Oral delivery of therapeutic nanoparticles offers a non-invasive approach for treating gastrointestinal diseases, but achieving localized and sustained mucosal exposure while avoiding systemic toxicity remains a major challenge. Here, a Sucralfate-based oral formulation is developed that incorporates therapeutic nanoparticles and transforms into a paste-like coacervate upon contact with intestinal fluid, uniformly coating the entire gastrointestinal tract within 6 h, and clearing through fecal transit by 12 h. Systematic investigation shows that nanoparticle hydrophobicity is essential for stable incorporation into Sucralfate-based formulation, supporting compatibility with a wide range of nanoparticle types. The incorporated nanoparticles are stabilized by strong non-covalent interactions, which limit gastric leaching and reduce cellular uptake by 0.044% compared with PEGylated nanoparticles. As a representative example, antioxidant cerium oxide nanoparticles are tested in two distinct oxidative stress-related models of intestinal injury, including immune-mediated colitis and radiation-induced enteropathy. In DSS colitis, our system reduced weight loss from 17.2% to 2.2% and restored colon structure and oxidative-stress injury. In radiation-induced enteropathy, our system attenuated weight loss from 25.5% to 11.4%, doubled villus length, and markedly enhanced epithelial regeneration. The formulation also accommodates nanoparticles with imaging capability, demonstrating versatility for both therapeutic and diagnostic applications in gastrointestinal diseases.
Regeneration of the central and peripheral nervous system is challenging because of the inherent low regenerative capacity. Transplantation of neural stem cells (NSCs) is a promising strategy to increase regenerative capacity, but limited viability, slow proliferation, and differentiation create significant hurdles. Combining neurostimulator bio-functional ions such as magnesium (Mg2+) and zinc (Zn2+) to mitigate this limitation could be a breakthrough for future nerve regeneration treatments. This is the first study to investigate the effects of combined Mg2+ and Zn2+ ion therapy on the proliferation and differentiation of NSCs. The results showed an optimal concentration of Mg2+ and Zn2+ ions individually improved NSC proliferation, with a synergistic effect observed when ions were combined. The synergistic effect also significantly enhanced neurite outgrowth, promoted advanced neuronal network formation, and increased Nestin, βIII-tubulin, and MAP2 gene expression. These findings highlight the potential of combination therapy of Mg2+ and Zn2+ ions, which can be used as complementary modulators with NSCs-based treatments, providing promising ion-based therapeutic strategies in neural repair and regenerative medicine.
Autologous nerve grafting remains the gold standard for treating peripheral nerve injuries; however, it is constrained by limited donor nerve availability, the need for secondary surgeries, and sensory loss at the donor site. Biodegradable material-based nerve conduits have emerged as a promising alternative to address these limitations and enhance nerve regeneration. Among these materials, magnesium stands out due to its exceptional biocompatibility, biofunctionality, and neuroprotective properties. Despite its potential, magnesium's rapid corrosion rate and the need for controlled ion release necessitate advanced modifications, such as the development of Mg alloys. However, these approaches often face challenges, including viability concerns and material hardness, which can hinder nerve repair and damage surrounding tissues. In this study, a novel solution is introduced by sputtering magnesium onto a soft collagen sheet, achieving controlled magnesium ion release while preserving the material's nerve-like softness. This Mg-sputtered collagen sheet demonstrates excellent biocompatibility and significantly improves axon regeneration, muscle reinnervation, and functional recovery in a sciatic nerve defect model. These findings highlight the potential of an innovative Mg-based biodegradable nerve conduit, offering transformative applications across various medical fields.
Peripheral nerve injury is a common health issue in modern aging societies, with the only treatment available being autograft transplantation. Unfortunately, autograft is often limited due to donor availability and immune rejection. Additionally, the peripheral nervous system has limited regenerative capacity, making the treatment of peripheral nerve injuries challenging. Metal-based regenerative medicine and tissue engineering strategies provide advanced solutions to the problem. Metal-based biomaterials such as conduits, filaments, alloys, hydrogels, and ceramics can deliver biofunctional metal ions and promote axonal growth and functional recovery. In parallel, metal-based electromagnetic stimulation demonstrates potential for nerve regeneration and inflammation regulation. The potential of metal-based biomaterials in promoting peripheral nerve regeneration highlights the need for further research in tissue engineering and regenerative medicine. However, rapid degradation, long-term biocompatibility, and necessary optimization regarding injury types remain to be explored. This review summarizes the reported metal-based biomaterials utilized in peripheral nerve regeneration research. The aim is to showcase advanced technologies available in the field, which may potentially become a viable alternative to autografts, offering transformative applications in the regenerative medical field.
Medical stents are vital for treating vascular complications and restoring blood flow in millions of patients. Despite its widespread effectiveness, restenosis, driven by the complex interplay of cellular responses, remains a concern. This study investigated the reactions of vascular cells to nano/microscale wrinkle (nano-W and micro-W) patterns created on laser-textured nitinol (NiTi) surfaces by adjusting laser processing parameters, such as spot overlap ratio and line overlap ratio. Evaluation of topographical effects on endothelial and smooth muscle cells (SMCs) revealed diverse morphologies, proliferation rates, and gene expressions. Notably, microscale wrinkle patterns exhibited reduced monocyte adhesion and inflammation-related gene expression, demonstrating their potential applications in mitigating vascular complications after stent insertion. Additionally, an ex vivo metatarsal assay was utilized to bridge the gap between in vitro and in vivo studies, demonstrating enhanced angiogenesis on laser-textured NiTi surfaces. Laser-textured NiTi exhibits a guided formation process, emphasizing their potential to promote swift endothelialization. These findings underscore the efficacy of laser texturing for tailored cellular interactions on metallic surfaces and offer valuable insights into optimizing biocompatibility and controlling cellular responses, which may pave the way for innovative advances in vascular care and contribute to the ongoing improvement of stent insertion.
Whitlockite (WH), a magnesium-enriched bone mineral, offers significant potential for bone regeneration due to its high bioresorbability and osteogenic properties. Despite these advantages, its application has been hindered by challenges in synthesizing WH directly on implant surfaces. To address this, a laser-assisted strategy is developed for the in situ formation of WH-containing coatings on bone implants. To overcome the thermodynamic and kinetic barriers of WH synthesis, a magnesium calcium phosphate (MCP) intermediate is employed, a kinetically accessible and magnesium-rich phase, as a precursor to WH. The MCP intermediate is readily produced via laser-induced hydrothermal processing from a magnesium-enriched solution. Subsequent localized laser irradiation enabled partial transformation of the MCP into WH. Multiscale analyses confirmed successful WH formation, showing rhombohedral morphology and distinct chemical features. In vivo testing in a rat femoral defect model showed that WH-integrated implants significantly enhanced bone-implant integration and early-stage vascularization, attributed to the sustained release of osteogenic calcium and magnesium ions. This laser-assisted method can offer a scalable and effective strategy for implant surface modification in regenerative medicine.
In this study, we have developed a biodegradable Mg-Zn alloy with good strength and elongation. Various Mg alloys have been developed over the years because of their excellent properties and biodegradability. However, their limited elongation and rapid corrosion limit their widespread use. In this study, a Mg-3 wt.
Stable and reliable operation of implantable electronics must ensure both high-quality electrical performance and chronic biocompatibility. Here, immune-stealth implantable electronics fabricated by multiphoton ablation lithography are introduced. The cell-repellent interface, consisting of micro-grooves and nano-islands, can be created by laser-assisted topography patterning on a thin film substrate. This patterned surface demonstrates a 20-fold increase in cell-repellent effectiveness against immune cells such as macrophages and fibroblasts due to disturbance of focal adhesion. Furthermore, the cell-repellent interface can also be patterned on the sub-micron electrode layer without compromising its electrical and electrochemical performance. When the electrocardiogram (ECG) sensor applying the cell-repellent interface is implanted into a rat subcutaneous tissue, inflammation and fibrotic reactions are effectively suppressed for 6 weeks. Consequently, stable ECG readings with clear PQRST waveforms are obtained in real-time for 4 weeks, suggesting its potential to enhance chronic biocompatibility of implantable electronics.
High-density, large-area electronic interfaces are a key component of brain-computer interface technologies. However, current designs typically require patients to undergo invasive procedures, which can lead to various complications. Here, we report a biodegradable and self-deployable tent electrode for brain cortex interfacing. The system can be integrated with multiplexing arrays and a wireless module for near-field communication and data transfer. It can be programmably packaged and self-deployed using a syringe for minimally invasive delivery through a small hole. Following delivery, it can expand to cover an area around 200 times its initial size. The electrode also naturally decomposes within the body after use, minimizing the impact of subsequent removal surgery. Through in vivo demonstrations, we show that our cortical-interfacing platform can be used to stimulate large populations of cortical activities. A biodegradable electronic tent electrode array that can be inserted into the brain cortex using a syringe, where it then expands to 200 times its original size, can be used for electrocorticography monitoring.
Catheter-associated urinary tract infection (CAUTI) is the most common healthcare-associated infection; however, current therapeutic strategies remain insufficient for standard clinical application. A novel urinary catheter featuring a dual-layer nanoengineering approach using zinc (Zn) and silver nanoparticles (AgNPs) is successfully fabricated. This design targets microbial resistance, minimizes cytotoxicity, and maintains long-term efficacy. The inner AgNPs layer provides immediate antibacterial effects against the UTI pathogens, while the outer porous Zn layer controls zero-order Ag release and generates reactive oxygen species, thus enhancing long-term bactericidal performance. Enhanced antibacterial properties of Zn/AgNPs-coated catheters are observed, resulting in 99.9% of E. coli and 99.7% of S. aureus reduction, respectively. The Zn/AgNPs-coated catheter significantly suppresses biofilm with sludge formation compared to AgNP-coated and uncoated catheters (all, p < 0.05). The Zn/AgNP-coated catheter in a rabbit model demonstrated a durable, effective barrier against bacterial colonization, maintaining antimicrobial properties during the catheter indwelling period with significantly reduced inflammation and epithelial disruption compared with AgNP and uncoated groups. This innovation has the potential to revolutionize the design of antimicrobial medical devices, particularly for applications requiring long-term implantation. Although further preclinical studies are required to verify its efficacy and safety, this strategy seems to be a promising approach to preventing CAUTI-related complications.
Wound healing involves a complex series of coordinated events throughout the inflammatory, proliferative, and maturation phases of tissue repair. Current treatment modalities lack a device catering to all wound healing stages for tissue recovery, angiogenesis and epithelialization. Herein, we developed an integrated wound healing system with multiple functions of self-electrical stimulation (ES), reactive oxygen species (ROS) regulation, and bioactive metal-releasing patch (ERMP) to address all wound healing stages including hemostasis, inflammation, proliferation, and remodeling. The multiple functions of ERMP are ES, generated by the movement of the mice, for tissue regeneration, magnesium (Mg) ion release via iontophoresis triggered by ES for pro-angiogenic effects, and simultaneous regulation of ROS. This system employs self-generating ES utilizing the movements of the individuals to trigger triboelectric nanogenerators (TENGs), which consequently transfer ES through Mg microneedles while effectively delivering enhanced Mg ions with an iontophoresis via ES to the wound site. Specially, Prussian blue (PB) was utilized to not only enhance output performance on TENG as charge trap, but also regulate excessive ROS via modified PB with carbon–nitrogen vacancies in the wound site. The synergistic effects of ES, ROS regulation, and enhanced Mg ions releases led to a nine-fold recovery rates in wound healing compared to the control group in vivo tests. This approach addresses the inherent limitations of conventional wound healing methods and provides a viable treatment for various severe wound types.
Polyetheretherketone (PEEK), a bioinert polymer known for its mechanical properties similar to bone, is capable of averting stress shielding. Due to these attributes, it finds applications in diverse fields like orthopedics, encompassing cervical disc replacement for the neck and spine, along with dentistry and plastic surgery. However, due to insufficient bonding with bone, various methods such as hydroxyapatite (HA) coating on the surface are attempted. Nonetheless, the interface between the polymer and ceramic, two different materials, tended to delaminate after transplantation, posing challenges in preventing implant escape or dislodgement. This research delves into the laser-driven hydroxyapatite penetration-synthesis technique. Differing from conventional coating methods that bond layers of dissimilar materials like HA and PEEK, this technology focuses on synthesizing and infiltrating ionized HA within the PEEK substrate resulting in an interface-free HA-PEEK surface. Conversely, HA-PEEK with this technology applied achieves complete, gap-free direct bone-implant integration. Our research involved the analysis of various aspects. By means of these, we quantitatively assesed the enhanced bone bonding characteristics of HA-PEEK surfaces treated with this approach and offered and explanation for the mechanism responsible for direct bone integration.
The musculoskeletal system, which is vital for movement, support, and protection, can be impaired by disorders such as osteoporosis, osteoarthritis, and muscular dystrophy. This review focuses on the advances in tissue engineering and regenerative medicine, specifically aimed at alleviating these disorders. It explores the roles of cell therapy, particularly Mesenchymal Stem Cells (MSCs) and Adipose-Derived Stem Cells (ADSCs), biomaterials, and biomolecules/external stimulations in fostering bone and muscle regeneration. The current research underscores the potential of MSCs and ADSCs despite the persistent challenges of cell scarcity, inconsistent outcomes, and safety concerns. Moreover, integrating exogenous materials such as scaffolds and external stimuli like electrical stimulation and growth factors shows promise in enhancing musculoskeletal regeneration. This review emphasizes the need for comprehensive studies and adopting innovative techniques together to refine and advance these multi-therapeutic strategies, ultimately benefiting patients with musculoskeletal disorders.
NiTi shape memory alloys, known as Nitinol, are highly valuable in medical fields for their unique attributes, including superelasticity, wear resistance, and biocompatibility. Laser treatment provides precise control over surface characteristics, enhancing biocompatibility. This study focuses on the effects of laser irradiation on NiTi alloy surfaces, particularly considering the number of laser scans and their impact on surface features. Even at low laser power, multiple high-frequency scans significantly alter surface roughness and induce phase transformation. After 16 repeated laser irradiations, amorphous Ti oxide transforms into crystalline anatase. Remarkably, anatase can further transform into rutile due to the influence of Ni nearby and TiO, due to insufficient oxygen content. The most notable outcome is the formation of a thick Ti oxide layer, causing unbound Ni to emerge on the surface, resulting in a Ni oxide layer. These findings highlight the importance of precisely adjusting laser parameters to achieve tailored surface properties for medical applications, addressing challenges and enhancing biocompatibility.
Developing soft robots that can control their own life cycle and degrade on-demand while maintaining hyperelasticity is a notable research challenge. On-demand degradable soft robots, which conserve their original functionality during operation and rapidly degrade under specific external stimulation, present the opportunity to self-direct the disappearance of temporary robots. This study proposes soft robots and materials that exhibit excellent mechanical stretchability and can degrade under ultraviolet light by mixing a fluoride-generating diphenyliodonium hexafluorophosphate with a silicone resin. Spectroscopic analysis revealed the mechanism of Si─O─Si backbone cleavage using fluoride ion (F − ) and thermal analysis indicated accelerated decomposition at elevated temperatures. In addition, we demonstrated a robotics application by fabricating electronics integrated gaiting robot and a fully closed-loop trigger disintegration robot for autonomous, application-oriented functionalities. This study provides a simple yet novel strategy for designing life cycle mimicking soft robotics that can be applied to reduce soft robotics waste, explore hazardous areas, and ensure hardware security with on-demand destructive material platforms.
Conformal contact with skin is a critical requirement for wearable electronics in medical healthcare, artificial electronics, and human–computer interfaces. Tattoo‐like electronics exploiting water‐dissolvable polymers have been introduced to directly transfer electronics to the skin increasing conformality and adhesion. However, water‐dissolvable polymers cannot be anchored on the skin while maintaining electrical properties because water‐based sweat can destroy the polymer substrate. In this study, we present a transparent and skin‐attachable electrode (TSE) composed of highly conductive silver nanowires and biocompatible polyurethane composite using surface redissolution by ethanol. The TSE can be fabricated into various patterns by a simple fabrication method and firmly mounted on the skin. There was no reddishness or residue on the attached spot after detachment. Additionally, the TSE showed low mechanical modulus of 225 kPa and an optical transmittance of ≈70% at 550 nm. Stable and conformal contact with the skin leads to effective body motion sensing and sensitive electrophysiological signal acquisition due to the low electrical interfacial impedance.
Biodegradable metals as electrodes, interconnectors, and device conductors are essential components in the emergence of transient electronics, either for passive implants or active electronic devices, especially in the fields of biomedical electronics. Magnesium and its alloys are strong candidates for biodegradable and implantable conducting materials because of their high conductivity and biocompatibility, in addition to their well-understood dissolution behavior. One critical drawback of Mg and its alloys is their considerably high dissolution rates originating from their low anodic potential, which disturbs the compatibility to biomedical applications. Herein, we introduce a single-phase thin film of a Mg–Zn binary alloy formed by sputtering, which enhances the corrosion resistance of the device electrode, and verify its applicability in biodegradable electronics. The formation of a homogeneous solid solution of single-phase Mg–3Zn was confirmed through X-ray diffraction and transmission electron microscopy. In addition, the dissolution behavior and chemistry was also investigated in various biological fluids by considering the effect of different ion species. Micro-tensile tests showed that the Mg–3Zn alloy electrode exhibited an enhanced yield strain and elongation in relation to a pure Mg electrode. Cell viability test revealed the high biocompatibility rate of the Mg–3Zn binary alloy thin film. Finally, the fabrication of a wireless heater demonstrated the integrability of biodegradable electrodes and highlighted the ability to prolong the lifecycle of thermotherapy-relevant electronics by enhancing the dissolution resistance of the Mg alloy.
Photolithography is a well-established fabrication method for realizing multilayer electronic circuits. However, it is challenging to adopt photolithography to fabricate intrinsically stretchable multilayer electronic circuits fully composed of an elastomeric matrix, due to the opacity of thick stretchable nanocomposite conductors. Here, we present photothermal lithography that can pattern elastomeric conductors and via holes using pulsed lasers. The photothermal-patterned stretchable nanocomposite conductor exhibits 3 times higher conductivity (5940 S cm-1) and 5 orders of magnitude lower resistance change (R/R0 = 40) under a 30% strained 5000th cyclic stretch, compared to those of a screen-printed conductor, based on the percolation network formed by spatial heating of the laser. In addition, a 50 μm sized stretchable via holes can be patterned on the passivation without material ablation and electrical degradation of the bottom conductor. By repeatedly patterning the conductor and via holes, highly conductive and durable multilayer circuits can be stacked with layer-by-layer material integration. Finally, a stretchable wireless pressure sensor and passive matrix LED array are demonstrated, thus showing the potential for a stretchable multilayer electronic circuit with durability, high density, and multifunctionality.
The adoption of dynamic mechanomodulation to regulate cellular behavior is an alternative to the use of chemical drugs, allowing spatiotemporal control. However, cell-selective targeting of mechanical stimuli is challenging due to the lack of strategies with which to convert macroscopic mechanical movements to different cellular responses. Here, we designed a nanoscale vibrating surface that controls cell behavior via selective repetitive cell deformation based on a poroelastic cell model. The vibrating indentations induce repetitive water redistribution in the cells with water redistribution rates faster than the vibrating rate; however, in the opposite case, cells perceive the vibrations as a one-time stimulus. The selective regulation of cell-cell adhesion through adjusting the frequency of nanovibration was demonstrated by suppression of cadherin expression in smooth muscle cells (fast water redistribution rate) with no change in vascular endothelial cells (slow water redistribution rate). This technique may provide a new strategy for cell-type-specific mechanical stimulation.