Hyaluronic acid (HA), a main component of the extracellular matrix, is widely utilized to deliver anticancer drugs due to its biocompatibility, biodegradability, non-toxicity, non-immunogenicity and numerous modification sites, such as carboxyl and hydroxyl groups. Moreover, HA serves as a natural ligand for tumor-targeted drug delivery systems, as it contains the endocytic HA receptor, CD44, which is overexpressed in many cancer cells. Therefore, HA-based nanocarriers have been developed to improve drug delivery efficiency and distinguish between healthy and cancerous tissues, resulting in reduced residual toxicity and off-target accumulation. This article comprehensively reviews the fabrication of anticancer drug nanocarriers based on HA in the context of prodrugs, organic carrier materials (micelles, liposomes, nanoparticles, microbubbles and hydrogels) and inorganic composite nanocarriers (gold nanoparticles, quantum dots, carbon nanotubes and silicon dioxide). Additionally, the progress achieved in the design and optimization of these nanocarriers and their effects on cancer therapy are discussed. Finally, the review provides a summary of the perspectives, the lessons learned so far and the outlook towards further developments in this field.

Conductive hydrogels (CHs) represent a burgeoning class of intelligent wound dressings, providing innovative strategies for chronic wound repair and monitoring. Notably, CHs excel in promoting cell migration and proliferation, exhibit powerful antibacterial and anti-inflammatory properties, and enhance collagen deposition and angiogenesis. These capabilities, combined with real-time monitoring functions, play a pivotal role in accelerating collagen synthesis, angiogenesis and continuous wound surveillance. This review delves into the preparation, mechanisms and applications of CHs in wound management, highlighting their diverse and significant advantages. It emphasizes the effectiveness of CHs in treating various chronic wounds, such as diabetic ulcers, infected wounds, temperature-related injuries and athletic joint wounds. Additionally, it explores the diverse applications of multifunctional intelligent CHs in advanced wound care technologies, encompassing self-powered dressings, electrically-triggered drug delivery, comprehensive diagnostics and therapeutics and scar-free healing. Furthermore, the review highlights the challenges to their broader implementation, explores the future of intelligent wound dressings and discusses the transformative role of CHs in chronic wound management, particularly in the context of the anticipated integration of artificial intelligence (AI). Additionally, this review underscores the challenges hindering the widespread adoption of CHs, delves into the prospects of intelligent wound dressings and elucidates the transformative impact of CHs in managing chronic wounds, especially with the forthcoming integration of AI. This integration promises to facilitate predictive analytics and tailor personalized treatment plans, thereby further refining the healing process and elevating patient satisfaction. Addressing these challenges and harnessing emerging technologies, we postulate, will establish CHs as a cornerstone in revolutionizing chronic wound care, significantly improving patient outcomes.

Three-dimensional (3D) bioprinting is one of the most promising additive manufacturing technologies for fabricating various biomimetic architectures of tissues and organs. In this context, the bioink, a critical element for biofabrication, is a mixture of biomaterials and living cells used in 3D printing to create cell-laden structures. Recently, decellularized extracellular matrix (dECM)-based bioinks derived from natural tissues have garnered enormous attention from researchers due to their unique and complex biochemical properties. This review initially presents the details of the natural ECM and its role in cell growth and metabolism. Further, we briefly emphasize the commonly used decellularization treatment procedures and subsequent evaluations for the quality control of the dECM. In addition, we summarize some of the common bioink preparation strategies, the 3D bioprinting approaches, and the applicability of 3D-printed dECM bioinks to tissue engineering. Finally, we present some of the challenges in this field and the prospects for future development.

Due to its hydrophobicity, fisetin (FIS) often suffers from several limitations in terms of its applicability during the fabrication of pharmaceutical formulations. To overcome this intrinsic limitation of hydrophobicity, we demonstrate here the generation of poly (vinyl pyrrolidone) (PVP)-encapsulated FIS nanoparticles (FIS-PVP NPs) utilizing a supercritical antisolvent (SAS) method to enhance its aqueous solubility and substantial therapeutic effects. In this context, the effects of various processing and formulation parameters, including the solvent/antisolvent ratio, drug/polymer (FIS/PVP) mass ratio, and solution flow rate, on the eventual particle size as well as on distribution were investigated using a 2³ factorial experimental design. Notably, the FIS/PVP mass ratio significantly affected the morphological attributes of the resultant particles. Initially, the designed constructs were characterized systematically using various techniques (e.g., chemical functionalities were examined with Fourier-transform infrared (FTIR) spectroscopy, and physical states were examined with X-ray diffraction analysis (XRD) and differential scanning calorimetry (DSC) techniques). In addition, drug release as well as cytotoxicity evaluations in vitro indicated that the nanosized polymer-coated particles showed augmented performance efficiency compared to the free drug, which was attributable to the improvement in the dissolution rate of the FIS-PVP NPs due to their small size, facilitating a higher surface area over the raw form of FIS. Our findings show that the designed SAS process-assisted nanoconstructs with augmented bioavailability, have great potential for applications in pharmaceutics.

For combinatorial monitoring and chemotherapy of hepatocellular carcinoma, the macromolecular prodrug based on hyaluronic acid and doxorubicin hydrochloride was prepared by an acid-labile hydrazone linkage, and then conjugated with amine-modified iron oxide nanoparticles by a carbodiimide mediated coupling reaction. The resultant hybrid nanoparticles have the characteristics of good water dispersibility, superparamagnetic property and high magnetic relaxivity for magnetic resonance imaging. In particular, they demonstrated significant cellular uptake and specific accumulation in human hepatocellular liver carcinoma HepG2 cells due to specific biological recognition of hyaluronic acid. In addition, in vitro cumulative release of doxorubicin hydrochloride from the resultant hybrid nanoparticles was significantly accelerated at a mildly acidic pH of 5.0–6.0 when compared to its release at the physiological pH of 7.4, suggesting the pH-responsive feature of this conjugated prodrug for effective chemotherapy of hepatocellular carcinoma. In vivo antitumor efficacy of the mice further confirmed the effect.

Ulcerative colitis (UC) is manifested by excessive oxidative stress and immune dysregulation in the colonic microenvironment. To address these pathological features, we developed a microfluidics-engineered oral delivery system comprising methacrylated hyaluronic acid (HAMA) hydrogel microspheres encapsulating polydopamine-coated selenium nanoparticles (CS-Se@PDA). The uniform microspheres featured a microfluidics-enabled structure that enabled stable CS-Se@PDA nanoparticles anchoring via electrostatic and covalent interactions. The PDA coating enhanced the stability, mucosal adhesion, and scavenging of reactive oxygen species (ROS) of the nanoparticles. At the same time, the HAMA shell provided pH-responsive protection and CD44-mediated targeting to inflamed colonic tissues. In vitro studies demonstrated excellent biocompatibility, effective ROS neutralization, and macrophage polarization toward the anti-inflammatory M2 phenotype. In a dextran sulfate sodium-induced colitis mouse model, oral administration of these microspheres significantly alleviated clinical symptoms, including ∼25 % mitigation of weight loss, increased colon length from 4.78 ± 0.3 cm to 6.83 ± 0.25 cm, and reduced histological damage. Furthermore, the treatment restored tight junction protein expression to approximately 60 % of normal levels for ZO-1 and about 55 % for Occludin, indicating substantial epithelial barrier repair, and effectively suppressed pro-inflammatory cytokines such as TNF-α and IL-6. Overall, this microfluidics-enabled, colon-targeted delivery system with integrated antioxidative and immunomodulatory functions offers a promising strategy for the non-invasive treatment of UC and other inflammation-associated gastrointestinal disorders.