An autonomous wearable biosensor powered by a perovskite solar cell.

Wearable sweat sensors can potentially be used to continuously and non-invasively monitor physicochemical biomarkers that contain information related to disease diagnostics and fitness tracking. However, the development of such autonomous sensors faces a number of challenges including achieving steady sweat extraction for continuous and prolonged monitoring, and addressing the high power demands of multifunctional and complex analysis. Here we report an autonomous wearable biosensor that is powered by a perovskite solar cell and can provide continuous and non-invasive metabolic monitoring. The device uses a flexible quasi-two-dimensional perovskite solar cell module that provides ample power under outdoor and indoor illumination conditions (power conversion efficiency exceeding 31% under indoor light illumination). We show that the wearable device can continuously collect multimodal physicochemical data - glucose, pH, sodium ions, sweat rate, and skin temperature - across indoor and outdoor physical activities for over 12 hours.

Wearable Bioelectronics for Chronic Wound Management.

Chronic wounds are a major healthcare issue and can adversely affect the lives of millions of patients around the world. The current wound management strategies have limited clinical efficacy due to labor-intensive lab analysis requirements, need for clinicians' experiences, long-term and frequent interventions, limiting therapeutic efficiency and applicability. The growing field of flexible bioelectronics enables a great potential for personalized wound care owing to its advantages such as wearability, low-cost, and rapid and simple application. Herein, recent advances in the development of wearable bioelectronics for monitoring and management of chronic wounds are comprehensively reviewed. First, the design principles and the key features of bioelectronics that can adapt to the unique wound milieu features are introduced. Next, the current state of wound biosensors and on-demand therapeutic systems are summarized and highlighted. Furthermore, we discuss the design criteria of the integrated closed loop devices. Finally, the future perspectives and challenges in wearable bioelectronics for wound care are discussed.

Engineering a naturally derived hemostatic sealant for sealing internal organs.

Controlling bleeding from a raptured tissue, especially during the surgeries, is essentially important. Particularly for soft and dynamic internal organs where use of sutures, staples, or wires is limited, treatments with hemostatic adhesives have proven to be beneficial. However, major drawbacks with clinically used hemostats include lack of adhesion to wet tissue and poor mechanics. In view of these, herein, we engineered a double-crosslinked sealant which showed excellent hemostasis (comparable to existing commercial hemostat) without compromising its wet tissue adhesion. Mechanistically, the engineered hydrogel controlled the bleeding through its wound-sealing capability and inherent chemical activity. This mussel-inspired hemostatic adhesive hydrogel, named gelatin methacryloyl-catechol (GelMAC), contained covalently functionalized catechol and methacrylate moieties and showed excellent biocompatibility both in vitro and in vivo. Hemostatic property of GelMAC hydrogel was initially demonstrated with an in vitro blood clotting assay, which showed significantly reduced clotting time compared to the clinically used hemostat, Surgicel®. This was further assessed with an in vivo liver bleeding test in rats where GelMAC hydrogel closed the incision rapidly and initiated blood coagulation even faster than Surgicel®. The engineered GelMAC hydrogel-based seaalant with excellent hemostatic property and tissue adhesion can be utilized for controlling bleeding and sealing of soft internal organs.

Development and characterization of a hydrogel-based adhesive patch for sealing open-globe injuries.

Full-thickness wounds to the eye can lead to serious vision impairment. Current standards of care (from suturing to tissue transplantation) usually require highly skilled surgeons and use of an operating theater. In this study, we report the synthesis, optimization, and in vitro and ex vivo testing of photocrosslinkable hydrogel-based adhesive patches that can easily be applied to globe injuries or corneal incisions. According to the type and concentration of polymers used in the adhesive formulations, we were able to finely tune the physical properties of the bioadhesive including viscosity, elastic modulus, extensibility, ultimate tensile strength, adhesion, transparency, water content, degradation time, and swellability. Our in vitro studies showed no sign of cytotoxicity of the hydrogels. Moreover, the hydrogel patches showed higher adhesion on freshly explanted pig eyeballs compared to a marketed ocular sealant. Finally, ex vivo feasibility studies showed that the hydrogel patches could seal complex open-globe injuries such as large incision, cruciform injury, and injury associated with tissue loss. These results suggest that our photocrosslinkable hydrogel patch could represent a promising solution for the sealing of open-globe injuries or surgical incisions. STATEMENT OF SIGNIFICANCE: Current management of severe ocular injuries require advanced surgical skills and access to an operating theater. To address the need for emergent management of wounds that cannot be handled in the operating room, surgical adhesives have gained popularity, but none of the currently available adhesives have optimal bioavailability, adhesive or mechanical properties. This study describes the development, optimization and testing of a light-sensitive adhesive patch that can easily be applied to the eye. After solidification using visible light, the patch shows no toxicity and is more adherent to the tissue than a marketed sealant. Thus this technology could represent a promising solution to stabilize ocular injuries in emergency settings before definitive surgical repair.

Growth factor-eluting hydrogels for management of corneal defects.

With 1.5-2.0 million new cases annually worldwide, corneal injury represents a common cause of vision loss, often from irreversible scarring due to surface corneal defects. In this study, we assessed the use of hepatocyte growth factor (HGF) loaded into an in situ photopolymerizable transparent gelatin-based hydrogel for the management of corneal defects. In vitro release kinetics showed that, in regard to the total amount of HGF released over a month, 55 ± 11% was released during the first 24 h, followed by a slow release profile for up to one month. The effect of HGF was assessed using an ex vivo model of pig corneal defect. After three days of organ culture, epithelial defects were found to be completely healed for 89% of the corneas treated with HGF, compared to only 11% of the corneas that had fully re-epithelialized when treated with the hydrogel without HGF. The thickness of the epithelial layer was found to be significantly higher for the HGF-treated group compared to the group treated with hydrogel without HGF (p = 0.0012). Finally, histological and immunostaining assessments demonstrated a better stratification and adhesion of the epithelial layer in the presence of HGF. These results suggest that the HGF-loaded hydrogel system represents a promising solution for the treatment of persistent corneal defects at risk of scarring.

Nanoengineered shear-thinning and bioprintable hydrogel as a versatile platform for biomedical applications.

The development of bioinks based on shear-thinning and self-healing hydrogels has recently attracted significant attention for constructing complex three-dimensional physiological microenvironments. For extrusion-based bioprinting, it is challenging to provide high structural reliability and resolution of printed structures while protecting cells from shear forces during printing. Herein, we present shear-thinning and printable hydrogels based on silicate nanomaterials, laponite (LA), and glycosaminoglycan nanoparticles (GAGNPs) for bioprinting applications. Nanocomposite hydrogels (GLgels) were rapidly formed within seconds due to the interactions between the negatively charged groups of GAGNPs and the edges of LA. The shear-thinning behavior of the hydrogel protected encapsulated cells from aggressive shear stresses during bioprinting. The bioinks could be printed straightforwardly into shape-persistent and free-standing structures with high aspect ratios. Rheological studies demonstrated fast recovery of GLgels over multiple strain cycles. In vitro studies confirmed the ability of GLgels to support cell growth, proliferation, and spreading. In vitro osteogenic differentiation of pre-osteoblasts murine bone marrow stromal cells encapsulated inside the GLgels was also demonstrated through evaluation of ALP activity and calcium deposition. The subcutaneous implantation of the GLgel in rats confirmed its in vivo biocompatibility and biodegradability. The engineered shear-thinning hydrogel with osteoinductive characteristics can be used as a new bioink for 3D printing of constructs for bone tissue engineering applications.

Human-Recombinant-Elastin-Based Bioinks for 3D Bioprinting of Vascularized Soft Tissues.

Bioprinting has emerged as an advanced method for fabricating complex 3D tissues. Despite the tremendous potential of 3D bioprinting, there are several drawbacks of current bioinks and printing methodologies that limit  the ability to print elastic and highly vascularized tissues. In particular, fabrication of complex biomimetic structure that are entirely based on 3D bioprinting is still challenging primarily due to the lack of suitable bioinks with high printability, biocompatibility, biomimicry, and proper mechanical properties. To address these shortcomings, in this work the use of recombinant human tropoelastin as a highly biocompatible and elastic bioink for 3D printing of complex soft tissues is demonstrated. As proof of the concept, vascularized cardiac constructs are bioprinted and their functions are assessed in vitro and in vivo. The printed constructs demonstrate endothelium barrier function and spontaneous beating of cardiac muscle cells, which are important functions of cardiac tissue in vivo. Furthermore, the printed construct elicits minimal inflammatory responses, and is shown to be efficiently biodegraded in vivo when implanted subcutaneously in rats. Taken together, these results demonstrate the potential of the elastic bioink for printing 3D functional cardiac tissues, which can eventually be used for cardiac tissue replacement.

Effects, uptake, and translocation of aluminum oxide nanoparticles in lettuce: A comparison study to phytotoxic aluminum ions.

The widespread use of aluminum oxide nanoparticles (Al2O3 NPs) unavoidably causes the release of NPs into the environment, potentially having unforeseen consequences for biological processes. Due to the well-known issue of Al phytoxicity, plant interactions with Al2O3 NPs are cause for concern, but these interactions remain poorly understood. This study investigated the effects of Al2O3 NPs on lettuce (Lactuca sativa L.) to elucidate the similarities and differences in plant growth responses when compared to those of Al ions. Seed germination, root length, biomass production, and uptake of Al and nutrients were measured from hydroponically-grown lettuce with varying concentrations of Al2O3 NPs (0, 0.4, 1, and 2 mg/mL) or AlCl3 (0, 0.04, 0.4, and 1 mg/mL). The Al2O3 NPs treatments had a positive influence on root elongation, whereas AlCl3 significantly reduced emerging root lengths. While 0.4 mg/mL Al2O3 NPs promoted biomass, 1 and 2 mg/mL showed a 10.4% and 17.9% decrease in biomass, respectively, when compared to the control. Similarly, 0.4 and 1 mg/mL AlCl3 reduced biomass to 22.3% and 9.96%, respectively. Both treatments increased Al uptake by roots linearly; however, translocation of Al2O3 NPs into shoots was limited, whereas translocation of AlCl3 increased with increasing treatment concentration. Further, Al2O3 NPs adsorbed on the roots serve as adsorbents for macronutrients, promoting their absorption and uptake in plants, but not micronutrients. Calcium uptake was the most inhibited by AlCl3. A new in vivo imaging technique, with elemental analysis, confirmed that Al2O3 NPs were assimilated as particles, not ions, suggesting that the observed phytotoxicity is not due to Al ions being released from the NPs. Thus, it is concluded that Al2O3 NPs pose less phytoxicity than AlCl3, primarily due to NPs role on stimulated root growth, significant adsorption/aggregation on roots, limited lateral translocation to shoots, and increased uptake of macronutrients.

Bioactive and Elastic Nanocomposites with Antimicrobial Properties for Bone Tissue Regeneration.

Bone injuries represent a major challenge in the medical field. The commonly used treatments for bone regeneration rely on the use of bone grafts that are usually associated with complications such as donor site morbidity, disease transmission, high cost, and lack of availability. Bone tissue engineering has become a golden solution for the repair of bone injuries by regenerating the damaged biological tissues using biocompatible scaffolds. However, most of the tissue engineered scaffolds do not possess the combined properties of high elasticity, appropriate stiffness, biocompatibility, osteoinductivity, and antimicrobial properties. In this study, we engineered bioactive and antimicrobial nanocomposites that can promote bone formation while simultaneously provide a barrier against bacterial infections commonly associated with bone implants. We used PEGylated polyglycerol sebacate as nanocomposites base, which was functionalized with Laponite nanosilicates, a synthetic nanoclay, and an antimicrobial peptide (AMP). The successful synthesis of the PEGylated polyglycerol sebacate and Laponite incorporation within the nanocomposites were confirmed through nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR). The scaffolds had an elastic modulus and ultimate tensile strength within a range of 3.8-4.7 MPa and 1.5-3 MPa, respectively. Furthermore, the scaffolds loaded with antimicrobial peptide exhibited a significant antimicrobial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. The in vitro cytocompatibility tests showed >90% viability of preosteoblast (W-20-17) cells. Moreover, in vitro differentiation assays demonstrated the scaffolds' ability to promote osteogenic differentiation of W-20-17. Collectively, the nanocomposites containing Laponite and antimicrobial peptide were proven to have osteoinductive and antimicrobial activity, making them desirable for bone tissue engineering applications.

An Antimicrobial Dental Light Curable Bioadhesive Hydrogel for Treatment of Peri-Implant Diseases.

Dental implants constitute the standard of care to replace the missing teeth, which has led to an increase in the number of patients affected by peri-implant diseases (PIDs). Here, we report the development of an antimicrobial bioadhesive, GelAMP, for the treatment of PIDs. The hydrogel is based on a visible light-activated naturally-derived polymer (gelatin) and an antimicrobial peptide (AMP). The optimized formulation of GelAMP could be rapidly crosslinked using commercial dental curing systems. When compared to commercial adhesives, the bioadhesives exhibited significantly higher adhesive strength to physiological tissues and titanium. Moreover, the bioadhesive showed high cytocompatibility and could efficiently promote cell proliferation and migration in vitro. GelAMP also showed remarkable antimicrobial activity against Porphyromonas gingivalis. Furthermore, it could support the growth of autologous bone after sealing calvarial bone defects in mice. Overall, GelAMP could be used as a platform for the development of more effective therapeutics against PIDs.

Engineering a naturally-derived adhesive and conductive cardiopatch.

Myocardial infarction (MI) leads to a multi-phase reparative process at the site of damaged heart that ultimately results in the formation of non-conductive fibrous scar tissue. Despite the widespread use of electroconductive biomaterials to increase the physiological relevance of bioengineered cardiac tissues in vitro, there are still several limitations associated with engineering biocompatible scaffolds with appropriate mechanical properties and electroconductivity for cardiac tissue regeneration. Here, we introduce highly adhesive fibrous scaffolds engineered by electrospinning of gelatin methacryloyl (GelMA) followed by the conjugation of a choline-based bio-ionic liquid (Bio-IL) to develop conductive and adhesive cardiopatches. These GelMA/Bio-IL adhesive patches were optimized to exhibit mechanical and conductive properties similar to the native myocardium. Furthermore, the engineered patches strongly adhered to murine myocardium due to the formation of ionic bonding between the Bio-IL and native tissue, eliminating the need for suturing. Co-cultures of primary cardiomyocytes and cardiac fibroblasts grown on GelMA/Bio-IL patches exhibited comparatively better contractile profiles compared to pristine GelMA controls, as demonstrated by over-expression of the gap junction protein connexin 43. These cardiopatches could be used to provide mechanical support and restore electromechanical coupling at the site of MI to minimize cardiac remodeling and preserve normal cardiac function.

Engineering a highly elastic human protein-based sealant for surgical applications.

Surgical sealants have been used for sealing or reconnecting ruptured tissues but often have low adhesion, inappropriate mechanical strength, cytotoxicity concerns, and poor performance in biological environments. To address these challenges, we engineered a biocompatible and highly elastic hydrogel sealant with tunable adhesion properties by photocrosslinking the recombinant human protein tropoelastin. The subcutaneous implantation of the methacryloyl-substituted tropoelastin (MeTro) sealant in rodents demonstrated low toxicity and controlled degradation. All animals survived surgical procedures with adequate blood circulation by using MeTro in an incisional model of artery sealing in rats, and animals showed normal breathing and lung function in a model of surgically induced rat lung leakage. In vivo experiments in a porcine model demonstrated complete sealing of severely leaking lung tissue in the absence of sutures or staples, with no clinical or sonographic signs of pneumothorax during 14 days of follow-up. The engineered MeTro sealant has high potential for clinical applications because of superior adhesion and mechanical properties compared to commercially available sealants, as well as opportunity for further optimization of the degradation rate to fit desired surgical applications on different tissues.

A highly adhesive and naturally derived sealant.

Conventional surgical techniques to seal and repair defects in highly stressed elastic tissues are insufficient. Therefore, this study aimed to engineer an inexpensive, highly adhesive, biocompatible, and biodegradable sealant based on a modified and naturally derived biopolymer, gelatin methacryloyl (GelMA). We tuned the degree of gelatin modification, prepolymer concentration, photoinitiator concentration, and crosslinking conditions to optimize the physical properties and adhesion of the photocrosslinked GelMA sealants. Following ASTM standard tests that target wound closure strength, shear resistance, and burst pressure, GelMA sealant was shown to exhibit adhesive properties that were superior to clinically used fibrin- and poly(ethylene glycol)-based glues. Chronic in vivo experiments in small as well as translational large animal models proved GelMA to effectively seal large lung leakages without the need for sutures or staples, presenting improved performance as compared to fibrin glue, poly(ethylene glycol) glue and sutures only. Furthermore, high biocompatibility of GelMA sealant was observed, as evidenced by a low inflammatory host response and fast in vivo degradation while allowing for adequate wound healing at the same time. Combining these results with the low costs, ease of synthesis and application of the material, GelMA sealant is envisioned to be commercialized not only as a sealant to stop air leakages, but also as a biocompatible and biodegradable hydrogel to support lung tissue regeneration.