ageing. In the present study, the effective generation of reversible wrinkled polydimethylsiloxane (PDMS) substrates was undertaken to mimic the undulating anatomy of the limbal epithelial stem cell niche. This undulating surface pattern was formed through a dual treatment with acid oxidation and plasma using an innovatively designed stretching frame. This system enabled the PDMS substrate to undergo deformation and relaxation, creating a reversible and tuneable wrinkle pattern with cell culture applications. The crypt-like pattern exhibited a width of 70–130 µm and a depth of 17–40 µm, resembling the topography of a limbal epithelial stem cell niche, which is characterised by an undulating anatomy. The cytocompatibility of the patterned substrate was markedly improved using a gelatin methacrylate polymer (GelMa) coating. It was also observed that these wrinkled PDMS surfaces were able to dictate cell growth patterns, showing alignment in motile cells and colony segregation in colony-forming cells when using human and porcine limbal cells, respectively.

Cryogel formation is an effective approach to produce porous scaffolds for tissue engineering. In this study, cryogelation was performed to produce boron-containing scaffolds for bone tissue engineering. A combination of the synthetic polymer, poly(vinyl alcohol) (PVA), and the natural polymers, chitosan and starch, was used to formulate the cryogels. Boron was used with a dual purpose: as an additive to alter gelation properties, and to exploit its bioactive effect since boron has been found to be involved in several metabolic pathways, including the promotion of bone growth. This project designs a fabrication protocol enabling the competition of both physical and chemical cross-linking reactions in the cryogels using different molecular weight PVA and borax content (boron source). Using a high ratio of high-molecular-weight PVA resulted in the cryogels exhibiting greater mechanical properties, a lower degradation rate (0.6–1.7% vs. 18–20%) and a higher borax content release (4.98 vs. 1.85, 1.08 nanomole) in contrast to their counterparts with low-molecular-weight PVA. The bioactive impacts of the released borax on cellular behaviour were investigated using MG63 cells seeded into the cryogel scaffolds. It was revealed that the borax-containing scaffolds and their extracts induced MG63 cell migration and the formation of nodule-like aggregates, whilst cryogel scaffolds without borax did not. Moreover, the degradation products of the scaffolds were analysed through the quantification of boron release by the curcumin assay. The impact on cellular response in a scratch assay confirmed that borax released by the scaffold into media (~0.4 mg/mL) induced bone cell migration, proliferation and aggregation. This study demonstrated that boron-containing three-dimensional PVA/starch–chitosan scaffolds can potentially be used within bone tissue engineering applications.

Advancements in surface engineering and material fabrication techniques have enabled the creation and replication of naturally occurring surface topographies or the extrapolation of natural patterns to become achievable targets. Polymers are used extensively in the field of biomedical sciences for containment, handling, and as cell culture substrates. It is well established that several polymers exhibit good biocompatibility for cell culture, with properties that include exhibiting minimal to no cytotoxicity and being sufficiently hydrophilic to facilitate cell adhesion. However, when using biologically representative materials, there is always a challenge of achieving tissue representative surface topography and architecture. Wrinkles in human skin represent a considerably common surface topography, resulting from aging and maturity of the tissue. Inspired by this natural topography, the present review article discusses the various techniques for generating wrinkle-like patterns on the polymer surfaces, along with their potential biomedical applications. Wrinkling as material science and as a physical concept has been explored only during the last century. The transfer of the knowledge related to wrinkling from hard engineering materials to soft elastomers has resulted in the development of an active research field, although it remains in its infancy in terms of application in biomedical science and engineering. It is suggested that wrinkling of polymers, particularly elastomers, would have numerous applications, ranging from tissue modeling in drug and therapy design to in vitro organogenesis for therapeutic explants in the field of regenerative medicine.