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Most of us may mistakenly believe that sciences within the nano regime are a simple extension of what is observed in micrometer regions. We may be misled to think that nanotechnology is merely a far advanced version of microtechnology. These thoughts are basically wrong. For true developments in nanosciences and related engineering outputs, a simple transformation of technology concepts from micro to nano may not be perfect. A novel concept, nanoarchitectonics, has emerged in conjunction with well-known nanotechnology. In the first part of this review, the concept and examples of nanoarchitectonics will be introduced. In the concept of nanoarchitectonics, materials are architected through controlled harmonized interactions to create unexpected functions. The second emerging concept is to control nano-functions by easy macroscopic mechanical actions. To utilize sophisticated forefront science in daily life, high-tech-driven strategies must be replaced by low-tech-driven strategies. As a required novel concept, hand-operation nanotechnology can control nano and molecular systems through incredibly easy action. Hand-motion-like macroscopic mechanical motions will be described in this review as the second emerging concept. These concepts are related bio-processes that create the third emerging concept, mechanobiology and related mechano-control of bio-functions. According to this story flow, we provide some incredible recent examples such as atom-level switches, operation of molecular machines by hand-like easy motions, and mechanical control of cell fate. To promote and activate science and technology based on these emerging concepts in nanotechnology, the contribution and participation of polymer scientists are crucial. We hope that some readers would have interests within what we describe. This review tests you for survival in modern science and technology.Q1: Can we operate molecular machines by our hands?Ans: YES (Hand-Operating Nanotechnology)!Q2: Can we mechanically control life and bio-events?Ans: YES (Mechanobiology)!Q3: What comes after nanotechnology?Ans: It is definitely Nanoarchitectonics.

Stem cells and their microenvironment interact cooperatively to dictate their fates. Biomaterials are dynamically remodeled by stem cells, and stem cells sense and translate the changes into cell fate decisions. We have previously reported that adaptive biomaterials composed of fibronectin inserted into protein nanosheets at a liquid interface enhance neuronal differentiation of human mesenchymal stem cells (hMSCs). However, we could not decouple clearly the effect of ligand density from that of fibrillary structure on cellular function and fate. Here we present an adaptive biomaterial based on two-dimensional networks of protein nanofibrils at a liquid–liquid interface. Compared with flat protein nanosheets, this biomaterial enhances neuronal differentiation of hMSCs through a signaling mechanism involving focal adhesion kinase. Lipid raft microdomains in plasma membrane are found to play a central role in which hMSCs rapidly adapt to the dynamic microenvironment at the fluid interface. Our finding has substantial implications for regenerative medicine and tissue engineering. In this work the authors report how human mesenchymal stem cells rapidly adapt to dynamic microenvironment through lipid raft in membrane microdomains that direct neurogenesis.

The mechanical properties of the cellular microenvironment contribute significantly to cell behavior. Thus, deformable phospholipid‐decorated perfluorocarbon interfaces have emerged for further expansion of material mechanics to an ultimate soft range as cell scaffolds. In addition, a highly deformable state requires the material to be robust enough to adapt to dynamic cellular forces. However, the effect of interfacial viscosity on the cell adhesion behavior and material robustness remains unknown on the super‐soft substrate. To address these issues, an interfacial phospholipid membrane (IPLM) with tunable viscosity is constructed by varying the mixing ratio of saturated and unsaturated lipid layers. By co‐assembling a cell adhesive and fluorescent lipid into the IPLM, it is shown that higher viscosity interfaces with lower unsaturated lipid content are preferred from the viewpoint of cell spreading. However, a viscosity that is too high for 0% unsaturated lipid alters the lipid layer to a brittle solid‐like nature, making it less adaptive to cell traction‐induced high deformation. Therefore, at least a trace amount of unsaturated lipids is required to maintain the robustness of fluid scaffolds. These findings are useful for the design of biomimetic materials and the long‐term investigation of cell‐matrix mechanical interactions in highly adaptive environments. Viscosity‐tunable fluid scaffolds are developed by decorating a perfluorocarbon interface with phospholipid membranes (IPLMs) of varying unsaturated lipid contents. A solid‐like IPLM is cell‐adhesive but brittle, whereas the least viscous IPLM does not allow cell adhesion. Moderately viscous IPLMs serve as highly adaptive cellular scaffolds. These findings aid in designing biomimetic materials that require cell adhesion to fluid surfaces.

Cytotoxic agents targeting the epidermal growth factor receptor (EGFR) exhibit significant potential for cancer therapy as EGFR is overexpressed in various cancers. As alternatives to conventional EGFR inhibitors (EGFRi), which exert side effects on non-cancer cells, EGF-immobilized gold nanoparticles exhibit selective cytotoxicity in EGFR-overexpressing cancer cells by locally enhancing EGFR activation and modulating signal transduction through a signal condensation mechanism. However, considering real therapeutic applications, it is important to confirm that the same principle can be applied to polymeric nanoparticles, which are more suitable carriers owing to their biodegradability and biocompatibility, remains unclear. Therefore, in this study, we aimed to investigate the anti-cancer activities of EGF-conjugates with two kinds of polymeric nanoparticles: polystyrene nanoparticles and polymeric micelles. Initial mechanistic studies on phosphorylation signaling and cholesterol depletion revealed that EGF-polystyrene nanoparticles exhibited cytotoxicity against human cervical adenocarcinoma HeLa cells via local enhancement of EGFR activity in membrane rafts. Moreover, EGF-polymeric micelles exerted selective anti-cancer effects against EGFRi-resistant MDA-MB468 refractory triple-negative breast cancer cells after optimization of particle size. These results suggest that the unique anti-cancer effects of EGF nanoparticles are not dependent on the carrier platform. Furthermore, EGF nanoparticles exhibited high cytotoxicity against cancer cells responding poorly to conventional EGFR-targeted anti-cancer drugs, showing potential for future medical applications.

The reduced workspace in endonasal endoscopic surgery (EES) hinders the execution of complex surgical tasks such as suturing. Typically, surgeons need to manipulate non-dexterous long surgical instruments with an endoscopic view that makes it difficult to estimate the distances and angles required for precise suturing motion. Recently, robot-assisted surgical systems have been used in laparoscopic surgery with promising results. Although robotic systems can provide enhanced dexterity, robot-assisted suturing is still highly challenging. In this paper, we propose a robot-assisted stitching method based on an online optimization-based trajectory generation for curved needle stitching and a constrained motion planning framework to ensure safe surgical instrument motion. The needle trajectory is generated online by using a sequential convex optimization algorithm subject to stitching kinematic constraints. The constrained motion planner is designed to reduce surrounding damages to the nasal cavity by setting a remote center of motion over the nostril. A dual concurrent inverse kinematics (IK) solver is proposed to achieve convergence of the solution and optimal time execution, in which two constrained IK methods are performed simultaneously; a task-priority based IK and a nonlinear optimization-based IK. We evaluate the performance of the proposed method in a stitching experiment with our surgical robotic system in a robot-assisted mode and an autonomous mode in comparison to the use of a conventional surgical tool. Our results demonstrate a noticeable improvement in the stitching success ratio in the robot-assisted mode and the shortest completion time for the autonomous mode. In addition, the force interaction with the tissue was highly reduced when using the robotic system.

Endoscopic endonasal surgery (EES) is a minimally invasive technique for removal of pituitary adenomas or cysts at the skull base. This approach can reduce the invasiveness and recovery time compared to traditional open surgery techniques. However, it represents challenges to surgeons because of the constrained workspace imposed by the nasal cavity and the lack of dexterity with conventional surgical instruments. While robotic surgical systems have been previously proposed for EES, issues concerned with proper interface design still remain. In this paper, we present a cooperative, compact, and versatile bimanual human-robot interface aimed to provide intuitive and safe operation in robot-assisted EES. The proposed interface is attached to a robot arm and holds a multi-degree-of-freedom (DOF) articulated forceps. In order to design the required functionalities in EES, we consider a simplified surgical task scenario, with four basic instrument operations such as positioning, insertion, manipulation, and extraction. The proposed cooperative strategy is based on the combination of force based robot control for tool positioning, a virtual remote-center-of-motion (VRCM) during insertion/extraction tasks, and the use of a serial-link interface for precise and simultaneous control of the position and the orientation of the forceps tip. Virtual workspace constraints and motion scaling are added to provide safe and smooth control of our robotic surgical system. We evaluate the performance and usability of our system considering reachability, object manipulability, and surgical dexterity in an anatomically realistic human head phantom compared to the use of conventional surgical instruments. The results demonstrate that the proposed system can improve the precision, smoothness and safety of the forceps operation during an EES.

As an alternative to conventional plastic dishes, the interface between water-immiscible hydrophobic fluids, such as perfluorocarbons and silicones, permits cell adhesion and growth. Thus, it is expected to replace the petroleum-derived products in a sustainable society. However, most hydrophobic fluids are cytotoxic, which limits the range of mechanical and chemical cues exposed to the cells. Using a data-driven approach, this study aimed to identify non-cytotoxic ionic liquids (ILs) as fluid culture platforms to take advantage of their 'designer' nature for broadening the possible physicochemical ranges exposed to cells and their repeated use owing to their high heat stability before their biological applications. The new candidates within the readily synthesized ammonium-type ILs were identified through the active cycle of regression and a limited number of cytotoxicity tests. Structure - cytotoxicity analysis indicated that the presence of multiple long alkyl branches was critical for low cytotoxicity. Particularly, we successfully cultured human mesenchymal stem cells (hMSCs) at the trihexylethylammonium trifluoromethylsulfonylimide interface and repeated their use after solvent extraction and heat sterilization. This study identified non-cytotoxic ILs that fulfill plastics' ( educe, ecycle, and eplace) requirements and opens new avenues for hMSC fate manipulation through mechanotransduction.

Purpose While a wide variety of platelet-rich plasma (PRP) solutions has been developed, innovation continues. In this case, the freeze-dried platelet factor concentrate (PFC-FD) represents another step in PRP refinement. The preparation of PFC-FD at a central laboratory with freeze drying for shelf stabilization should provide additional quality improvements if clinical effectiveness can be demonstrated. Therefore, this study was undertaken to assess the safety and effectiveness of PFC-FD in a prospective open-label trial of patients suffering from knee osteoarthritis (OA). Methods 312 consecutive knee OA patients (67% female, mean age 63 ± 10 years), were prospectively recruited in an outpatient knee clinic in Japan. Of these, 10 (3.2%) were lost to follow-up at < 12 months and 17 (5.5%) sought additional knee therapy during the follow-up period. The primary outcome of interest was achievement of the OMERACT-OARSI responder criteria with secondary outcomes of adverse events and PROMs scores 1, 3, 6, 12 months following a single PFC-FD injection. Results 285 patients (91%) completed 12 month PROMs. The 17 who sought additional therapy were considered failures leaving an effective sample size of 302 for our primary outcome in which 62% of patients achieved OMERACT-OARSI responder status by 12 months. This varied by OA class with Kellgren–Lawrence grade 4 patients 3.6 times less likely to be responders than grade 1–2 patients. 6% of patients experienced a non-serious adverse event, primarily pain or swelling at the injection site. Conclusions PFC-FD provides an observable clinical improvement in 62% of knee OA patients at 12 months post-injection with very little risk of any clinically relevant adverse event. Of course, nearly 40% of patients did not experience an observable clinical improvement, primarily among those with worse KL grades. Level of evidence Therapeutic, Level II.

Background The relationship between internal root resorption and oxidative stress has not yet been reported. This study aimed to add molecular insight into internal root resorption. The present study was conducted to investigate the effect of hydrogen peroxide (H 2 O 2 ) as an inducer of oxidative stress on the calcification ability of human dental pulp cells (hDPCs) and the involvement of inositol 1, 4, 5-trisphosphate (IP3). Material and methods hDPCs (Lonza, Basel, Switzerland) were exposed to H 2 O 2 . Cell viability and reactive oxygen species (ROS) production were then evaluated. To investigate the effect of H 2 O 2 on the calcification ability of hDPCs, real-time PCR for alkaline phosphatase (ALP) mRNA expression, ALP staining, and Alizarin red staining were performed. Data were compared with those of hDPCs pretreated with 2-aminoethyldiphenylborate (2-APB), which is an IP3 receptor inhibitor. Results H 2 O 2 at concentrations above 250 µM significantly reduced cell viability ( P  < 0.01). More ROS production occurred in 100 µM H 2 O 2 -treated hDPCs than in control cells ( P  < 0.01). 2-APB significantly decreased the production ( P  < 0.05). H 2 O 2 -treated hDPCs showed significant reductions in ALP mRNA expression ( P  < 0.01), ALP activity ( P  < 0.01), and mineralized nodule deposition compared with negative control cells ( P  < 0.01). 2-APB significantly inhibited these reductions ( P  < 0.01, P  < 0.05 and P  < 0.01, respectively). Data are representative of three independent experiments with three replicates for each treatment and values are expressed as means ± SD. Conclusion To the best of our knowledge, this is the first study documenting the involvement of IP 3 signaling in the calcification ability of human dental pulp cells impaired by H 2 O 2 .

Enabling robots to interact physically with complex, unstructured environments remains a significant challenge. Methods relying solely on joint‐torque sensing suffer from ambiguity in multicontact scenarios, while vision is prone to occlusion. This article presents an approach using a whole‐body tactile skin sensor network to address these limitations by integrating feedback for compliance, force control, and collision avoidance. The control framework uses quadratic programming to integrate rich tactile and proximity feedback from the skin network. To maintain real‐time performance with this dense sensory data, the method clusters sensor activations into active regions. This enables the robot to generate whole‐body compliance, regulate interaction forces across various body parts, and transform proximity feedback into distance constraints to dynamically avoid collisions in unmodeled environments. The effectiveness and real‐time feasibility of this approach are demonstrated through experiments on a humanoid robot performing tasks such as transporting bulky objects, controlling interaction forces, and avoiding dynamic obstacles. Inspired by human tactile interaction, this work integrates large‐area artificial skin feedback (force and proximity) into real‐time quadratic programming control for humanoids. This enables robots to leverage distributed sensing to manage forces, safely move around unknown and dynamic obstacles, and robustly handle objects with uncertain geometry.