Bacterial spores respond to humidity similarly to hydrogels.

Bacterial spores have outstanding properties from the materials science perspective, which allow them to survive extreme environmental conditions. Recent work by [S. G. Harrellson et al., Nature 619, 500-505 (2023)] studied the mechanical properties of Bacillus subtilis spores and the evolution of these properties with the change of humidity. The experimental measurements were interpreted assuming that the spores behave as water-filled porous solids, subjected to hydration forces. Here, we revisit their experimental data using literature data on vapor sorption on spores and ideas from polymer physics. We demonstrate that upon the change of humidity, the spores behave like rubber with respect to their swelling, elasticity, and relaxation times. This picture is consistent with the knowledge of the materials comprising the bacterial cell walls-cross-linked peptidoglycan. Our results provide an interpretation of the mechanics of bacterial spores and can help in developing synthetic materials mimicking the mechanical properties of the spores.

LRRC8/VRAC volume-regulated anion channels are crucial for hearing.

Hearing crucially depends on cochlear ion homeostasis as evident from deafness elicited by mutations in various genes encoding cation or anion channels and transporters. Ablation of ClC­K/barttin chloride channels causes deafness by interfering with the positive electrical potential of the endolymph, but roles of other anion channels in the inner ear have not been studied. Here we report the intracochlear distribution of all five LRRC8 subunits of VRAC, a volume-regulated anion channel that transports chloride, metabolites, and drugs such as the ototoxic anti-cancer drug cisplatin, and explore its physiological role by ablating its subunits. Sensory hair cells express all LRRC8 isoforms, whereas only LRRC8A, D and E were found in the potassium-secreting epithelium of the stria vascularis. Cochlear disruption of the essential LRRC8A subunit, or combined ablation of LRRC8D and E, resulted in cochlear degeneration and congenital deafness of Lrrc8a-/- mice. It was associated with a progressive degeneration of the organ of Corti and its innervating spiral ganglion. Like disruption of ClC-K/barttin, loss of VRAC severely reduced the endocochlear potential. However, the mechanism underlying this reduction seems different. Disruption of VRAC, but not ClC-K/barttin, led to an almost complete loss of Kir4.1 (KCNJ10), a strial K+ channel crucial for the generation of the endocochlear potential. The strong downregulation of Kir4.1 might be secondary to a loss of VRAC-mediated transport of metabolites regulating inner ear redox potential such as glutathione. Our study extends the knowledge of the role of cochlear ion transport in hearing and ototoxicity.

Glycosaminoglycans modulate long-range mechanical communication between cells in collagen networks.

Cells can sense and respond to mechanical forces in fibrous extracellular matrices (ECMs) over distances much greater than their size. This phenomenon, termed long-range force transmission, is enabled by the realignment (buckling) of collagen fibers along directions where the forces are tensile (compressive). However, whether other key structural components of the ECM, in particular glycosaminoglycans (GAGs), can affect the efficiency of cellular force transmission remains unclear. Here we developed a theoretical model of force transmission in collagen networks with interpenetrating GAGs, capturing the competition between tension-driven collagen fiber alignment and the swelling pressure induced by GAGs. Using this model, we show that the swelling pressure provided by GAGs increases the stiffness of the collagen network by stretching the fibers in an isotropic manner. We found that the GAG-induced swelling pressure can help collagen fibers resist buckling as the cells exert contractile forces. This mechanism impedes the alignment of collagen fibers and decreases long-range cellular mechanical communication. We experimentally validated the theoretical predictions by comparing the intensity of collagen fiber alignment between cellular spheroids cultured on collagen gels versus collagen­GAG cogels. We found significantly lower intensities of aligned collagen in collagen­GAG cogels, consistent with the prediction that GAGs can prevent collagen fiber alignment. The role of GAGs in modulating force transmission uncovered in this work can be extended to understand pathological processes such as the formation of fibrotic scars and cancer metastasis, where cells communicate in the presence of abnormally high concentrations of GAGs.

Mechanism of temperature-induced asymmetric swelling and shrinking kinetics in self-healing hydrogels.

Understanding the physical principle that governs the stimuli-induced swelling and shrinking kinetics of hydrogels is indispensable for their applications. Here, we show that the shrinking and swelling kinetics of self-healing hydrogels could be intrinsically asymmetric. The structure frustration, formed by the large difference in the heat and solvent diffusions, remarkably slows down the shrinking kinetics. The plateau modulus of viscoelastic gels is found to be a key parameter governing the formation of structure frustration and, in turn, the asymmetric swelling and shrinking kinetics. This work provides fundamental understandings on the temperature-triggered transient structure formation in self-healing hydrogels. Our findings will find broad use in diverse applications of self-healing hydrogels, where cooperative diffusion of water and gel network is involved. Our findings should also give insight into the molecular diffusion in biological systems that possess macromolecular crowding environments similar to self-healing hydrogels.

NKCC1 inhibition reduces periaxonal swelling, increases white matter sparing, and improves neurological recovery after contusive SCI.

Ultrastructural studies of contusive spinal cord injury (SCI) in mammals have shown that the most prominent acute changes in white matter are periaxonal swelling and separation of myelin away from their axon, axonal swelling, and axonal spheroid formation. However, the underlying cellular and molecular mechanisms that cause periaxonal swelling and the functional consequences are poorly understood. We hypothesized that periaxonal swelling and loss of connectivity between the axo-myelinic interface impedes neurological recovery by disrupting conduction velocity, and glial to axonal trophic support resulting in axonal swelling and spheroid formation. Utilizing in vivo longitudinal imaging of Thy1YFP+ axons and myelin labeled with Nile red, we reveal that periaxonal swelling significantly increases acutely following a contusive SCI (T13, 30 kdyn, IH Impactor) versus baseline recordings (laminectomy only) and often precedes axonal spheroid formation. In addition, using longitudinal imaging to determine the fate of myelinated fibers acutely after SCI, we show that ∼73% of myelinated fibers present with periaxonal swelling at 1 h post SCI and âˆ¼ 51% of those fibers transition to axonal spheroids by 4 h post SCI. Next, we assessed whether cation-chloride cotransporters present within the internode contributed to periaxonal swelling and whether their modulation would increase white matter sparing and improve neurological recovery following a moderate contusive SCI (T9, 50 kdyn). Mechanistically, activation of the cation-chloride cotransporter KCC2 did not improve neurological recovery and acute axonal survival, but did improve chronic tissue sparing. In distinction, the NKKC1 antagonist bumetanide improved neurological recovery, tissue sparing, and axonal survival, in part through preventing periaxonal swelling and disruption of the axo-myelinic interface. Collectively, these data reveal a novel neuroprotective target to prevent periaxonal swelling and improve neurological recovery after SCI.

Methylene blue dose-dependently induces cutaneous inflammation and heat hyperalgesia in a novel rat model.

Methylene blue (MB) has been shown to reduce mortality and morbidity in vasoplegic patients after cardiac surgery. Though MB is considered to be safe, extravasation of MB leading to cutaneous toxicity has been reported. In this study, we sought to characterize MB-induced cutaneous toxicity and investigate the underlying mechanisms. To induce MB-induced cutaneous toxicity, we injected 64 adult male Sprague-Dawley rates with 200 µL saline (vehicle) or 1%, 0.1%, or 0.01% MB in the plantar hind paws. Paw swelling, skin histologic changes, and heat and mechanical hyperalgesia were measured. Injection of 1%, but not 0.1% or 0.01% MB, produced significant paw swelling compared to saline. Injection of 1% MB produced heat hyperalgesia but not mechanical hyperalgesia. Pain behaviors were unchanged following injections of 0.1% or 0.01% MB. Global transcriptomic analysis by RNAseq identified 117 differentially expressed genes (111 upregulated, 6 downregulated). Ingenuity Pathway Analysis showed an increased quantity of leukocytes, increased lipids, and decreased apoptosis of myeloid cells and phagocytes with activation of IL-1ß and Fos as the two major regulatory hubs. qPCR showed a 16-fold increase in IL-6 mRNA. Thus, using a novel rat model of MB-induced cutaneous toxicity, we show that infiltration of 1% MB into cutaneous tissue causes a dose-dependent pro-inflammatory response, highlighting potential roles of IL-6, IL-1ß, and Fos. Thus, anesthesiologists should administer dilute MB intravenously through peripheral venous catheters. Higher concentrations of MB (1%) should be administered through a central venous catheter to minimize the risk of cutaneous toxicity.

A Protein-Adsorbent Hydrogel with Tunable Stiffness for Tissue Culture Demonstrates Matrix-Dependent Stiffness Responses.

Although tissue culture plastic has been widely employed for cell culture, the rigidity of plastic is not physiologic. Softer hydrogels used to culture cells have not been widely adopted in part because coupling chemistries are required to covalently capture extracellular matrix (ECM) proteins and support cell adhesion. To create an in vitro system with tunable stiffnesses that readily adsorbs ECM proteins for cell culture, we present a novel hydrophobic hydrogel system via chemically converting hydroxyl residues on the dextran backbone to methacrylate groups, thereby transforming non-protein adhesive, hydrophilic dextran to highly protein adsorbent substrates. Increasing methacrylate functionality increases the hydrophobicity in the resulting hydrogels and enhances ECM protein adsorption without additional chemical reactions. These hydrophobic hydrogels permit facile and tunable modulation of substrate stiffness independent of hydrophobicity or ECM coatings. Using this approach, we show that substrate stiffness and ECM adsorption work together to affect cell morphology and proliferation, but the strengths of these effects vary in different cell types. Furthermore, we reveal that stiffness mediated differentiation of dermal fibroblasts into myofibroblasts is modulated by the substrate ECM. Our material system demonstrates remarkable simplicity and flexibility to tune ECM coatings and substrate stiffness and study their effects on cell function.

Network of Inorganic Nanocrystals Can Swell: Study of Swelling-Induced Surface Instability.

A unique organic-inorganic hybrid network composed of inorganic nanocores (ranging from semiconductors to metallic ones) interconnected through organic molecules can be produced by crosslinking the organic ligands of colloidal inorganic nanocrystals in assemblies. This work reports that this network, which is conventionally considered an inorganic film, can swell when exposed to a solvent because of the interaction between the solvent and the organic linkage within the network. Intriguingly, this work discovers that drying the solvent of the swollen organic-inorganic hybrid network can significantly affect the morphology owing to the swelling-induced compress stress, which is widely observed in various organic network systems. This work studies the surface instability of crosslinked organic-inorganic hybrid networks swollen by various organic solvents, which led to buckling delamination. Specifically, this work investigates the effects of the i) solvent-network interaction, ii) crosslinking density of the network, and iii) thickness of the film on the delamination behavior of the crosslinked network.

Reversible Electrochemical Swelling of Straight Carbon Nanotube Yarns for High-Performance Linear Actuation.

Coiled artificial muscle yarns outperform their straight counterparts in contractile strokes. However, challenges persist in the fabrication complexity and the susceptibility of the coiled yarns to becoming stuck by surrounding objects during contraction and recovery. Additionally, torsional stability remains a concern. In this study, it is reported that straight carbon nanotube (CNT) yarns when driven by a low-voltage electrochemical approach, can achieve a contractile stroke that surpasses even NiTi shape memory alloy fibers. The key lies in the suitable match between a yarn consisting of randomly aligned CNTs and the reversible and substantial electrochemical swelling induced by solvated ions. Wrinkled structures are formed on the surface of the CNT yarn to adapt to the swelling process. This not only assures torsional stability but also enhances the surface area for improved electrode-electrolyte interaction during electrochemical actuation. Remarkably, the CNT artificial muscle yarn generates a contractile stroke of 8.8% and an isometric stress of 7.5 MPa under 2.5 V actuation voltages, demonstrating its potential for applications requiring low energy consumption while maintaining high operational efficiency. This study highlights the crucial impact of CNT orientation on the effectiveness of electrochemically-driven artificial muscles, signaling new possibilities in smart material and biomechanical system development.

Lightweight, Strong, and Transparent Wood Films Produced by Capillary Driven Self-Densification.

Wood delignification and densification enable the production of high strength and/or transparent wood materials with exceptional properties. However, processing needs to be more sustainable and besides the chemical delignification treatments, energy intense hot-pressing calls for alternative approaches. Here, this study shows that additional softening of delignified wood via a mild swelling process using an ionic liquid-water mixture enables the densification of tube-line wood cells into layer-by-layer sheet structures without hot-pressing. The natural capillary force induces self-densification in a simple drying process resulting in a transparent wood film. The as-prepared films with ≈150 µm thickness possess an optical transmittance ≈70%, while maintaining optical haze >95%. Due to the densely packed sheet structure with a large interfacial area, the reassembled wood film is fivefold stronger and stiffer than the delignified wood in fiber direction. Owing to a low density, the specific tensile strength and elastic modulus are as high as 282 MPa cm3 g-1 and 31 GPa cm3 g-1. A facile and highly energy efficient wood nanotechnology approach are demonstrated toward more sustainable materials and processes by directly converting delignified wood into transparent wood omitting polymeric matrix infiltration or mechanical pressing.

Wearable and Recyclable Water-Toleration Sensor Derived from Lipoic Acid.

Flexible wearable sensors recently have made significant progress in human motion detection and health monitoring. However, most sensors still face challenges in terms of single detection targets, single application environments, and non-recyclability. Lipoic acid (LA) shows a great application prospect in soft materials due to its unique properties. Herein, ionic conducting elastomers (ICEs) based on polymerizable deep eutectic solvents consisting of LA and choline chloride are prepared. In addition to the good mechanical strength, high transparency, ionic conductivity, and self-healing efficiency, the ICEs exhibit swelling-strengthening behavior and enhanced adhesion strength in underwater environments due to the moisture-induced association of poly(LA) hydrophobic chains, thus making it possible for underwater sensing applications, such as underwater communication. As a strain sensor, it exhibits highly sensitive strain response with repeatability and durability, enabling the monitoring of both large and fine human motions, including joint movements, facial expressions, and pulse waves. Furthermore, due to the enhancement of ion mobility at higher temperatures, it also possesses excellent temperature-sensing performance. Notably, the ICEs can be fully recycled and reused as a new strain/temperature sensor through heating. This study provides a novel strategy for enhancing the mechanical strength of poly(LA) and the fabrication of multifunctional sensors.

The Role of the Swollen State in Cell Proliferation.

Cell swelling is known to be involved in various stages of the growth of plant cells and microorganisms but in mammalian cells how crucial a swollen state is for determining the fate of the cellular proliferation remains unclear. Recent evidence has increased our understanding of how the loss of the cell surface interactions with the extracellular matrix at early mitosis decreases the membrane tension triggering curvature changes in the plasma membrane and the activation of the sodium/hydrogen (Na +/H +) exchanger (NHE1) that drives osmotic swelling. Such a swollen state is temporary, but it is critical to alter essential membrane biophysical parameters that are required to activate Ca2 + channels and modulate the opening of K + channels involved in setting the membrane potential. A decreased membrane potential across the mitotic cell membrane enhances the clustering of Ras proteins involved in the Ca2 + and cytoskeleton-driven events that lead to cell rounding. Changes in the external mechanical and osmotic forces also have an impact on the lipid composition of the plasma membrane during mitosis.

The tuber-specific StbHLH93 gene regulates proplastid-to-amyloplast development during stolon swelling in potato.

In potato, stolon swelling is a complex and highly regulated process, and much more work is needed to fully understand the underlying mechanisms. We identified a novel tuber-specific basic helix-loop-helix (bHLH) transcription factor, StbHLH93, based on the high-resolution transcriptome of potato tuber development. StbHLH93 is predominantly expressed in the subapical and perimedullary region of the stolon and developing tubers. Knockdown of StbHLH93 significantly decreased tuber number and size, resulting from suppression of stolon swelling. Furthermore, we found that StbHLH93 directly binds to the plastid protein import system gene TIC56 promoter, activates its expression, and is involved in proplastid-to-amyloplast development during the stolon-to-tuber transition. Knockdown of the target TIC56 gene resulted in similarly problematic amyloplast biogenesis and tuberization. Taken together, StbHLH93 functions in the differentiation of proplastids to regulate stolon swelling. This study highlights the critical role of proplastid-to-amyloplast interconversion during potato tuberization.

Stem Growth and Dehydration Responses of Mediterranean Tree Species to Atmospheric and Soil Drought.

Stem growth responses to soil and atmospheric drought are critical to forecasting the tree carbon sink strength. Yet, responses of drought-prone forests remain uncertain despite global aridification trends. Stem diameter variations at an hourly resolution were monitored in five Mediterranean tree species from a mesic and a xeric site for 6 and 12 years. Stem growth and dehydration responses to soil (REW) and atmospheric (VPD) drought were explored at different timescales. Annually, growth was determined by the number of growing days and hours. Seasonally, growth was bimodal (autumn growth ≈ 8%-18% of annual growth), varying among species and sites across the hydrometeorological space, while dehydration consistently responded to REW. Sub-daily, substantial growth occurred during daytime, with nighttime-to-daytime ratios ranging between 1.2 and 3.5 (Arbutus unedo ≈ Quercus faginea < Quercus ilex < Pinus halepensis in the mesic site, and Juniperus thurifera < P. halepensis in the xeric site). Overall, time windows favourable for growth were limited by soil (rather than atmospheric) drought, modulating annual and seasonal growth in Mediterranean species, and stems maintained non-negligible growth during daytime. These patterns contrast with observations from wetter or cooler biomes, demonstrating the growth plasticity of drought-prone species to more arid climate conditions.

Dual-Responsive Gradient Structured Actuator via Photopolymerization-Induced Diffusion.

Stimuli-responsive materials have recently gained significant attention in the field of soft robotics, sensors, and biomimetic devices. The most facile way for the fabrication of such materials remains to endow bilayer structures which are fabricated with the combination of active and passive layers. Although, easily fabricated, these structures suffer from the generation of stress points between connection areas. In this work we develop a method to create a thin film with controlled cross-link variation across its thickness. The cross-link gradient is achieved through polymerization induced diffusion of dithiol molecules in thiol-ene network. As a result, the film exhibits bending deformation upon illumination with light or exposure to a chemical solvent, thereby demonstrating dual responsiveness. Light actuation of the film is achieved via photothermal effects due to the incorporation of dye into the system which can absorb UV light and heat the network. While solvent induced actuation is due to anisotropic swelling. Furthermore, the straightforward fabrication procedure allows for the creation of more complex deformations by patterning the film using a photomask during photopolymerization.

Comparison of Structural, Water-Retaining and Sorption Properties of Acrylamide-Based Hydrogels Cross-Linked by Physical and Chemical Methods.

Two series of hydrogels based on acrylamide and its copolymers with acrylonitrile and acrylic acid were synthesized by two cross-linking methods - chemical (using N,N'-methylene bis-acrylamide) and physical (using montmorillonite (MMT)) ones. The structure of the gels was characterized by Fourier Transform Infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The swelling and sorption properties were analyzed as a function of both the monomer composition and the cross-linking method. The shift of the band corresponding to Si-O (995-1030 cm-1 ) confirmed the formation of intercalation structures for MMT-cross-linked gels. Moreover, physically cross-linked gels demonstrated a non-monotonic dependence of the swelling degree on the MMT concentration, and acrylamide-acrylic acid copolymer MMT-cross-linked gels showed pH sensitivity and the highest swelling degree of 150 g/g. The highest sorption capacity towards cadmium(II) ions was demonstrated by acrylamide-acrylic acid copolymer gels, both covalently cross-linked (30 mg/g) and MMT-cross-linked (8.9 mg/g).

Identification of corneal and intra-epidermal axonal swellings in amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: In patients with amyotrophic lateral sclerosis (ALS), axonal spheroids in motor axons have been identified in post-mortem studies. In this study, axonal spheroids and swellings on C-fibers of ALS patients were investigated using corneal confocal microscopy (CCM) and skin biopsy, respectively. METHODS: Thirty-one ALS patients and 20 healthy subjects were evaluated with CCM to assess corneal nerve-fiber length (CNFL), -fiber density (CNFD), -branch density (CNBD), dendritic cell (DC) density, and axonal spheroids originating from C-fibers (>100 µm2 ). In addition, intraepidermal nerve fiber density (IENFD) and axonal swellings (>1.5 µm) were assessed in skin biopsies obtained from the arms and legs of 22 patients and 17 controls. RESULTS: In ALS patients, IENFD, CNFD, CNFL, and CNBD were not different from controls. The density of DCs and the number of patients with increased DC density were higher in ALS patients than controls (p = .0005 and p = .008). The number of patients with axonal spheroids was higher than controls (p = .03). DISCUSSION: Evaluation of DCs and axonal bulbs in C-fibers of ALS patients could provide insights into pathophysiology or potentially serve as biomarkers in ALS.

Sonochemical synthesis of bioinspired graphene oxide-zinc oxide hydrogel for antibacterial painting on biodegradable polylactide film.

Graphene oxide nanosheet (GO) is a multifunctional platform for binding with nanoparticles and stacking with two dimensional substrates. In this study, GO nanosheets were sonochemically decorated with zinc oxide nanoparticles (ZnO) and self-assembled into a hydrogel of GO-ZnO nanocomposite. The GO-ZnO hydrogel structure is a bioinspired approach for preserving graphene-based nanosheets from van der Waals stacking. X-ray diffraction analysis (XRD) showed that the sonochemical synthesis led to the formation of ZnO crystals on GO platforms. High water content (97.2%) of GO-ZnO hydrogel provided good property of ultrasonic dispersibility in water. Ultraviolet-visible spectroscopic analysis (UV-vis) revealed that optical band gap energy of ZnO nanoparticles (∼3.2 eV) GO-ZnO nanosheets (∼2.83 eV). Agar well diffusion tests presented effective antibacterial activities of GO-ZnO hydrogel against gram-negative bacteria (E. coli) and gram-positive bacteria (S. aureus). Especially, GO-ZnO hydrogel was directly used for brush painting on biodegradable polylactide (PLA) thin films. Graphene-based nanosheets with large surface area are key to van der Waals stacking and adhesion of GO-ZnO coating to the PLA substrate. The GO-ZnO/PLA films were characterized using photography, light transmittance spectroscopy, coating stability, scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopic mapping (EDS), antibacterial test and mechanical tensile measurement. Specifically, GO-ZnO coating on PLA substrate exhibited stability in aqueous food simulants for packaging application. GO-ZnO coating inhibited the infectious growth ofE. colibiofilm. GO-ZnO/PLA films had strong tensile strength and elastic modulus. As a result, the investigation of antibacterial GO-ZnO hydrogel and GO-ZnO coating on PLA film is fundamental for sustainable development of packaging and biomedical applications.

National survey of patient symptoms and therapies among 707 women with a lipedema phenotype in the United States.

BACKGROUND: National survey data exploring the patient experience with lipedema are lacking. METHODS: We conducted national surveys from 2016 to 2022 of women with lipedema as well as female controls. Surveys collected information on symptomatology, pain, and therapies. We performed logistic regression comparing symptoms among those with lipedema versus controls adjusting for age and BMI. RESULTS: A total of 707 women with lipedema and 216 controls completed the surveys. Those with lipedema had a mean age of 48.6 years and mean BMI of 40.9 kg/m2. Lipedema symptom onset occurred frequently at puberty (48.0%) or pregnancy (41.2%). Compared to controls, women with lipedema were more likely to report leg swelling in heat (odds ratio [OR], 66.82; 95% CI, 33.04-135.12; p < 0.0001), easy bruising (OR, 26.23; 95% CI, 15.58-44.17; p < 0.0001), altered gait (OR, 15.54; 95% CI, 7.58-31.96; p < 0.0001), flu-like symptoms (OR, 12.99; 95% CI, 4.27-39.49; p < 0.0001), joint hypermobility (OR, 12.88; 95% CI, 6.68-24.81; p < 0.0001), cool skin (OR, 12.21; 95% CI, 5.20-28.69; p < 0.0001), varicose veins (OR, 11.29; 95% CI, 6.71-18.99; p < 0.0001), and fatigue (OR, 9.59; 95% CI, 6.10-15.09; p < 0.0001). Additionally, 70.3% had upper arm involvement, 21.2% reported foot swelling, and 16.6% reported foot pain. Most (52.2%) reported no symptom improvement with diet or exercise. Common therapies used included compression therapy (45.0%), gastric bypass (15.7%), and lower-extremity liposuction (14.0%). CONCLUSION: In a large, national, symptom survey, women with lipedema reported excess pain, swelling, and fat in the legs along with numerous symptoms beyond those classically described. Symptom responses to common therapies remain understudied.

Advances in lymphedema: An under-recognized disease with a hopeful future for patients.

Lymphedema has traditionally been underappreciated by the healthcare community. Understanding of the underlying pathophysiology and treatments beyond compression have been limited until recently. Increased investigation has demonstrated the key role of inflammation and resultant fibrosis and adipose deposition leading to the clinical sequelae and associated reduction in quality of life with lymphedema. New imaging techniques including magnetic resonance imaging (MRI), indocyanine green lymphography, and high-frequency ultrasound offer improved resolution and understanding of lymphatic anatomy and flow. Nonsurgical therapy with compression, exercise, and weight loss remains the mainstay of therapy, but growing surgical options show promise. Physiologic procedures (lymphovenous anastomosis and vascularized lymph node transfers) improve lymphatic flow in the diseased limb and may reduce edema and the burden of compression. Debulking, primarily with liposuction to remove the adipose deposition that has accumulated, results in a dramatic decrease in limb girth in appropriately selected patients. Though early, there are also exciting developments of potential therapeutic targets tackling the underlying drivers of the disease. Multidisciplinary teams have developed to offer the full breadth of evaluation and current management, but the development of a greater understanding and availability of therapies is needed to ensure patients with lymphedema have greater opportunity for optimal care.