Local anesthetics (LAs) have been indispensable in clinical pain management, yet their limitations, such as short duration of action and systemic toxicity, necessitate improved delivery strategies. Hydrogels, with their biocompatibility, tunable properties, and ability to modulate drug release, have been extensively explored as platforms for enhancing LA efficacy and safety. This narrative review explores the historical development of LAs, their physicochemical properties, and clinical applications, providing a foundation for understanding the integration of hydrogels in anesthetic delivery. Advances in thermoresponsive, stimuli-responsive, and multifunctional hydrogels have demonstrated significant potential in prolonging analgesia and reducing systemic exposure in preclinical studies, while early clinical findings highlight the feasibility of thermoresponsive hydrogel formulations. Despite these advancements, challenges such as burst release, mechanical instability, and regulatory considerations remain critical barriers to clinical translation. Emerging innovations, including nanocomposite hydrogels, biofunctionalized matrices, and smart materials, offer potential solutions to these limitations. Future research should focus on optimizing hydrogel formulations, expanding clinical validation, and integrating advanced fabrication technologies such as 3D printing and artificial intelligence-driven design to enhance personalized pain management. By bridging materials science and anesthetic pharmacology, this review provides a comprehensive perspective on current trends and future directions in hydrogel-based LA delivery systems.

Multifunctional hydrogels represent an emerging technological advancement in cancer therapeutics, integrating diagnostic imaging capabilities with therapeutic modalities into comprehensive, multifunctional systems. These hydrogels exhibit exceptional biocompatibility, biodegradability, high water retention capacity, and tunable mechanical properties, enabling precise drug delivery while minimizing systemic side effects. Recent innovations in stimuli-responsive components facilitate intelligent, controlled drug release mechanisms triggered by various stimuli, including changes in pH, temperature, magnetic fields, and near-infrared irradiation. Incorporating diagnostic imaging agents, such as magnetic nanoparticles, fluorescent dyes, and radiolabeled isotopes, substantially improves tumor visualization and real-time therapeutic monitoring. Multifunctional hydrogels effectively integrate chemotherapy, photothermal therapy, photodynamic therapy, immunotherapy, and their synergistic combinations, demonstrating superior therapeutic outcomes compared to conventional methods. Particularly, injectable and in situ-forming hydrogels provide sustained local drug delivery postoperatively, effectively reducing tumor recurrence. However, challenges persist, including initial burst release, mechanical instability, regulatory barriers, and scalability concerns. Current research emphasizes advanced nanocomposite formulations, biofunctionalization strategies, and innovative manufacturing technologies like 3D bioprinting to facilitate clinical translation. This review comprehensively summarizes recent advancements, clinical applications, and future perspectives of multifunctional hydrogel systems for enhanced cancer treatment, underscoring their potential to revolutionize personalized oncology.

The aim of this study was to determine the role of myeloid monoamine oxidase A (Mao A) in diet-induced obesity (DIO). Ten-week-old male and female LysMCre^tg/tg (CTL) and LysMCre^tg/tgMaoA^fl/fl (Mao A_Myeloid^-/-) mice were fed a high-fat diet for 20 week. Male but not female mice with myeloid Mao A deficiency showed increased weight gain, increased visceral adipose tissue (AT) weight as well as elevated fasting blood glucose and leptin levels. However, both male and female Mao A_Myeloid^-/- mice showed increased insulin resistance of the AT and glucose intolerance. Mao A mRNA levels were reduced by 90% and 94% in bone marrow-derived macrophages (BMDM) from male and female Mao A_Myeloid^-/- mice, respectively, but neither Mao A mRNA expression nor protein levels or Mao A activity in AT were altered by myeloid Mao A deficiency. Targeted gene profiling of M_TNFα+IFNγ and M_IL-4-polarized BMDM from Mao A KO mice and 129S1 strain-matched control mice revealed that Mao A deficiency amplifies the expression of polarization state-specific marker genes in BMDM from male mice but affects only a few selected marker genes in female polarized BMDM. Myeloid Mao A protects male but not female mice from AT inflammation, AT expansion and DIO, possibly by suppressing the polarization of monocyte-derived macrophages recruited into the AT. However, myeloid Mao A deficiency promoted insulin resistance in AT and glucose intolerance in both male and female mice suggesting that macrophage Mao A in other tissues contributes to the maintenance of glucose tolerance and homeostasis.

Background and AimsMetabolic stress-induced by Western-style diets stimulates H2O2 production in blood monocytes, resulting in increased protein S-glutathionylation, reprogramming of the monocyte proteome and the subsequent conversion of blood monocytes into hyperchemotactic, proatherogenic phenotypes. Here we tested the hypothesis that hematopoietic NADPH Oxidase 4 (Nox4) deficiency protects mice against atherogenesis by preventing monocyte reprogramming and macrophage overrecruitment.MethodsWe generated hematopoietic cell-specific Nox4 deficient (Nox4HC-/-) and the corresponding control mice by transplantation of bone marrow isolated from Nox4-/- or C57BL/6J donor mice into male and female 10-week-old lethally irradiated LDLR-/- mice. The mice were fed with high-calorie diet (HCD) for 19 weeks to induce atherogenesis. Atherosclerotic lesions were quantified by en face analysis of aortic lesion areas and histologically in the aortic root. We assessed in vivo monocyte chemotactic activity in these mice, performed RNA-seq analysis on bone marrow-derived macrophages and validated potential targets of Nox4 regulation by Western blot analysis.ResultsBoth male and female Nox4HC-/- mice showed reduced MCP-1-induced monocyte chemotaxis in vivo and smaller atherosclerotic lesions with lower macrophage content. RNA-seq analysis revealed that Nox4 deficiency primarily affects genes and pathways involved in the MCP-1/CCR2 signaling axis, controlling monocyte adhesion and migration by sex-specific mechanisms. Reduced total plasma cholesterol and circulating IL-6 levels likely contributed to the atheroprotective effects of hematopoietic Nox4 deficiency in male mice.ConclusionsHematopoietic Nox4 is a major driver of atherogenesis by enhancing monocyte chemotaxis through the MCP-1/CCR2 - ERK1/2 signaling axis, thereby accelerating macrophage recruitment and accumulation within atherosclerotic plaques.

Background and Aims: Metabolic stress-induced by Western-style diets stimulates H2O2 production in blood monocytes, resulting in increased protein S-glutathionylation, reprogramming of the monocyte proteome and the subsequent conversion of blood monocytes into hyperchemotactic, proatherogenic phenotypes. Here we tested the hypothesis that hematopoietic NADPH Oxidase 4 (Nox4) deficiency protects mice against atherogenesis by preventing monocyte reprogramming and macrophage overrecruitment.Methods: We generated hematopoietic cell-specific Nox4 deficient (Nox4HC-/-) and the corresponding control mice by transplantation of bone marrow isolated from Nox4-/- or C57BL/6J donor mice into male and female 10-week-old lethally irradiated LDLR-/- mice. The mice were fed with high-calorie diet (HCD) for 19 weeks to induce atherogenesis. Atherosclerotic lesions were quantified by en face analysis of aortic lesion areas and histologically in the aortic root. We assessed in vivo monocyte chemotactic activity in these mice, performed RNA-seq analysis on bone marrow-derived macrophages and validated potential targets of Nox4 regulation by Western blot analysis.Results: Both male and female Nox4HC-/- mice showed reduced MCP-1-induced monocyte chemotaxis in vivo and smaller atherosclerotic lesions with lower macrophage content. RNA-seq analysis revealed that Nox4 deficiency primarily affects genes and pathways involved in the MCP-1/CCR2/ERK1/2 signaling axis, controlling monocyte adhesion and migration by sex-specific mechanisms. Reduced total plasma cholesterol and circulating IL-6 levels likely contributed to the atheroprotective effects of hematopoietic Nox4 deficiency in male mice.Conclusions: Hematopoietic Nox4 is a major driver of atherogenesis by enhancing monocyte chemotaxis through the MCP-1/CCR2/ERK1/2 signaling axis, thereby accelerating macrophage recruitment and accumulation within atherosclerotic plaques.