Anthony Callanan

Loss of functional thyrocytes following thyroid injury or radiotherapy remains a significant clinical challenge, motivating development of biomaterial-based strategies to support thyroid cell survival and function. 17 β -Estradiol (E2) has been shown to promote thyrocyte proliferation and antioxidant responses, although systemic or bolus delivery may induce cytotoxicity and raises concerns regarding long-term pathological effects. Here, electrospun polycaprolactone (PCL) scaffolds incorporating varying concentrations of E2 were developed as a localised hormone delivery platform for thyroid epithelial cells. E2 incorporation altered scaffold mechanical behaviour, hydrophilicity, and porosity in a concentration-dependent manner while preserving fibre morphology, crystallinity, and thermal stability. Scaffold-mediated E2 delivery supported sustained thyrocyte viability and proliferation compared with bolus E2 exposure, with intermediate E2 concentrations producing the most favourable biological response. Morphological analysis demonstrated extensive cell spreading and organised cytoskeletal structures without features associated with apoptosis. Although E2-loaded scaffolds did not exhibit direct radical scavenging activity, they promoted upregulation of antioxidant-associated genes, indicating indirect modulation of cellular redox homeostasis. Thyroid-specific functional markers associated with hormone synthesis and maintenance of the differentiated thyroid phenotype were largely preserved across scaffold groups during the 14 d culture period. Furthermore, no detectable BRAF V600E or V600K mutations were identified under any condition tested. Collectively, these findings demonstrate that electrospun E2@PCL scaffolds provide a tunable microenvironment capable of supporting thyrocyte survival, proliferation, and functional maintenance, highlighting their potential for thyroid tissue engineering applications targeting radiation-induced thyroid injury.

There is a pressing need for alternative treatment approaches for chronic kidney disease (CKD), a condition which affects a significant proportion of the global population. In vitro tissue-engineered models offer a promising solution by developing a physiologically relevant representation of the kidney’s microenvironment. Key criteria in the development of such an environment include a three-dimensional cell culture material, consideration of the interactions of multiple cell types, and the provision of a fluidic environment. Herein, we investigate the use of a bioreactor platform which can maintain epithelial and endothelial cells, seeded on an either side of electrospun scaffolds, within a dynamic fluidic environment. Validation of the bioreactor’s capacity to maintain these cell types in co-culture and deliver a physiologically relevant shear stress was demonstrated via colorimetric testing and computational fluid dynamics respectively. Subsequent analysis of the viability, DNA content, morphology, protein and gene expression of both cell types indicate significant variations in cellular responses depending on their culture environments. The results of this work support the use of the bioreactor system as an effective means of replicating aspects of the renal tubule microenvironment, and thus may progress future treatments of CKD.

Oxidative stress is a key driver of articular cartilage degeneration, disrupting chondrocyte redox homeostasis and the extracellular matrix (ECM). N‐acetylcysteine (NAC) can modulate both extracellular and intracellular redox balance, making it a promising therapeutic agent for cartilage damage. However, delivery of NAC to the damaged cartilage site is limited. Therefore, this study incorporates NAC into polycaprolactone (PCL) fibers, aiming to regulate ROS levels and the genes related to glutathione production and transsulfuration pathways. The scaffolds containing NAC at concentrations of 0%, 0.5%, and 1% (w/v) are fabricated via electrospinning and characterized using FTIR, DPPH assay, and mechanical testing. For in vitro assessments, primary bovine chondrocytes are isolated and cultured on scaffolds for 21 days. The results demonstrate that NAC maintains its stability after exposure to environmental factors. Furthermore, NAC addition significantly increases the antioxidant activity of scaffolds while affecting the fiber diameter and mechanical properties. Seeded chondrocytes maintain viability for 21 days, showcasing no toxic effects of NAC. Critically, gene expression analysis reveals that 1% NAC scaffolds significantly upregulate GCLC, GSS, CBS, and CTH genes, indicating potential activation of the glutathione and transsulfuration pathways. These findings highlight a promising strategy for using redox‐modulating antioxidants in future regenerative medicine applications.

Radiation‐induced hypothyroidism (RIHT) is a frequent consequence of head and neck radiotherapy, driven by oxidative stress, inflammation, and immune dysregulation. Current therapies address hormonal imbalance but not underlying tissue damage. Strategies involving macrophage modulation and oxidative stress reduction represent a promising target for restoring homeostasis in the irradiated thyroid. Electrospun polycaprolactone (PCL) scaffolds incorporating 0.5%–3% adenosine are developed to provide localized modulation of oxidative and inflammatory responses. Adenosine incorporation does not alter scaffold morphology or stability. In vitro studies demonstrate that 1% adenosine scaffolds enhance thyrocyte proliferation, epithelial cohesion, and expression of antioxidant enzymes glutathione peroxidase ( GPX1 ) and catalase ( CAT ), while reducing markers of senescence and apoptosis ( RGN , CDKN2A , CASP3 ). In parallel, adenosine scaffolds regulate THP‐1‐derived macrophage behaviour, promoting a pro‐reparative CD206+/CD163+ phenotype and reducing CD86, CD80 , and TNF α expression associated with inflammatory activation. This study identifies fibrosis and oxidative stress as contributors to RIHT and demonstrates the feasibility of adenosine‐blended scaffolds as a platform for targeting these mechanisms. Macrophage heterogeneity was characterized in the thyroid pre‐ and post‐irradiation for an immune‐guided design. The resulting scaffolds provide a targeted strategy to modulate key contributors to RIHT pathology, laying the groundwork for future in vivo validation.

Chronic kidney disease stands as a significant global health challenge, exacerbated by an ongoing scarcity of available organs for transplantation. Kidney tissue engineering is emerging as a promising innovation in the development of in vitro kidney models, which can enhance discoveries of new drug treatment strategies. Current efforts are mainly focused on 2D cell cultures, and substantial emphasis has been placed on the use of extracellular matrix materials as a 3D scaffolding environment. In this study, we propose an innovative approach to controlling a kidney cell microenvironment that utilizes a 3D‐printed bioreactor, in conjunction with electrospun PCL scaffolds. Our novel bioreactor design has been engineered to apply a consistent average shear stress distribution across the scaffold surface within a dual‐chamber configuration. This shear stress distribution was designed with the use of computational fluid dynamics and a modified fluid viscosity that mimics blood properties. Herein, we demonstrate the capacity of this system to create a microenvironment that can sustain kidney cells while promoting the upregulation of vital transmembrane and tight junction genes. Notably, this device has the potential to represent renal microenvironments, positioning it as a valuable tool in the development of in vitro kidney models.

Cardiovascular diseases are one of the leading causes of global mortality. Treatment methods such as bypass graft operations, while often successful, can fail in cases of systemic disease or compliance mismatch. Tissue engineered vascular grafts may offer a potential solution, by means of an implantable cell‐seeded scaffold that can integrate into the graft site. Modifications to the cell culture environment, such as through physical modification of the scaffold structure, or culturing cells in a dynamic fluidic environment, have been shown to alter cellular behavior. Herein, we combine these two approaches by incorporating electrospun polycaprolactone scaffolds consisting of smooth and modified fiber surface topographies within a series of novel 3D printed microfluidic bioreactors. The bioreactors successfully maintained the viability of human umbilical vein endothelial cells over a 24‐h period, with the smooth scaffolds in static culture and dimpled scaffolds under dynamic culture indicating the highest cell viability. An increase in stiffness and hydrophilicity of the modified scaffold is also noted in comparison to the scaffold consisting of smooth fibers. These results indicate that both the bioreactor system and the modified electrospun scaffold are capable of inducing variations in cellular response, thus warranting further investigation for the advancement of vascular tissue engineering.

Passive anti-icing coatings are a promising solution to the dangers of ice accumulation on surfaces. We studied plain polydimethylsiloxane (PDMS) and (commercially available) NuSil R-2180 coatings alongside PDMS coatings infused with two molecular weights and percentages of silicone oil. The icephobicity of the coatings was measured via ice adhesion strength and freezing time. 100 repeated deicing cycles were performed, which showed the oil-infused coatings had consistently lower ice adhesion strengths (∼10-20 kPa) than nonoil-infused coatings (∼100 kPa). The nonoil-infused coatings also showed increasing instances of exceptionally high ice adhesion strengths (>650 kPa), reducing the reliability of their icephobicity long-term. Oil infusion did not negatively affect the freezing time of the coatings, and despite decreases in freezing time after 100 deicing cycles, the coatings maintained an improvement compared to uncoated aluminum. Analysis showed adhesion strength is more strongly affected by shear modulus than coating thickness, work of adhesion, or static water contact angle. Wear from the deicing cycles was minimal. Any wear that was present did not significantly affect icephobicity. Oil infusion of elastomer coatings reduces ice accumulation on surfaces and provides a more reliable long-term solution for anti-icing applications.

Liver disease cases are rapidly expanding worldwide, and transplantation remains the only effective cure for end-stage disease. There is an increasing demand for developing potential drug treatments, and regenerative therapies using in-vitro culture platforms. Human decellularized extracellular matrix (dECM) is an appealing alternative to conventional animal tissues as it contains human-specific proteins and can serve as scaffolding materials. Herein we exploit this with human donor tissue from discarded liver which was not suitable for transplant using a synergistic approach to combining biological and topographical cues in electrospun materials as an in-vitro culture platform. To realise this, we developed a methodology for incorporating human liver dECM into electrospun polycaprolactone (PCL) fibres with surface nanotopographies (230–580 nm). The hybrid scaffolds were fabricated using varying concentrations of dECM; their morphology, mechanical properties, hydrophilicity and stability were analysed. The scaffolds were validated using HepG2 and primary mouse hepatocytes, with subsequent results indicating that the modified scaffolds-maintained cell growth and influenced cell attachment, proliferation and hepatic-related gene expression. This work demonstrates a novel approach to harvesting the potential from decellularized human tissues in the form of innovative in-vitro culture platforms for liver.