Search

Hydrogels hold great promise in the field of flexible electronics. Attempts in this area tend to the microstructure design of hydrogels, giving them specific adhesion and multi‐sensing functions. Here, a novel phase separation‐derived anisotropic adhesive structural color hydrogel film is presented for visually flexible electronics. The hydrogel film is generated by template replicating colloidal crystal by using phase separation emulsions of hydrophilic monomer (acrylic acid, AA), hydrophobic monomer (lauryl methacrylate, LMA), co‐monomer ([2‐(methacryloyloxy) ethyl] dimethyl‐(3‐sulfopropyl) ammonium hydroxide (SBMA)), surfactants (hexadecyl trimethyl ammonium bromide, CTAB) and initiator (ammonium persulphate (APS)). The appearance of phase separation results in asymmetric morphologies of hydrogel film, imparting them with anisotropic adhesive performance. Attributed to the formation of inverse opal scaffold structure, the hydrogel film is featured with vivid structural color, showing superior capability in self‐reporting mechanical behavior. Additionally, benefitting from the presence of abundant ions, the hydrogel film exhibits great conductivity. Thus, the resultant hydrogel film is demonstrated with stable dual‐signal sensing properties involving color‐changing and conductivity feedback ability to respond to human activities. These features make the proposed anisotropic adhesive structural color hydrogel film highly potential in the flexible electronic field. [ABSTRACT FROM AUTHOR]

Engineered liver lobule is highly practical in hepatic disease treatment, while constructing a 3D biomimetic lobule with a heterogeneous architecture on a large scale is challenging. Here, inspired by the natural architectural construction of hepatic lobules, biomimetic hepatic lobules are proposed with coaxially through‐pores for nutrient exchange via microfluidic technology. This multi‐channel microfluidic chip is made by parallelly installing capillaries. Sodium alginate (Alg) is pumped through its central channel, while Ca2+‐loaded gelatin methacrylate (GelMA) solutions encapsulating hepatocytes, mesenchymal stem cells, and endothelia cells are pumped through surrounding channels, respectively. The rapid gelation of Alg and Ca2+ brings about an in situ formation of Alg fiber, with heterogeneous multi‐cell‐laden GelMA microcarriers forming around it. The peeled‐off microcarriers each featured with a coaxially through pore, simulating the cord‐like structure of hepatic lobule and facilitating nutrients exchange. Meanwhile, the spatially anisotropic arrangement of cells highly simulates the hepatic architecture. It is demonstrated that by transplanting these biomimetic microparticles into liver in situ, the failed liver in rat shows increased regeneration and decreased necrosis. These results indicated that the microfluidic multi‐compartmental microcarriers provide a new strategy to engineer 3D artificial livers for clinical translation. [ABSTRACT FROM AUTHOR]

Surgical excision remains the principal treatment for melanoma, while tumor recurrence and delayed wound healing often occur due to the residual tumor cells and hypoxic microenvironment in the postoperative skin wounds. Herein, we present a living photosynthetic microneedle (MN) patch (namely MA/CM@MN) loaded with microalgae (MA) and cuttlefish melanin (CM) for postsurgical melanoma therapy and skin wound healing. Benefiting from the oxygenic photosynthesis of the alive MA in the MN base, the MA/CM@MN can generate oxygen under light exposure, thus facilitating skin cell proliferation and protecting cells against hypoxia-induced cell death. In addition, with CM nanoparticles embedded in the MN tips, the MA/CM@MN can be effectively heated up under near-infrared (NIR) irradiation, contributing to a strong tumor killing efficacy on melanoma cells in vitro. Further experiments demonstrate that the NIR-irradiated MA/CM@MN effectively prevents local tumor recurrence and simultaneously promotes the healing of tumor-induced wounds after incomplete tumor resection in melanoma-bearing mice, probably because the MA/CM@MN can inhibit tumor cell proliferation, stimulate tumor cell apoptosis, and mitigate tissue hypoxia in light. These results indicate that the living photosynthetic MN patch offers an effective therapeutic strategy for postoperative cancer therapy and wound healing applications. [ABSTRACT FROM AUTHOR]

Riboflavin-5-phosphate (riboflavin) is the most commonly used photosensitizer in corneal crosslinking (CXL); while its efficient delivery into the stroma through the corneal epithelial barrier is challenging. In this paper, we presented novel responsive porous microneedles with ocular microinjection capability to deliver riboflavin controllably inside the cornea to facilitate CXL. The microneedle patch was composed of Poly (N-isopropyl acrylamide) (PNIPAM), graphene oxide (GO), and riboflavin-loaded gelatin. After penetrating the cornea by the stiff and porous gelatin needle tip, the photothermal-responsive characteristic of the PNIPAM/GO hydrogel middle layer could realize the contraction of the gel under the stimulation of near-infrared light, which subsequently could control the release of riboflavin from the backing layer into the cornea stromal site both in vitro and in vivo. Based on the microneedles system, we have demonstrated that this microinjection technique exhibited superior riboflavin delivery capacity and treatment efficacy to the conventional epithelial-on protocol in a rabbit keratoconus model, with benefits including minimal invasiveness and precise administering. Thus, we believe the responsive porous microneedles with riboflavin ocular microinjection capability are promising for clinical corneal crosslinking without epithelial debridement. [ABSTRACT FROM AUTHOR]

Bioartificial livers have showcased significant value in the treatment of acute liver failure (ALF). Current efforts are directed toward overcoming challenges in the development of microcarriers, with a specific emphasis on integrating higher‐density liver cells to enhance detoxification capabilities. Here, inspired by the radial filtration model in hepatic lobules, ion‐specific silk fibroin microcarriers are proposed with biomimetic niches for cultivating functional liver cells at high density. These biomimetic microcarriers are generated by capillary microfluidic device with controllable adjustments of ion type or concentration within the aqueous phase. When cultivating human induced pluripotent stem cell ‐differentiated mature liver cells on these recrystallized microcarriers, notably enhanced cell proliferation activity, as well as increased metabolic and secretory functionality is observed. Based on these features, the microcarrier‐integrated bioreactor can effectively reduce hepatic transaminase levels and significantly improve urea, albumin production, and survival rate in rabbit ALF models is demonstrated. Thus, it is believed that the biomimetic microcarriers and their derived bioreactor may hold potential for clinical applications in managing ALF and other liver diseases. [ABSTRACT FROM AUTHOR]

Macrophages play a pivotal role in systemic lupus erythematosus (SLE) therapy. Efforts have been made to develop multifunctional drug delivery systems capable of directing macrophage polarization. Here, we present a novel hyaluronic acid methacrylate (HAMA) hydrogel microparticle encapsulating multiple cytokines for SLE remission though enhancing macrophage functions. The HAMA microparticles loaded with monocyte chemotactic protein-1 (MCP-1) and interleukin-4 (IL-4) were fabricated by using a microfluidic technology. The released MCP-1 facilitates the aggregation of inflammatory macrophages, after which IL-4 induces the macrophage phenotype shift from inflammatory M1 to immune-protective M2, thus restoring immune balance. We have demonstrated in MRL/lpr mice that the hydrogel microparticles could improve their efficacy of intraperitoneal drug delivery, modulate immune function, and attenuate the disease symptoms. These results suggest that our proposed microparticles delivery platform has potential clinical value for treating autoimmune diseases. [ABSTRACT FROM AUTHOR]

Nano‐delivery systems hold great promise for the treatment of rheumatoid arthritis (RA). Current research efforts are primarily focused on enhancing their targeting capabilities and efficacy. Here, this study proposes a novel viral‐mimicking ternary polyplexes system for the controlled delivery of the anti‐inflammatory drug Cyclosporin A (CsA) to effectively treat RA. The ternary polyplexes consist of a nanogel core loaded with CsA and a hyaluronic acid shell, which facilitates CD44‐mediated targeting. By mimicking the Trojan Horse strategy employed by viruses, these polyplexes undergo a stepwise process of deshielding and disintegration within the inflamed joints. This process leads to the release of CsA within the cells and the scavenging of pathogenic factors. This study demonstrates that these viral‐mimicking ternary polyplexes exhibit rapid targeting, high accumulation, and prolonged persistence in the joints of RA mice. As a result, they effectively reduce inflammation and alleviate symptoms. These results highlight the potential of viral‐mimicking ternary polyplexes as a promising therapeutic approach for the targeted and programmed delivery of drugs to treat not only RA but also other autoimmune diseases. [ABSTRACT FROM AUTHOR]

Advanced artificial nerve conduits offer a promising alternative for nerve injury repair. Current research focuses on improving the therapeutic effectiveness of nerve conduits by optimizing scaffold materials and functional components. In this study, a novel poly(3,4‐ethylenedioxythiophene) (PEDOT)‐integrated fish swim bladder (FSB) is presented as a conductive nerve conduit with ordered topology and electrical stimulation to promote nerve regeneration. PEDOT nanomaterials and adhesive peptides (IKVAV) are successfully incorporated onto the decellularized FSB substrate through pre‐coating with polydopamine. The obtained PEDOT/IKVAV‐integrated FSB substrate exhibits outstanding mechanical properties, high electrical conductivity, stability, as well as excellent biocompatibility and bioadhesive properties. In vitro studies confirm that the PEDOT/IKVAV‐integrated FSB can effectively facilitate the growth and directional extension of pheochromocytoma 12 cells and dorsal root ganglion neurites. In addition, in vivo experiments demonstrate that the proposed PEDOT/IKVAV‐integrated FSB conduit can accelerate defective nerve repair and functional restoration. The findings indicate that the FSB‐derived conductive nerve conduits with multiple regenerative inducing signals integration provide a conducive milieu for nerve regeneration, exhibiting great potential for repairing long‐segment neural defects. [ABSTRACT FROM AUTHOR]

Microcarrier is a promising drug delivery system demonstrating significant value in treating cancers. One of the main goals is to devise microcarriers with ingenious structures and functions to achieve better therapeutic efficacy in tumors. Here, inspired by the nucleus-cytoplasm structure of cells and the material exchange reaction between them, we develop a type of biorthogonal compartmental microparticles (BCMs) from microfluidics that can separately load and sequentially release cyclooctene-modified doxorubicin prodrug (TCO-DOX) and tetrazine-modified indocyanine green (Tz-ICG) for tumor therapy. The Tz-ICG works not only as an activator for TCO-DOX but also as a photothermal agent, allowing for the combination of bioorthogonal chemotherapy and photothermal therapy (PTT). Besides, the modification of DOX with cyclooctene significantly decreases the systemic toxicity of DOX. As a result, the developed BCMs demonstrate efficient in vitro tumor cell eradication and exhibit notable tumor growth inhibition with favorable safety. These findings illustrate that the formulated BCMs establish a platform for bioorthogonal prodrug activation and localized delivery, holding significant potential for cancer therapy and related applications. [ABSTRACT FROM AUTHOR]

Microfibers from natural products are endowed with remarkable biocompatibility, biodegradability, sustainable utilization as well as environmental protection characteristics etc. Benefitting from these advantages, microfibers have demonstrated their prominent values in biomedical applications. This review comprehensively summarizes the relevant research progress of sustainable microfibers from natural products and their biomedical applications. To begin, common natural elements are introduced for the microfiber fabrication. After that, the focus is on the specific fabrication technology and process. Subsequently, biomedical applications of sustainable microfibers are discussed in detail. Last but not least, the main challenges during the development process are summarized, followed by a vision for future development opportunities. [ABSTRACT FROM AUTHOR]

Osteoarthritis has been regarded as a complex and serious degenerative disease. Attempts in this area are focused on improving the curative effect of stem cell‐based therapies. In this work, we present a novel inverse opal microcarriers‐based cytokines delivery system to induce autologous stem cell homing for osteoarthritis treatment. Considering their important role in stem cell recruitment and chondrogenic differentiation respectively, platelet‐derived growth factor BB (PDGF‐BB) and transforming growth factor β3 (TGF‐β3) are loaded into inverse opal microcarriers as model cytokines. Since cytokine release induces the corresponding variations in characteristic reflection spectra and structural colors, the inverse opal microcarriers possess the optical self‐reporting capacity to monitor the release process. In vitro cell experiments reveal that inverse opal microcarriers could successfully recruit the gathering of mesenchymal stem cells through the release of loaded cytokines. Based on these features, we have demonstrated the enhanced therapeutic effect of PDGF‐BB and TGF‐β3 loaded inverse opal microcarriers in the treatment of rat osteoarthritis models. These results indicate that the multifunctional inverse opal microcarriers‐based cytokines delivery system would find broad prospects in osteoarthritis treatment and other biomedical fields. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) have certain effect in cancer treatment, thus many studies have been focused on developing functional systems to generate ROS in tumor. Here, inspired by the multi‐enzyme biocatalysis in organisms, novel ultrasound‐triggered temporospatial catalytic cascades systems are presented based on barium titanate (BTO) and platinum (Pt) co‐loaded multi‐component microparticles (Pt/BTO@MCMPs) to successively achieve oxygen and ROS production for tumor sonodynamic therapy. By using a customized capillary microfluidic device, the Pt/BTO@MCMPs are fabricated with Pt nanoparticles located in their core part and BTO nanocubes located in their peripheral part, alternating with blank porous hydrogel components for increasing interaction areas between the encapsulated nanomaterials and the ambient substrates. In the microparticles, the Pt can catalyze hydrogen peroxide from the tumor microenvironment to generate O2 and H2O serving as substrates for piezoelectric catalytic reactions, contributing to additional generation of ROS under US activation. Based on the system, it is demonstrated that the Pt/BTO@MCMPs are featured with excellent biocompatibility under normal biological conditions and show desired tumor eradication properties under ultrasound irradiation in mice carrying pancreatic tumors. These results indicate that the proposed ultrasound‐triggered temporospatial catalytic cascades systems are promising for clinic anti‐tumor applications. [ABSTRACT FROM AUTHOR]

Diabetic wound healing is a serious, complex, and chronic process; one current promising and focusing technology in this area is stem cell treatment. Here, novel porous microneedle (MN) arrays is fabricated, which can highly mimetic stem cell niches, through template filling, and particle etching method. The human adipose‐derived stem cells (ADSCs) are encapsulated in Matrigel then loaded into the porous MN arrays by post‐perfusion. Because of the extracellular matrix‐mimicking, the biocompatible Matrigel offers a bionic microenvironment of stem cell nest suitable for growth. Benefiting from the numerous pore structures of MNs, the loaded ADSCs have enough space to fully absorb nutrients, proliferate greatly and exhibit prompted function. In addition, the cell‐loaded MN arrays have enough mechanical strength to penetrate the skin, allowing the ADSCs to get into the deep wound areas. Based on these features, the performance of the resultant MN arrays in promoting tissue regeneration is demonstrated, collagen deposition and angiogenesis in diabetes wounds of rat models. Thus, it is believe that the bioinspired porous MNs can act as excellent stem cell scaffolds and will find many practical values in clinic wound healing. [ABSTRACT FROM AUTHOR]

Highlights: Derived from silica photonic crystals, inverse opal microspheres have a regularly connected porous structure and inherit structural color properties. Combined with the stable scaffold and the photothermal phase-transition of the secondary filling material, the inverse opal composite microspheres are endowed with self-healing properties and the ability for controllable drug release. Inverse opal microspheres were significantly treated for diabetic wound, via promoting tissue regeneration, collagen deposition and angiogenesis. Meanwhile, the release of drugs could be monitored by the structural color characteristic. Chronic diabetic wounds confront a significant medical challenge because of increasing prevalence and difficult-healing circumstances. It is vital to develop multifunctional hydrogel dressings, with well-designed morphology and structure to enhance flexibility and effectiveness in wound management. To achieve these, we propose a self-healing hydrogel dressing based on structural color microspheres for wound management. The microsphere comprised a photothermal-responsive inverse opal framework, which was constructed by hyaluronic acid methacryloyl, silk fibroin methacryloyl and black phosphorus quantum dots (BPQDs), and was further re-filled with a dynamic hydrogel. The dynamic hydrogel filler was formed by Knoevenagel condensation reaction between cyanoacetate and benzaldehyde-functionalized dextran (DEX-CA and DEX-BA). Notably, the composite microspheres can be applied arbitrarily, and they can adhere together upon near-infrared irradiation by leveraging the BPQDs-mediated photothermal effect and the thermoreversible stiffness change of dynamic hydrogel. Additionally, eumenitin and vascular endothelial growth factor were co-loaded in the microspheres and their release behavior can be regulated by the same mechanism. Moreover, effective monitoring of the drug release process can be achieved through visual color variations. The microsphere system has demonstrated desired capabilities of controllable drug release and efficient wound management. These characteristics suggest broad prospects for the proposed composite microspheres in clinical applications. [ABSTRACT FROM AUTHOR]

Localized chemotherapy is emerging as a potential strategy for cancer treatment due to its low systemic toxicity. However, the immune evasion of tumor cells and the lack of an intelligent design of the delivery system limit its clinical application. Herein, photothermal responsive microcarriers are designed by microfluidic electrospray for colorectal tumor treatment. The microcarriers loaded with Cangrelor, 5‐FU and MXene (G‐M@F/C+NIR) show sustained delivery of antiplatelet drug Cangrelor, thus inhibiting the activity of platelets, interactions of platelet‐tumor cell, as well as the tumor cells invasion and epithelial‐mesenchymal transition (EMT). In addition, the sustained delivery of chemotherapeutics 5‐FU and the photothermal effect provided by MXene enable the microcarriers to inhibit tumor cells proliferation and migration. In vivo studies validate that the G‐M@F/C+NIR microcarriers significantly inhibites tumor growth, decreased the expression of Ki‐67 in tumor cells and vascular endothelial growth factor (VEGF) in the tumor microenvironment, while increased the expression of E‐cadherin. It is believe that by means of the proposed photothermal responsive microcarriers, the synergistic strategy of platelet inhibition, chemotherapy, and photothermal therapy can find practical applications in cancer treatment. [ABSTRACT FROM AUTHOR]

Bacterial skin infections are highly prevalent and pose a significant public health threat. Current strategies are primarily focused on the inhibition of bacterial activation while disregarding the excessive inflammation induced by dead bacteria remaining in the body and the effect of the acidic microenvironment during therapy. In this study, a novel dual‐functional MgB2 microparticles integrated microneedle (MgB2 MN) patch is presented to kill bacteria and eliminate dead bacteria for skin infection management. The MgB2 microparticles not only can produce a local alkaline microenvironment to promote the proliferation and migration of fibroblasts and keratinocytes, but also achieve >5 log bacterial inactivation. Besides, the MgB2 microparticles effectively mitigate dead bacteria‐induced inflammation through interaction with lipopolysaccharide (LPS). With the incorporation of these MgB2 microparticles, the resultant MgB2 MN patches effectively kill bacteria and capture dead bacteria, thereby mitigating these bacteria‐induced inflammation. Therefore, the MgB2 MN patches show good therapeutic efficacy in managing animal bacterial skin infections, including abscesses and wounds. These results indicate that reactive metal borides‐integrated microneedle patches hold great promise for the treatment of clinical skin infections. [ABSTRACT FROM AUTHOR]

Anticoagulation is vital to maintain blood fluidic status and physiological functions in the field of clinical blood‐related procedures. Here, novel biomimetic anticoagulated porous inverse opal hydrogel particles is presented as anticoagulant bearing dynamic screening capability. The inverse opal hydrogel particles possess abundant sulfonic and carboxyl groups, which serve as binding sites with multiple coagulation factors and inhibit the blood coagulation process. Owing to the variations of refractive index and pore sizes during the binding process, the particles appeared corresponding structure color variations, which can be adopted as sensory index of anticoagulation. Based on these features, a sensor containing these diverse structure color particle units is constructed for pattern recognition of coagulation factors level in clinical plasma samples. By analyzing the sensory information of the unit, the colorimetric "fingerprint" for each target can be obtained and summarized as a database. Besides, a portable test‐strip integrating sensory units is developed to distinguish the sample regarding abnormal coagulation factors‐derived diseases via multivariate data analysis. It is believed that such biomimetic anticoagulated structural color particles and their derived sensor will open new avenue for clinical detection and disease diagnosis. [ABSTRACT FROM AUTHOR]

The intricate physiological structure of the inner ear presents challenges for traditional medication treatment strategies, including systemic adverse responses, trouble penetrating the blood–labyrinth barrier, and low local cochlear concentration, resulting in poor therapeutic outcomes. An intriguing tactic that is extensively developed over decades is utilizing drug delivery systems to transport medication molecules to the inner ear. Herein, the challenges associated with inner ear delivery are discussed, cutting‐edge achievements in inner ear drug delivery systems are emphasized, including nano‐, micro‐, and macrocarriers, and finally opportunities to leverage advanced technologies to improve existing drug delivery strategies are highlighted. [ABSTRACT FROM AUTHOR]

The management of infected wounds is always of great significance and urgency in clinical and biomedical fields. Recent efforts in this area are focusing on the development of functional wound patches with effective antibacterial, drug delivery, and sensor properties. Here, we present novel hyaluronic acid (HA) microneedle patches with these features by encapsulating aminobenzeneboronic acid‐modified gold nanoclusters (A‐GNCs) for infected wound management. The A‐GNCs loaded microneedle patches were derived from negative‐mold replication and showed high mechanical strength to penetrate the skin. The release of the A‐GNCs was realized by the degradation of HA, and the self‐monitor of the released actives was based on the dynamic bright orange fluorescence emitted from A‐GNCs under ultraviolet radiation. As the A‐GNCs could destroy bacteria membranes, the microneedle patches were with excellent in vitro antibiosis ability. Based on these features, we have demonstrated the bacteria inhibition, residual drug self‐monitoring, and wound healing promotion abilities of the microneedle patches in Escherichia coli‐ or Staphylococcus aureus‐infected wound management. These results indicated the great potential of such A‐GNCs loaded microneedle patches for clinical applications. [ABSTRACT FROM AUTHOR]

Biomedical patches offer significant potential for keratitis treatment. Building on advances in multifunctionality and biomimicry, an innovative, multifunctional hydrogel patch with high therapeutic efficacy, inspired by the native architecture and functions of the cornea, is introduced. By engineering a composite patch comprising recombinant human collagen (RHC) hydrogel, near‐field electrospinning (NFES) microfibers, and gold‐nanoparticle‐decorated tetragonal barium titanates (BTO@Au), structural mimicry, mechanical reinforcement, tissue‐specific adhesion, and bacterial inhibition are achieved. The RHC hydrogel recreates a three‐dimensional (3D) microenvironment that emulates the natural structure of the corneal tissue, demonstrating excellent tissue adhesion. Integrated within this hydrogel, the NFES microfibers, designed to emulate the orthogonal arrangement of native corneal stroma, not only reinforce the mechanical strength of the RHC hydrogel but also act as scaffolds to guide the aligned growth of human keratocytes. A unique aspect of this advanced patch is the incorporation of BTO@Au nanoparticles, which generate reactive oxygen species for effective bacterial eradication when subjected to ultrasound stimulation. Through in vivo studies on rat models with infected corneal wounds, this hydrogel patch exhibits superior therapeutic efficacy compared to the current treatment. It is posited that these cornea‐inspired ultrasound‐responsive adhesive hydrogel patches represent a significant scientific advancement with high potential for clinical applications. [ABSTRACT FROM AUTHOR]

Human organoid models potentially offer a physiologically relevant platform to replace traditional monolayer cultures and animal models. In particular, the rapid development of engineered strategies including microfluidics, hydrogel, 3D printing and others, which have enormous advantages in comparison to conventional methods, is expected to further advance organoid technology. Up to now, many studies have demonstrated the engineered organoid models with complex cell composition, controlled structure, enhanced maturation, reduced heterogeneity, and so on. These engineered organoids are high promising for studies in development, disease, tissue repair, precision medicine and drug screening. In this review, a comprehensive summary of the engineered organoid model systems is provided based on microfluidics, hydrogel, 3D printing and so on. Then, the biomedical applications of these models are highlighted, which have displayed the great power in organoid field. Finally, the key bottlenecks and future development of organoid models are discussed about from an engineering perspective. [ABSTRACT FROM AUTHOR]

Noise‐induced hearing loss (NIHL) is a common outcome of excessive reactive oxygen species in the cochlea, and the targeted delivery of antioxidants to the inner ear is a potential therapeutic strategy. In this paper, a novel natural biomaterials‐derived multifunctional delivery system using silk fibroin‐polydopamine (PDA)‐composited inverse opal microcarriers (PDA@SFMCs) is presented for inner ear drug delivery and NIHL therapy. Due to their large specific surface area and interpenetrating nanochannels, PDA@SFMCs can rapidly load active biomolecules making them a convenient medium for the storage and delivery of such molecules. In addition, surface modification of PDA enables the microcarriers to remain in the round window niche, thus facilitating the precise local and directed delivery of loaded drugs. Based on these features, it is demonstrated here that n‐acetylcysteine‐loaded silk microcarriers have satisfactory antioxidant properties on cells and can successfully prevent NIHL in guinea pigs. These results indicate that the natural multifunctional silk microcarriers are promising agents for local inner ear drug delivery in the clinic. [ABSTRACT FROM AUTHOR]

Tumor tissue engineering holds great promise for replicating the physiological and behavioral characteristics of tumors in vitro. Advances in this field have led to new opportunities for studying the tumor microenvironment and exploring potential anti‐cancer therapeutics. However, the main obstacle to the widespread adoption of tumor models is the poor understanding and insufficient reconstruction of tumor heterogeneity. In this review, the current progress of engineering heterogeneous tumor models is discussed. First, the major components of tumor heterogeneity are summarized, which encompasses various signaling pathways, cell proliferations, and spatial configurations. Then, contemporary approaches are elucidated in tumor engineering that are guided by fundamental principles of tumor biology, and the potential of a bottom‐up approach in tumor engineering is highlighted. Additionally, the characterization approaches and biomedical applications of tumor models are discussed, emphasizing the significant role of engineered tumor models in scientific research and clinical trials. Lastly, the challenges of heterogeneous tumor models in promoting oncology research and tumor therapy are described and key directions for future research are provided. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is one of the leading causes of disability due to the autoimmune destruction of synovial joints. Great efforts have been put into developing multifunctional drug delivery systems for delaying the progression of RA. Herein, a novel locally injectable, hierarchically structured delivery system with a hyaluronic acid (HA) microparticle and an MTX‐conjugated nanoparticle for promoted RA treatment is proposed. In this system, MTX is chemically grafted onto a peptide dendrimer‐based nanoparticle (G‐MTX). These nanoparticles are encapsulated inside HA microparticles (H‐G‐MTX) using microfluidics to realize the system. The G‐MTX can be released from the degradable HA microparticles in the acidic environment of inflamed RA joints. As the G‐MTX shows an enhanced intracellular delivery of the conjugated MTX, the H‐G‐MTX can reverse the dominant macrophage phenotype from M1 to M2. Through a collagen‐induced arthritis (CIA) rat model, the great therapeutic outcomes of this hierarchically structured delivery system are demonstrated, including inflammation reduction, cartilage protection, and bone mineral density promotion. These results indicate that the proposed hierarchical delivery system has potential clinical value in the treatment of RA and other diseases. [ABSTRACT FROM AUTHOR]

The development of bioactive scaffolds by mimicking bone tissue extracellular matrix is promising for bone regeneration. Herein, inspired by the bone tissue composition, a novel pearl powder (PP) hybrid fish gelatin methacrylate (GelMa) hydrogel scaffold loaded with vascular endothelial growth factor (VEGF) for bone regeneration is presented. With the help of microfluidic‐assisted 3D printing technology, the composition and structure of the hybrid scaffold can be accurately controlled to meet clinical requirements. The combination of fish skin GelMa and PP also endowed the hybrid scaffold with good biocompatibility, cell adhesion, and osteogenic differentiation ability. Moreover, the controlled release of VEGF enables the scaffold to promote angiogenesis. Thus, the bone regeneration in the proposed scaffolds could be accelerated under the synergic effect of osteogenesis and angiogenesis, which has been proved in the rat skull defect model. These features indicate that the PP hybrid scaffolds will be an ideal candidate for bone regeneration in clinical applications. [ABSTRACT FROM AUTHOR]

Hyaluronic acid (HA) is an attractive anionic polysaccharide polymer with inherent pharmacological properties and versatile chemical groups for modification. Due to their water retention ability, biocompatibility, biodegradation, cluster of differentiation‐44 targeting, and highly designable capacity, HA hydrogels have been an emerging biomaterial, showing tailoring performance in terms of chemical modifications and hydrogel forms. Various preparation technologies have been developed for the fabrication of the tailoring HA hydrogels with unique structures and functions. They have been utilized in diverse biomedical applications like drug delivery and tissue engineering scaffolds. Herein, this review comprehensively summarizes the HA derivatives with different molecule weights and functional modifications. Then the various fabrication methods to obtain tailoring hydrogels in the forms of nanogel, nanofiber, microparticle, microneedle patch, injectable hydrogel, and scaffold are reviewed as well. The emphasis is focused on the shining biomedical applications of these tailoring HA hydrogels in anti‐bacteria, anti‐inflammation, wound healing, cancer treatment, regenerative medicine, psoriasis treatment, diagnosis, etc. The potentials and prospects are subsequently given to inspire further investigation, aiming at accelerating product translation from research to clinic. [ABSTRACT FROM AUTHOR]

Metal–organic framework (MOF)‐based drug delivery systems have demonstrated values in oncotherapy. Current research endeavors are centralized on the functionality enrichment of featured MOF materials with designed versatility for synergistic multimodal treatments. Here, inspired by the multifarious biological functions including ferroptosis pattern, porphyrins, and cancer cell membrane (CCM) camouflage technique, novel multi‐biomimetic MOF nanocarriers from microfluidics are prepared. The Fe3+, meso‐tetra(4‐carboxyphenyl)porphine and oxaliplatin prodrug are incorporated into one MOF nano‐system (named FeTPt), which is further cloaked by CCM to obtain a "Trojan Horse"‐like vehicle (FeTPt@CCM). Owing to the functionalization with CCM, FeTPt@CCM can target and accumulate at the tumor site via homologous binding. After being internalized by cancer cells, FeTPt@CCM can be activated by a Fenton‐like reaction as well as a redox reaction between Fe3+ and glutathione and hydrogen peroxide to generate hydroxyl radical and oxygen. Thus, the nano‐platform effectively initiates ferroptosis and improves photodynamic therapy performance. Along with the Pt‐drug chemotherapy, the nano‐platform exhibits synergistic multimodal actions for inhibiting cancer cell proliferation in vitro and suppressing tumor growth in vivo. These features indicate that such a versatile biomimetic MOF delivery system from microfluidics has great potential for synergistic cancer treatment. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cell (MSC) therapy is a promising candidate for inflammatory bowel disease (IBD) treatment, while overcoming the limitations of naive seeding cells function and realizing efficient intestinal targeting remains a challenge. Here, a bioadhesive microparticle carrying interleukin‐27 (IL‐27) MSC‐derived extracellular vesicles (MSCIL‐27 EVs) is developed to treat IBD. The MSCIL‐27 EVs prepared through lentivirus‐mediated gene transfection technology show ideal anti‐inflammatory and damage repair function. By encapsulating MSCIL‐27 EVs into dopamine methacrylamide‐modified hydrogel, a bioadhesive EVs microcarrier via microfluidic technology is fabricated. The resultant microcarriers exhibit ideal MSCIL‐27 EVs sustained release effect and effective wet adhesion property. Furthermore, the therapeutic potential of MSCIL‐27 EVs‐loaded microcarriers in treating IBD is demonstrated. Through giving IBD rats a rectal administration, it is found that the microcarriers can firmly anchor to the surface of colon, reduce the inflammatory response, and repair the damaged barrier. Therefore, the bioadhesive MSCIL‐27 EVs‐loaded microcarriers provide a promising strategy for the biomedical application of MSC‐derived EVs, and broaden the clinical potential of MSC therapy. [ABSTRACT FROM AUTHOR]

In diabetic wound healing, M1 macrophage accumulation and elevated inflammation are prevalent issues. Intelligent delivery systems that can sustainably release antioxidizing and anti‐inflammatory ingredients are expected for effective wound healing. Herein, a novel glycyrrhetinic acid (GA) liposomes encapsulated microcapsules delivery system that has desired features for inflammatory wound repair is presented. As the bacteria could break down the alginate shells, the GA liposomes could be controllably released from the microcapsules, which promotes M2 macrophage polarization and regulate their responses in the inflammatory wound microenvironment. Based on these, it is demonstrated that the GA liposomes encapsulated microcapsules delivery system exhibits an anti‐inflammatory and immunomodulatory effect for diabetic wound healing in a full‐thickness defect model in diabetic rats. These results indicate that the immunomodulatory capabilities of the microcapsules can be unitized for efficient wound repair, and such a delivery system is valuable for clinical wound healing applications. [ABSTRACT FROM AUTHOR]