“Boundarics in Biomedicine” is a cutting-edge interdisciplinary discipline, which is of great significance for understanding the origin of life, the interaction between internal and external environments, and the mechanism of disease occurrence and evolution. Here, the definition of Boundarics in Biomedicine is first described, including its connotation, research object, research method, challenges, and future perspectives.

“Boundarics in Biomedicine” is a cutting-edge interdisciplinary discipline involving multiple fields (e.g., bioscience, medicine, chemistry, materials science, and information science) dedicated to investigating and solving key scientific questions in the formation, identification, and evolution of living organism boundaries. Specifically, it encompasses 3 levels: (a) the boundary between the living organism and the external environment, (b) internal boundary within living organism, and (c) the boundary related to disease in living organism. The advancement of research in Boundarics in Biomedicine is of great scientific significance for understanding the origin of life, the interaction between internal and external environments, and the mechanism of disease occurrence and evolution, thus providing novel principles, technologies, and methods for early diagnosis and prevention of major diseases, personalized drug development, and prognosis assessment (Fig. 1).

In recent years, the unique mechanism of sliding ferroelectricity with ultralow switching barriers has been experimentally verified in a series of 2-dimensional (2D) materials. However, its practical applications are hindered by the low polarizations, the challenges in synthesis of ferroelectric phases limited in specific stacking configurations, and the low density for data storage since the switching process involves large-area simultaneous sliding of a whole layer. Herein, through first-principles calculations, we propose a type of semi-sliding ferroelectricity in the single metal porphyrin molecule intercalated in 2D bilayers. An enhanced vertical polarization can be formed independent on stacking configurations and switched via sliding of the molecule accompanied by the vertical displacements of its metal ion anchored from the upper layer to the lower layer. Such semi-sliding ferroelectricity enables each molecule to store 1 bit data independently, and the density for data storage can be greatly enhanced. When the bilayer exhibits intralayer ferromagnetism and interlayer antiferromagnetic coupling, a considerable difference in Curie temperature between 2 layers and a switchable net magnetization can be formed due to the vertical polarization. At a certain range of temperature, the exchange of paramagnetic–ferromagnetic phases between 2 layers is accompanied by ferroelectric switching, leading to a hitherto unreported type of multiferroic coupling that is long-sought for efficient “magnetic reading + electric writing”.

Flexible epidermal electrodes hold substantial promise in realizing human electrophysiological information collections. Conventional electrodes exhibit certain limitations, including the requirement of skin pretreatment, reliance on external object-assisted fixation, and a propensity of dehydration, which severely hinder their applications in medical diagnosis. To tackle those issues, we developed a hydrogel electrode with both transcutaneous stimulation and neural signal acquisition functions. The electrode consists of a composite conductive layer (CCL) and adhesive conductive hydrogel (ACH). The CCL is designed as a laminated structure with high conductivity and charge storage capacity (CSC). Based on the optimization of Hoffmeister effect, the ACH demonstrates excellent electrical (resistivity of 3.56 Ω·m), mechanical (tensile limit of 1,650%), and adhesion properties (peeling energy of 0.28 J). The utilization of ACH as electrode/skin interface can reduce skin contact impedance and noise interference and enhance the CSC and charge injection capacity of electrodes. As a proof of concept, peripheral nerve conduction studies were performed on human volunteers to evaluate the as-fabricated hydrogel electrodes. Compared with the commercial electrodes, our hydrogel electrodes achieved better signal continuity and lower distortion, higher signal-to-noise ratio (~35 dB), and lower stimulation voltages (up to 27% lower), which can improve the safety and comfort of nerve conduction studies.

Natural biomaterials have been showing extensive potential in wound healing; attempts therefore focus on productions achieving both antimicrobial and tissue regenerative abilities. Here, we construct a decellularized human colon tumor (DHCT)-derived scaffold for wound remolding via microfluidic bioprinting. The DHCT retains a series of growth factors, fibrin, and the collagen configuration, that favor tissue repair and reconstruction. Specifically, the scaffold shows superior abilities in cell migration and angiogenesis. The biocompatible scaffold is also imparted with tissue adhesion ability and photothermal effect due to the coating of biologically derived polydopamine on the surface. The strong photothermal effect under near-infrared irradiation also present the scaffold with an antibacterial rate exceeding 90%. Furthermore, in vivo experiments convinced that the polydopamine-integrated DHCT scaffold can markedly expedite the healing process of acute extensive wounds. These findings indicate that composite materials derived from natural tumors have substantial potential in pertinent clinical applications.

Candida albicans is an opportunistic fungal pathogen of humans. It causes a variety of infections ranging from superficial mucocutaneous conditions to severe systemic diseases that result in substantial morbidity and mortality. This pathogen frequently forms biofilms resistant to antifungal drugs and the host immune system, leading to treatment failures. Recent research has demonstrated the potential of nanorobots to penetrate biological barriers and disrupt fungal biofilms. In this perspective paper, we provide a brief overview of recent breakthroughs in nanorobots for candidiasis treatment and discuss current challenges and prospects.

Topological insulating states in 2-dimensional (2D) materials are ideal systems to study different types of quantized response signals due to their in gap metallic states. Very recently, the quantum spin Hall effect was discovered in monolayer TaIrTe₄ via the observation of quantized longitudinal conductance that rarely exists in other 2D topological insulators. The nontrivial Z₂ topological charges can exist at both charge neutrality point and the van Hove singularity point with correlation-effect-induced bandgap. On the basis of this model 2D material, we studied the switch of quantized signals between longitudinal conductance and transversal Hall conductance via tuning external magnetic field. In Z₂ topological phase of monolayer TaIrTe₄, the zero Chern number can be understood as 1 – 1 = 0 from the double band inversion from spin-up and spin-down channels. After applying a magnetic field perpendicular to the plane, the Zeeman split changes the band order for one branch of the band inversion from spin-up and spin-down channels, along with a sign charge of the Berry phase. Then, the net Chern number of 1 – 1 = 0 is tuned to 1 + 1 = 2 or −1 – 1 = −2 depending on the orientation of the magnetic field. The quantized signal not only provides another effective method for the verification of topological state in monolayer TaIrTe₄ but also offers a strategy for the utilization of the new quantum topological states based on switchable quantized responses.

Auxetic materials have been extensively studied for their design, fabrication and mechanical properties. These material systems exhibit unique mechanical characteristics such as high impact resistance, shear strength, and energy absorption capacity. Most existing auxetic materials are two-dimensional (2D) and demonstrate half-auxetic behavior, characterized by a negative Poisson's ratio when subjected to either tensile or compressive forces. Here, we present novel three-dimensional (3D) auxetic mechanical metamaterials, termed coupling chiral cuboids, capable of achieving negative Poisson's ratio under both tension and compression. We perform experiments, theoretical analysis, and numerical simulations to validate the wholly auxetic response of the proposed coupling chiral cuboids. Parametric studies are carried out to investigate the effects of structural parameters on the elastic modulus and Poisson's ratio of the coupling chiral cuboids. The results imply that the Poisson's ratio sign-switching from negative to positive can be implemented by manipulating the thickness of Z-shaped ligaments. Finally, the potential application of the coupling chiral cuboids as inner cores for impact-resistant sandwich panels is envisioned and validated. Test results demonstrate a remarkable 49.3% enhancement in energy absorption compared to conventional solid materials.

Stereoscopic imaging of single molecules at the plasma membrane of single cell requires spatial resolutions in 3 dimensions (x-y-z) at 10-nm level, which is rarely achieved using most optical super-resolution microscopies. Here, electrochemical stereoscopic microscopy with a detection limit down to a single molecule is achieved using a photoreduction-assisted cycle inside a 20-nm gel electrolyte nanoball at the tip of a nanopipette. On the basis of the electrochemical oxidation of Ru(bpy)₃²⁺ into Ru(bpy)₃³⁺ followed by the reduction of Ru(bpy)₃³⁺ into Ru(bpy)₃²⁺ by photogenerated isopropanol radicals, a charge of 1.5 fC is obtained from the cycling electron transfers involving one Ru(bpy)₃^2+/3+ molecule. By using the nanopipette to scan the cellular membrane modified with Ru(bpy)₃²⁺-tagged antibody, the morphology of the cell membrane and the distribution of carcinoembryonic antigen (CEA) on the membrane are electrochemically visualized with a spatial resolution of 14 nm. The resultant stereoscopic image reveals more CEA on membrane protrusions, providing direct evidence to support easy access of membrane CEA to intravenous antibodies. The breakthrough in single-molecule electrochemistry at the cellular level leads to the establishment of high-resolution 3-dimensional single-cell electrochemical microscopy, offering an alternative strategy to remedy the imperfection of stereoscopic visualization in optical microscopes.

Nanomaterial-based drug delivery systems are susceptible to premature drug leakage and systemic toxicity due to lack of specific targeting, and live-cell drug delivery is also prone to be restricted by drug carrier–cell interactions. Here, a method is established to adsorb drug-loaded nanomaterials externally to the live cells, which reduces cytotoxicity caused by drug uptake and improves the bioactivity of the carrier cells and drug release at the lesion site. It was found that polyphenols act like “double-sided tape” to bridge metal–organic framework (MOF) nanoparticles with live macrophages (Mφ), attaching MOFs to the Mφ surface and minimizing intracellular uptake, with no negative effect on cell proliferation. On this basis, a “macrophage missile” with peroxymonosulfate (PMS)-loaded MOF nanoparticles on the cell surface was constructed. As a “propellant”, the Mφ, in which bioactivity is preserved, can selectively identify and target tumor cells, precisely bringing nanomedicines to the lesion. MOF nanoparticles are used to load and catalyze PMS, which acts as an exogenous source of reactive oxygen species, showing higher efficacy and lower toxicity in an oxygen-independent manner. The primary study results demonstrate that this innovative combination of biology and nanomaterials remarkably enhances tumor targeting and therapeutic efficacy while reducing systemic side effects. This approach is expected to provide a more effective and safer treatment for lung cancer and holds promise for broader applications in other cancer therapies.

Mitophagy maintains tissue homeostasis by self-eliminating defective mitochondria through autophagy. How mitophagy regulates stem cell activity during hair regeneration remains unclear. Here, we found that mitophagy promotes the proliferation of hair germ (HG) cells by regulating glutathione (GSH) metabolism. First, single-cell RNA sequencing, mitochondrial probe, transmission electron microscopy, and immunofluorescence staining showed stronger mitochondrial activity and increased mitophagy-related gene especially Prohibitin 2 (Phb2) expression at early-anagen HG compared to the telogen HG. Mitochondrial inner membrane receptor protein PHB2 binds to LC3 to initiate mitophagy. Second, molecular docking and functional studies revealed that PHB2-LC3 activates mitophagy to eliminate the damaged mitochondria in HG. RNA-seq, single-cell metabolism, immunofluorescence staining, and functional validation discovered that LC3 promotes GSH metabolism to supply energy for promoting HG proliferation. Third, transcriptomics analysis and immunofluorescence staining indicated that mitophagy was down-regulated in the aged compared to young-mouse HG. Activating mitophagy and GSH pathways through small-molecule administration can reactivate HG cell proliferation followed by hair regeneration in aged hair follicles. Our findings open up a new avenue for exploring autophagy that promotes hair regeneration and emphasizes the role of the self-elimination effect of mitophagy in controlling the proliferation of HG cells by regulating GSH metabolism.