Injectable Nanoengineered Adhesive Hydrogel for Treating Enterocutaneous Fistulas.

Enterocutaneous fistula (ECF) is a severe medical condition where an abnormal connection forms between the gastrointestinal tract and skin. ECFs are, in most cases, a result of surgical complications such as missed enterotomies or anastomotic leaks. The constant leakage of enteric and fecal contents from the fistula site leads to skin breakdown and increases the risk of infection. Despite advances in surgical techniques and postoperative management, ECF accounts for significant mortality rates, estimated between 15-20%, and causes debilitating morbidity. Therefore, there is a critical need for a simple and effective method to seal and heal ECF. Injectable hydrogels with combined properties of robust mechanical properties and cell infiltration/proliferation have the potential to block and heal ECF. Herein, we report the development of an injectable nanoengineered adhesive hydrogel (INAH) composed of a synthetic nanosilicate (Laponite®) and a gelatin-dopamine conjugate for treating ECF. The hydrogel undergoes fast cross-linking using a co-injection method, resulting in a matrix with improved mechanical and adhesive properties. INAH demonstrates appreciable blood clotting abilities and is cytocompatible with fibroblasts. The adhesive properties of the hydrogel are demonstrated in ex vivo adhesion models with skin and arteries, where the volume stability in the hydrated internal environment facilitates maintaining strong adhesion. In vivo assessments reveal that the INAH is biocompatible, supporting cell infiltration and extracellular matrix deposition while not forming fibrotic tissue. These findings suggest that this INAH holds promising translational potential for sealing and healing ECF.

Rapid integration of screen-printed electrodes into thermoplastic organ-on-a-chip devices for real-time monitoring of trans-endothelial electrical resistance.

Trans-endothelial electrical resistance (TEER) is one of the most widely used indicators to quantify the barrier integrity of endothelial layers. Over the last decade, the integration of TEER sensors into organ-on-a-chip (OOC) platforms has gained increasing interest for its efficient and effective measurement of TEER in OOCs. To date, microfabricated electrodes or direct insertion of wires has been used to integrate TEER sensors into OOCs, with each method having advantages and disadvantages. In this study, we developed a TEER-SPE chip consisting of carbon-based screen-printed electrodes (SPEs) embedded in a poly(methyl methacrylate) (PMMA)-based multi-layered microfluidic device with a porous poly(ethylene terephthalate) membrane in-between. As proof of concept, we demonstrated the successful cultures of hCMEC/D3 cells and the formation of confluent monolayers in the TEER-SPE chip and obtained TEER measurements for 4 days. Additionally, the TEER-SPE chip could detect changes in the barrier integrity due to shear stress or an inflammatory cytokine (i.e., tumor necrosis factor-α). The novel approach enables a low-cost and facile fabrication of carbon-based SPEs on PMMA substrates and the subsequent assembly of PMMA layers for rapid prototyping. Being cost-effective and cleanroom-free, our method lowers the existing logistical and technical barriers presenting itself as another step forward to the broader adoption of OOCs with TEER measurement capability.

Injectable, Antibacterial, and Hemostatic Tissue Sealant Hydrogels.

Hemorrhage and bacterial infections are major hurdles in the management of life-threatening surgical wounds. Most bioadhesives for wound closure lack sufficient hemostatic and antibacterial properties. Furthermore, they suffer from weak sealing efficacy, particularly for stretchable organs, such as the lung and bladder. Accordingly, there is an unmet need for mechanically robust hemostatic sealants with simultaneous antibacterial effects. Here, an injectable, photocrosslinkable, and stretchable hydrogel sealant based on gelatin methacryloyl (GelMA), supplemented with antibacterial zinc ferrite (ZF) nanoparticles and hemostatic silicate nanoplatelets (SNs) for rapid blood coagulation is nanoengineered. The hydrogel reduces the in vitro viability of Staphylococcus aureus by more than 90%. The addition of SNs (2% w/v) and ZF nanoparticles (1.5 mg mL-1 ) to GelMA (20% w/v) improves the burst pressure of perforated ex vivo porcine lungs by more than 40%. Such enhancement translated to ≈250% improvement in the tissue sealing capability compared with a commercial hemostatic sealant, Evicel. Furthermore, the hydrogels reduce bleeding by ≈50% in rat bleeding models. The nanoengineered hydrogel may open new translational opportunities for the effective sealing of complex wounds that require mechanical flexibility, infection management, and hemostasis.

An All-In-One Transient Theranostic Platform for Intelligent Management of Hemorrhage.

Developing theranostic devices to detect bleeding and effectively control hemorrhage in the prehospital setting is an unmet medical need. Herein, an all-in-one theranostic platform is presented, which is constructed by sandwiching silk fibroin (SF) between two silver nanowire (AgNW) based conductive electrodes to non-enzymatically diagnose local bleeding and stop the hemorrhage at the wound site. Taking advantage of the hemostatic property of natural SF, the device is composed of a shape-memory SF sponge, facilitating blood clotting, with ≈82% reduction in hemostatic time in vitro as compared with untreated blood. Furthermore, this sandwiched platform serves as a capacitive sensor that can detect bleeding and differentiate between blood and other body fluids (i.e., serum and water) via capacitance change. In addition, the AgNW electrode endows anti-infection efficiency against Escherichia coli and Staphylococcus aureus. Also, the device shows excellent biocompatibility and gradually biodegrades in vivo with no major local or systemic inflammatory responses. More importantly, the theranostic platform presents considerable hemostatic efficacy comparable with a commercial hemostat, Dengen, in rat liver bleeding models. The theranostic platform provides an unexplored strategy for the intelligent management of hemorrhage, with the potential to significantly improve patients' well-being through the integration of diagnostic and therapeutic capabilities.

Gelatin methacryloyl and Laponite bioink for 3D bioprinted organotypic tumor modeling.

Three-dimensional (3D)in vitrotumor models that can capture the pathophysiology of human tumors are essential for cancer biology and drug development. However, simulating the tumor microenvironment is still challenging because it consists of a heterogeneous mixture of various cellular components and biological factors. In this regard, current extracellular matrix (ECM)-mimicking hydrogels used in tumor tissue engineering lack physical interactions that can keep biological factors released by encapsulated cells within the hydrogel and improve paracrine interactions. Here, we developed a nanoengineered ion-covalent cross-linkable bioink to construct 3D bioprinted organotypic tumor models. The bioink was designed to implement the tumor ECM by creating an interpenetrating network composed of gelatin methacryloyl (GelMA), a light cross-linkable polymer, and synthetic nanosilicate (Laponite) that exhibits a unique ionic charge to improve retention of biological factors released by the encapsulated cells and assist in paracrine signals. The physical properties related to printability were evaluated to analyze the effect of Laponite hydrogel on bioink. Low GelMA (5%) with high Laponite (2.5%-3.5%) composite hydrogels and high GelMA (10%) with low Laponite (1.0%-2.0%) composite hydrogels showed acceptable mechanical properties for 3D printing. However, a low GelMA composite hydrogel with a high Laponite content could not provide acceptable cell viability. Fluorescent cell labeling studies showed that as the proportion of Laponite increased, the cells became more aggregated to form larger 3D tumor structures. Reverse transcription-polymerase chain reaction (RT-qPCR) and western blot experiments showed that an increase in the Laponite ratio induces upregulation of growth factor and tissue remodeling-related genes and proteins in tumor cells. In contrast, cell cycle and proliferation-related genes were downregulated. On the other hand, concerning fibroblasts, the increase in the Laponite ratio indicated an overall upregulation of the mesenchymal phenotype-related genes and proteins. Our study may provide a rationale for using Laponite-based hydrogels in 3D cancer modeling.

Aerogel-Based Biomaterials for Biomedical Applications: From Fabrication Methods to Disease-Targeting Applications.

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.

Deep Eutectic Solvents-based Ionogels with Ultrafast Gelation and High Adhesion in Harsh Environments.

Adhesive materials have recently drawn intensive attention due to their excellent sealing ability, thereby stimulating advances in materials science and industrial usage. However, reported adhesives usually exhibit weak adhesion strength, require high pressure for strong bonding, and display severe adhesion deterioration in various harsh environments. In this work, instead of water or organic solvents, a deep eutectic solution (DES) was used as the medium for photopolymerization of zwitterionic and polarized monomers, thus generating a novel ionogel with tunable mechanical properties. Multiple hydrogen bonds and electrostatic interactions between DES and monomers facilitated ultrafast gelation and instant bonding without any external pressure, which was rarely reported previously. Furthermore, high adhesion in different harsh environments (e.g., water, acidic and basic buffers, and saline solutions) and onto hydrophilic (e.g., glass and tissues) and hydrophobic (e.g., polymethyl methacrylate, polystyrene, and polypropylene) adherends was demonstrated. Also, high stretchability of the ionogel at extreme temperatures (-80 and 80 °C) indicated its widespread applications. Furthermore, the biocompatible ionogel showed high burst pressure onto stomach and intestine tissues to prevent liquid leakage, highlighting its potential as an adhesive patch. This ionogel provides unprecedented opportunities in the fields of packaging industry, marine engineering, medical adhesives, and electronic assembly.

Tunable hybrid hydrogels with multicellular spheroids for modeling desmoplastic pancreatic cancer.

The tumor microenvironment consists of diverse, complex etiological factors. The matrix component of pancreatic ductal adenocarcinoma (PDAC) plays an important role not only in physical properties such as tissue rigidity but also in cancer progression and therapeutic responsiveness. Although significant efforts have been made to model desmoplastic PDAC, existing models could not fully recapitulate the etiology to mimic and understand the progression of PDAC. Here, two major components in desmoplastic pancreatic matrices, hyaluronic acid- and gelatin-based hydrogels, are engineered to provide matrices for tumor spheroids composed of PDAC and cancer-associated fibroblasts (CAF). Shape analysis profiles reveals that incorporating CAF contributes to a more compact tissue formation. Higher expression levels of markers associated with proliferation, epithelial to mesenchymal transition, mechanotransduction, and progression are observed for cancer-CAF spheroids cultured in hyper desmoplastic matrix-mimicking hydrogels, while the trend can be observed when those are cultured in desmoplastic matrix-mimicking hydrogels with the presence of transforming growth factor-ß1 (TGF-ß1). The proposed multicellular pancreatic tumor model, in combination with proper mechanical properties and TGF-ß1 supplement, makes strides in developing advanced pancreatic models for resembling and monitoring the progression of pancreatic tumors, which could be potentially applicable for realizing personalized medicine and drug testing applications.

Skin-interfaced electronics: A promising and intelligent paradigm for personalized healthcare.

Skin-interfaced electronics (skintronics) have received considerable attention due to their thinness, skin-like mechanical softness, excellent conformability, and multifunctional integration. Current advancements in skintronics have enabled health monitoring and digital medicine. Particularly, skintronics offer a personalized platform for early-stage disease diagnosis and treatment. In this comprehensive review, we discuss (1) the state-of-the-art skintronic devices, (2) material selections and platform considerations of future skintronics toward intelligent healthcare, (3) device fabrication and system integrations of skintronics, (4) an overview of the skintronic platform for personalized healthcare applications, including biosensing as well as wound healing, sleep monitoring, the assessment of SARS-CoV-2, and the augmented reality-/virtual reality-enhanced human-machine interfaces, and (5) current challenges and future opportunities of skintronics and their potentials in clinical translation and commercialization. The field of skintronics will not only minimize physical and physiological mismatches with the skin but also shift the paradigm in intelligent and personalized healthcare and offer unprecedented promise to revolutionize conventional medical practices.

Poly-Catecholic Functionalization of Biomolecules for Rapid Gelation, Robust Injectable Bioadhesion, and Near-Infrared Responsiveness.

Mussel-inspired catechol-functionalization of degradable natural biomaterials has garnered significant interest as an approach to achieve bioadhesion for sutureless wound closure. However, conjugation capacity in standard coupling reactions, such as carbodiimide chemistry, is limited by low yield and lack of abundant conjugation sites. Here, a simple oxidative polymerization step before conjugation of catechol-carrying molecules (i.e., 3,4-dihydroxy-l-phenylalanine, l-DOPA) as a potential approach to amplify catechol function in bioadhesion of natural gelatin biomaterials is proposed. Solutions of gelatin modified with poly(l-DOPA) moieties (GelDOPA) are characterized by faster physical gelation and increased viscosity, providing better wound control on double-curved tissue surfaces compared to those of l-DOPA-conjugated gelatin. Physical hydrogels treated topically with low concentrations of NaIO4 solutions are crosslinked on-demand via through-thickness diffusion. Poly(l-DOPA) conjugates enhance crosslinking density compared to l-DOPA conjugated gelatin, resulting in lower swelling and enhanced cohesion in physiological conditions. Together with cohesion, more robust bioadhesion at body temperature is achieved by poly(l-DOPA) conjugates, exceeding those of commercial sealants. Further, poly(l-DOPA) motifs introduced photothermal responsiveness via near-infrared (NIR) irradiation for controlled drug release and potential applications in photothermal therapy. The above functionalities, along with antibacterial activity, render the proposed approach an effective biomaterial design strategy for wound closure applications.

Oxygen-generating microparticles downregulate HIF-1α expression, increase cardiac contractility, and mitigate ischemic injury.

Myocardial hypoxia is the low oxygen tension in the heart tissue implicated in many diseases, including ischemia, cardiac dysfunction, or after heart procurement for transplantation. Oxygen-generating microparticles have recently emerged as a potential strategy for supplying oxygen to sustain cell survival, growth, and tissue functionality in hypoxia. Here, we prepared oxygen-generating microparticles with poly D,L-lactic-co-glycolic acid, and calcium peroxide (CPO), which yielded a continuous morphology capable of sustained oxygen release for up to 24 h. We demonstrated that CPO microparticles increased primary rat cardiomyocyte metabolic activity while not affecting cell viability during hypoxia. Moreover, hypoxia-inducible factor (HIF)-1α, which is upregulated during hypoxia, can be downregulated by delivering oxygen using CPO microparticles. Single-cell traction force microscopy data demonstrated that the reduced energy generated by hypoxic cells could be restored using CPO microparticles. We engineered cardiac tissues that showed higher contractility in the presence of CPO microparticles compared to hypoxic cells. Finally, we observed reduced myocardial injuries in ex vivo rabbit hearts treated with CPO microparticles. In contrast, an acute early myocardial injury was observed for the hearts treated with control saline solution in hypoxia. In conclusion, CPO microparticles improved cell and tissue contractility and gene expression while reducing hypoxia-induced myocardial injuries in the heart. STATEMENT OF SIGNIFICANCE: Oxygen-releasing microparticles can reduce myocardial ischemia, allograft rejection, or irregular heartbeats after heart transplantation. Here we present biodegradable oxygen-releasing microparticles that are capable of sustained oxygen release for more than 24 hrs. We then studied the impact of sustained oxygen release from microparticles on gene expresseion and cardiac cell and tissue function. Previous studies have not measured cardiac tissue or cell mechanics during hypoxia, which is important for understanding proper cardiac function and beating. Using traction force microscopy and an engineered tissue-on-a-chip, we demonstrated that our oxygen-releasing microparticles improve cell and tissue contractility during hypoxia while downregulating the HIF-1α expression level. Finally, using the microparticles, we showed reduced myocardial injuries in rabbit heart tissue, confirming the potential of the particles to be used for organ transplantation or tissue engineering.

Thermoresponsive shear-thinning hydrogel (T-STH) hemostats for minimally invasive treatment of external hemorrhages.

Hemorrhage is the leading cause of death following battlefield injuries. Although several hemostats are commercially available, they do not meet all the necessary requirements to stop bleeding in combat injuries. Here, we engineer thermoresponsive shear-thinning hydrogels (T-STH) composed of a thermoresponsive polymer, poly(N-isopropyl acrylamide) (p(NIPAM)), and hemostatic silicate nanodisks, LAPONITE®, as minimally invasive injectable hemostatic agents. Our T-STH is a physiologically stable hydrogel that can be easily injected through a syringe and needle and exhibits rapid mechanical recovery. Additionally, it demonstrates temperature-dependent blood coagulation owing to the phase transition of p(NIPAM). It decreases in vitro blood clotting times over 50% at physiological temperatures compared to room temperature. Furthermore, it significantly prevents blood loss in an ex vivo bleeding model at different blood flow rates (1 mL min-1 and 5 mL min-1) by forming a wound plug. More importantly, our T-STH is comparable to a commercially available hemostat, Floseal, in terms of blood loss and blood clotting time in an in vivo rat liver bleeding model. Furthermore, once the hemorrhage is stabilized, our T-STH can be easily removed using a cold saline wash without any rebleeding or leaving any residues. Taken together, our T-STH can be used as a first aid hemostat to treat external hemorrhages in emergency situations.

Sodium Phytate-Incorporated Gelatin-Silicate Nanoplatelet Composites for Enhanced Cohesion and Hemostatic Function of Shear-Thinning Biomaterials.

Shear-thinning biomaterials (STBs) based on gelatin-silicate nanoplatelets (SNs) are emerging as an alternative to conventional coiling and clipping techniques in the treatment of vascular anomalies. Improvements in the cohesion of STB hydrogels pave the way toward their translational application in minimally invasive therapies such as endovascular embolization repair. In the present study, sodium phytate (Phyt) additives are used to tune the electrostatic network of SNs-gelatin STBs, thereby promoting their mechanical integrity and facilitating injectability through standard catheters. We show that an optimized amount of Phyt enhances storage modulus by approximately one order of magnitude and reduces injection force by ≈58% without compromising biocompatibility and hydrogel wet stability. The Phyt additives are found to decrease the immune responses induced by SNs. In vitro embolization experiments suggest a significantly lower rate of failure in Phyt-incorporated STBs than in control groups. Furthermore, the addition of Phyt leads to accelerated blood coagulation (reduces clotting time by ≈45% compared to controls) due to the contributions of negatively charged phosphate groups, which aid in the prolonged durability of STB in coagulopathic patients. Therefore, the proposed approach is an effective method for the design of robust and injectable STBs for minimally invasive treatment of vascular malformations.

A Breathable, Passive-Cooling, Non-Inflammatory, and Biodegradable Aerogel Electronic Skin for Wearable Physical-Electrophysiological-Chemical Analysis.

Real-time monitoring of human health can be significantly improved by designing novel electronic skin (E-skin) platforms that mimic the characteristics and sensitivity of human skin. A high-quality E-skin platform that can simultaneously monitor multiple physiological and metabolic biomarkers without introducing skin discomfort or irritation is an unmet medical need. Conventional E-skins are either monofunctional or made from elastomeric films that do not include key synergistic features of natural skin, such as multi-sensing, breathability, and thermal management capabilities in a single patch. Herein, a biocompatible and biodegradable E-skin patch based on flexible gelatin methacryloyl aerogel (FGA) for non-invasive and continuous monitoring of multiple biomarkers of interest is engineered and demonstrated. Taking advantage of cryogenic temperature treatment and slow polymerization, FGA is fabricated with a highly interconnected porous structure that displays good flexibility, passive-cooling capabilities, and ultra-lightweight properties that make it comfortable to wear for long periods of time. It also provides numerous permeable capillary channels for thermal-moisture transfer, ensuring its excellent breathability. Therefore, the engineered FGA-based E-skin can simultaneously monitor body temperature, hydration, and biopotentials via electrophysiological sensors and detect glucose, lactate, and alcohol levels via electrochemical sensors. This work offers a previously unexplored materials strategy for next-generation E-skin platforms with superior practicality.

A Microfluidic Contact Lens to Address Contact Lens-Induced Dry Eye.

The contact lens (CL) industry has made great strides in improving CL-wearing experiences. However, a large amount of CL wearers continue to experience ocular dryness, known as contact lens-induced dry eye (CLIDE), stemming from the reduction in tear volume, tear film instability, increased tear osmolarity followed by inflammation and resulting in ocular discomfort and visual disturbances. In this article, to address tear film thinning between the CL and the ocular surface, the concept of using a CL with microchannels to deliver the tears from the pre-lens tear film (PrLTF) to the post-lens ocular surface using in vitro eye-blink motion is investigated. This study reports an eye-blink mimicking system with microfluidic poly(2-hydroxyethyl methacrylate) (poly(HEMA)) hydrogel with integrated microchannels to demonstrate eye-blink assisted flow through microchannels. This in vitro experimental study provides a proof-of-concept result that tear transport from PrLTF to post-lens tear film can be enhanced by an artificial eyelid motion in a pressure range of 0.1-5 kPa (similar to human eyelid pressure) through poly(HEMA) microchannels. Simulation is conducted to support the hypothesis. This work demonstrates the feasibility of developing microfluidic CLs with the potential to help prevent or minimize CLIDE and discomfort by the enhanced transport of pre-lens tears to the post-lens ocular surface.

Tissue adhesive hemostatic microneedle arrays for rapid hemorrhage treatment.

Blood loss by hemorrhaging wounds accounts for over one-third of ∼5 million trauma fatalities worldwide every year. If not controlled in a timely manner, exsanguination can take lives within a few minutes. Developing new biomaterials that are easy to use by non-expert patients and promote rapid blood coagulation is an unmet medical need. Here, biocompatible, and biodegradable microneedle arrays (MNAs) based on gelatin methacryloyl (GelMA) biomaterial hybridized with silicate nanoplatelets (SNs) are developed for hemorrhage control. The SNs render the MNAs hemostatic, while the needle-shaped structure increases the contact area with blood, synergistically accelerating the clotting time from 11.5 min to 1.3 min in vitro. The engineered MNAs reduce bleeding by ∼92% compared with the untreated injury group in a rat liver bleeding model. SN-containing MNAs outperform the hemostatic effect of needle-free patches and a commercial hemostat in vivo via combining micro- and nanoengineered features. Furthermore, the tissue adhesive properties and mechanical interlocking support the suitability of MNAs for wound closure applications. These hemostatic MNAs may enable rapid hemorrhage control, particularly for patients in developing countries or remote areas with limited or no immediate access to hospitals.

Recent Advances in Bioinspired Hydrogels: Materials, Devices, and Biosignal Computing.

The remarkable ability of biological systems to sense and adapt to complex environmental conditions has inspired new materials and novel designs for next-generation wearable devices. Hydrogels are being intensively investigated for their versatile functions in wearable devices due to their superior softness, biocompatibility, and rapid stimulus response. This review focuses on recent strategies for developing bioinspired hydrogel wearable devices that can accommodate mechanical strain and integrate seamlessly with biological systems. We will provide an overview of different types of bioinspired hydrogels tailored for wearable devices. Next, we will discuss the recent progress of bioinspired hydrogel wearable devices such as electronic skin and smart contact lenses. Also, we will comprehensively summarize biosignal readout methods for hydrogel wearable devices as well as advances in powering and wireless data transmission technologies. Finally, current challenges facing these wearable devices are discussed, and future directions are proposed.

Injectable Shear-Thinning Hydrogels with Sclerosing and Matrix Metalloproteinase Modulatory Properties for the Treatment of Vascular Malformations.

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 incorporated doxycycline (DOX), a well-known sclerosant and MMPs inhibitor, into a shear-thinning biomaterial (STB)-based vascular embolizing hydrogel. The addition of DOX was expected to improve embolizing efficacy while preventing endoleaks by inhibiting MMP activity and promoting endothelial removal. The results showed that STBs containing 4.5% w/w silicate nanoplatelet and 0.3% w/v of DOX were injectable and had a 2-fold 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 showed sclerosing effects after 6 h in an ex vivo pig aorta model. Sustained release of DOX from hydrogels on endothelial cells showed MMP inhibition (ca. an order of magnitude larger than control groups) after 7 days. The hydrogels successfully occluded 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.

Recent advances in biopolymer-based hemostatic materials.

Hemorrhage is the leading cause of trauma-related deaths, in hospital and prehospital settings. Hemostasis is a complex mechanism that involves a cascade of clotting factors and proteins that result in the formation of a strong clot. In certain surgical and emergency situations, hemostatic agents are needed to achieve faster blood coagulation to prevent the patient from experiencing a severe hemorrhagic shock. Therefore, it is critical to consider appropriate materials and designs for hemostatic agents. Many materials have been fabricated as hemostatic agents, including synthetic and naturally derived polymers. Compared to synthetic polymers, natural polymers or biopolymers, which include polysaccharides and polypeptides, have greater biocompatibility, biodegradability and processibility. Thus, in this review, we focus on biopolymer-based hemostatic agents of different forms, such as powder, particles, sponges and hydrogels. Finally, we discuss biopolymer-based hemostatic materials currently in clinical trials and offer insight into next-generation hemostats for clinical translation.

Bio-macromolecular design roadmap towards tough bioadhesives.

Emerging sutureless wound-closure techniques have led to paradigm shifts in wound management. State-of-the-art biomaterials offer biocompatible and biodegradable platforms enabling high cohesion (toughness) and adhesion for rapid bleeding control as well as robust attachment of implantable devices. Tough bioadhesion stems from the synergistic contributions of cohesive and adhesive interactions. This Review provides a biomacromolecular design roadmap for the development of tough adhesive surgical sealants. We discuss a library of materials and methods to introduce toughness and adhesion to biomaterials. Intrinsically tough and elastic polymers are leveraged primarily by introducing strong but dynamic inter- and intramolecular interactions either through polymer chain design or using crosslink regulating additives. In addition, many efforts have been made to promote underwater adhesion via covalent/noncovalent bonds, or through micro/macro-interlock mechanisms at the tissue interfaces. The materials settings and functional additives for this purpose and the related characterization methods are reviewed. Measurements and reporting needs for fair comparisons of different materials and their properties are discussed. Finally, future directions and further research opportunities for developing tough bioadhesive surgical sealants are highlighted.