The distinct spatial architecture of the apical actin cables (or actin cap) facilitates rapid biophysical signaling between extracellular mechanical stimuli and intracellular responses, including nuclear shaping, cytoskeletal remodeling, and the mechanotransduction of external forces into biochemical signals. These functions are abrogated in lamin A/C-deficient mouse embryonic fibroblasts that recapitulate the defective nuclear organization of laminopathies, featuring disruption of the actin cap. However, how nuclear lamin A/C mediates the ability of the actin cap to regulate nuclear morphology remains unclear. Here, we show that lamin A/C expressing cells can form an actin cap to resist nuclear deformation in response to physiological mechanical stresses. This study reveals how the nuclear lamin A/C-mediated formation of the perinuclear apical actin cables protects the nuclear structural integrity from extracellular physical disturbances. Our findings highlight the role of the physical interactions between the cytoskeletal network and the nucleus in cellular mechanical homeostasis.

Recent findings about cell fate change induced by physical stimuli have expedited the discovery of underlying regulatory mechanisms that determine stem cell differentiation. Progress with regards to micro‐/nanofabrication technology have led to the development of advanced materials that can mimic biophysical features of in vivo related circumstances of the human body. Since the cellular microenvironment directly defines cellular structure and function, diverse material properties including stiffness, topology, and surface chemistry are investigated to regulate multiple signaling cascades involved in stem cell differentiation for the development of innovative tools that can be widely utilized in various fields ranging from basic research to medical applications. This progress report addresses essential biophysical regulation and alteration of material properties applied to control stem cell differentiation. It also presents novel strategies to regulate stem cell differentiation based on relationships between recently discovered mechanotransduction pathways and cell differentiation signaling. A new perspective on stem cell physiology will further provide a framework of biomedical applications such as regenerative medicine and stem cell therapy.

Over the last 30 years, diverse types of nano-sized drug delivery systems (nanoDDSs) have been intensively explored for cancer therapy, exploiting their passive tumor targetability with an enhanced permeability and retention effect. However, their systemic administration has aroused some unavoidable complications, including insufficient tumor-targeting efficiency, side effects due to their undesirable biodistribution, and carrier-associated toxicity. In this review, the recent studies and advancements in intratumoral nanoDDS administration are generally summarized. After identifying the factors to be considered to enhance the therapeutic efficacy of intratumoral nanoDDS administration, the experimental results on the application of intratumoral nanoDDS administration to various types of cancer therapies are discussed. Subsequently, the reports on clinical studies of intratumoral nanoDDS administration are addressed in short. Intratumoral nanoDDS administration is proven with its versatility to enhance the tumor-specific accumulation and retention of therapeutic agents for various therapeutic modalities. Specifically, it can improve the efficacy of therapeutic agents with poor bioavailability by increasing their intratumoral concentration, while minimizing the side effect of highly toxic agents by restricting their delivery to normal tissues. Intratumoral administration of nanoDDS is considered to expand its application area due to its potent ability to improve therapeutic effects and relieve the systemic toxicities of nanoDDSs.

The multifaceted biological defense system modulating complex immune responses against pathogens and foreign materials plays a critical role in tissue homeostasis and disease progression. Recently developed biomaterials that can specifically regulate immune responses, nanoparticles, graphene, and functional hydrogels have contributed to the advancement of tissue engineering as well as disease treatment. The interaction between innate and adaptive immunity, collectively determining immune responses, can be regulated by mechanobiological recognition and adaptation of immune cells to the extracellular microenvironment. Therefore, applying immunomodulation to tissue regeneration and cancer therapy involves manipulating the properties of biomaterials by tailoring their composition in the context of the immune system. This review provides a comprehensive overview of how the physicochemical attributes of biomaterials determine immune responses, focusing on the physical properties that influence innate and adaptive immunity. This review also underscores the critical aspect of biomaterial‐based immune engineering for the development of novel therapeutics and emphasizes the importance of understanding the biomaterials‐mediated immunological mechanisms and their role in modulating the immune system.

Stem cells have been extensively used in regenerative medicine and tissue engineering; however, they often lose their functionality because of the inflammatory microenvironment. This leads to their poor survival, retention, and engraftment at transplantation sites. Considering the rapid loss of transplanted cells due to poor cell-cell and cell-extracellular matrix (ECM) interactions during transplantation, it has been reasoned that stem cells mainly mediate reparative responses via paracrine mechanisms, including the secretion of extracellular vesicles (EVs). Ameliorating poor cell-cell and cell-ECM interactions may obviate the limitations associated with the poor retention and engraftment of transplanted cells and enable them to mediate tissue repair through the sustained and localized presentation of secreted bioactive cues. Biomaterial-mediated strategies may be leveraged to confer stem cells enhanced immunomodulatory properties, as well as better engraftment and retention at the target site. In these approaches, biomaterials have been exploited to spatiotemporally present bioactive cues to stem cell-laden platforms (e.g., aggregates, microtissues, and tissue-engineered constructs). An array of biomaterials, such as nanoparticles, hydrogels, and scaffolds, has been exploited to facilitate stem cells function at the target site. Additionally, biomaterials can be harnessed to suppress the inflammatory microenvironment to induce enhanced tissue repair. In this review, we summarize biomaterial-based platforms that impact stem cell function for better tissue repair that may have broader implications for the treatment of various diseases as well as tissue regeneration.