Soft-Contact Acoustic Microgripper Based on a Controllable Gas-Liquid Interface for Biomicromanipulations.

The manipulation of microscale bioentities is desired in many biological and biomedical applications. However, the potential unobservable damage to bioparticles due to rigid contact has always been a source of concern. Herein, a soft-contact acoustic microgripper to handle microparticles to improve the interaction safety is introduced. The system takes advantage of the acoustic-enhanced adhesion of flexible gas-liquid interfaces to capture-release, transport, and rotate the target, such as microbeads (20-65 µm) and zebrafish embryos (from 950 µm to 1.4 mm). The gas-liquid interface generated at the tip of a microcapillary can be precisely controlled by a pneumatic pressure source. The gas-liquid interface oscillation excited by acoustic energy imposes coupled radiation force and drag force on the microparticles, enabling multidimensional movements. Experiments with the microbeads are conducted to evaluate the claimed function and quantify the key parameters that influence the manipulation result. Additionally, 250 zebrafish embryos are captured, transported, and rotated. The hatching rate of the 250 manipulated embryos is approximately 98% similar to that of the nonmanipulated group, which proves the noninvasiveness of the method. The derived theories and experimental data indicate that the developed soft-contact microgripper is functional and beneficial for biological and medical applications.

Magnetically attracting hydrogel reshapes iron metabolism for tissue repair.

Ferroptosis, caused by disorders of iron metabolism, plays a critical role in various diseases, making the regulation of iron metabolism essential for tissue repair. In our analysis of degenerated intervertebral disc tissue, we observe a positive correlation between the concentration of extracellular iron ions (ex-iron) and the severity of ferroptosis in intervertebral disc degeneration (IVDD). Hence, inspired by magnets attracting metals, we combine polyether F127 diacrylate (FDA) with tannin (TA) to construct a magnetically attracting hydrogel (FDA-TA). This hydrogel demonstrates the capability to adsorb ex-iron and remodel the iron metabolism of cells. Furthermore, it exhibits good toughness and self-healing properties. Notably, it can activate the PI3K-AKT pathway to inhibit nuclear receptor coactivator 4-mediated ferritinophagy under ex-iron enrichment conditions. The curative effect and related mechanism are further confirmed in vivo. Consequently, on the basis of the pathological mechanism, a targeted hydrogel is designed to reshape iron metabolism, offering insights for tissue repair.

Neutrophil membrane-coated multifunctional biomimetic nanoparticles for spinal cord injuries.

Spinal cord injury (SCI) is one of the most complex diseases. After SCI, severe secondary injuries can cause intense inflammatory storms and oxidative stress responses, leading to extensive neuronal apoptosis. Effective regulation of inflammation and oxidative stress after SCI remains an unresolved challenge. In this study, resveratrol-loaded nanoparticles coated with neutrophil membranes (NMR) were prepared using the emulsion-solvent evaporation method and membrane encapsulation technology. Multifunctional biomimetic nanoparticles retain neutrophil membrane-related receptors and possess a strong adsorption capacity for inflammatory factors. As a drug carrier, NMR can sustainably release resveratrol for >72 h. Moreover, co-culture studies in vitro show that the NMR help regulate macrophage polarization to relieve inflammatory response, reduce intracellular reactive oxygen species by approximately 50%, and improve mitochondrial membrane potential to alleviate oxidative stress. After injecting NMR into the injury site, it reduces early apoptosis, inhibit scar formation, and promote neural network recovery to improve motor function. This study demonstrates the anti-inflammatory, antioxidant, and neuroprotective effects of NMR, thus providing a novel therapeutic strategy for SCI.

Functionalized acellular periosteum guides stem cell homing to promote bone defect repair.

The periosteum plays a key role in bone tissue regeneration, especially in the promotion and protection of new bones. However, among the bone repair materials, many biomimetic artificial periosteum lack the natural periosteal structure, stem cells, and immunoregulation required for bone regeneration. In this study, we used natural periosteum to produce acellular periosteum. To retain the appropriate cell survival structure and immunomodulatory proteins, we grafted the functional polypeptide SKP on the surface collagen of the periosteum via an amide bond, providing the acellular periosteum with the ability to recruit mesenchymal stem cells. Thus, we developed a biomimetic periosteum (DP-SKP) with the ability to promote stem cell homing and immunoregulation in vivo. Compared to the blank and simple decellularized periosteum groups, DP-SKP was more conducive to stem cell adhesion, growth, and osteogenic differentiation in vitro. Additionally, compared with the other two groups, DP-SKP significantly promoted mesenchymal stem cell homing to the periosteal transplantation site, improved the bone immune microenvironment, and accelerated new lamellar bone formation in the critical size defect of rabbit skulls in vivo. Therefore, this acellular periosteum with a mesenchymal stem cell homing effect is expected to be used as an extracellular artificial periosteum in clinical practice.

Standing Air Bubble-Based Micro-Hydraulic Capacitors for Flow Stabilization in Syringe Pump-Driven Systems.

Unstable liquid flow in syringe pump-driven systems due to the low-speed vibration of the step motor is commonly observed as an unfavorable phenomenon, especially when the flow rate is relatively small. Upon the design of a convenient and cost-efficient microfluidic standing air bubble system, this paper studies the physical principles behind the flow stabilization phenomenon of the bubble-based hydraulic capacitors. A bubble-based hydraulic capacitor consists of three parts: tunable microfluidic standing air bubbles in specially designed crevices on the fluidic channel wall, a proximal pneumatic channel, and porous barriers between them. Micro-bubbles formed in the crevices during liquid flow and the volume of the bubble can be actively controlled by the pneumatic pressure changing in the proximal channel. When there is a flowrate fluctuation from the upstream, the flexible air-liquid interface would deform under the pressure variation, which is analogous to the capacitive charging/discharging process. The theoretical model based on Euler law and the microfluidic equivalent circuit was developed to understand the multiphysical phenomenon. Experimental data characterize the liquid flow stabilization performance of the flow stabilizer with multiple key parameters, such as the number and the size of microbubbles. The developed bubble-based hydraulic capacitor could minimize the flow pulses from syringe pumping by 75.3%. Furthermore, a portable system is demonstrated and compared with a commercial pressure-driven flow system. This study can enhance the understanding of the bubble-based hydraulic capacitors that would be beneficial in microfluidic systems where the precise and stable liquid flow is required.

Hierarchical micro/nanofibrous membranes of sustained releasing VEGF for periosteal regeneration.

The periosteum plays a vital role in both development and injury healing process of bone. However, few researches have focused on artificial periosteum, which was also limited by the complexity on its construction and biological risks for clinical practice. In order to tackle this issue, inspired by the structural development of periosteum, we put forward a hierarchical micro/nanofibrous bionic periosteum with sustained releasing of VEGF as exogenous vascularized fibrous layer of periosteum to induce endogenous cambium layer in vivo for complete regeneration of periosteal and bone tissue, through collagen self-assembly and micro-sol electrospinning technologies. The VEGF encapsulated in hyaluronan-PLLA core-shell structure was demonstrated to be released in a durable way for angiogenesis in fibrous layer and bone defect area. Meanwhile, the self-assembly of collagen together with electrospun fibers contributed to a hierarchical micro/nanostructure which greatly mimicked the microenvironment of extracellular matrix to provide structural and biochemical cues for cell adhesion, proliferation and differentiation, and lead to the formation of cambium layer which mimicked the in-situ ossification manner as intramembranous ossification. As the motif of this study, the periosteal regeneration was characterized both by osteoblasts and periostin, which represented structural and molecular mechanisms respectively. Furthermore, the periosteal biomaterial proposed here possessed the superior abilities of scar inhibition, angiogenesis, osteogenesis to repair the bone defect in a uniform and rapid manner by inherent periosteal ossific mechanism involved in both intramembranous and endochondral ossification. Thus, the endogenous-exogenous combined bionic periosteum proved to be efficient and versatile in triggering periosteal and bone regeneration and hopefully supply a promising strategy for solving clinical issue.

Tunable microfluidic standing air bubbles and its application in acoustic microstreaming.

Microbubbles are often used in chemistry, biophysics, and medicine. Properly controlled microbubbles have been proved beneficial for various applications by previous scientific endeavors. However, there is still a plenty of room for further development of efficient microbubble handling methods. Here, this paper introduces a tunable, stable, and robust microbubble interface handling mechanism, named as microfluidic standing air bubbles (µSABs), by studying the multiphysical phenomena behind the gas-liquid interface formation and variation. A basic µSAB system consists specially structured fluidic channels, pneumatic channels, and selectively permeable porous barriers between them. The µSABs originate inside the crevice structures on the fluidic channel walls in a repeatable and robust manner. The volumetric variation of the µSAB is a multiphysical phenomenon that dominated by the air diffusion between the pneumatic channel and the bubble. Theoretical analysis and experimental data illustrate the coupling processes of the repeatable and linear µSAB volumetric variation when operated under common handling conditions (control pneumatic pressure: -90 kPa to 200 kPa). Furthermore, an adjustable acoustic microstreaming is demonstrated as an application using the alterable µSAB gas-liquid interface. Derived equations and microscopic observations elucidate the mechanism of the continuous and linear regulation of the acoustic microstreaming using varying µSAB gas-liquid interfaces. The µSAB system provides a new tool to handle the flexible and controllable gas-liquid interfaces in a repeatable and robust manner, which makes it a promising candidate for innovative biochemical, biophysical, and medical applications.