Therapeutic Hydrogels: Properties and Biomedical Applications.

Hydrogels have emerged as versatile therapeutic platforms with immense potential for treating various diseases, due to their tunable properties and biocompatibility. Recent innovations, including injectable, self-assembling, and bioadhesive hydrogels, have broadened their biomedical applications, driven by advancements in materials chemistry. This review systematically examines the role of chemical principles in designing and customizing therapeutic hydrogels, with a focus on hydrogelation mechanisms, swelling ratios, mechanical properties, and biological interactions.

Thermoresponsive antioxidant metal-free carbon nanodot hydrogel: An effective therapeutic approach for ocular surface disease.

Oxidative stress, an imbalance between the body's oxidative and antioxidant systems, contributes markedly to the development of numerous ocular surface diseases, particularly dry eye disease (DED). Effective elimination or reduction of reactive oxygen species (ROS) can halt disease progression and alleviate symptoms. This study presents an innovative thermoresponsive, metal-free carbon nanodot (CD) hydrogel, termed F-CD hydrogel, which exhibits potent neutralization capabilities against multiple free radicals, including OH·, O·, and ·DPPH.

Cell Shock Absorption via Stress Relaxation Hydrogel Microspheres for Alleviating Endoplasmic Reticulum Stress in Chondrocytes.

Chronic mechanical vibrations and endoplasmic reticulum (ER) stress are major contributors to osteoarthritis (OA) progression. This study proposes a novel "cellular shock absorption" approach by developing viscoelastic hydrogel microspheres with tunable stress relaxation properties. By modulating the chemical bonds in the hydrogel network through oxidation and hydrazine coupling reaction, hydrogel microspheres capable of absorbing shock and reducing mechanical stimulus-induced ER stress in chondrocytes are created.

Oral delivery of liquid mRNA therapeutics by an engineered capsule for treatment of preclinical intestinal disease.

Oral delivery of messenger RNA (mRNA) therapeutics could offer noninvasive and self-administered treatments and vaccinations. However, the development of oral mRNA therapeutics remains challenging because of the degradative conditions of the gastrointestinal (GI) tract. Here, we engineered a capsule-based device, named RNACap, designed for oral delivery of liquid mRNA nanoparticle (NP) therapeutics to the intestines.

Macrophage hitchhiking nanomedicine for enhanced β-elemene delivery and tumor therapy.

Nanoparticle-based drug delivery systems hold promise for tumor therapy; however, they frequently encounter challenges such as low delivery efficiency and suboptimal efficacy. Engineered living cells can redirect drug delivery systems to effectively reach targeted sites. Here, we used living macrophages as vehicles, attaching them with GeS nanosheets (GeSNSs) carrying β-elemene for transport to tumor sites.

Promoting mitocytosis via gene-engineered aligned fibers for fascia regeneration.

The abnormal accumulation of damaged mitochondria severely impedes tissue repair, and conventional therapeutic approaches, such as drug treatments, are often ineffective to remove damaged mitochondria. In this study, we developed gene-engineered aligned electrospun fibers by integrating microfluidic chip technology with a micro-sol oriented electrospinning technique. This study is the first to demonstrate the repair of damaged fascia by promoting mitocytosis through upregulating tetraspanin-9 (TSPAN9).

Innate immunity-modulating nanobiomaterials for controlling inflammation resolution.

The acute inflammatory response is an inherent protective mechanism, its unsuccessful resolution can contribute to disease pathogenesis and potentially lead to death. Innate immune cells are the first line of host defenders and play a substantial role in inflammation initiation, amplification, resolution, or subsequent disease progression. As the resolution of inflammation is an active and highly regulated process, modulating innate immune cells, including neutrophils, monocytes and macrophages, and endothelial cells, and their interactions offer opportunities to control excessive inflammation.

Dual mRNA nanoparticles strategy for enhanced pancreatic cancer treatment and β-elemene combination therapy.

Pancreatic ductal adenocarcinoma (PDAC) is notoriously immune-resistant, limiting the clinical efficacy of single-agent immune modulators and thereby necessitating the exploration of multimodal immunotherapy combinations. Traditional approaches combining conventional immune checkpoint inhibitors with neoantigen vaccines have shown some promise in treating PDAC but are often compromised by intratumoral T lymphocyte exhaustion and systemic toxicity. Hence, novel approaches are needed to address these challenges.

Lactate-Modulating Nanozyme-Mediated Mitochondrial Respiration Block for Tumor Immunosuppression Remodeling.

Abnormal lactate metabolism in tumor cells leads to immune escape in the tumor microenvironment. Intervening in specific lactate metabolic pathways while blocking downstream pyruvate influx holds great promise for overcoming conventional lactate-targeted therapy limitations such as short half-life, insufficient lactate consumption, and pathological microenvironment elasticity. Herein, a nanocatalytic medicine based on carbondoping engineered copper nitride enzyme (CuN-C NE) with enhanced lactate oxidase (LOX) activity was carefully designed.

Elemene Hydrogel Modulates the Tumor Immune Microenvironment for Enhanced Treatment of Postoperative Cancer Recurrence and Metastases.

As a representative active ingredient of traditional Chinese medicine (TCM) and a clinically approved anticancer drug, elemene (ELE) exhibits exciting potential in the antitumor field; however, appropriate drug formulations still need to be explored for specific diseases such as postoperative cancer recurrence and metastasis. Herein, we report an ELE hydrogel with controlled drug release kinetics that can allow ELE to maintain effective concentrations at local lesion sites for extended periods to enhance the bioavailability of ELE. Concretely, dopamine-conjugated hyaluronic acid is synthesized and utilized to prepare ELE nanodrug-embedded hydrogels.

Electrospun fiber-based immune engineering in regenerative medicine.

Immune engineering, a burgeoning field within regenerative medicine, involves a spectrum of strategies to optimize the intricate interplay between tissue regenerative biomaterials and the host tissue. These strategies are applied across different types of biomaterials and various disease models, which encompasses finely modulating the immune response at the levels of immune cells and factors, aiming to mitigate adverse effects like fibrosis and persistent inflammation that may arise at the injury site and consequently promote tissue regeneration. With the continuous progress in electrospinning technology, the immunoregulatory capabilities of electrospun fibers have gained substantial attention over the years.

Innovative Nanotechnology in Drug Delivery Systems for Advanced Treatment of Posterior Segment Ocular Diseases.

Funduscopic diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), significantly impact global visual health, leading to impaired vision and irreversible blindness. Delivering drugs to the posterior segment of the eye remains a challenge due to the presence of multiple physiological and anatomical barriers. Conventional drug delivery methods often prove ineffective and may cause side effects.

Functional modification of gut bacteria for disease diagnosis and treatment.

Intestinal bacteria help keep humans healthy by regulating lipid and glucose metabolism as well as the immunological and neurological systems. Oral treatment using intestinal bacteria is limited by the high acidity of stomach fluids and the immune system's attack on foreign bacteria. Scientists have created coatings and workarounds to overcome these limitations and improve bacterial therapy.

Resolvin D1 delivery to lesional macrophages using antioxidative black phosphorus nanosheets for atherosclerosis treatment.

The buildup of plaques in atherosclerosis leads to cardiovascular events, with chronic unresolved inflammation and overproduction of reactive oxygen species (ROS) being major drivers of plaque progression. Nanotherapeutics that can resolve inflammation and scavenge ROS have the potential to treat atherosclerosis. Here we demonstrate the potential of black phosphorus nanosheets (BPNSs) as a therapeutic agent for the treatment of atherosclerosis.

Macrophage-modulating nanomedicine for cancer immunotherapy.

Tumor-associated macrophages (TAMs) play crucial roles in the immunosuppressive solid tumor microenvironment (TME). Despite their tumor-promoting functions, TAMs can also be therapeutically modulated to exhibit tumor-killing properties, making them attractive targets for tumor immunotherapy. This review highlights the recent advances in nanomedicine-based strategies centered around macrophages for enhanced cancer immunotherapy.

Chemically Modified Platforms for Better RNA Therapeutics.

RNA-based therapies have catalyzed a revolutionary transformation in the biomedical landscape, offering unprecedented potential in disease prevention and treatment. However, despite their remarkable achievements, these therapies encounter substantial challenges including low stability, susceptibility to degradation by nucleases, and a prominent negative charge, thereby hindering further development. Chemically modified platforms have emerged as a strategic innovation, focusing on precise alterations either on the RNA moieties or their associated delivery vectors.

Targeted Protein Fate Modulating Functional Microunits Promotes Intervertebral Fusion.

Stable regulation of protein fate is a prerequisite for successful bone tissue repair. As a ubiquitin-specific protease (USP), USP26 can stabilize the protein fate of β-catenin to promote the osteogenic activity of mesenchymal cells (BMSCs) and significantly increased bone regeneration in bone defects in aged mice. However, direct transfection of Usp26 in vivo is inefficient.

Bone Organoids: Recent Advances and Future Challenges.

Bone defects stemming from tumorous growths, traumatic events, and diverse conditions present a profound conundrum in clinical practice and research. While bone has the inherent ability to regenerate, substantial bone anomalies require bone regeneration techniques. Bone organoids represent a new concept in this field, involving the 3D self-assembly of bone-associated stem cells guided in vitro with or without extracellular matrix material, resulting in a tissue that mimics the structural, functional, and genetic properties of native bone tissue.

Intelligent Vascularized 3D/4D/5D/6D-Printed Tissue Scaffolds.

Blood vessels are essential for nutrient and oxygen delivery and waste removal. Scaffold-repairing materials with functional vascular networks are widely used in bone tissue engineering. Additive manufacturing is a manufacturing technology that creates three-dimensional solids by stacking substances layer by layer, mainly including but not limited to 3D printing, but also 4D printing, 5D printing and 6D printing.

Nano-bio interactions in mRNA nanomedicine: Challenges and opportunities for targeted mRNA delivery.

Upon entering the biological milieu, nanomedicines swiftly interact with the surrounding tissue fluid, subsequently being enveloped by a dynamic interplay of biomacromolecules, such as carbohydrates, nucleic acids, and cellular metabolites, but with predominant serum proteins within the biological corona. A notable consequence of the protein corona phenomenon is the unintentional loss of targeting ligands initially designed to direct nanomedicines toward particular cells or organs within the in vivo environment. mRNA nanomedicine displays high demand for specific cell and tissue-targeted delivery to effectively transport mRNA molecules into target cells, where they can exert their therapeutic effects with utmost efficacy.