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Hepatocellular carcinoma (HCC) is a malignant and deadly form of liver cancer with limited treatment options. Transcatheter arterial chemoembolization, a procedure that delivers embolic and chemotherapeutic agents through blood vessels, is a promising cancer treatment strategy. However, it still faces limitations, such as inefficient agent delivery and the inability to address tumor‐induced immunosuppression. Here, a drug‐eluting shear‐thinning hydrogel (DESTH) loaded with chemotherapeutic and immunotherapeutic agents in nanocomposite hydrogels composed of gelatin and nanoclays is presented as a therapeutic strategy for a catheter‐based endovascular anticancer approach. DESTH is manually deliverable using a conventional needle and catheter. In addition, drug release studies show a sustained and pH‐dependent co‐delivery of the chemotherapy doxorubicin (acidic pH) and the immune‐checkpoint inhibitor aPD‐1 (neutral pH). In a mouse liver tumor model, the DESTH‐based chemo/immunotherapy combination has the highest survival rate and smallest residual tumor size. Finally, immunofluorescence analysis confirms that DESTH application enhances cell death and increases intratumoral infiltration of cytotoxic T‐cells. In conclusion, the results show that DESTH, which enables efficient ischemic tumor cell death and effective co‐delivery of chemo‐ and immunotherapeutic agents, may have the potential to be an effective therapeutic modality in the treatment of HCC. [ABSTRACT FROM AUTHOR]

Sac embolization of abdominal aortic aneurysms (AAAs) remains clinically limited by endoleak recurrences. These recurrences are correlated with recanalization due to the presence of endothelial lining and matrix metalloproteinases (MMPs)‐mediated aneurysm progression. This study incorporates doxycycline (DOX), a well‐known sclerosant and MMPs inhibitor, into a shear‐thinning biomaterial (STB)‐based vascular embolizing hydrogel. The addition of DOX is expected to improve embolizing efficacy while preventing endoleaks by inhibiting MMP activity and promoting endothelial removal. The results show that STBs containing 4.5% w/w silicate nanoplatelet and 0.3% w/v of DOX are injectable and have a twofold increase in storage modulus compared to those without DOX. STB‐DOX hydrogels also reduced clotting time by 33% compared to untreated blood. The burst release of DOX from the hydrogels show sclerosing effects after 6 h in an ex vivo pig aorta model. Sustained release of DOX from hydrogels on endothelial cells shows MMP inhibition (approximately an order of magnitude larger than control groups) after 7 days. The hydrogels successfully occlude a patient‐derived abdominal aneurysm model at physiological blood pressures and flow rates. The sclerosing and MMP inhibition characteristics in the engineered multifunctional STB‐DOX hydrogels may provide promising opportunities for the efficient embolization of aneurysms in blood vessels. [ABSTRACT FROM AUTHOR]

Aerogel‐based biomaterials are increasingly being considered for biomedical applications due to their unique properties such as high porosity, hierarchical porous network, and large specific pore surface area. Depending on the pore size of the aerogel, biological effects such as cell adhesion, fluid absorption, oxygen permeability, and metabolite exchange can be altered. Based on the diverse potential of aerogels in biomedical applications, this paper provides a comprehensive review of fabrication processes including sol‐gel, aging, drying, and self‐assembly along with the materials that can be used to form aerogels. In addition to the technology utilizing aerogel itself, it also provides insight into the applicability of aerogel based on additive manufacturing technology. To this end, how microfluidic‐based technologies and 3D printing can be combined with aerogel‐based materials for biomedical applications is discussed. Furthermore, previously reported examples of aerogels for regenerative medicine and biomedical applications are thoroughly reviewed. A wide range of applications with aerogels including wound healing, drug delivery, tissue engineering, and diagnostics are demonstrated. Finally, the prospects for aerogel‐based biomedical applications are presented. The understanding of the fabrication, modification, and applicability of aerogels through this study is expected to shed light on the biomedical utilization of aerogels. [ABSTRACT FROM AUTHOR]

A recent article in Advanced Functional Materials discusses a breakthrough in liver cancer treatment. Researchers have developed a drug-eluting shear-thinning hydrogel (DESTH) that can deliver both chemotherapy and immunotherapy agents. In tests on a mouse liver tumor model, the treatment showed high survival rates and reduced tumor sizes. The hydrogel is delivered via a catheter and promotes efficient ischemic tumor cell death, making it a promising therapy for hepatocellular carcinoma. [Extracted from the article]

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. Unlabelled Image [ABSTRACT FROM AUTHOR]

An emerging approach to improve the physicobiochemical properties and the multifunctionality of biomaterials is to incorporate functional nanomaterials (NMs) onto 2D surfaces and into 3D hydrogel networks. This approach is starting to generate promising advanced functional materials such as self‐assembled monolayers (SAMs) and nanocomposite (NC) hydrogels of NMs with remarkable properties and tailored functionalities that are beneficial for a variety of biomedical applications, including tissue engineering, drug delivery, and developing biosensors. A wide range of NMs, such as carbon‐, metal‐, and silica‐based NMs, can be integrated into 2D and 3D biomaterial formulations due to their unique characteristics, such as magnetic properties, electrical properties, stimuli responsiveness, hydrophobicity/hydrophilicity, and chemical composition. The highly ordered nano‐ or microscale assemblies of NMs on surfaces alter the original properties of the NMs and add enhanced and/or synergetic and novel features to the final SAMs of the NM constructs. Furthermore, the incorporation of NMs into polymeric hydrogel networks reinforces the (soft) polymer matrix such that the formed NC hydrogels show extraordinary mechanical properties with superior biological properties. [ABSTRACT FROM AUTHOR]

Abstract Closure of ocular wounds after an accident or surgery is typically performed by suturing, which is associated with numerous potential complications, including suture breakage, inflammation, secondary neovascularization, erosion to the surface and secondary infection, and astigmatism; for example, more than half of post-corneal transplant infections are due to suture related complications. Tissue adhesives provide promising substitutes for sutures in ophthalmic surgery. Ocular adhesives are not only intended to address the shortcomings of sutures, but also designed to be easy to use, and can potentially minimize post-operative complications. Herein, recent progress in the design, synthesis, and application of ocular adhesives, along with their advantages, limitations, and potential are discussed. This review covers two main classes of ocular adhesives: (1) synthetic adhesives based on cyanoacrylates, polyethylene glycol (PEG), and other synthetic polymers, and (2) adhesives based on naturally derived polymers, such as proteins and polysaccharides. In addition, different technologies to cover and protect ocular wounds such as contact bandage lenses, contact lenses coupled with novel technologies, and decellularized corneas are discussed. Continued advances in this area can help improve both patient satisfaction and clinical outcomes. [ABSTRACT FROM AUTHOR]

Abstract The recent decade has witnessed a growing demand to substitute synthetic materials with naturally-derived platforms for minimizing their undesirable footprints in biomedicine, environment, and ecosystems. Among the natural materials, cellulose, the most abundant biopolymer in the world with key properties, such as biocompatibility, biorenewability, and sustainability has drawn significant attention. The hierarchical structure of cellulose fibers, one of the main constituents of plant cell walls, has been nanoengineered and broken down to nanoscale building blocks, providing an infrastructure for nanomedicine. Microorganisms, such as certain types of bacteria, are another source of nanocelluloses known as bacterial nanocellulose (BNC), which benefit from high purity and crystallinity. Chemical and mechanical treatments of cellulose fibrils made up of alternating crystalline and amorphous regions have yielded cellulose nanocrystals (CNC), hairy CNC (HCNC), and cellulose nanofibrils (CNF) with dimensions spanning from a few nanometers up to several microns. Cellulose nanocrystals and nanofibrils may readily bind drugs, proteins, and nanoparticles through physical interactions or be chemically modified to covalently accommodate cargos. Engineering surface properties, such as chemical functionality, charge, area, crystallinity, and hydrophilicity, plays a pivotal role in controlling the cargo loading/releasing capacity and rate, stability, toxicity, immunogenicity, and biodegradation of nanocellulose-based delivery platforms. This review provides insights into the recent advances in nanoengineering cellulose crystals and fibrils to develop vehicles, encompassing colloidal nanoparticles, hydrogels, aerogels, films, coatings, capsules, and membranes, for the delivery of a broad range of bioactive cargos, such as chemotherapeutic drugs, anti-inflammatory agents, antibacterial compounds, and probiotics. Synopsis Engineering certain types of microorganisms as well as the hierarchical structure of cellulose fibers, one of the main building blocks of plant cell walls, has yielded unique families of cellulose-based nanomaterials, which have leveraged the effective delivery of bioactive molecules. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Millions of people worldwide suffer from debilitating, progressive, and often permanent loss of vision without any viable treatment options. The complex physiological barriers of the eye contribute to the difficulty in developing novel therapies by limiting our ability to deliver therapeutics in a sustained and controlled manner; especially when attempting to deliver drugs to the posterior eye or trying to regenerate the diseased retina. Cell-based therapies offer a significant potential advancement in these situations. In particular, encapsulating, or immunoisolating, cells within implantable, semi-permeable membranes has emerged as a clinically viable means of delivering therapeutic molecules to the eye for indefinite periods of time. The optimization of encapsulation device designs is occurring together with refinements in biomaterials, genetic engineering, and stem-cell production, yielding, for the first time, the possibility of widespread therapeutic use of this technology. Here, we highlight the status of the most advanced and widely explored iteration of cell encapsulation with an eye toward translating the potential of this technological approach to the medical reality. [ABSTRACT FROM AUTHOR]

Nanoparticles are uniquely suited for the study and development of potential therapies against atherosclerosis by virtue of their size, fine-tunable properties, and ability to incorporate therapies and/or imaging modalities. Furthermore, nanoparticles can be specifically targeted to the atherosclerotic plaque, evading off-target effects and/or associated cytotoxicity. There has been a wealth of knowledge available concerning the use of nanotechnologies in cardiovascular disease and atherosclerosis, in particular in animal models, but with a major focus on imaging agents. In fact, roughly 60% of articles from an initial search for this review included examples of imaging applications of nanoparticles. Thus, this review focuses on experimental therapy interventions applied to and observed in animal models. Particular emphasis is placed on how nanoparticle materials and properties allow researchers to learn a great deal about atherosclerosis. The objective of this review was to provide an update for nanoparticle use in imaging and drug delivery studies and to illustrate how nanoparticles can be used for sensing and modelling, for studying fundamental biological mechanisms, and for the delivery of biotherapeutics such as proteins, peptides, nucleic acids, and even cells all with the goal of attenuating atherosclerosis. Furthermore, the various atherosclerosis processes targeted mainly for imaging studies have been summarized in the hopes of inspiring new and exciting targeted therapeutic and/or imaging strategies. [ABSTRACT FROM AUTHOR]

Abstract: This study reports the development of a microfluidic system capable of repeated infusions of anti‐inflammatory factors post‐implantation for use as a coating for neural probes. This system consists of a microchannel in a thin gelatin methacryloyl–polyethylene glycol composite hydrogel surrounded by a porous polydimethylsiloxane membrane, where the hydrogel can be dried to increase the stiffness for easy insertion. Reswelling allows the perfusion of interleukin (IL)‐4 and dexamethasone as anti‐inflammatory factors through the channel with minimal burst release and significant amounts of IL‐4 are observed to release for up to 96 h post‐infusion. Repeated injections of IL‐4 increase the ratio of prohealing M2 versus proinflammatory M1 phenotypes of macrophages encapsulated in the hydrogel by sixfold compared with a single injection, over a 2‐week period. These repeated infusions also significantly downregulate the expression of inflammatory markers tumor necrosis factor‐α and IL‐6 in astrocytes encapsulated in hydrogel. To demonstrate the system as a coating of neural probes for in vivo applications, a prototype device is further fabricated, where a thin dual‐layered microfluidic system is integrated onto a metal probe. Such a drug delivery system can help reduce the formation of a glial scar around neural probes. [ABSTRACT FROM AUTHOR]

Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pathophysiology of chronic wounds have resulted in the development of drugs designed to target different aspects of the impaired processes. However, the hostility of the wound environment rich in degradative enzymes and its elevated pH, combined with differences in the time scales of different physiological processes involved in tissue regeneration require the use of effective drug delivery systems. In this review, we will first discuss the pathophysiology of chronic wounds and then the materials used for engineering drug delivery systems. Different passive and active drug delivery systems used in wound care will be reviewed. In addition, the architecture of the delivery platform and its ability to modulate drug delivery are discussed. Emerging technologies and the opportunities for engineering more effective wound care devices are also highlighted. [ABSTRACT FROM AUTHOR]

Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine’s extremely short half-life in human blood (<10 s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this article, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted. [ABSTRACT FROM PUBLISHER]

Novel microfluidic tools allow new ways to manufacture and test drug delivery systems. Organ-on-a-chip systems — microscale recapitulations of complex organ functions — promise to improve the drug development pipeline. This review highlights the importance of integrating microfluidic networks with 3D tissue engineered models to create organ-on-a-chip platforms, able to meet the demand of creating robust preclinical screening models. Specific examples are cited to demonstrate the use of these systems for studying the performance of drug delivery vectors and thereby reduce the discrepancies between their performance at preclinical and clinical trials. We also highlight the future directions that need to be pursued by the research community for these proof-of-concept studies to achieve the goal of accelerating clinical translation of drug delivery nanoparticles. [ABSTRACT FROM AUTHOR]

Abstract: The rapid advancement of nanotechnology has raised the possibility of using engineered nanoparticles that interact within biological environments for treatment of diseases. Nanoparticles interacting with cells and the extracellular environment can trigger a sequence of biological effects. These effects largely depend on the dynamic physicochemical characteristics of nanoparticles, which determine the biocompatibility and efficacy of the intended outcomes. Understanding the mechanisms behind these different outcomes will allow prediction of the relationship between nanostructures and their interactions with the biological milieu. At present, almost no standard biocompatibility evaluation criteria have been established, in particular for nanoparticles used in drug delivery systems. Therefore, an appropriate safety guideline of nanoparticles on human health with assessable endpoints is needed. In this review, we discuss the data existing in the literature regarding biocompatibility of nanoparticles for drug delivery applications. We also review the various types of nanoparticles used in drug delivery systems while addressing new challenges and research directions. Presenting the aforementioned information will aid in getting one step closer to formulating compatibility criteria for biological systems under exposure to different nanoparticles. [Copyright &y& Elsevier]

Abstract: Protein drugs have low bioavailability after oral administration, which is due in part to fast transit of the drugs or drug delivery vehicles through the gastrointestinal tract. Increasing the time that the drugs spend in the intestine after dosing would allow for greater absorption and increased bioavailability. We developed a formulation strategy that can be used to prolong intestinal retention of drug delivery vehicles without substantial alterations to current polymeric encapsulation strategies. A model drug, insulin, was encapsulated in negatively charged poly(lactic-co-glycolic acid) (PLGA) microparticles, and the microparticles were subsequently mixed with positively charged micromagnets, whose size will prevent them from being absorbed. Stable complexes formed through electrostatic interaction. The complexes were effectively immobilized in vitro in a model of the mouse small intestine by application of an external magnetic field. Mice that were gavaged with radio-labeled complexes and fitted with a magnetic belt retained 32.5% of the 125I-insulin in the small intestine compared with 5.4% for the control group 6h after administration (p =0.005). Furthermore, mice similarly gavaged with complexes encapsulating insulin (120Units/kg) exhibited long-term glucose reduction in the groups with magnetic belts. The corresponding bioavailability of insulin was 5.11% compared with 0.87% for the control group (p =0.007). [Copyright &y& Elsevier]

One of the goals of biomaterials science is to reverse engineer aspects of human and non-human physiology. Similar to the body's regulatory mechanisms, such devices must transduce changes in the physiological environment or the presence of an external stimulus into a detectable or therapeutic response. This review is a comprehensive evaluation and critical analysis of the design and fabrication of environmentally responsive cell-material constructs for bioinspired machinery and biomimetic devices. In a bottom-up analysis, we begin by reviewing fundamental principles that explain materials' responses to chemical gradients, biomarkers, electromagnetic fields, light, and temperature. Strategies for fabricating highly ordered assemblies of material components at the nano to macro-scales via directed assembly, lithography, 3D printing and 4D printing are also presented. We conclude with an account of contemporary material-tissue interfaces within bioinspired and biomimetic devices for peptide delivery, cancer theranostics, biomonitoring, neuroprosthetics, soft robotics, and biological machines. [ABSTRACT FROM AUTHOR]