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Cellular senescence refers to a state of irreversible arrest of cell proliferation in response to various forms of cellular stress. It is known that the accumulation of senescent cells is a hallmark of aging, and mounting evidence has shown that the chronic accumulation of senescent cells is a significant contributor to various deleterious age-related pathologies. To limit the detrimental impacts of cellular senescence, there has been growing interest in targeted delivery of therapeutics to senescent cells to treat age-related pathologies and promote healthy aging. Two popular strategies include the elimination of senescent cells using senolytic drugs, and rejuvenation of senescent cells. To that end, it is integral that the delivery of senolytics, senomorphics or rejuvenating biomolecules to senescent cells are highly selective to enhance delivery efficacy and safety. However, there is little understanding of how senescence-associated biophysical changes such as cellular size and stiffness can be exploited for targeted therapeutics delivery. In this review, the biomolecular and biophysical markers of senescence along with senescence models and emerging therapeutics are first described. This review then focuses on how biophysical properties can be exploited for targeted therapeutics delivery, using approaches like nanoparticles, electroporation, sonoporation, photoporation and high aspect-ratio nanostructures to senescent cells.

Cells interact with their surrounding environment through a combination of static and dynamic mechanical signals that vary over stimulus types, intensity, space, and time. Compared to static mechanical signals such as stiffness, porosity, and topography, the current understanding on the effects of dynamic mechanical stimulations on cells remains limited, attributing to a lack of access to devices, the complexity of experimental set-up, and data interpretation. Yet, in the pursuit of emerging translational applications (e.g., cell manufacturing for clinical treatment), it is crucial to understand how cells respond to a variety of dynamic forces that are omnipresent in vivo so that they can be exploited to enhance manufacturing and therapeutic outcomes. With a rising appreciation of the extracellular matrix (ECM) as a key regulator of biofunctions, researchers have bioengineered a suite of ECM-mimicking hydrogels, which can be fine-tuned with spatiotemporal mechanical cues to model complex static and dynamic mechanical profiles. This review first discusses how mechanical stimuli may impact different cellular components and the various mechanobiology pathways involved. Then, how hydrogels can be designed to incorporate static and dynamic mechanical parameters to influence cell behaviors are described. The Scopus database is also used to analyze the relative strength in evidence, ranging from strong to weak, based on number of published literatures, associated citations, and treatment significance. Additionally, the impacts of static and dynamic mechanical stimulations on clinically relevant cell types including mesenchymal stem cells, fibroblasts, and immune cells, are evaluated. The aim is to draw attention to the paucity of studies on the effects of dynamic mechanical stimuli on cells, as well as to highlight the potential of using a cocktail of various types and intensities of mechanical stimulations to influence cell fates (similar to the concept of biochemical cocktail to direct cell fate). It is envisioned that this progress report will inspire more exciting translational development of mechanoresponsive hydrogels for biomedical applications.

Polymeric Janus particles can be exploited for a myriad of applications. Through the understanding of interfacial tensions, theragnostic agents such as drugs or nanomaterials can be successfully encapsulated into Janus particles without losing their anisotropic structure. In this work, it is reported that how Janus superstructures, as a further extension of the Janus morphology, can be obtained by blending other synthesis parameters into the solvent emulsion process, while adhering to the requirements of the Harkin's spreading coefficient (HSC) theory. Designing such unique structures for drug delivery can provide a broader range of possibilities and applications beyond conventional Janus particles.

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