Carbon nanotubes (CNTs) are attractive nanostructures that serve as multifunctional transporters in biomedical applications, especially in the field of cancer therapy and diagnosis. Owing to their easily tunable nature and remarkable properties, numerous functionalizations and treatments of CNTs have been attempted for their utilization as hybrid nano-carriers in the delivery of various anticancer drugs, genes, proteins, and immunotherapeutic molecules. In this review, we discuss the current advances in the applications of CNT-based novel delivery systems with an emphasis on the various functionalizations of CNTs. We also highlight recent findings that demonstrate their important roles in cancer imaging applications, demonstrating their potential as unique agents with high-level ultrasonic emission, strong Raman scattering resonance, and magnetic properties.

Under physiological and pathological conditions, mechanical forces generated from cells themselves or transmitted from extracellular matrix (ECM) through focal adhesions (FAs) and adherens junctions (AJs) are known to play a significant role in regulating various cell behaviors. Substantial progresses have been made in the field of mechanobiology towards novel methods to understand how cells are able to sense and adapt to these mechanical forces over the years. To address these issues, this review will discuss recent advancements of traction force microscopy (TFM), intracellular force microscopy (IFM), and monolayer stress microscopy (MSM) to measure multiple aspects of cellular forces exerted by cells at cell-ECM and cell-cell junctional intracellular interfaces. We will also highlight how these methods can elucidate the roles of mechanical forces at interfaces of cell-cell/cell-ECM in regulating various cellular functions.

The tumor microenvironment presents spatiotemporal shifts in biomechanical properties with cancer progression. Hydrogel biomaterials like GelAGE offer the stiffness tuneability to recapitulate dynamic changes in tumor tissues by altering photo‐energy exposures. Here, a tuneable hydrogel with spatiotemporal control of stiffness and mesh‐network is developed. The volume of MCF7 spheroids encapsulated in a linear stiffness gradient demonstrates an inverse relationship with stiffness ( p < 0.0001). As spheroids are exposed to increased crosslinking (stiffer) and greater mechanical confinement, spheroid stiffness increases. Protein expression (TRPV4, β1 integrin, E‐cadherin, and F‐actin) decreases with increasing stiffness while showing strong correlations to spheroid volume ( r ² > 0.9). To further investigate the role of volume, MCF7 spheroids are grown in a soft matrix for 5 days prior to a second polymerisation which presents a stiffness gradient to equally expanded spheroids. Despite being exposed to variable stiffness, these spheroids show even protein expression, confirming volume as a key regulator. Overall, this work showcases the versatility of GelAGE and demonstrates volume expansion as a key regulator of 3D mechanosensation in MCF7 breast cancer spheroids. This platform has the potential to further investigation into the role of stiffness and dimensionality in 3D spheroid culture for other types of cancers and diseases.

Articular cartilage has a very limited regeneration capacity. Therefore, injury or degeneration of articular cartilage results in an inferior mechanical stability, load-bearing capacity, and lubrication capability. Here, we developed a biomimetic scaffold consisting of macroporous polyvinyl alcohol (PVA) sponges as a platform material for the incorporation of cell-embedded photocrosslinkable poly(ethylene glycol) diacrylate (PEGDA), PEGDA-methacrylated chondroitin sulfate (PEGDA-MeCS; PCS), or PEGDA-methacrylated hyaluronic acid (PEGDA-MeHA; PHA) within its pores to improve in vitro chondrocyte functions and subsequent in vivo ectopic cartilage tissue formation. Our findings demonstrated that chondrocytes encapsulated in PCS or PHA and loaded into macroporous PVA hybrid scaffolds maintained their physiological phenotypes during in vitro culture, as shown by the upregulation of various chondrogenic genes. Further, the cell-secreted extracellular matrix (ECM) improved the mechanical properties of the PVA-PCS and PVA-PHA hybrid scaffolds by 83.30% and 73.76%, respectively, compared to their acellular counterparts. After subcutaneous transplantation in vivo, chondrocytes on both PVA-PCS and PVA-PHA hybrid scaffolds significantly promoted ectopic cartilage tissue formation, which was confirmed by detecting cells positively stained with Safranin-O and for type II collagen. Consequently, the mechanical properties of the hybrid scaffolds were biomimetically reinforced by 80.53% and 210.74%, respectively, compared to their acellular counterparts. By enabling the recapitulation of biomimetically relevant structural and functional properties of articular cartilage and the regulation of in vivo mechanical reinforcement mediated by cell–matrix interactions, this biomimetic material offers an opportunity to control the desired mechanical properties of cell-laden scaffolds for cartilage tissue regeneration.

Poly(propylene fumarate) (PPF) has known to be a good candidate material for cartilage tissue regeneration because of its excellent mechanical properties during its degradation processes. Here, we describe the potential application of PPF-based materials as 3D printing bioinks to create macroporous cell scaffolds using micro-stereolithography. To improve cell-matrix interaction of seeded human chondrocytes within the PPF-based 3D scaffolds, we immobilized arginine-glycine-aspartate (RGD) peptide onto the PPF scaffolds. We also evaluated various cellular behaviors of the seeded chondrocytes using MTS assay, microscopic and histological analyses. The results indicated that PPF-based biocompatible scaffolds with immobilized RGD peptide could effectively support initial adhesion and proliferation of human chondrocytes. Such a 3D bio-printable scaffold can offer an opportunity to promote cartilage tissue regeneration.

The substantial progress made in the field of stem cell-based therapy has shown its significant potential applications for the regeneration of defective tissues and organs. Although previous studies have yielded promising results, several limitations remain and should be overcome for translating stem cell-based therapies to clinics. As a possible solution to current bottlenecks, cell sheet engineering (CSE) is an efficient scaffold-free method for harvesting intact cell sheets without the use of proteolytic enzymes, and may be able to accelerate the adoption of stem cell-based treatments for damaged tissues and organs regeneration. CSE uses a temperature-responsive polymer-immobilized surface to form unique, scaffold-free cell sheets composed of one or more cell layers maintained with important intercellular junctions, cell-secreted extracellular matrices, and other important cell surface proteins, which can be achieved by changing the surrounding temperature. These three-dimensional cell sheet-based tissues can be designed for use in clinical applications to target-specific tissue regeneration. This review will highlight the principles, progress, and clinical relevance of current approaches in the cell sheet-based technology, focusing on stem cell-based therapies for bone, periodontal, skin, and vascularized muscles.