Implantable micro-scale LED device guided photodynamic therapy to potentiate antitumor immunity with mild visible light.

BACKGROUND: Photodynamic therapy (PDT) is a promising strategy to promote antitumor immunity by inducing immunogenic cell death (ICD) in tumor cells. However, practical PDT uses an intense visible light owing to the shallow penetration depth of the light, resulting in immunosuppression at the tumor tissues. METHODS: Herein, we propose an implantable micro-scale light-emitting diode device (micro-LED) guided PDT that enables the on-demand light activation of photosensitizers deep in the body to potentiate antitumor immunity with mild visible light. RESULTS: The micro-LED is prepared by stacking one to four micro-scale LEDs (100 µm) on a needle-shape photonic device, which can be directly implanted into the core part of the tumor tissue. The photonic device with four LEDs efficiently elicits sufficient light output powers without thermal degradation and promotes reactive oxygen species (ROS) from a photosensitizer (verteporfin; VPF). After the intravenous injection of VPF in colon tumor-bearing mice, the tumor tissues are irradiated with optimal light intensity using an implanted micro-LED. While tumor tissues under intense visible light causes immunosuppression by severe inflammatory responses and regulatory T cell activation, mild visible light elicits potent ICD in tumor cells, which promotes dendritic cell (DC) maturation and T cell activation. The enhanced therapeutic efficacy and antitumor immunity by micro-LED guided PDT with mild visible light are assessed in colon tumor models. Finally, micro-LED guided PDT in combination with immune checkpoint blockade leads to 100% complete tumor regression and also establishes systemic immunological memory to prevent the recurrence of tumors. CONCLUSION: Collectively, this study demonstrates that micro-LED guided PDT with mild visible light is a promising strategy for cancer immunotherapy.

Cuticular pad-inspired selective frequency damper for nearly dynamic noise-free bioelectronics.

Bioelectronics needs to continuously monitor mechanical and electrophysiological signals for patients. However, the signals always include artifacts by patients' unexpected movement (such as walking and respiration under approximately 30 hertz). The current method to remove them is a signal process that uses a bandpass filter, which may cause signal loss. We present an unconventional bandpass filter material-viscoelastic gelatin-chitosan hydrogel damper, inspired by the viscoelastic cuticular pad in a spider-to remove dynamic mechanical noise artifacts selectively. The hydrogel exhibits frequency-dependent phase transition that results in a rubbery state that damps low-frequency noise and a glassy state that transmits the desired high-frequency signals. It serves as an adaptable passfilter that enables the acquisition of high-quality signals from patients while minimizing signal process for advanced bioelectronics.

Strong, Multifaceted Guanidinium-Based Adhesion of Bioorganic Nanoparticles to Wet Biological Tissue.

Gluing dynamic, wet biological tissue is important in injury treatment yet difficult to achieve. Polymeric adhesives are inconvenient to handle due to rapid cross-linking and can raise biocompatibility concerns. Inorganic nanoparticles adhere weakly to wet surfaces. Herein, an aqueous suspension of guanidinium-functionalized chitin nanoparticles as a biomedical adhesive with biocompatible, hemostatic, and antibacterial properties is developed. It glues porcine skin up to 3000-fold more strongly (30 kPa) than inorganic nanoparticles at the same concentration and adheres at neutral pH, which is unachievable with mussel-inspired adhesives alone. The glue exhibits an instant adhesion (2 min) to fully wet surfaces, and the glued assembly endures one-week underwater immersion. The suspension is lowly viscous and stable, hence sprayable and convenient to store. A nanomechanic study reveals that guanidinium moieties are chaotropic, creating strong, multifaceted noncovalent bonds with proteins: salt bridges comprising ionic attraction and bidentate hydrogen bonding with acidic moieties, cation-π interactions with aromatic moieties, and hydrophobic interactions. The adhesion mechanism provides a blueprint for advanced tissue adhesives.

Photocatalytic exoskeleton: Chitin nanofiber for retrievable and sustainable TiO2 carriers for the decomposition of various pollutants.

Loading a photocatalytic TiO2 to organic carriers has been desired for volumetric TiO2 incorporation, facile retrieval, and sustainable utilization. Traditionally, suspended TiO2 nanoparticles or its thin film on two-dimensional substrate are popularly fabricated for pollutants decomposition without carriers; due to poor thermomechanical properties of the organic carriers. Herein, a combination of the chitin nanofiber carrier and atomic layer deposition proves relevance for formation of anatase TiO2 thin layer so that photocatalytic decomposition in three-dimensional surface. Moreover, chitin nanofiber is capable of holding the TiO2 nanoparticles for multiple cycles of photocatalysis. Those types of TiO2 show characteristic degradation performance for gaseous (acetaldehyde) and aqueous pollutants (4-chlorophenol and rhodamine B). After catalytic reaction, chitin/TiO2 is retrievable owing to carrier's robustness even in water without TiO2 aggregation and loss. This work suggests that chitin-based photocatalyst is applicable to numerous pollutants through chitin's relatively high chemical resistance and stably wedged TiO2 during photocatalytic reaction.

Biomimetic Janus chitin nanofiber membrane for potential guided bone regeneration application.

Biopolymer-based membranes are at the forefront of the guided bone regeneration (GBR) in orthopaedics and dentistry, which prevent fast-growing soft tissue migration to the defected alveolar ridge or implants and allow the bone regeneration. In this study, we fabricated a novel Janus -two-faced, GBR membrane composed of a chitin nanofiber face for bone regeneration and a cell membrane mimetic antifouling 2-Methacryloyloxyethyl phosphorylcholine (MPC) polymeric face for suppressing the migration of the soft tissue. In vitro cell study showed a higher cell proliferation rate of osteoblast cells on the chitin nanofiber surface and a lower proliferation rate of fibroblasts cells on the antifouling MPC side. An increased of Alkaline Phosphatase (ALP) rate was observed in the chitin nanofiber face, indicating the ability to maintain proliferation and differentiation of osteogenic cells. These results suggest the biomimetic Janus chitin membrane may have the potential to develop as an advance GBR membrane.

Mechanical properties and thermal stability of intermolecular-fitted poly(vinyl alcohol)/α-chitin nanofibrous mat.

The major disadvantage of electrospun nanofibrous mats is their poor mechanical properties, which result from interfibrillar slips, porous structures, and the isotropic conformation of functional groups in fibers. In this work, we develop a tough electrospun mat without cost of both the stiffness and extensibility by combining two mutually exclusive polymers, i.e., generally "ductile" poly(vinyl alcohol) (PVA) and "stiff" α-chitin. The toughness of PVA/α-chitin is considerably higher (∼20 times) compared to PVA via intermolecular-fitted design and stoichiometric balance between hydrogen bonding donors and acceptors. Moreover, consistently oriented functional groups that are perpendicular to nanofibers improve mechanical properties. As a result, stiffness and extensibility are simultaneously increased by ∼19.3 and ∼3.8 times, respectively compared to PVA. The thermal stability with a 2.80-fold larger melting enthalpy of 823.95 ± 7.05 J g-1 than PVA. The great thermomechanical performance provides an insight for molecular design in electrospun nanofibers with chitin polymorphs.

Prolonged Biodegradation and Improved Mechanical Stability of Collagen via Vapor-Phase Ti Stitching for Long-Term Tissue Regeneration.

Collagen, one of the most popular biomedical materials, exhibits rapid biodegradation accompanied by a notable decrease of mechanical stability in the human body. This is a key challenge for its use in large-sized tissue regeneration, which takes a long time. In order to resolve this problem, we introduced vapor-phase titanium (Ti) derivatives into the interchain regions in collagen via TiO2 atomic layer deposition (ALD), which has been widely used for thin-film deposition. The introduced Ti simultaneously enhanced both the tensile strength (∼384.45 MPa) and Young's modulus (∼1.56 GPa) by approximately 29 and 26% compared to the pristine commercial collagen membrane. In vitro tests demonstrated that approximately 31% of Ti-infiltrated collagen is retained after 4 weeks, whereas the pristine commercial collagen rapidly degrades by up to 90% within 1 week. The in vivo biodegradation rate was greatly improved and inversely proportional to the number of TiO2 ALD cycles. Moreover, bone mineralization, which is observed during the late stage of bone healing, appeared only in the Ti-infiltrated collagen. We believe that our simple vapor-phase treatment method could be widely used with xenograft materials, which typically require adequate biodegradation rates and stable mechanical properties.

Sustainable and recyclable super engineering thermoplastic from biorenewable monomer.

Environmental and health concerns force the search for sustainable super engineering plastics (SEPs) that utilise bio-derived cyclic monomers, e.g. isosorbide instead of restricted petrochemicals. However, previously reported bio-derived thermosets or thermoplastics rarely offer thermal/mechanical properties, scalability, or recycling that match those of petrochemical SEPs. Here we use a phase transfer catalyst to synthesise an isosorbide-based polymer with a high molecular weight >100 kg mol-1, which is reproducible at a 1-kg-scale production. It is transparent and solvent/melt-processible for recycling, with a glass transition temperature of 212 °C, a tensile strength of 78 MPa, and a thermal expansion coefficient of 23.8 ppm K-1. Such a performance combination has not been reported before for bio-based thermoplastics, petrochemical SEPs, or thermosets. Interestingly, quantum chemical simulations show the alicyclic bicyclic ring structure of isosorbide imposes stronger geometric restraint to polymer chain than the aromatic group of bisphenol-A.

Different Molecular Interaction between Collagen and α- or ß-Chitin in Mechanically Improved Electrospun Composite.

Although collagens from vertebrates are mainly used in regenerative medicine, the most elusive issue in the collagen-based biomedical scaffolds is its insufficient mechanical strength. To solve this problem, electrospun collagen composites with chitins were prepared and molecular interactions which are the cause of the mechanical improvement in the composites were investigated by two-dimensional correlation spectroscopy (2DCOS). The electrospun collagen is composed of two kinds of polymorphs, α- and ß-chitin, showing different mechanical enhancement and molecular interactions due to different inherent configurations in the crystal structure, resulting in solvent and polymer susceptibility. The collagen/α-chitin has two distinctive phases in the composite, but ß-chitin composite has a relatively homogeneous phase. The ß-chitin composite showed better tensile strength with ~41% and ~14% higher strength compared to collagen and α-chitin composites, respectively, due to a favorable secondary interaction, i.e., inter- rather than intra-molecular hydrogen bonds. The revealed molecular interaction indicates that ß-chitin prefers to form inter-molecular hydrogen bonds with collagen by rearranging their uncrumpled crystalline regions, unlike α-chitin.

Enhancement of nanofluid stability and critical heat flux in pool boiling with nanocellulose.

A nanofluid, which is an aqueous fluid with nanoparticles, is an attractive medium for enhancing critical heat flux (CHF); however, its instability over a long period of time due to sedimentation and aggregation has impeded its successful application in industry. In this study, lightweight negatively charged TEMPO-oxidized cellulose nanofibers (CNFs) were utilized as a nano-sized substance in water and examined to enhance both the CHF performance and thermal stability of nanofluids. Owing to low density of the CNFs and long range repulsion between negatively charged CNFs, there were no aggregation and sedimentation of CNFs with multiple boiling/cooling cycles. In addition, with CNF concentrations of 0.01, 0.03, 0.05, and 0.10 wt%, CHF enhancement increases of 40.7%, 45.1%, 54.9%, and 69.4%, respectively, were achieved over that of pure water. The present results demonstrated the great potential of CNFs as eco-friendly and cost-effective nano-substances that can overcome the instability of nanofluids.

Tough and Immunosuppressive Titanium-Infiltrated Exoskeleton Matrices for Long-Term Endoskeleton Repair.

Although biodegradable membranes are essential for effective bone repair, severe loss of mechanical stability because of rapid biodegradation, soft tissue invasion, and excessive immune response remain intrinsically problematic. Inspired by the exoskeleton-reinforcing strategy found in nature, we have produced a Ti-infiltrated chitin nanofibrous membrane. The membrane employs vapor-phase infiltration of metals, which often occurs during metal oxide atomic layer deposition (ALD) on organic substrates. This metal infiltration manifests anomalous mechanical improvement and stable integration with chitin without cytotoxicity and immunogenicity. The membrane exhibits both impressive toughness (∼13.3 MJ·m-3) and high tensile strength (∼55.6 MPa), properties that are often mutually exclusive. More importantly, the membrane demonstrates notably enhanced resistance to biodegradation, remaining intact over the course of 12 weeks. It exhibits excellent osteointegrative performance and suppresses the immune response to pathogen-associated molecular pattern molecules indicated by IL-1ß, IL-6, and granulocyte-macrophage colony-stimulating factor expression. We believe the excellent chemico-biological properties achieved with ALD treatment can provide insight for synergistic utilization of the polymers and ALD in medical applications.

Formation, Removal, and Reformation of Surface Coatings on Various Metal Oxide Surfaces Inspired by Mussel Adhesives.

Mussels survive by strongly attaching to a variety of different surfaces, primarily subsurface rocks composed of metal oxides, through the formation of coordinative interactions driven by protein-based catechol repeating units contained within their adhesive secretions. From a chemistry perspective, catechols are known to form strong and reversible complexes with metal ions or metal oxides, with the binding affinity being dependent on the nature of the metal ion. As a result, catechol binding with metal oxides is reversible and can be broken in the presence of a free metal ion with a higher stability constant. It is proposed to exploit this competitive exchange in the design of a new strategy for the formation, removal, and reformation of surface coatings and self-assembled monolayers (SAM) based on catechols as the adhesive unit. In this study, catechol-functionalized tri(ethylene oxide) (TEO) was synthesized as a removable and recoverable self-assembled monolayer (SAM) for use on oxides surfaces. Attachment and detachment of these catechol derivatives on a variety of surfaces was shown to be reversible and controllable by exploiting the high stability constant of catechol to soluble metal ions, such as Fe(III). This tunable assembly based on catechol binding to metal oxides represents a new concept for reformable coatings with applications in fields ranging from friction/wettability control to biomolecular sensing and antifouling.