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Design of nanovectors inspired by nature is a short cut to improve the efficacy and bioavailability of chemotherapeutic agents, while reduce the toxicity. In this work, strongly hydrophobic camptothecin (CPT) was modified with different chain length of fatty acid (C4, C9 and C18) to synthesize CPT4C, CPT9C and CPT18C, respectively. CPT4C, CPT9C and CPT18C could complex with human serum albumin (HSA) readily to prepare CPT4C-HSA, CPT9C-HSA and CPT18C-HSA nanoagents. In vitro MTT assays demonstrated CPT18C-HSA possessed the highest cell killing capacity, due to the elevated cellular uptake that resulted from albumin-mediated transportation. In vivo tumor inhibition experiments verified that CPT18C-HSA had the most remarkable antitumor efficiency with distinctly lowered physiological toxicity. It could be used in large doses without obvious side effects. We believe this albumin-mediated transportation mode has great potential for efficient delivery of hydrophobic and/or physiologically unstable drugs.

We developed insulin loaded biomimetic microsphere by laccase-mediated crosslinking using a microfluidic device in the water-in-oil emulsion system as an injectable vehicle for the repair of sciatic tissue. Aqueous polymeric solution of phenol-substituted hyaluronic acid (HAPh) and collagen (ColPh) containing insulin and laccase flowed from the inner channel into oil flow within an outer channel which leads formation of hydrogel microsphere. The physical properties of prepared specimens including swelling rate, mechanical resistance and the prolonged release rate of microspheres proved applicability of fabricated vehicles for tissue engineering and drug delivery systems. The growth profile and behavior of cells in microspheres indicated cytocompatibility of the method and prepared vehicles for microtissue development. Histopathological examination revealed a significant increase in axonal regeneration, and remyelination process in injured sciatic nerve following treatment with HAPh/ColPh microspheres containing insulin compared to control groups. Also, the functional characteristic of sciatic tissue showed that the presence of biomimetic microsphere and insulin simultaneously had improved sciatic tissue functions including functional sciatic index (SFI) values, reaction to hot plate and muscle weight of rats. In summary, the results proved that composite biomimetic microspheres containing insulin effectively improved nerve regeneration in the rat model.

Fabrication of ultra-strong, ultra-tough, sustainable, and degradable bio-based composites is urgently needed but remains challenging. Here, a biomimetic sustainable, degradable, and multi-stimuli responsive cellulose/PCL/Fe

Cholesterol plays a critical role in modulating the lipid membrane properties of biological and biomimetic systems and recent attention has focused on its role in the functions of sub-100 nm lipid vesicles and lipid nanoparticles. These functions often rely on multivalent ligand-receptor interactions involving membrane attachment and dynamic shape transformations while the extent to which cholesterol can influence such interaction processes is largely unknown. To address this question, herein, we investigated the attachment of sub-100 nm lipid vesicles containing varying cholesterol fractions (0-45 mol %) to membrane-mimicking supported lipid bilayer (SLB) platforms. Biotinylated lipids and streptavidin proteins were used as model ligands and receptors, respectively, while the localized surface plasmon resonance sensing technique was employed to track vesicle attachment kinetics in combination with analytical modeling of vesicle shape changes. Across various conditions mimicking low and high multivalency, our findings revealed that cholesterol-containing vesicles could bind to receptor-functionalized membranes but underwent appreciably less multivalency-induced shape deformation than vesicles without cholesterol, which can be explained by a cholesterol-mediated increase in membrane bending rigidity. Interestingly, the extent of vesicle deformation that occurred in response to increasingly strong multivalent interactions was less pronounced for vesicles with greater cholesterol fraction. The latter trend was rationalized by taking into account the strong dependence of the membrane bending energy on the area of the vesicle-SLB contact region and such insights can aid the engineering of membrane-enveloped nanoparticles with tailored biophysical properties. This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korean government (MSIT; Nos. 2020R1C1C1004385 and 2021R1A4A1032782), the International Research & Development Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2020K1A3A1A39112724), and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant Number: HI19C1328). This work was also partially supported by the SKKU Global Research Platform Research Fund, Sungkyunkwan University, 2022.

Inspired by a new biosynthetic hypothesis, we report a biomimetic total synthesis of atrachinenins A and B that explains their racemic nature. The synthesis exploits an intermolecular Diels-Alder reaction between a quinone meroterpenoid and

Thermal actuation is a common actuation method for soft robots. However, a major limitation is the relatively slow actuation speed. Here we report significant increase in the actuation speed of a bimorph thermal actuator by harnessing the snap-through instability. The actuator is made of silver nanowire/polydimethylsiloxane composite. The snap-through instability is enabled by simply applying an offset displacement to part of the actuator structure. The effects of thermal conductivity of the composite, offset displacement, and actuation frequency on the actuator speed are investigated using both experiments and finite element analysis. The actuator yields a bending speed as high as 28.7 cm

From the early days of research on RNA biology and biochemistry, there was an interest to utilize this knowledge and RNA itself for therapeutic applications. Today, we have a series of oligonucleotide therapeutics on the market and many more in clinical trials. These drugs - exploit different chemistries of oligonucleotides, such as modified DNAs and RNAs, peptide nucleic acids (PNAs) or phosphorodiamidate morpholino oligomers (PMOs), and different mechanisms of action, such as RNA interference (RNAi), targeted RNA degradation, splicing modulation, gene expression and modification. Despite major successes e.g. mRNA vaccines developed against SARS-CoV-2 to control COVID-19 pandemic, development of therapies for other diseases is still limited by inefficient delivery of oligonucleotides to specific tissues and organs and often prohibitive costs for the final drug. This is even more critical when targeting multifactorial disorders and patient-specific biological variations. In this review, we will present the evolution of complexity of oligonucleotide delivery methods with focus on increasing complexity of formulations from gymnotic delivery to bioconjugates and to lipid nanoparticles in respect to developments that will enable application of therapeutic oligonucleotides as drugs in personalized therapies.

Biphasic calcium phosphate (BCP) is used as a bone substitute and bone tissue repair material due to its better control over bioactivity and biodegradability. It is crucial to stabilize the implanted biomaterial while promoting bone ingrowth. However, a lack of standard experimental and theoretical protocols to characterize the physicochemical properties of BCP limits the optimization of its composition and properties. Computational simulations can help us better to learn BCP at a nanoscale level. Here, the Voronoi tessellation method was combined with simulated annealing molecular dynamics to construct BCP nanoparticle models of different sizes, which were used to understand the physicochemical properties of BCP (e.g., melting point, infrared spectrum, and mechanical properties). We observed a ∼20 to 30 Å layer of calcium-deficient hydroxyapatite at the HAP/β-TCP interface due to particle migration, which may contribute to BCP stability. The BCP model may stimulate further research into BCP ceramics and multiphasic ceramics. Moreover, our study may facilitate the optimization of compositions of BCP-based biomaterials.

In recognition of the potential of calreticulin (CRT) protein in enhancing the rate and quality of wound healing in excisional animal wound models, this study was to incorporate CRT via polyblend electrospinning into polycaprolactone (PCL)/type 1 collagen (Col1) nanofibers (NFs; 334 ± 75 nm diameter) as biomimetic extracellular matrices to provide a novel mode of delivery and protection of CRT with enhanced synergistic activities for tissue regeneration. Release kinetic studies using fluoresceinated CRT (CRT-FITC) polyblend NFs showed a burst release within 4 h reaching a plateau at 72 h, with further intervals of release upon incubation with fresh phosphate buffered saline for up to 8 weeks. By measuring fluorescence during the first 4 h of release, CRT-FITC-containing NFs were shown to protect CRT from proteolytic digestion (e.g., by subtilisin) compared to CRT-FITC in solution. CRT incorporated into NFs (CRT-NFs) also showed retention of biological activities and potency for stimulating proliferation and migration of human keratinocytes and fibroblasts. Fibroblasts seeded on CRT-NFs, after 2 days, showed increased amounts of fibronectin, TGF-β1, and integrin β1 in cell lysates by immunoblotting. Compared to NFs without CRT, CRT-NFs supported cell responses consistent with greater cell polarization and increased laminin-5 deposition of keratinocytes and a more motile phenotype of fibroblasts, as suggested by vinculin-capping F-actin fibers nonuniformly located throughout the cell body and the secretion of phosphorylated focal adhesion kinase-enriched migrasomes. Altogether, CRT electrospun into PCL/Col1 NFs retained its structural integrity and biological functions while having additional benefits of customizable loading, protection of CRT from proteolytic degradation, and sustained release of CRT from NFs, coupled with innate physicochemical cues of biomimetic PCL/Col1 NFs. Such synergistic activities have potential for healing recalcitrant wounds such as diabetic foot ulcers.

Lithium-sulfur (Li-S) batteries are widely considered to be next-generation storage technologies due to their high energy density, low cost and non-toxicity. However, the soluble lithium polysulfides (LiPS) migrating to the anode side inevitably causes side reactions with the Li anode, resulting in severe corrosion of the Li anode, loss of active materials, and rapid battery failure. Therefore, it is necessary to develop effective strategies to avoid LiPS exposure to Li anodes. Herein, a stable UiO-66-ClO

Fenton reaction-based chemodynamic therapy (CDT), which applies metal ions to convert less active hydrogen peroxide (H

Pervasive mechanical impact is growing requirement for advanced high-performance protective materials, while the electromagnetic interference (EMI) confers severe risk to human health and equipment operation. Bioinspired structural composites achieving outstanding safeguards against a single threat have been developed, whereas the synergistic implementation of impact/EMI coupling protection remains a challenge. This work proposes the concept of nacre-mimetic hierarchical composite duplicating the "brick-and-mortar" arrangement, which consists of freeze-drying constructed chitosan/MXene lamellar architecture skeleton embedded in a shear stiffening polyborosiloxane matrix. The resulting composite effectively attenuates the impact force of 85.9%-92.8% with extraordinary energy dissipation capacity, in the coordinative manner of strain-rate enhancement, structural densification, lamella dislocation and crack propagation. Attributed to the alternate laminated structure promoting the reflection loss of electromagnetic waves, it demonstrates an ultraefficient EMI shielding effectiveness of 47.2-71.8 dB within extremely low MXene loadings of 1.1-1.3 wt %. Furthermore, it serves favorably in impact monitoring and wireless alarm systems and accomplishes performance optimization through the combination of multiple biomimetic strategies. In conclusion, this function-integrated structural composite is shown to be a competitive candidate for sophisticated environments by resisting impact damage and EMI hazards.

The current proliferation of mobile robots spans ecological monitoring, warehouse management and extreme environment exploration, to an individual consumer's home

Biomimetic scaffolds composed of bioactive ceramic-based materials incorporated within a polymeric framework have shown immense promise for use in bone tissue engineering (BTE) applications. However, studies on direct comparison of the efficacy of different bioceramics on bone bioactivity and osteogenic differentiation are lacking. Herein, we performed an in vitro direct comparison of three different bioceramics-Bioglass 45S5 (BG), Laponite XLG (LAP), and β-Tricalcium Phosphate (TCP)-on the physical properties and bone bioactivity of methacrylated collagen (CMA) hydrogels (10% w/w bioceramic:CMA). In addition, human MSCs (hMSCs) were encapsulated in bioceramic-laden CMA hydrogels and the effect of different bioceramics on osteogenic differentiation of hMSCs was investigated in two different culture medium-osteoconductive (without dexamethasone [DEX]) and osteoinductive (with DEX). Results showed that the stability of CMA hydrogels was maintained upon bioceramic addition. Compression testing revealed that BG incorporation significantly decreased (p 0.05) the modulus of photochemically crosslinked CMA hydrogels. Incubation of TCP-CMA and LAP-CMA hydrogels in simulated body fluid showed deposition of hydroxycarbonate apatite layer on the surface indicating that these hydrogels may be more bone bioactive than BG-CMA and CMA only hydrogels. Cell cytoskeleton staining results showed greater cell spreading in TCP-CMA hydrogels. Furthermore, TCP incorporation significantly increased alkaline phosphatase activity (ALP; p 0.05) in hMSCs. Together, these results indicate that TCP has superior osteogenic potential compared with BG and LAP and hence should be considered as a bioceramic of preferred choice for use in the biomimetic design of cell-laden hydrogels for BTE applications.

Despite increasing recognition of extracellular vesicles being important circulating biomarkers in disease diagnosis and prognosis, current strategies for extracellular vesicle detection remain limited due to the compromised sample purification and extensive labeling procedures in complex body fluids. Here, we developed a 2D magnetic platform that greatly improves capture efficiency and readily realizes visible signal conversion for extracellular vesicle detection. The technology, termed

Cartilage regeneration remains a current challenge with no satisfactory strategy in surgery. Hydrogels with structurally and biochemically biomimicking characteristics have been regarded as a promising approach for the success of cartilage regeneration. Naturally sourced hydrogels from exopolysaccharides are ideal candidates for the construction of biomimetic extracellular matrix (ECM) because of their biomimetic networks, high water content, cytocompatibility, and biodegradability. Here, an approach that integrates covalent and ionic bonds in a hydrogel system is shown to form a natural polymeric hydrogel double network (DN) for promoting the adhesion and proliferation of chondrocytes and supporting the formation of matured cartilage tissue. DN hydrogels comprised of chemically crosslinked hyaluronan (HA) and physically crosslinked gellan gum (GG) were developed for potential scaffold fabrication. Compared with HA single network (SN) hydrogel and GG SN hydrogel, the obtained HA/GG DN hydrogel with Young's modulus of 28.6 kPa exhibited adequate compressive strength (208.9 kPa) and high toughness (dissipated energy 2837 J/m

The mechanical phenotype of the cell is critical for survival following deformations due to confinement and fluid flow. One idea is that cancer cells are plastic and adopt different mechanical phenotypes under different geometries that aid in their survival. Thus, an attractive goal, is to disrupt the cancer cells’ ability to adopt multiple mechanical states. To begin to address this question, we aimed to quantify the diversity of these mechanical states usingin vitrobiomimetics to mimicin vivo2D and 3D extracellular matrix environments. Here, we used two modalities Brillouin microscopy (∼GHz) and broadband frequency (3-15kHz) optical tweezer microrheology to measure microscale cell mechanics. We measured the response of intracellular mechanics of cancer cells cultured in 2D and 3D environments where we modified substrate stiffness, dimensionality (2D versus 3D), and presence of fibrillar topography. We determined that there was good agreement between two modalities despite the difference in timescale of the two measurements. These findings on cell mechanical phenotype in different environments confirm a correlation between modalities that employ different mechanisms at different temporal scales (Hz-kHz vs. GHz). We also determined that observed heterogeneity in cell shape that is more closely linked to the cells’ mechanical state. We also determined that individual cells in multicellular spheroids exhibit a lower degree of mechanical heterogeneity when compared to single cells cultured in monodisperse 3D cultures. Moreover, the observed decreased heterogeneity among cells in spheroids suggested that there is mechanical cooperativity between cells that make up a single spheroid.

The integration of renewable solar energy-driven interfacial evaporation and photocatalysis has recently emerged as one of the most promising technologies for simultaneous freshwater production and pollutant removal. However, the construction of an advanced integrated system with the merit of a fast supply of water and pollutant molecules remains challenging for efficient solar-driven evaporation and photocatalytic performance. Herein, inspired by the transpiration of plants, we fabricate a biomimetic, vertically channeled polypyrrole/foam-like carbon nitride/poly(vinyl alcohol) hydrogel (PCH) by directional freeze-drying. We prove that the vertically aligned channels not only reduce heat loss and improve energy conversion efficiency but also facilitate the transport of water and organic pollutants to the air-water interface. Benefiting from the advantages above, the PCH evaporator presents a high solar evaporation efficiency of 92.5%, with the evaporation rate achieving 2.27 kg m

Mineral-based bulk structural materials (MBSMs) are known for their long history and extensive range of usage. The inherent brittleness of minerals poses a major problem to the performance of MBSMs. To overcome this problem, design principles have been extracted from natural biominerals, in which the extraordinary mechanical performance is achieved via the hierarchical organization of minerals and organics. Nevertheless, precise and efficient fabrication of MBSMs with bioinspired hierarchical structures under mild conditions has long been a big challenge. This Perspective provides a panoramic view of an emerging fabrication strategy, matrix-directed mineralization, which imitates the in vivo growth of some biominerals. The advantages of the strategy are revealed by comparatively analyzing the conventional fabrication techniques of artificial hierarchically structured MBSMs and the biomineral growth processes. By introducing recent advances, we demonstrate that this strategy can be used to fabricate artificial MBSMs with hierarchical structures. Particular attention is paid to the mass transport and the precursors that are involved in the mineralization process. We hope this Perspective can provide some inspiring viewpoints on the importance of biomimetic mineralization in material fabrication and thereby spur the biomimetic fabrication of high-performance MBSMs.

As the postsynthesis-processed metal-organic material-based catalysts for energy applications add additional cost to the whole process, the importance of developing synthesized usable pristine catalysts is quite evident. The present work reports a new Cu-based coordination polymer (Cu-CP) catalyst to be used in its pristine form for oxygen reduction reaction (ORR) application. The catalyst was characterized using single-crystal X-ray diffraction, field emission scanning electron microscopy, and X-ray photoemission spectroscopy. The Cu-CP exhibits admirable electrocatalytic ORR activity with an onset potential of 0.84 V versus RHE and a half wave potential of 0.69 V versus RHE. As revealed by the density functional theory-based computational mechanistic investigation of the electrocatalytic ORR process, the electrochemically reduced Cu(I) center binds to the molecular O

Branch migration (BM) of DNA Holliday junctions (HJs) occurs through base-pair rearrangements between homologous DNA molecules during the repair of double-strand breaks (DSBs) by homologous recombination. Despite the fact that BM is conserved among organisms and is essential to stabilize recombination intermediates, which occurs by avoiding the reversal of strand exchange leading to the faithful repair of DSBs, molecular insights into the BM process including kinetics, the effects of microenvironments, and the role of HJ-binding proteins are poorly understood. In this article, using single-molecule fluorescence analysis of a synthetic, mobile HJ as a model system, we systematically investigated the effects of cell-mimic solvent composition and crowding on BM by varying the concentration of cosolutes, namely dimethyl sulfoxide (DMSO) and poly(ethylene glycol) (PEG). The single-molecule analyses revealed that BM is affected by cosolutes in a concentration-dependent manner. In addition, the kinetic analysis of the fluorescence resonance energy transfer (FRET) traces showed that the BM is significantly accelerated under the crowding environments. The finding that the mobility of the HJ is enhanced by cell-like environments not only provides a better insight into BM but also may open up new avenues for targeting HJs and the associated BM process for possible therapeutic interventions.

Fabrication of a hydrogel scaffold for full-thickness osteochondral defect repair remains a grand challenge. Developing layered and multiphasic hydrogels to mimic the intrinsic hierarchical structure of the osteochondral unit is a promising strategy. Chitosan-based hydrogels are widely applied for biomedical applications. However, insufficient mechanical strength and lack of biological cues to restore damaged cartilage and subchondral tissue significantly hinder their application in osteochondral tissue engineering. In this study, a strong and tough, osteochondral-mimicking functional chitosan-based hydrogel (bilayer-gel) with an

Platelets are multifunctional effectors of inflammatory responses and inseparable from the occurrence and development of various inflammatory diseases. The platelet membrane (PM) is integrated onto the surface of a nano-drug delivery system to form the PM-cloaked nanoparticles (PM@NPs), which can increase the biocompatibility of the nano-drug delivery system and mitigate adverse drug reactions. Owing to the strong affinity of immune regulation and adhesion-related antigens on the surface of PM to the focal sites of inflammatory diseases, which endows PM@NPs with the potential to actively target lesions and improve the therapeutic efficacy of drugs for inflammatory diseases. Based on latest developments in PM biomimetic technique and nanomedicine for the treatment of inflammatory diseases, this paper mainly elaborates three aspects: advantages of PM@NPs, experimental foundation of PM biomimetic nanotechnology, and applications of PM@NPs to the treatment of inflammatory diseases. The aim is to provide reference for the development and application of PM@NPs and novel insights into the treatment of inflammatory diseases.

The periodontium supports the teeth by dentoalveolar fibrous joints that serve unique oral functions. Endogenous regeneration of the periodontium around artificial teeth (dental implants) provides a cost-effective solution for the extension of healthy life expectancy but remains a challenge in regenerative medicine. Biomimetics can create smart biomaterials that tune endogenous cells at a tissue-material interface. Here, we created a smart titanium nanosurface mimicking the surface nanotopography and micromechanical properties of the tooth root cementum (TRC), which is essential for the induction of dentoalveolar fibrous joints to regenerate the periodontium. After transplantation into the rat renal capsule, only the titanium artificial tooth with the TRC-mimetic nanosurface formed a complex dentoalveolar fibrous joint structure, with bone tissue, periodontal ligament (PDL), and TRC, in the decellularized jawbone matrix. TRC-mimetic titanium implants induce the formation of functional periodontium, even in a jawbone implantation model, which generally causes osseointegration (ankyloses). In human PDL cells, TRC analogousness in the surface mechanical microenvironment regulates matrix mineralization through bone sialoprotein expression and phosphorus metabolism, which are critical for cementogenesis. Therefore, the titanium nanosurfaces with nanotopographical and mechanical microenvironments mimicking the TRC surface induce dentoalveolar fibrous joints for periodontal regeneration by interfacial tuning of endogenous cells.

Biomimetic nanozyme with natural enzyme-like activities has drawn extensive attention in cancer therapy, while its application was hindered by the limited catalytic efficacy in the complicated tumor microenvironment (TME). Herein, a hybrid biomimetic nanozyme combines polydopamine-decorated CuO with a natural enzyme of glucose oxidase (GOD), among which CuO is endowed with a high loading rate (47.1%) of GOD due to the elaborately designed hollow mesoporous structure that is constructed to maximize the cascade catalytic efficacy. In the TME, CuO could catalyze endogenous H

In the context of regenerative endodontics research with the development of biomaterials, this work aimed to develop and test a prototype biomimetic bioreactor of a human tooth. The bioreactor was designed to reproduce a shaped dental canal connected with a cavity reproducing the periapical region and irrigated through two fluidic channels intended to reproduce the apical residual vascular supply. A test biomaterial composed of polylactic acid/polycaprolactone-tannic acid (PLA/PCL-TA) was produced by electrospinning/electrospraying and calibrated to be inserted in a dental canal. This biomaterial was first used to evaluate its imbibition capacity and the oximetry inside the bioreactor. Then, Dental Pulp Stem Cells (DPSCs) were cultured on PLA/PCL-TA cones for 1-3 weeks in the bioreactor; afterward cell adhesion, proliferation, and migration were histologically assessed. Complete imbibition biomaterial was obtained in 10 min and oximetry was stable over time. In the bioreactor, DPSCs were able to adhere, proliferate and migrate onto the surface and inside the biomaterial. In conclusion, this bioreactor was used successfully to test a biomaterial intended to support pulp regeneration and constitutes a new in vitro experimental model closer to clinical reality.

Silk nanofibrils (SNFs) extracted from natural silkworm silk represent a class of high-potential protein nanofiber material with unexplored biomedical applications. In this study, a SNF-assembled microsphere with extracellular matrix (ECM)-mimicking architecture and high specific surface area was developed. The SNFs were exfoliated from silkworm silks through an all-aqueous process and used as the building blocks for constructing the microspheres. Inspired by the structure and bioactive composition of ECM, hyaluronic acid (HA) was used as a bio-glue to regulate SNF assembly. With the assistance of HA, the SNF microspheres with stable fluffy nanofibrous structures were synthesized through electrospray. The biomimetic structure and nature derived composition endow the microspheres with excellent biocompatibility and enhanced osteogenic differentiation-inducing ability to mesenchymal stem cells. As proof of versatility, the SNF microspheres were further functionalized with other molecules and nanomaterials. Taking the advantages of the excellent blood compatibility and modifiability from the molecular level to the nanoscale of SNF microspheres, we demonstrated their versatile applications in protease detection and blood purification. On the basis of these results, we foresee that this natural silk-based nanofibrous microsphere may serve as a superior biomedical material for tissue engineering, early disease diagnosis, and therapeutic devices.

An ability to integrate adaptive coloration and tissue-like compositions, structures, as well as mechanical properties, and so forth into a material remains elusive. To address this problem, this work presents a solution whereby these features were integrated into a proteinic artificial skin through biomimetic design. In this artificial skin, silk fibroin was used to mimic the structural framework of the cytoskeleton due to its unique molecular network structure and outstanding and tunable mechanical properties. Meanwhile, a thermochromic filamentous network consisting of C

Nocardioazines A and B are prenylated, bioactive pyrroloindoline natural products, isolated from

For the preparation of chiral drugs, both stereochemically stable and flexible catalysts in combination with chiral auxiliaries can be used. Here, chiral induction plays an important role in generating an enantiomerically pure catalyst. We demonstrate a successful approach to the spontaneous deracemization of

Periodontal ligament (PDL) is assembled from highly organized collagen fiber bundles (PDL principal fibers) that are crucial in supporting teeth and buffering mechanical force. Therefore, regeneration of PDL needs to reconstruct these well-ordered fiber bundles to restore PDL functions. However, the formation of PDL principal fibers has long been a challenge due to the absence of an effective three-dimensional (3D) matrix to guide the growth of periodontal ligament stem cells (PDLSCs) and to inhibit the osteogenic differentiation of PDLSCs during the PDL principal fibers deposition. In this work, we designed and fabricated a bio-inspired tubular 3D matrix to guide the migration and growth of human PDLSCs and form well-aligned PDL principal fibers. As a biomimetic 3D template, the tubular matrix controlled PDLSCs migration inside the tubules and aligned the cells to the designated direction. Inside the tubular matrix, the PDLSCs expressed PDL markers and formed oriented fiber bundles with the same size and density as those of natural PDL principal fibers. Furthermore, the tubular matrix downregulated the osteogenic differentiation of PDLSCs. A mechanism study revealed that the Yap1/Twist1 signaling pathway was involved in the inhibition of PDLSCs osteogenesis within the tubular matrix. This work provides an effective approach to induce PDLSCs to form principal fibers and gives insight into the underlying mechanism of inhibiting the osteogenic differentiation of PDLSCs in biomimetic tubular matrices.

The periosteum plays an important role in the regeneration of critical-size bone defects, with functions of recruiting multiple cells, accelerating vascular network reconstruction, and guiding bone tissue regeneration. However, these functions cannot be easily implemented by simply simulating the periosteum via a material structure design or by loading exogenous cytokines. Herein, inspired by the periosteal function, we propose a biomimetic periosteum preparation strategy to enhance natural polymer hydrogel membranes using inorganic bioactive materials. The biomimetic periosteum having bone tissue self-adhesive functions and resembling an extracellular matrix was prepared using dopamine-modified gelatin and oxidized hyaluronan (GA/HA), and micro/nanobioactive glass (MNBG) was further incorporated into the hydrogel to fabricate an organic/inorganic co-crosslinked hydrogel membrane (GA/HA-BG). The addition of MNBG enhanced the stability of the natural polymer hydrogel membrane, resulting in a sustained degradation time, biomineralization, and long-term release of ions. The Ca

Melanoma is a cancer of melanocytes present at the basal layer of the skin. Nanomedicine has armed us with competent platform to manage such fatal neoplastic diseases. Nevertheless, it suffers from numerous pitfalls such as rapid clearance and opsonization of surface-functionalized carriers, biocompatibility and idiopathic reactions which could be difficult to predict in the patient. Biomimetic approach, a novel step towards personalized medicine bridges these drawbacks by employing endogenous cell membranes to traverse physiological barriers. Camouflaged carriers coated with natural cell membranes possess unique characteristics such as high circulatory periods, and the absence of allogenic and xenogenic responses. Proteins residing on the cell membranes render a diverse range of utilities to the coated nanoparticles including natural efficiency to identify cellular targets, homologous targeting, reticuloendothelial system evasion, biocompatibility and reduced adverse and idiopathic effects. In the present article, we have focused on cell membrane camouflaged nanocarriers for melanoma management. We have discussed various types of biomimetic systems, their processing and coating approaches, and their characterization. We have also enumerated novel avenues in melanoma treatment and the combination of biomimetic systems with smart nanoparticulate systems with the potential to bring breakthroughs in the near future. Additionally, immunotherapy-based biomimetic systems to combat melanoma have been highlighted. Hurdles towards clinical translation and ways to overcome them have been explained in detail.

Exploring the reusability of wood-based panels is imperative in the wood industry for sustainable development and carbon balance. Non-reusable adhesives make wood-based panel recycling difficult. In this study, inspired by the adhesion and de-adhesion behavior of snail slime, we built dynamic covalent/hydrogen hybrid networks into adhesive system for achieving both high bonding performance and reusability. Specifically, the softwood lignin was purified and pretreated by ultrasonication to form a catechol structure (UAL) and then combined with soybean protein to develop a 100 % bio-based wood adhesive. The catechol structure of UAL formed dynamic covalent bonds (CN) with the amino groups of the protein to improve the water resistance and formed multiple hydrogen bonds as a sacrificial network to improve the toughness of the adhesive. Thus, the wet shear strength of plywood bonded by the resultant adhesive improved by 101.4 % to 1.37 MPa. The adhesive also exhibited flame retardancy (LOI = 37.7 %), mildew resistance (60 h), and antibacterial performance (inhibition zone = 8 mm). Notably, owing to the rearrangement of dynamic covalent/hydrogen hybrid networks and the thermoplastic property of UAL, the resultant adhesive was reusable (3 cycles) and degradable (2 months), which provides a potential method for the reuse of wood-based panels.

Tissue engineering has historically involved research combining scaffolds, cells, and active biomolecules to treat multiple pathologies. The current research seeks to determine if the wound healing cascade can be modulated using acellular scaffolds, engineered to create an acellular electrospun dermal biomimetic.The dermal biomimetic has a similar architecture to the dermis, porosity and fiber diameter, as well as physiologically relevant ratios of the primary structural dermal proteins, collagen and tropoelastin. This biomimetic wound healing device (BMWHD) was implanted into a full thickness dermal wound murine model for six days.WHD-treated wounds had 30% greater re-epithelialization with a thicker epidermis, new elastin fibers in the wound bed, and healed architecture that matched unwounded extracellular matrix.Using these WHDs that closely match the native architecture and protein concentrations, accelerated the wound through the wound healing cascade and supports the hypothesis that structure alone can influence function when engineering acellular dermal biomimetic devices.

Cell dissemination during tumor development is a characteristic of cancer metastasis. Dissemination from three-dimensional spheroid models on extracellular matrices designed to mimic tissue-specific physiological microenvironments may allow us to better elucidate the mechanism behind cancer metastasis and the response to therapeutic agents. The orientation of fibrillar collagen plays a key role in cellular processes and mediates metastasis through contact-guidance. Understanding how cells migrate on aligned collagen fibrils requires in vitro assays with reproducible and standardized orientation of collagen fibrils on the macro-to-nanoscale. Herein, we implement a spheroid-based migration assay, integrated with a fibrillar type I collagen matrix, in a manner compatible with high throughput image acquisition and quantitative analysis. The migration of highly proliferating U2OS osteosarcoma cell spheroids onto an aligned fibrillar type I collagen matrix were quantified. Cell dissemination from the spheroid was polarized with increased invasion in the direction of fibril alignment. The resulting area of cell dissemination had an aspect ratio of 1.2 ± 0.1 and an angle of maximum invasion distance of 5° ± 44° relative to the direction of collagen fibril alignment. The assay described here can be applied to a fully automated imaging and analysis pipeline for the assessment of tumor cell migration with high throughput screening. European Commission Horizon 2020 Science Foundation Ireland Marie Skłodowska-Curie UCD School of Physics (SIRAT − Scholarship in Research and Teaching) Sustainable Energy Authority of Ireland (SEAI) In Press, Corrected Proof. To check details in 6 months

Soft robots, made from elastomers, easily bend and flex, but deformability constraints severely limit navigation through and within narrow, confined spaces. Using aqueous two-phase systems we print water-in-water constructs that, by aqueous phase-separation-induced self-assembly, produce ultrasoft liquid robots, termed aquabots, comprised of hierarchical structures that span in length scale from the nanoscopic to microsciopic, that are beyond the resolution limits of printing and overcome the deformability barrier. The exterior of the compartmentalized membranes is easily functionalized, for example, by binding enzymes, catalytic nanoparticles, and magnetic nanoparticles that impart sensitive magnetic responsiveness. These ultrasoft aquabots can adapt their shape for gripping and transporting objects and can be used for targeted photocatalysis, delivery, and release in confined and tortuous spaces. These biocompatible, multicompartmental, and multifunctional aquabots can be readily applied to medical micromanipulation, targeted cargo delivery, tissue engineering, and biomimetics.

The ever-increasing rate of medical device implantations is met by a proportionately high burden of implant-associated infections. To mitigate this threat, much research has been directed toward the development of antibacterial surface modifications by various means. One recent approach involves surfaces containing sharp nanostructures capable of killing bacteria upon contact. Herein, we report that the mechanical interaction between Staphylococcus aureus and such surface nanostructures leads to a sensitization of the pathogen to the glycopeptide antibiotic vancomycin. We demonstrate that this is due to cell wall damage and impeded bacterial defenses against reactive oxygen species. The results of this study promise to be impactful in the clinic, as a combination of nanostructured antibacterial surfaces and antibiotics commonly used in hospitals may improve antimicrobial therapy strategies, helping clinicians to prevent and treat implant-associated infections using reduced antibiotic concentrations instead of relying on invasive revision surgeries with often poor outcomes. Refereed/Peer-reviewed

Upon replacement of molybdenum by tungsten in DMSO reductase isolated from the Rhodobacteraceae family, the derived enzyme catalyzes DMSO reduction faster. To better understand this behavior, we synthesized two tungsten(VI) dioxido complexes [W

Brain-inspired intelligent systems demand diverse neuromorphic devices beyond simple functionalities. Merging biomimetic sensing with weight-updating capabilities in artificial synaptic devices represents one of the key research focuses. Here, we report a multiresponsive synapse device that integrates synaptic and optical-sensing functions. The device adopts vertically stacked graphene/h-BN/WSe

Hymexazol (HYM) is irreplaceable for treating soil-borne diseases due to its high efficiency and low cost, as a broad-spectrum fungicide. However, when HYM is absorbed by plants, it is rapidly converted into two glycoside metabolites, and the antifungal activities of these glycosides are inferior to that of HYM. Therefore, in this study, to maintain strong antifungal activity in vitro and in vivo, HYM was glycosylated with amino sugars that have diverse biological activities to simulate plant glycosylation. The antifungal experiment proved that glycoside

The intense metabolism of cancer cells leads to hypoxia and lack of crucial nutrients in the tumor microenvironment, which hinders the function of immune cells. We designed a biomimetic immune metabolic nanoplatform, in which a type I aggregation-induced emission photosensitizer and a glutamine antagonist are encapsulated into a cancer cell membrane for achieving specific delivery

Temporomandibular disorder (TMD) remained a huge clinical challenge, with high prevalence but limited, unstable, and only palliative therapeutic methods available. As one of the most vulnerable sites implicated in TMD, the temporomandibular joint disc (TMJD) displayed a complicated microstructure, region-specific fibrocartilaginous distribution, and poor regenerative property, which all further hindered its functional regeneration. To address the problem, with versatile and relatively simple electrospinning (ELS) technique, our study successfully fabricated a biomimetic, three-dimensional poly (ϵ-caprolactone) (PCL)/polylactide (PLA)/carbon nanotubes (CNTs) disc scaffold, whose biconcave gross anatomy and regionally anisotropic microstructure recapitulating those of the native disc. As in vitro results validated the superior mechanical, bioactive, and regenerative properties of the biomimetic scaffolds with optimal CNTs reinforcement, we further performed in vivo experiments. After verifying its biocompatibility and ectopic fibrochondrogenicity in nude mice subcutaneous implantation models, the scaffolds guided disc regeneration and subchondral bone protection were also confirmed orthotopically in rabbits TMJD defected areas, implying the pivotal role of morphological cues in contact-guided tissue regeneration. In conclusion, our work represents a significant advancement in complex, inhomogeneous tissue engineering, providing promising clinical solutions to intractable TMD ailments. STATEMENT OF SIGNIFICANCE: Complex tissue regeneration remains a huge scientific and clinical challenge. Although frequently implicated in temporomandibular joint disorder (TMD), functional regeneration of injured temporomandibular joint disc (TMJD) is extremely hard to achieve, mainly because of the complex anatomy and microstructure with regionally variant, anisotropic fiber alignments in the native disc. In this study, we developed the biomimetic electrospun scaffold with optimal CNTs reinforcement and regionally anisotropic fiber orientations. The excellent mechanical and bioactive properties were confirmed both in vitro and in vivo, effectively promoting defected discs regeneration in rabbits. Besides demonstrating the crucial role of morphological biomimicry in tissue engineering, our work also presents a feasible clinical solution for complex tissue regeneration.

Hedgehog spines with evolved unique structures are studied on account of their remarkable mechanical efficiency. However, because of limitations of existing knowledge, it remains unclear how spines work as a material with a balance of stiffness and toughness. By combining qualitative three-dimensional (3D) structural characterization, material composition analysis, biomechanical analysis, and parametric simulations, the relationship between microstructural characteristic and multifunctional features of hedgehog spines is revealed here. The result shows that the fibers transform from the outer cortex to the interior cellular structures by the "T" section composed of the "L" section and a deltoid. The outer cortex, however, shows an arrangement of a layered fibrous structure. An inward change in Young's moduli is observed. In addition, these spines are featured with a sandwich structure that combines an inner porous core with an outer dense cortex. This feature confirms that the hedgehog spines are a kind of biological functionally graded fiber-reinforced composite. Biomimetic models based on the spine are then built, and the corresponding mechanical performance is tested. The results confirm that the internal cellular structure of the spine effectively improve impact resistance. Furthermore, the transverse diaphragm can prevent ellipticity, which may delay buckling. The longitudinal stiffeners also contribute to promote buckling resistance. The design strategies of the spine proposed here provide inspirations for designing T-joint composites. It also exhibits potential applications in low-density, impact and buckling resistance artificial composites. STATEMENT OF SIGNIFICANCE: The spines of a hedgehog are its protective armor that combines strength and toughness. The animal can not only withstand longitudinal and radial forces that are 1 × 10

Backgroud: At present, tumors are leading cause of death. Biomimetic nanocarriers for precision cancer therapy are attracting increasing attention. Nanocarriers with a good biocompatible surface could reduce the recognition and elimination of nanoparticles as foreign substances by the immune system, offer specific targeting, and improve the efficacy of precision medicine for tumors, thereby providing outstanding prospects for application in cancer therapy. In particular, cell membrane biomimetic camouflaged nanocarriers have become a research hotspot because of their excellent biocompatibility, prolonged circulation in the blood, and tumor targeting. Objective: The objective of this study is to summarize the biological targeting mechanisms of different cell membraneencapsulated nanocarriers in cancer therapy. In this article, the characteristics, applications, and stages of progress of bionic encapsulated nanocarriers for different cell membranes are discussed, as are the field’s developmental prospects. Method: The findings on the characteristics of bionic encapsulated nanocarriers for different cell membranes and tumor treatment have been analyzed and summarized. Results: Biomimetic nanosystems based on various natural cell and hybrid cell membranes have been shown to efficiently control targeted drug delivery systems. They can reduce immune system clearance, prolong blood circulation time, and improve drug loading and targeting, thereby enhancing the diagnosis and treatment of tumors and reducing the spread of CTCs. Conclusion: With advances in the development of biomimetic nanocarrier DDSs, novel ideas for tumor treatment and drug delivery have been emerged. However, there are still some problems in biomimetic nanosystems. Therefore, it needs to be optimized through further research, from the laboratory to the clinic to benefit a wide range of patients.

3D bioprinting is currently widely used to build engineered mammalian tissue constructs with complex spatial structures. It has revolutionized tissue engineering and is a promising avenue for regenerative medicine. Recently, 3D bioprinting has also been used for the fabrication of living tissues that cultivate microorganisms including photosynthetic single-celled microalgae and bacterial cells. Here we review the principles and applications of biomimetic 3D living materials powered by microorganisms. We envision that there will be great potential for the application of microorganism-driven materials in biomedicine, biotechnology, and living device fabrication as well as for ecosystem restoration.

Direct biomimetic modification of nanoparticles (NPs) with endogenous surfactants is helpful to improve the biocompatibility of NPs and avoid damage to the physiological function of the lung. Therefore, the objective of this study is to investigate the influence of biomimetic endogenous pulmonary surfactant phospholipid modification on the in vivo fate of NPs after lung delivery. Here, two neutral phospholipids (dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylamine (DPPE)) and two negatively charged phospholipids (dipalmitoylphosphatidylglycerol (DPPG), dipalmitoylphosphatidylserine (DPPS)) were selected to modify paclitaxel (PTX)-loaded PLGA NPs with different molar ratio. DPPC, DPPE, and DPPG improved mucoadhesion, in contrast, DPPS improved the mucus permeability of the NPs. Neutral DPPC and DPPE reduced, but negatively charged DPPS and DPPG increased the uptake by alveolar macrophages, all types of phospholipid increased the uptake by lung epithelial cells and increased PTX retention in the whole lung. Whereas, DPPC, DPPE, and DPPG promoted PTX retention in bronchoalveolar lavage fluid (BALF), while DPPS promoted PTX absorption in the lung tissue. Only DPPS-PLGA (1:1) NPs remarkably increased PTX systemic exposure. A good correlation between PTX percentage in the supernatant of BALF and PTX concentration in plasma was established, implying PTX entered the system circulation mainly in molecular form. Phospholipid modification had no effect on extrapulmonary organ distribution of PTX. Taken together, our study disclosed that different phospholipid modification can endow the NPs mucoadhesive or mucus penetration and cellular uptake properties, with tunable retention in BALF and absorption in the lung tissue, providing the scientific background for translational nanocarrier design for inhalation as required. STATEMENT OF SIGNIFICANCE: Inhaled nanomedicines will inevitably interact with pulmonary surfactant and form "surfactant corona". However, the contribution of individual pulmonary surfactant phospholipid on the in vivo fate of nanomedicines is still unclear. In this regard, the most abundant pulmonary surfactant phospholipid dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylamine, and dipalmitoylphosphatidylglycerol and dipalmitoylphosphatidylserine were selected to modify the paclitaxel loaded PLGA nanoparticles and the effect of these pulmonary surfactant phospholipids on their in vivo fate was investigated. It was demonstrated that different phospholipid modification can endow the nanoparticles mucoadhesive or mucus penetration properties, with tunable retention in bronchoalveolar lavage fluid, alveolar macrophages uptake and absorption in the lung tissue. The present study provided a comprehensive understanding for the role of pulmonary surfactant phospholipid on inhaled nanomedicines.

This study presents a biomimetic 3D customizable artificial vascular graft with a highly porous and uniform microscale structure. The structural features were obtained by dip coating of a highly close-packed microsphere suspension on a 3D printed sacrificial template. Considering the structured arrangement of microspherical porogens in the coating layer, the microsphere-leached constructs showed higher uniformity and porosity than the conventionally particulate-leached structures, leading to ultrasoft mechanical compliance. Considering biomechanical compatibility, the resulting elastic moduli were at the sub-MPa level, comparable with those of native vascular tissues. In addition, the developed porous graft was reinforced selectively at the edge regions using a nonporous coating to secure its practical sutureability for clinical use. The sufficiently low cytotoxicity was clinically confirmed to alleviate the stiffness mismatch issues at the anastomotic interface between the native tissue and the artificial graft, thus overcoming the relevant clinical complications. Furthermore, the overall superior properties could be implemented on the 3D printed template for patient-specific medicare, thus implying the manufacturability of patient-specific vascular grafts.

A facile synthesis of apatite nanocrystals analogous to bioapatites with increased biocompatibility and biodegradability can remedy the shortcomings of the widely applied synthetic hydroxyapatite (HAp) for bone defect treatment. Here, we propose an expeditious synthesis method to develop a biomimetic B-type carbonate apatite (CAp) with a simple capillary microfluidic device at room temperature. The process not only eliminates fluctuations with the addition of carbonate but also produces safe CAp drug carriers through simultaneous alendronate incorporation to the CAp structure. CAp displayed superior mineralization on osteoblast-like MG-63 cells when compared with HAp and HAp drug carriers that were produced using identical methods. Furthermore, alendronate-incorporated CAp drug carriers potentially displayed higher cancer cell suppression when applied to breast cancer cells attached to the bone tissue model, which signifies enhanced cancer metastasis to bone suppression due to the likelihood of increased alendronate release of CAp owing to its faster dissolution. Overall, our results may provide promising opportunities for enhanced clinical CAp application for bone defect treatment, particularly for bone loss and cancer to bone metastasis.

Drug-based oncotherapy is seriously challenged by insufficient drug accumulation at tumor sites, mainly resulting from low drug loading efficiency and poor tumor-targeting ability of drug carriers. We herein proposed a "one-stone, two-bird" strategy to circumvent both obstacles, utilizing the source cancer cell membrane (CM) as a dual-function carrier to simultaneously achieve sufficient drug loading and homologous tumor targeting. Combining the use of TPGS (d-α-tocopherol polyethylene glycol 1000 succinate) to inhibit the drug efflux process of drug-resistant tumor, we constructed core-shell-structured nanocomposites CMGNPs consisting of ICG (indocyanine green)/DOX (doxorubicin)-loaded, TPGS/OA (oleic acid)-stabilized upconversion nanoparticles as the core and ICG-loaded MCF7/ADR CMs as the shell, for combined chemo/phototherapy of MCF7/ADR tumor. The employment of phospholipid bilayers of CMs as natural pockets for extra drug loading while preserving the homologous targeting ability greatly enhanced drug concentration at tumor sites, endowing CMGNPs with excellent therapeutic efficacy. Our effort provides a versatile approach for facilitating drug delivery in diverse therapeutic systems.