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Clinical application of antibiotic-free agents like silver nanoparticle-derived materials remains a critical challenge due to their limited long-term antibacterial activity and potential system toxicity. Herein, a highly biocompatible Ag nanocluster-reinforced hydrogel with enhanced synergistic antibacterial ability has been developed. Specifically, bioactive curcumin was incorporated into lysozyme-protected ultrasmall Ag nanoclusters (LC-AgNCs) and further integrated with sodium alginate (Sa) hydrogel (LC-AgNCs@Sa) through multiple interaction forces. Due to the synergistic antibacterial activity, LC-AgNCs could effectively kill both S. aureus and E. coli bacteria with a concentration down to 2.5 μg mL

Heavy metal Cadmium (Cd) will continuously pollute the atmosphere, soil and various water environments through material circulation, and even pose a threat to human safety. It has been designated as a first-class pollutant in sewage by China, therefore there is an urgent need to find new, more effective, and low-cost method to accurately detect Cadmium ion (Cd2+) concentration. We experimentally prepared a new Cd2+ sensor based on NiS2 nanomaterials capable of measuring Cd2+ concentration. The corresponding relationship between over potential of NiS2 nanomaterials in H2SO4 electrolyte solutions with different Cd2+ concentration and reduction peak with change of Cd2+ concentration was obtained by electrochemical method.

Silk fibroin (SF) is a promising biomaterial for tendon repair, but its relatively rigid mechanical properties and low cell affinity have limited its usefulness and utility in regenerative medicine. Meanwhile, gelatin-based polymers have advantages in cell attachment and tissue remodeling, but have insufficient mechanical strength to regenerate tough tissue such as tendons. Taking these aspects into account, in this study, gelatin methacryloyl (GelMA) was combined with SF to create a mechanically strong and bioactive nanofibrous scaffold (SG). The mechanical properties of SG nanofibers could be flexibly modulated by varying the ratio of SF and GelMA. Compared to SF nanofibers, mesenchymal stem cells (MSCs) seeded on SG fibers with optimal composition (SG7) exhibited enhanced growth, proliferation, vascular endothelial growth factor (VEGF) production and tenogenic gene expression behavior. Conditioned media from MSCs cultured on SG7 scaffolds, compared to MSCs cultured on SF or GelMA alone nanofibers could greatly promote the migration and proliferation of tenocytes. Histological analysis and tenogenesis related immunofluorescence staining indicated SG7 scaffolds demonstrated enhanced in vivo tendon tissue regeneration compared to other groups. Therefore, rational combinations of SF and GelMA hybrid nanofibers may help to improve therapeutic outcomes and address the challenges of tissue-engineered scaffolds for tendon regeneration.

Fluorescent nanomaterials have been widely used in biological imaging due to their selectivity, sensitivity, and noninvasive nature. These characteristics make the materials suitable for real-time and in situ imaging. However, further development of highly biocompatible nanosystems with long-lasting fluorescent intensity and photostability is needed for advanced bioimaging. We have used electrospraying to generate gelatin methacryloyl (GelMA)-based fluorescent nanoparticles (NPs) with chemically conjugated rhodamine B (RB). The extent of conjugation can be controlled by varying the mass ratio of RB and GelMA precursors to obtain RB-conjugated GelMA (RB-GelMA) NPs with optimal fluorescent properties and particle size. These NPs exhibited superior biocompatibility when compared with pure RB in in vitro cell viability and proliferation assays using multiple cell types. Moreover, RB-GelMA NPs showed enhanced cell internalization and improved brightness compared with unconjugated RB. Our experiments demonstrate that engineered RB-GelMA NPs can be used as a biocompatible fluorescent label for bioimaging.

Diabetic wound repair and skin regeneration remains a worldwide challenge due to the impaired functionality of re-vascularization. Methods: This study reports a bioactive self-healing antibacterial injectable dual-network silica-based nanocomposite hydrogel scaffolds that can significantly enhance the diabetic wound healing/skin tissue formation through promoting early angiogenesis without adding any bioactive factors. The nanocomposite scaffold comprises a main network of polyethylene glycol diacrylate (PEGDA) forming scaffolds, with an auxiliary dynamic network formed between bioactive glass nanoparticles containing copper (BGNC) and sodium alginate (ALG) (PABC scaffolds). Results: PABC scaffolds exhibit the biomimetic elastomeric mechanical properties, excellent injectabilities, self-healing behavior, as well as the robust broad-spectrum antibacterial activity. Importantly, PABC hydrogel significantly promoted the viability, proliferation and angiogenic ability of endothelial progenitor cells (EPCs) in vitro. In vivo, PABC hydrogel could efficiently restore blood vessels networks through enhancing HIF-1α/VEGF expression and collagen matrix deposition in the full-thickness diabetic wound, and significantly accelerate wound healing and skin tissue regeneration. Conclusion: The prominent multifunctional properties and angiogenic capacity of PABC hydrogel scaffolds enable their promising applications in angiogenesis-related regenerative medicine.

Diabetic wound treatment faces significant challenges in clinical settings. Alternative treatment approaches are needed. Continuous bleeding, disordered inflammatory regulation, obstruction of cell proliferation, and disturbance of tissue remodeling are the main characteristics of diabetic wound healing. Hydrogels made of either naturally derived or synthetic materials can potentially be designed with a variety of functions for managing the healing process of chronic wounds. Here, a hemostatic and anti-inflammatory hydrogel patch is designed for promoting diabetic wound healing. The hydrogel patch is derived from dual-cross-linked methacryloyl-substituted Bletilla Striata polysaccharide (B) and gelatin (G) via ultraviolet (UV) light. It is demonstrated that the B-G hydrogel can effectively regulate the M1/M2 phenotype of macrophages, significantly promote the proliferation and migration of fibroblasts in vitro, and accelerate angiogenesis. It can boost wound closure by normalizing epidermal tissue regeneration and depositing collagen appropriately in vivo without exogenous cytokine supplementation. Overall, the B-G bioactive hydrogel can promote diabetic wound healing in a simple, economical, effective, and safe manner.

Electrical stimulation can facilitate wound healing with high efficiency and limited side effects. However, current electrical stimulation devices have poor conformability with wounds due to their bulky nature and the rigidity of electrodes utilized. Here, a flexible electrical patch (ePatch) made with conductive hydrogel as electrodes to improve wound management was reported. The conductive hydrogel was synthesized using silver nanowire (AgNW) and methacrylated alginate (MAA), with the former chosen as the electrode material considering its antibacterial properties, and the latter used due to its clinical suitability in wound healing. The composition of the hydrogel was optimized to enable printing on medical-grade patches for personalized wound treatment. The ePatch was shown to promote re-epithelization, enhance angiogenesis, mediate immune response, and prevent infection development in the wound microenvironment. In vitro studies indicated an elevated secretion of growth factors with enhanced cell proliferation and migration ability in response to electrical stimulation. An in vivo study in the Sprague-Dawley rat model revealed a rapid wound closure within 7 days compared to 20 days of usual healing process in rodents.

The key role of biomolecule adsorption onto engineered nanomaterials for therapeutic and diagnostic purposes has been well recognized by the nanobiotechnology community, and our mechanistic understanding of nano-bio interactions has greatly advanced over the past decades. Attention has recently shifted to gaining active control of nano-bio interactions, so as to enhance the efficacy of nanomaterials in biomedical applications. In this review, we summarize progress in this field and outline directions for future development. First, we briefly review fundamental knowledge about the intricate interactions between proteins and nanomaterials, as unraveled by a large number of mechanistic studies. Then, we give a systematic overview of the ways that protein-nanomaterial interactions have been exploited in biomedical applications, including the control of protein adsorption for enhancing the targeting efficiency of nanomedicines, the design of specific protein adsorption layers on the surfaces of nanomaterials for use as drug carriers, and the development of novel nanoparticle array-based sensors based on nano-bio interactions. We will focus on particularly relevant and recent examples within these areas. Finally, we conclude this topical review with an outlook on future developments in this fascinating research field.

Animal models and traditional cell cultures are essential tools for drug development. However, these platforms can show striking discrepancies in efficacy and side effects when compared to human trials. These differences can lengthen the drug development process and even lead to drug withdrawal from the market. The establishment of preclinical drug screening platforms that have higher relevancy to physiological conditions is desirable to facilitate drug development. Here, a heart-on-a-chip platform, incorporating microgrooves and electrical pulse stimulations to recapitulate the well-aligned structure and synchronous beating of cardiomyocytes (CMs) for drug screening, is reported. Each chip is made with facile lithographic and laser-cutting processes that can be easily scaled up to high-throughput format. The maturation and phenotypic changes of CMs cultured on the heart-on-a-chip is validated and it can be treated with various drugs to evaluate cardiotoxicity and cardioprotective efficacy. The heart-on-a-chip can provide a high-throughput drug screening platform in preclinical drug development.

The simultaneous therapy of tumors and bone defects resulting from tumor surgery is still a challenge in clinical orthopedics. Few nanomaterial systems simultaneously possess multifunctional capacities, including biodegradability, tumor treatment, and enhanced bone regeneration. Herein, we designed a biodegradable monodispersed bioactive glass nanoparticle (BGN) platform with multifunctional properties for enhanced colon cancer photothermo-chemotherapy and bone repair. The mussel-inspired surface assembly with BGN was established as a stable NIR-excited photothermal nanoplatform (BGN@PDA) for ablating tumors. BGN@PDA shows an ultrahigh anticancer drug (DOX) loading with on-demand (pH/NIR-responsive) drug release behavior and antibacterial activity for enhanced tumor chemotherapy (BGN@PDA-DOX). The growth of colon cancer cells (Hct116 cells) and cervical cancer cells (HeLa cells) was significantly inhibited in vitro, and superior local anticancer efficacy could be achieved by synergic chemo-photothermal therapy in vivo. BGN@PDA underwent a gradual degradation in vivo during 60 days and showed negligible toxic side effects. Meanwhile, BGN@PDA could positively induce the osteogenesis of osteoblasts in vitro and possess excellent in vivo bone repair ability in rat cranial defects. This work presents a distinctive strategy to design a bioactive multifunctional nanoplatform for treating tumor disease-resulted bone tissue regeneration.

The development of biodegradable inorganic nanoparticles with a tumor microenvironment-activated therapeutic mode of action is urgently needed for precision cancer medicine. Herein, the synthesis of ultrathin lanthanide nanoscrolls (Gd2 O3 NSs) is reported, which biodegrade upon encountering the tumor microenvironment. The Gd2 O3 NSs showed highly controlled magnetic properties, which enabled their high-resolution magnetic resonance imaging (MRI). Importantly, Gd2 O3 NSs degrade in a pH-responsive manner and selectively penetrate tumor tissue, enabling the targeted release of anti-cancer drugs. Gd2 O3 NSs can be efficiently loaded with an anti-cancer drug (DOX, 80 %) and significantly inhibit tumor growth with negligible cellular and tissue toxicity both in vitro and in vivo. This study may provide a novel strategy to design tumor microenvironment-responsive inorganic nanomaterials for biocompatible bioimaging and biodegradation-enhanced cancer therapy.

Biodegradable elastomers with good biocompatibility have attracted much attention in biomedical diagnosis/therapy/regenerative medicine, as bioresorbable electronics and implanted devices. The bacterial infection, tissue toxicity, serious inflammatory response and tumorigenesis for implanted devices are still the important obstacles for their biomedical applications. Herein, we reported biodegradable ultralong copper sulfide nanowire-reinforced poly(citrates-siloxane) (PCS-CSNW) nanocomposites elastomers with inherent multifunctional properties for potential biomedical applications. The structure-homogeneous nanocomposites were formed through the hydrophobic-hydrophobic interaction between the oleylamine capped CSNW and polymer chain. PCS-CSNW showed controlled elastomeric mechanical behavior, tunable electronic conductivity and broad-spectrum antibacterial activity against gram-positive/gram-negative bacterium in vitro/in vivo. PCS-CSNW also exhibited tailored photoluminescent property and strong near-infrared (NIR) photothermal capacity which enabled the high-resolution in vivo thermal imaging and biodegradation tracking. Additionally, PCS-CSNW also demonstrated good cell biocompatibility and decreased inflammatory reaction in vivo. The cancer cells on PCS-CSNW nanocomposites were efficiently killed through a selective NIR-induced photothermal therapy. This work may provide a new strategy to design next-regeneration smart implanted devices for biomedical applications in bioresorbable electronics, tissue engineering and regenerative medicine.

Targeted tumor imaging and efficient specific gene delivery in vivo has been one of the main challenges in gene-based cancer diagnosis and therapy. Herein, we engineered a citric acid-based polymer with intrinsical photoluminescence and gene loading capacity to achieve targeted delivery of siRNA and tumor imaging in vitro and in vivo. The multifunctional platform was formed from the self-assembling of poly (citric acid)-polymine conjugated with folic acid and rhodamine B (PPFR). PPFR showed stable photoluminescent ability and could effectively bind and protect the siRNA against RNase degradation. PPFR also exhibited good blood compatibility and cell compatibility against C2C12, MCF-7 and A549. Compared with commercial transfection agent Lipofectamine™ 2000, PPFR had a high cellular uptake, equivalent transfection efficiency and effectively down-regulated intracellular p65 expression in A549 cancer cells. Importantly, PPFR could efficiently accumulate and label the tumor tissue through the fluorescent imaging, selectively deliver siRNA into tumor tissue in vivo based on the tumor-bearing nude mice model. This work may provide a facile strategy to synthesize multifunctional biocompatible biomaterials for targeted tumor imaging and gene therapy.

Developing a reliable system to efficiently and safely deliver peptide drugs into tumor tissues still remains a great challenge since the instability of peptide drugs and low ability to traverse the cell membrane. Herein, we constructed a multifunctional nanoplatform based on porous europium/gadolinium (Eu/Gd)-doped NaLa(MoO4)2 nanoparticles (NLM NPs) to deliver antitumor peptide of B-cell lymphoma/leukemia-2-like protein 11 (BIM) for cancer therapy. The porous NLM NPs exhibited inherent photoluminescent, magnetic and X-ray absorbable properties, which enable them for triple-modal bioimaging, including fluorescence, magnetic resonance imaging (MRI) and computed tomography (CT). This triple-modal bioimaging can contribute to monitoring NLM NPs biodistribution and guiding therapy in vitro and in vivo. Furthermore, the NLM NPs showed negligible cytotoxicity in vitro and tissue toxicity in vivo. Importantly, NLM NPs could load the antitumor peptide of BIM and efficiently improve the resistance of peptide drugs to proteolysis. The BIM peptide was efficiently delivered into the tumor cells by NLM NPs, which can inhibit the growth and promote the apoptosis of cancer cells in vitro, significantly inhibit the tumor growth in vivo. Notably, NLM-BIM theranostic nanoplatform exhibits low systemic toxicity and fewer side effects in vivo. The NLM NPs can serve as a promising multifunctional peptide delivery nanoplatform for multi-modal bioimaging and cancer therapy.

Heavy metal Cadmium (Cd) will continuously pollute the atmosphere, soil and various water environments through material circulation, and even pose a threat to human safety. It has been designated as a first-class pollutant in sewage by China, therefore there is an urgent need to find new, more effective, and low-cost method to accurately detect Cadmium ion (Cd

Immunotherapy is a class of promising anticancer treatments that has recently gained attention due to surging numbers of FDA approvals and extensive preclinical studies demonstrating efficacy. Nevertheless, further clinical implementation has been limited by high variability in patient response to different immunotherapeutic agents. These treatments currently do not have reliable predictors of efficacy and may lead to side effects. The future development of additional immunotherapy options and the prediction of patient‐specific response to treatment require advanced screening platforms associated with accurate and rapid data interpretation. Advanced engineering approaches ranging from sequencing and gene editing, to tumor organoids engineering, bioprinted tissues, and organs‐on‐a‐chip systems facilitate the screening of cancer immunotherapies by recreating the intrinsic and extrinsic features of a tumor and its microenvironment. High‐throughput platform development and progress in artificial intelligence can also improve the efficiency and accuracy of screening methods. Here, these engineering approaches in screening cancer immunotherapies are highlighted, and a discussion of the future perspectives and challenges associated with these emerging fields to further advance the clinical use of state‐of‐the‐art cancer immunotherapies are provided., Advanced engineering approaches and progress in artificial intelligence can contribute to the development of cancer immunotherapy by uncovering alternative treatment targets and identifying hallmarks of treatment response, efficacy, and side effects. Screening approaches, including sequencing, gene editing, tumor organoids engineering, bioprinting, and organs‐on‐a‐chip, combined with high‐throughput screening and artificial intelligence are promising in accelerating broader application of cancer immunotherapy for a larger population.

We propose a visualization method to understand the effect of multidimensional projection on local subspaces, using implicit function differentiation. Here, we understand the local subspace as the multidimensional local neighborhood of data points. Existing methods focus on the projection of multidimensional data points, and the neighborhood information is ignored. Our method is able to analyze the shape and directional information of the local subspace to gain more insights into the global structure of the data through the perception of local structures. Local subspaces are fitted by multidimensional ellipses that are spanned by basis vectors. An accurate and efficient vector transformation method is proposed based on analytical differentiation of multidimensional projections formulated as implicit functions. The results are visualized as glyphs and analyzed using a full set of specifically-designed interactions supported in our efficient web-based visualization tool. The usefulness of our method is demonstrated using various multi- and high-dimensional benchmark datasets. Our implicit differentiation vector transformation is evaluated through numerical comparisons; the overall method is evaluated through exploration examples and use cases.

Bioactive glass nanoparticles (BGNs) have attracted widespread interest recently and been explored as the promising drug or gene delivery carriers due to their high biocompatibility and tissue repair ability. However, the synthesis of monodispersed photoluminescent BGNs and their corresponding biomedical applications are still not explored. Here, for the first time, we report monodispersed Eu-doped photoluminescent bioactive glass nanoparticles (BGN-Eu) and demonstrate their biomedical applications for drug delivery and cell imaging. By a long chain amine assisted sol–gel method, we synthesized the monodispersed BGN-Eu with combined dual functions of bioactivity and luminescence properties, and further investigated their physicochemical structure, biomineralization activity and biomedical applications. As-prepared BGN-Eu possessed the spherical morphology, relatively homogeneous particle size (200 ∼ 400 nm) and representative red fluorescence emission characteristic of Eu3+ at 616 nm. In simulated body fluids (SBFs), the BGN-Eu demonstrated excellent bioactivity by inducing biological apatite mineralization. BGN-Eu also presented controlled drug (theophylline) loading ability and release behavior. The osteoblast (MC3T3) growth was significantly enhanced when incubated with different dosages of BGN-Eu, suggesting the high biocompatibility. In addition, BGN-Eu was successfully used to label the MC3T3 cell by a strong red fluorescence with low background noise. Our results suggest the great potential of BGN-Eu as multifunctional bioactive nanomaterials for cell imaging and bone tissue regeneration applications.

Biodegradable poly(glycerol sebacate) (PGS) elastomers have received much attention as promising materials for potential applications in soft tissue repair and regeneration, due to their biomimetic viscoelastic properties. However, the low strength and the absence of bioactivity have limited their potential applications in hard (bone, tooth, tendon and ligament) tissue regeneration. Here, we introduced the molecular-level silica bioactive glass into the matrix of polymer elastomers to prepare bioactive hybrid elastomers (PGSSC) for bone tissue regeneration applications. We have shown here that our PGSSC provide some advantages over conventional bioactive materials and elastomers due to their controlled biomineralization (apatite-forming bioactivity), tunable elastic properties and biodegradation, and enhanced osteoblast proliferation. The tensile strength and the initial modulus of PGSSC hybrid elastomers ranged from 1 to 5 MPa and 2 to 32 MPa respectively by controlling silica phase contents, which are several times higher than pure PGS elastomers. PGSSC elastomers also showed enhanced hydrophilicity with contact angle ranging from 75 to 25 degree. The biological apatite was formed on the surfaces of PGSSC when soaked in simulated body fluid (SBF) for 1 day. The osteoblast (MC3T3) demonstrated significantly enhanced proliferation on PGSSC compared with PGS. The development of bioactive PGSSC hybrid elastomers may offer a new choice for bone tissue repair and regeneration.

Traditional skin tumor surgery and chronic bacterial-infection-induced wound healing/skin regeneration is still a challenge. The ideal strategy should eliminate the tumor, enhance wound healing/skin formation, and be anti-infection. Herein, we designed a multifunctional elastomeric poly(l-lactic acid)-poly(citrate siloxane)-curcumin@polydopamine hybrid nanofibrous scaffold (denoted as PPCP matrix) for tumor-infection therapy and infection-induced wound healing. The PPCP matrix showed intrinsically multifunctional properties including antioxidative, anti-inflammatory, photothermal, antibacterial, anticancer, and angiogenesis bioactivities. The polydopamine/curcumin presented an excellent near-infrared photothermal/cancer cell toxicity capacity, respectively, which supported PPCP for synergetic skin tumor therapy and antibacterial properties in vitro/in vivo. Additionally, the PPCP nanofibrous matrix significantly promotes the adhesion and proliferation of normal skin cells and accelerates the cutaneous wound healing in normal mice and bacterial-infected mice by enhancing the early angiogenesis. The PPCP nanofibrous matrix with multifunctional bioactivities provides a competitive strategy for skin tumor and bacterial-infection-induced wound healing.

Microneedles (MNs) have been used to deliver drugs for over two decades. These platforms have been proven to increase transdermal drug delivery efficiency dramatically by penetrating restrictive tissue barriers in a minimally invasive manner. While much of the early development of MNs focused on transdermal drug delivery, this technology can be applied to a variety of other non-transdermal biomedical applications. Several variations, such as multi-layer or hollow MNs, have been developed to cater to the needs of specific applications. The heterogeneity in the design of MNs has demanded similar variety in their fabrication methods; the most common methods include micromolding and drawing lithography. Numerous materials have been explored for MN fabrication which range from biocompatible ceramics and metals to natural and synthetic biodegradable polymers. Recent advances in MN engineering have diversified MNs to include unique shapes, materials, and mechanical properties that can be tailored for organ-specific applications. In this review, we discuss the design and creation of modern MNs that aim to surpass the biological barriers of non-transdermal drug delivery in ocular, vascular, oral, and mucosal tissue.

Under the severe trauma condition, the skeletal muscles regeneration process is inhibited by forming fibrous scar tissues. Understanding the interaction between bioactive nanomaterials and myoblasts perhaps has important effect on the enhanced skeletal muscle tissue regeneration. Herein, we investigate the effect of monodispersed gold and gold-silver nanoparticles (AuNPs and Au-AgNPs) on the proliferation, myogenic differentiation and associated molecular mechanism of myoblasts (C2C12), as well as the in vivo skeletal muscle tissue regeneration. Our results showed that AuNPs and Au-AgNPs could support myoblast attachment and proliferation with negligible cytotoxicity. Under various incubation conditions (normal and differentiation medium), AuNPs and Au-AuNPs significantly enhanced the myogenic differentiation of myoblasts by upregulating the expressions of myosin heavy chain (MHC) protein and myogenic genes (MyoD, MyoG and Tnnt-1). The further analysis demonstrated that AuNPs and Au-AgNPs could activate the p38α mitogen-activated protein kinase pathway (p38α MAPK) signaling pathway and enhance the myogenic differentiation. Additionally, the AuNPs and Au-AgNPs significantly promote the in vivo skeletal muscle regeneration in a tibialis anterior muscle defect model of rat. This study may provide a nanomaterials-based strategy to improve the skeletal muscle repair and regeneration.

Controlled biomineralization activity of biomaterials is rather important in bone regeneration and osseointegration avoiding the formation of fibrous capsule. However, most of conventional biodegradable elastomeric biomaterials for bone regeneration do not possess biomineralization ability and inherent multifunctional properties. Herein, we report a multifunctional bioactive glass (BG)-based hybrid poly(citrate-siloxane) (PCS) elastomer with intrinsical biomineralization activity and photoluminescent properties for potential bone tissue regeneration. Monodispersed BG nanoparticles (BGNs) were used to control the elastomeric behavior, biomineralization activity, photoluminescent ability, and osteogenic cellular response of PCS elastomers. BGNs significantly enhanced the elastomeric modulus of PCS from 20 to 200 MPa (10 times improvement) and the hydrophilicity (from 82° to 28° in water contact angle). The photoluminescent properties of PCS elastomers were also tailored through the incorporation of BGNs. The in vivo degradation of PCS-BGN nanocomposites could be efficiently tracked through noninvasively monitoring their fluorescent change. PCS-BGN nanocomposites enhanced the proliferation and osteoblastic differentiation of osteoblasts (MC3T3-E1) and decreased the in vivo inflammatory response. This study provided a novel tactics for designing the bioactive elastomeric biomaterials with multifunctional properties for bone regeneration medicine.

With the vigorous development of industry and information technology, people's requirements for sensors are becoming more and more diversified and universal. It is still a challenge to find a new type of pressure sensor with low cost, simple preparation, wider pressure test range, and higher sensitivity. Hereby, we report a novel flexible pressure sensor with a wide pressure detection range and robust mechanical properties, taking advantage of transition metal sulfide NiS2, adsorbed in melamine sponge as the active substance. The flexible sensor deforms under pressure with a internal microstructure change and a corresponding conductivity ramping. The addition of elastic polyvinylidene fluoride after curing improves the impact resistance and enables higher stability. Experiments show that the resistance pressure sensor responds within a wide range of 50 kPa with a high sensitivity of below 0.0345 kPa−1 and a fast response time of 0.64 s. Its excellent performance makes the sensor promising for wearable electronics and health monitoring devices.

Bioactive glass nanoparticles (BGNs) have attracted much attention in drug delivery and bone tissue regeneration, due to the advantages including biodegradation, high bone-bonding bioactivity, and facile large-scale fabrication. However, the wide biomedical applications of BGNs such as efficient gene delivery are limited due to their poor pore structure and easy aggregation. Herein, for the first time, this study reports novel monodispersed bioactive glass nanoclusters (BGNCs) with ultralarge mesopores (10-30 nm) and excellent miRNA delivery for accelerating critical-sized bone regeneration. BGNCs with different size (100-500 nm) are fabricated by using a branched polyethylenimine as the structure director and catalyst. BGNCs show an excellent apatite-forming ability and high biocompatibility. Importantly, BGNCs demonstrate an almost 19 times higher miRNA loading than those of conventional BGNs. Additionally, BGNCs-miRNA nanocomplexes exhibit a significantly high antienzymolysis, enhance cellular uptake and miRNA transfection efficiency, overpassing BGNs and commercial Lipofectamine 3000. BGNCs-mediated miRNA delivery significantly improves the osteogenic differentiation of bone marrow stromal stem cells in vitro and efficiently enhances bone formation in vivo. BGNCs can be a highly efficient nonviral vector for various gene therapy applications. The study may provide a novel strategy to develop highly gene-activated bioactive nanomaterials for simultaneous tissue regeneration and disease therapy.

The postoperative tissue healing of tumor excision, monitoring of remained tumor cells and inhibiting of tumor recurrence are still the great challenge. Herein, we develop a multifunctional biodegradable silicon-based Eu-Gd-Si-Ca bioactive glass nanoplatform (MBSGN) for tumor imaging, inhibiting tumor recurrence and enhancing tumor-impaired tissue regeneration. MBSGN exhibited a branched mesoporous structure (10–20 nm), controlled biodegradation, ultrahigh drug loading (602.52 mg g−1) and pH responsive release behavior, special magneto-optical properties and tumor cell-targeted surface. MBSGN possessed excellent biocompatibility and tumor cell-targeted capacity in vitro. MBSGN showed multi-model bioimaging capacity for skin tumor tissue (fluorescence/magnetic resonance/computed tomography imaging). MBSGN could efficiently eliminate the tumor growth, inhibit the local tumor recurrence through in situ removal of residual tumor cells, greatly enhance the full-thickness wound healing and tumor surgery-caused wounds repair. This study offers a reasonable and promising pathway for in situ integration of multi-modal bio-imaging, recurrent melanoma therapy and tissue regeneration.

The lack of safe and efficient drug and gene delivery vectors has become a major obstacle for the clinical applications of drug and nonviral gene therapy. To date, for nonviral gene vectors, most studies are focused on cationic polymers, liposomes, and modified inorganic nanoparticles which have shown high cellular toxicity, low transfection efficiency, or nondegradation. Additionally, few biodegradable biomaterials demonstrate intrinsic high binding abilities to both drug and gene. Bioactive glasses (BGs) have achieved successful applications in bone regeneration due to their high biocompatibility and biodegradation. Here, for the first time, we demonstrate the intrinsic ultrahigh drug and miRNA binding ability of bioactive glass nanoparticles (BGNs) without any cationic polymer modification. BGNs demonstrate an over 45-fold improvement in hydrophilic drug loading (diclofenac sodium) and 7-fold enhancement in miRNA binding over their corresponding silica nanoparticles. The hydrophilic drug loading ability of BGNs (45 wt % loading) is also higher than that of most other reported inorganic nanoparticles, including mesoporous silica nanoparticles. BGNs show significantly lower cytotoxicity and higher cellular uptake and miRNA transfection efficiency compared to those of commercial transfection reagents polyethylenimine and lipofectamine 3000. Our results demonstrate that BGNs may become a new competitive vehicle for drug and gene delivery applications. This study may also provide a new strategy to develop novel biomaterials with intrinsic drug and gene binding ability for disease therapy.

Cancer immunotherapies, including immune checkpoint inhibitor (ICI)-based therapies, have revolutionized cancer treatment. However, patient response to ICIs is highly variable, necessitating the development of methods to quickly assess efficacy. In this study, an array of miniaturized bioreactors has been developed to model tumor-immune interactions. This immunotherapeutic high-throughput observation chamber (iHOC) is designed to test the effect of anti-PD-1 antibodies on cancer spheroid (MDA-MB-231, PD-L1+) and T cell (Jurkat) interactions. This system facilitates facile monitoring of T cell inhibition and reactivation using metrics such as tumor infiltration and interleukin-2 (IL-2) secretion. Status of the tumor-immune interactions can be easily captured within the iHOC by measuring IL-2 concentration using a micropillar array where sensitive, quantitative detection is allowed after antibody coating on the surface of array. The iHOC is a platform that can be used to model and monitor cancer-immune interactions in response to immunotherapy in a high-throughput manner.

While nanotechnology-assisted cocktail therapy has emerged many advantages in anti-cancer treatment, significant challenges remain as regards efficiently and simultaneously loading two or more drugs with completely different physicochemical properties. The emergence of supramolecule offers an unprecedented opportunity to overcome this pharmaceutical bottleneck. Herein, an engineered Janus cyclopeptide was designed to self-assemble with hydrophilic miR-30C and hydrophobic carnosic acid into a supramolecular nanosphere ~100 nm in diameter termed iNanosphere that possessed excellent dimensional stability and satisfactory resistance against nuclease and peptidase. Moreover, iNanosphere showed an integrin-mediated cellular uptake, followed by GSH-triggered disassemble and release payloads. As expected, iNanosphere in vivo suppressed the xenografted HCT116 colon cancer and allografted MC38 colon cancer, while kept a low therapeutic toxicity and pathological immunogenicity. More importantly, combinations of iNanosphere and anti-PD1 checkpoint blockade therapy resulted in the augmented antitumor response. Collectively, this engineered cyclopeptide reported here will enable us to tame hydrophilic microRNA and hydrophobic molecule for cocktail combination therapy, and such peptide-derived supramolecular nano-architecture demonstrate to be innovative nano-cocktails for superior anti-cancer therapy and hold great potential to be applied in the near future.

Gelatin methacryloyl (GelMA) is a widely used hydrogel with skin-derived gelatin acting as the main constituent. However, GelMA has not been used in the development of wearable biosensors, which are emerging devices that enable personalized healthcare monitoring. This work highlights the potential of GelMA for wearable biosensing applications by demonstrating a fully solution-processable and transparent capacitive tactile sensor with microstructured GelMA as the core dielectric layer. A robust chemical bonding and a reliable encapsulation approach are introduced to overcome detachment and water-evaporation issues in hydrogel biosensors. The resultant GelMA tactile sensor shows a high-pressure sensitivity of 0.19 kPa(−1) and one order of magnitude lower limit of detection (0.1 Pa) compared to previous hydrogel pressure sensors owing to its excellent mechanical and electrical properties (dielectric constant). Furthermore, it shows durability up to 3000 test cycles because of tough chemical bonding, and long-term stability of 3 days due to the inclusion of an encapsulation layer, which prevents water evaporation (80% water content). Successful monitoring of various human physiological and motion signals demonstrates the potential of these GelMA tactile sensors for wearable biosensing applications.

Transdermal delivery of water-insoluble drugs via hydrogel-based microneedle (MN) arrays is crucial for improving their therapeutic efficacies. However, direct loading of water-insoluble drug into hydrophilic matrices remains challenging. Here, a biodegradable MN array patch that is fabricated from naturally derived polymer conjugates of gelatin methacryloyl and β-cyclodextrin (GelMA-β-CD) is reported. When curcumin, an unstable and water-insoluble anticancer drug, is loaded as a model drug, its stability and solubility are improved due to the formation of an inclusion complex. The polymer-drug complex GelMA-β-CD/CUR can be formulated into MN arrays with sufficient mechanical strength for skin penetration and tunable drug release profile. Anticancer efficacy of released curcumin is observed in three-dimensional B16F10 melanoma models. The GelMA-β-CD/CUR MN exhibits relatively higher therapeutic efficacy through more localized and deeper penetrated manner compared with a control nontransdermal patch. In vivo studies also verify biocompatibility and degradability of the GelMA-β-CD MN arrays patch.

Mesenchymal stem cells (MSCs) have been widely used for regenerative therapy. In most current clinical applications, MSCs are delivered by injection but face significant issues with cell viability and penetration into the target tissue due to a limited migration capacity. Some therapies have attempted to improve MSC stability by their encapsulation within biomaterials; however, these treatments still require an enormous number of cells to achieve therapeutic efficacy due to low efficiency. Additionally, while local injection allows for targeted delivery, injections with conventional syringes are highly invasive. Due to the challenges associated with stem cell delivery, a local and minimally invasive approach with high efficiency and improved cell viability is highly desired. In this study, we present a detachable hybrid microneedle depot (d-HMND) for cell delivery. Our system consists of an array of microneedles with an outer poly(lactic-co-glycolic) acid (PLGA) shell and an internal gelatin methacryloyl (GelMA)-MSC mixture (GMM). The GMM was characterized and optimized for cell viability and mechanical strength of the d-HMND required to penetrate mouse skin tissue was also determined. MSC viability and function within the d-HMND was characterized in vitro and the regenerative efficacy of the d-HMND was demonstrated in vivo using a mouse skin wound model.

Multidrug-resistant bacterial (MDRB) infections are still a critical challenge in tissue engineering and regenerative medicine. Bioactive biodegradable scaffolds with the ability to combat MDRB infections and that have high biocompatibility could likely address this problem. Herein, we develop a biomimetic photoluminescent and antibacterial gelatin-poly(citrate-siloxane)-e-poly( l -lysine) (GT-PCS-EPL) nanofibrous scaffold for multifunctional tissue regeneration applications. GT-PCS-EPL had biomimetic elastomeric behavior; tunable photoluminescence; broad-spectrum antibacterial activity, including against MDRB infections; and enhanced osteogenic bioactivity capacity. The photoluminescent property of GT-PCS-EPL scaffolds enabled their real-time noninvasive imaging tracking in vivo. GT-PCS-EPL scaffolds not only killed normal bacteria but also efficiently treated MDRB growth in vitro and infections in vivo. GT-PCS-EPL scaffolds also had excellent hemocompatibility and osteoblast biocompatibility. This study provides a novel strategy to design biomimetic bioactive scaffolds with multifunctional properties for smart infection-related tissue regeneration applications.