Mitochondrial-Oriented Injectable Hydrogel Microspheres Maintain Homeostasis of Chondrocyte Metabolism to Promote Subcellular Therapy in Osteoarthritis

Research, Journal Year: 2024, Volume and Issue: 7

Published: Jan. 1, 2024

Subcellular mitochondria serve as sensors for energy metabolism and redox balance, the dynamic regulation of functional dysfunctional plays a crucial role in determining cells' fate. Selective removal at subcellular level can provide chondrocytes with to prevent degeneration, thereby treating osteoarthritis. Herein, achieve an ideal therapy, cartilage affinity peptide (WYRGRL)-decorated liposomes loaded mitophagy activator (urolithin A) were integrated into hyaluronic acid methacrylate hydrogel microspheres through microfluidic technology, named HM@WY-Lip/UA, that could efficiently target selectively remove mitochondria. As result, this system demonstrated advantage function restoration, reactive oxygen species scavenging, cell survival rescue, chondrocyte homeostasis maintenance increasing mitophagy. In rat post-traumatic osteoarthritis model, intra-articular injection HM@WY-Lip/UA ameliorated matrix degradation, osteophyte formation, subchondral bone sclerosis 8 weeks. Overall, study indicated provided protective effect on degeneration efficacious clinically relevant manner, mitochondrial-oriented strategy has great potential therapy

Language: Английский

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Opsonization Inveigles Macrophages Engulfing Carrier‐Free Bilirubin/JPH203 Nanoparticles to Suppress Inflammation for Osteoarthritis Therapy

Advanced Science, Journal Year: 2024, Volume and Issue: 11(22)

Published: April 9, 2024

Abstract Osteoarthritis (OA) is a chronic inflammatory disease characterized by cartilage destruction, synovitis, and osteophyte formation. Disease‐modifying treatments for OA are currently lacking. Because inflammation mediated an imbalance of M1/M2 macrophages in the synovial cavities contributes to progression, regulating M1 M2 polarization can be potential therapeutic strategy. Basing on inherent immune mechanism pathological environment OA, immunoglobulin G‐conjugated bilirubin/JPH203 self‐assembled nanoparticle (IgG/BRJ) developed, its evaluated. After intra‐articular administration, IgG conjugation facilitates recognition engulfment nanoparticles macrophages. The internalized disassemble response increased oxidative stress, released bilirubin (BR) JPH203 scavenge reactive oxygen species (ROS), inhibit nuclear factor kappa‐B pathway, suppress activated mammalian target rapamycin result repolarization enhance M2/M1 ratios. Suppression IgG/BRJ promotes protection repair rat model, thereby improving outcomes. This strategy opsonization involving engulf carrier‐free BR/JPH203 therapy holds great intervention treatment.

Language: Английский

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Bifunctional TRPV1 Targeted Magnetothermal Switch to Attenuate Osteoarthritis Progression

Research, Journal Year: 2024, Volume and Issue: 7

Published: Jan. 1, 2024

Transient receptor potential vanilloid family member 1 (TRPV1) has been revealed as a therapeutic target of osteoarthritis (OA), the most common deteriorating whole joint disease, by impeding macrophagic inflammation and chondrocytes ferroptosis. However, clinical application for capsaicin TRPV1 agonist is largely limited its chronic toxicity. To address this issue, we developed bifunctional controllable magnetothermal switch targeting alleviation OA progression coupling magnetic nanoparticles (MNPs) to monoclonal antibodies (MNPs-TRPV1). Under alternating field (AMF) stimulation, MNPs-TRPV1 locally dissipated heat, which was sufficient trigger opening activation TRPV1, effectively impeded chondrocyte This modulation simultaneously attenuated synovitis cartilage degeneration in mice incurred destabilization medial meniscus surgery, indicating delayed progression. Furthermore, with AMF exposure remarkably reduced knee pain sensitivity, alleviated crippled gait, improved spontaneous ambulatory activity performance model. Overall, work provides pathogenesis-based precise therapy temporally spatially manner.

Language: Английский

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Regulated cell death‐amplified sonodynamic anti‐tumor immune nanotherapeutics

BMEMat, Journal Year: 2024, Volume and Issue: unknown

Published: March 4, 2024

Abstract Nanomedicine‐assisted sonodynamic therapy (SDT) has emerged as one of the most promising cancer therapies due to its unique advantages high penetration, non‐radiation, and excellent oxidative stress effect, but always suffered from self‐protection mechanism apoptosis resistance characteristics evolutionarily mutated cells. Regulated cell death (RCD) received increasing attention in precision treatments because significant role synergistically sensitizing reversing immunosuppressive microenvironment during SDT nanomedicine‐triggered immunogenic death. Herein, paradigmatic research RCD‐augmented tumor immunotherapeutics are typically introduced, such autophagy blockade, ferroptosis targeting, pyroptosis induction, necroptosis initiation, cuproptosis actuation, PANoptosis trigger, coordinated anti‐tumor mechanisms discussed detail. Multiple analysis focusing on currently unsolved problems future development prospects RCD‐based nano‐oncology medicine also prospected further strengthen expand scope therapeutic applications.

Language: Английский

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Innovative Bio‐based Hydrogel Microspheres Micro‐Cage for Neutrophil Extracellular Traps Scavenging in Diabetic Wound Healing

Advanced Science, Journal Year: 2024, Volume and Issue: 11(21)

Published: April 6, 2024

Abstract Neutrophil extracellular traps (NETs) seriously impede diabetic wound healing. The disruption or scavenging of NETs using deoxyribonuclease (DNase) cationic nanoparticles has been limited by liberating trapped bacteria, short half‐life, potential cytotoxicity. In this study, a positive correlation between the level in exudation and severity inflammation patients is established. Novel bio‐based hydrogel microspheres ‘micro‐cage’, termed mPDA‐PEI@GelMA, engineered integrating methylacrylyl gelatin (GelMA) with polyethyleneimine (PEI)‐functionalized mesoporous polydopamine (mPDA). This unique ‘micro‐cage’ construct designed to non‐contact scavenge surface, minimizing biological toxicity ensuring high biosafety. are introduced into along exudation, mPDA‐PEI immobilizes them inside through strong binding affinity cfDNA web structure. findings demonstrate that mPDA‐PEI@GelMA effectively mitigates pro‐inflammatory responses associated wounds both vivo vitro. work introduces novel nanoparticle strategy enhance healing processes, benefits clinical applications.

Language: Английский

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Nano‐Micron Combined Hydrogel Microspheres: Novel Answer for Minimal Invasive Biomedical Applications

Macromolecular Rapid Communications, Journal Year: 2024, Volume and Issue: 45(11)

Published: Feb. 24, 2024

Abstract Hydrogels, key in biomedical research for their hydrophilicity and versatility, have evolved with hydrogel microspheres (HMs) of micron‐scale dimensions, enhancing role minimally invasive therapeutic delivery, tissue repair, regeneration. The recent emergence nanomaterials has ushered a revolutionary transformation the field, which demonstrates tremendous potential targeted therapies, biological imaging, disease diagnostics. Consequently, integration advanced nanotechnology promises to trigger new revolution realm hydrogels. HMs loaded combine advantages both hydrogels nanomaterials, enables multifaceted functionalities such as efficient drug sustained release, therapy, lubrication, biochemical detection, medical biosensing monitoring, micro‐robotics. Here, this review comprehensively expounds upon commonly used classifications. Then, it provides comprehensive insights into raw materials preparation methods HMs. Besides, common strategies employed achieve nano‐micron combinations are summarized, latest applications these combined field elucidated. Finally, valuable future design development provided.

Language: Английский

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Precise Lubrication and Protection of Cartilage Damage by Targeting Hydrogel Microsphere

Advanced Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 18, 2024

Abstract Osteoarthritis (OA) is a degenerative bone and joint disease characterized by decreased cartilage lubrication, leading to continuous wear ultimately irreversible damage. This situation particularly challenging for early‐stage OA, as current bio‐lubricants lack precise targeting small inflammatory lesions. In this work, an antibody‐mediated hydrogel microspheres (HMS) developed precisely lubricate the local injury site of prevent progression early OA. Anti‐Collagen type I (Anti‐Col1) antibody that targets sites in OA stages. It anchored on HMS matrix made Gelatin methacrylate (GelMA) poly (sulfobetaine methacrylate) (PSBMA) create targeted (T‐G/S HMS). The T‐G/S HMS's high hydrophilicity, along with dynamic interaction between its surficial Anti‐Col1 Col1 site, ensures effective lubrication Consequently, injecting into rats significantly slows reduces symptoms. conclusion, injectable lubricating strategy represent promising, convenient technique treating slowing progression.

Language: Английский

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Bio‐Functional Hydrogel Microspheres for Musculoskeletal Regeneration

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(33)

Published: Feb. 29, 2024

Abstract The worldwide prevalence of musculoskeletal disorders is expected to rise due an accelerating aging population and increasing associated factors. Despite the high rate disability induction, clinical options for treatment remain limited. Hydrogel microspheres (HMSs), which are colloidal particles with crosslinked polymer networks at nanometer scale, characterized by excellent biocompatibility, easy‐to‐tune structures (e.g., stiffness, porosity, composition), encapsulation efficiency therapeutic agents drugs cells). At present, multiple techniques utilized fabrication HMSs agents. can be produced used in different states match specific utilizations. These desirable properties, along their injectability, bestow mutifunctionalities that a variety biomedical applications delivery biologics, tissue regeneration, bio‐lubrication), thus enable them promising tools tackling diseases. Herein, focus application i) bone disorders, ii) cartilage osteochondral iii) intervertebral disc (IVD) iv) neurovascular aim overviewing recent progress summarize key contributions findings highlight limitations opportunities this field.

Language: Английский

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Polymeric micelle-hydrogel composites design for biomedical applications

Chinese Chemical Letters, Journal Year: 2024, Volume and Issue: unknown, P. 110072 - 110072

Published: May 1, 2024

Language: Английский

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PdZn/Co_SA‐NC Nanozymes with Highly Efficient SOD/CAT Activities for Treatment of Osteoarthritis via Regulating Immune Microenvironment

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: unknown

Published: July 8, 2024

Abstract Inflammatory infiltration of synovial M1 macrophages, high levels ROS, and NO exacerbate osteoarthritis (OA) progression. The PdZn/Co SA ‐NC nanozymes, which are highly ordered PdZn intermetallic nanoparticles loaded with Co single atom N‐doped carbon‐rich in multi‐level pores, an attempt to serve as SOD CAT mimicking nanozymes for OA therapy is designed. nanozymes' electron transfer dual active site sufficient exposure enhances free radical adsorption lower reaction energies, accelerating SOD‐like, CAT‐like, GPx‐like catalyzed reactions, outperforming PdZn/NC alone. Furthermore, exhibit favorable biocompatibility, reduce macrophage oxidative stress OA, alleviate hypoxia, restore mitochondrial function, regulate energy metabolism, increase antioxidant factors, inflammatory thus effectively mitigating the progression OA. Mechanistically, downregulate M1‐type phenotypic markers like IL‐1β by regulating purine metabolism. offer a novel approach treating stress‐related diseases.

Language: Английский

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