Heart disease has become a major threat to global health. In recent years, extracellular vesicles (EVs) have become a research hotspot in heart regeneration and repair due to their unique intercellular communication function and advantages in cell-free therapy. This paper systematically summarizes the sources, characteristics, engineering, and clinical applications of EVs in heart regeneration. Cardiac therapy-related EVs significantly reduce cardiac fibrosis, regulate inflammation and immunity, improve the myocardial microenvironment, and promote angiogenesis by delivering biologically active molecules such as proteins, lipids, and microRNAs. In addition, bioengineering techniques (such as targeted peptide modification and hydrogel delivery systems) have further improved the cardiac targeting and long-lasting efficacy of specific EVs. The above methods have shown high repair potential in disease models such as cardiac ischemia-reperfusion injury, myocardial infarction, heart failure, and structural heart diseases. However, the clinical application of EVs still faces some challenges that need to be urgently addressed. Future research needs to focus on standardized and scaled production processes, long-lasting storage capacity, and precise and specific mechanisms of action of EVs to facilitate the translation of EVs from basic research to the clinic.

Myocardial infarction (MI)-induced persistent disruption of the myocardial microenvironment is one of the key mechanisms driving the onset of heart failure. Precise modulation of this pathological microenvironment in vitro has emerged as an important strategy to improve MI prognosis and delay heart failure progression. In this study, we constructed carrier-free choline chloride (ChCl)-ammonium glycyrrhizinate (AG) self-assembled hydrogels. Initially, network pharmacology combined with big data analysis was employed to predict the synergistic therapeutic effects of ChCl and AG. Subsequently, multi-scale characterisation techniques, including FT-IR, SEM, and rheology, were used to analyse the structural features of the gel system. Molecular dynamics and quantum chemical calculations indicated that hydrophobic, electrostatic, and hydrogen-bond interactions jointly drive self-assembly, and Cryo-SEM revealed for the first time a near-native interpenetrating sheet-like fibrous network. In an in vitro MI model, the ChCl-AG self-assembled hydrogel reduced oxidative stress, shifted macrophages from pro-inflammatory M1 to reparative M2, increased endogenous antioxidant enzyme activity, and downregulated pro-inflammatory cytokines, thereby preserving microenvironmental homeostasis and providing cardioprotection. Transcriptomics indicated positive regulation of pathways linked to cardiac structure, contractility, energy metabolism, and cardiovascular disease. In vivo MI models, the ChCl-AG self-assembled hydrogel markedly promoted myocardial repair and functional recovery while exhibiting good biocompatibility and sustained release. Overall, the carrier-free ChCl-AG self-assembled hydrogel provides a precise strategy to modulate post-MI inflammatory and oxidative imbalances, promote myocardial repair, and holds broader biomedical potential.

While hydroxyapatite (HA) is widely used in bone tissue engineering due to its biomimetic mineral composition, the influence of its nanoscale morphology on biological responses and surface functionalization has not been sufficiently investigated. Herein, spherical, short-rod, and long-rod HA nanoparticles were systematically evaluated for biofunctionalization via a metal–polyphenol network (MPN) coating composed of tannic acid (TA) and zinc ion (Zn2+). Among them, the long-rod HA (LR-HA) topology proved optimal, establishing a clear morphology-function relationship that maximized biological efficacy. Benefiting from the synergistic effect of its unique long-rod morphology and the MPN coating, the resultant LR-HA@TZ exhibited strong antioxidant capability, and effectively promoted macrophage polarization from the M1 to the M2 phenotype via activation of the integrin/FAK/RhoA/ROCK signaling pathway. Consequently, conditioned media from LR-HA@TZ-treated macrophages most effectively reversed the lipopolysaccharide derived from Porphyromonas gingivalis (Pg. LPS)-induced suppression of osteogenesis in bone marrow mesenchymal stem cells (BMSCs) and stimulated angiogenesis in human umbilical vein endothelial cells (HUVECs). Based on these findings, we integrated LR-HA@TZ into an injectable dual-network hydrogel and developed into G-LR-HA@TZ, a material exhibiting self-healing, tissue-adhesive, antibacterial, and hemostatic capabilities. In a rat periodontitis model, G-LR-HA@TZ effectively attenuated alveolar bone resorption, suppressed osteoclast activity, and promoted bone tissue regeneration through immunomodulation, outperforming the clinically commonly used Periocline® (minocycline ointment). This study establishes a pivotal role for HA nanoparticle morphology in determining functionalization efficacy and immune regulation, translating this insight into a novel regenerative strategy for periodontal bone repair via microenvironment reprogramming.

Current therapeutic approaches for muscle reconstruction face considerable challenges, particularly in generating sufficiently dense cell aggregates and in establishing effective methods for reactivating the function of exogenous cells. Herein, we developed a pre-priming cell sheet therapy for volumetric muscle loss (VML) that leverages highly dense, electro-mechanically bioactive constructs. To achieve this goal, we fabricated a multifunctional cell culture platform based on a near-infrared (NIR)-responsive, wrinkle-patterned, conductive substrate. This system enables scalable preparation (>6 mm in diameter), non-invasive harvesting, and bioactive pre-priming of cell sheets for transplantation. Non-invasive harvesting of the sheets is achieved via a NIR-triggered release mechanism, in which dynamic changes in wrinkle morphology induce a sufficient shift in mechanical stress at the cell-substrate interface, thereby disrupting focal adhesions. Compared with conventional cell-suspension therapy, the microstructured electroactive surface demonstrated superior efficacy for VML repair, as evidenced by integrated in vitro electrophysiology, RNA sequencing, and in vivo analysis. This enhancement is attributed to the substrate's provision of combined electrical and mechanical priming cues, which collectively promote myogenic differentiation, growth, and pro-regenerative calcium signaling in C2C12 myoblasts. In conclusion, this work establishes that engineering interfacial dynamics-rather than relying solely on static material properties-is pivotal for the development of advanced cell therapies. The dynamic electroactive substrate offers a versatile strategy for fabricating pre-functionalized tissue constructs, with immediate promise for regenerating electroexcitable tissues and broad application prospects in regenerative medicine.

The core challenge in engineering functional cardiac tissue in vitro is the lack of an integrated platform that simultaneously provides multiscale anisotropic topography and conductive signaling, leading to poor cellular alignment, weak electromechanical coupling, and asynchronous contraction. Herein, we developed a multiscale anisotropic conductive fiber scaffold featuring integrated nano- and micro-scale characteristics to mimic the hierarchical topological structure and electrochemical microenvironment of native myocardial tissue, thereby providing a biomimetic platform for cardiac tissue engineering. The engineered cardiac microtissues derived from this platform exhibit more ordered sarcomeres, a 5.45-fold increase in Cx43 expression, a 117.6% enhancement in contraction amplitude, and a 96.4% improvement in contraction frequency. Notably, the model demonstrates high sensitivity, responding accurately to drug concentrations as low as 1 nM-an order of magnitude improvement over conventional models. In addition, we developed a label-free CardioFlow analysis tool based on optical flow algorithms, enabling rapid extraction and visualization of the spatiotemporal beating patterns of cardiac microtissues. After implantation into MI rats, the microtissues promote angiogenesis, polarize macrophages toward the M2 phenotype, and inhibit fibrosis and ventricular remodeling, thereby improving cardiac function. This engineered cardiac microtissue platform with multi-level anisotropic architecture provides a universal platform and theoretical foundation for drug cardiotoxicity evaluation and clinical myocardial regeneration.

Injectable hydrogels capable of responding to pathological microenvironmental cues represent a promising therapeutic strategy for myocardial infarction (MI). However, existing systems that can simultaneously regulate metabolic abnormalities and drive multi-pathway for diabetic MI repair remain scarce. To address this, a glucose/reactive oxygen species (ROS)-dual responsive injectable hydrogel was developed with stimulus-responsive release properties and complementary multi-target therapeutic functions. The hydrogel exhibited favorable injectability and tissue adhesion, allowing stable retention at the injury site. In vitro studies demonstrated that the glucose-sensitive component enabled controlled puerarin release, while the ROS-sensitive segment showed nitric oxide (NO)-generating capability. When applied in vivo, the hydrogel system significantly reduced local ROS levels and promoted angiogenic responses in the infarcted myocardium. Importantly, the hydrogel improves cardiomyocyte energy supply and metabolic homeostasis by enhancing mitochondrial function and regulating glucose-lipid metabolic balance. Consequently, this combined approach significantly improved both vascular regeneration and myocardial repair in diabetic rats post-MI. This work provides a novel and effective strategy for the multifunctional treatment of diabetic myocardial injury and highlights the potential of smart responsive hydrogels in managing metabolic cardiovascular disorders.

Doxorubicin (DOX), a widely used chemotherapeutic agent, is clinically limited by DOX-induced heart failure (DIHF). Emerging evidence links gut microbial dysbiosis to exacerbating DIHF progression, yet the mechanisms remain elusive. Herein, we established a rat DIHF susceptibility model to investigate the gut microbiota’s regulatory role. Multi-omics analyses indicated that DIHF severity was associated with reduced butyrate-producing bacteria and systemic butyrate levels. Sodium butyrate (NaB) significantly alleviated DOX-induced cardiomyocyte toxicity and DIHF. Mechanistically, NaB strengthened the colonic and cardiac barrier functions and reduced gut microbiota translocation to the heart and cardiac lipopolysaccharide (LPS) accumulation. NaB altered cardiac bacterial composition and functions, reduced cardiac Fe2+ levels, and inhibited cardiomyocyte ferroptosis. Further results confirmed that NaB mitigated DOX-induced ferroptosis via the GPX4/GSH pathway. Collectively, this study indicated that butyrate ameliorates DIHF by inhibiting cardiomyocyte ferroptosis through the gut-heart axis, providing translational potential for microbiota-targeted cardioprotective strategies in DIHF.

The persistent imbalance of the wound microenvironment after volumetric muscle loss (VML) critically impedes endogenous repair. Therefore, establishing a favorable cellular milieu following skeletal muscle injury is essential for effective regeneration. Herein, we developed a microenvironment-responsive injectable hydrogel, with alginate as the primary component, crosslinked with salidroside through aminophenylboronic acid, which provides mechanical support with stiffness relevant to skeletal muscle repair and promotes muscle regeneration. The hydrogel exhibits excellent porosity, injectability, responsiveness, and biodegradability. In vitro experiments demonstrated its capacity to efficiently scavenge excessive reactive oxygen species, mitigate oxidative stress, and facilitate macrophage repolarization toward the M2 phenotype, thereby attenuating inflammation. It markedly promotes myoblast proliferation and differentiation, as well as endothelial cell growth, migration, and tube formation. In a rat tibialis anterior defect model, the hydrogel reshaped the local microenvironment by exerting anti-inflammatory and antioxidant effects, thereby facilitating angiogenesis and improved myofiber regeneration with a more orderly histological arrangement. Collectively, this work presents a promising therapeutic strategy to restore the stress microenvironment of skeletal muscle injuries, thereby promoting muscle tissue regeneration and functional recovery.

The effective restoration of mandibular defects continues to pose a significant clinical challenge. Although biomimetic hydrogels have shown potential in bone tissue engineering, existing approaches fail to simultaneously replicate the hierarchical architecture of native bone and dynamically regulate the osteogenic niche. This study presents a bioinspired hydrogel system engineered through green hydrogen-bond cross-linking integrated with tannic acid-mediated gradient mineralization, achieving precise emulation of cortical-trabecular bone interfaces across multiple scales. The hydrogel demonstrates multifunctional therapeutic capabilities, including targeted recruitment of bone marrow mesenchymal stem cells, synchronized modulation of oxidative stress, transition of M1 macrophages to M2 macrophages, broad-spectrum antimicrobial activity, and potent osteogenic differentiation. Through spatiotemporal control of microenvironmental cues, the construct establishes a self-regulating repair niche that coordinates angiogenesis and osteogenesis. In vivo evaluation utilizing a rat mandibular defect model confirmed the hydrogel's efficacy in enhancing osseous regeneration and restoring biomechanical competence. This work pioneers a structural-dynamic dual-regulation strategy, advancing translational solutions for complex craniofacial reconstruction.

Myocardial infarction (MI) is characterized by a paucity of cardiomyocyte regeneration, leading to significant morbidity and mortality. Contemporary therapeutic modalities, while mitigating ischemic effects, fail to reconstitute the impaired electromechanical coupling within the infracted myocardium. Emerging evidence supports the utility of electroconductive hydrogels (ECHs) in facilitating post-MI cardiac function recovery by restoring the conductive microenvironment of the infarcted tissue. This comprehensive review delineates the taxonomy of ECHs predicated on their constituent conductive materials. It also encapsulates prevailing research trends in ECH-mediated MI repair, encompassing innovative design paradigms and microenvironment-sensitive strategies. The review also provides a critical appraisal of various implantation techniques, underscored by a thorough examination of the attendant considerations. It elucidates the mechanistic underpinnings by which hydrogels exert salutary effects on myocardial repair, namely by augmenting mechanical and electrical integrity, exerting anti-inflammatory actions, fostering angiogenesis, and curtailing adverse remodeling processes. Furthermore, the review engages with the pressing challenge of optimizing ECH functionality to achieve superior reparative outcomes post-MI. The discourse concludes with an anticipatory perspective on the evolution of ECH scaffolds, advocating for a tailored approach that integrates multifaceted physicochemical properties to cater to the nuances of personalized medicine.

The activation of the stimulator of interferon genes (STING) pathway presents a promising therapeutic strategy for pancreatic cancer by enhancing immune responses and reprogramming the immunosuppressive tumor microenvironment (TME). Ferroptosis, an iron-dependent form of cell death, can synergize with STING activation through reactive oxygen species (ROS)-induced DNA damage. However, its efficacy is hindered by poor vascularization, inefficient delivery of STING agonists, and tumor resistance mechanisms that suppress ROS levels. To overcome these limitations, we developed a "nuclei bombing" nano-system using extremely small cuprous oxide modified magneto-human heavy chain ferritin (ES-CO@M-HFn). This system targets pancreatic cancer cells overexpressing transferrin receptor 1 (TfR1) and releases Cu+ and Fe3+ ions in response to the acidic (pH 6.8) and glutathione (GSH)-rich TME. These ions form a Cu-Fe catalytic cycle under high H2O2 levels, continuously generating Fe2+, Cu+, and robust ROS, thereby inducing ferroptosis and cuproptosis. This creates a synergistic feedback loop that amplifies oxidative damage, leading to extensive DNA damage and tumor cell destruction-termed the "nuclei bombing" effect. The resulting DNA fragments activate the STING pathway, reprogramming the TME by maturing dendritic cells, repolarizing macrophages, and activating CD8+ T cells. This comprehensive approach generates a potent immune response, significantly suppressing tumor growth and metastasis, and offers a transformative strategy for pancreatic cancer treatment.

Postinfarction revascularization is critical for repairing the infarcted myocardium and for stopping disease progression. Considering the limitations of surgical intervention, engineered cardiac patches (ECPs) are more effective in establishing rich blood supply networks. For efficacy, ECPs should promote the formation of more mature blood vessels to improve microcirculatory dysfunction and mitigate hypoxia-induced apoptosis. Developing collateral circulation between infarcted myocardium and ECPs for restoring blood perfusion remains a challenge. Here, an ion-conductive composite ECPs (GMA@OSM) with powerful angiogenesis-promoting ability was constructed. Based on dual-effect intervention of oxygen and strontium, the developed ECPs can promote the formation of high-density circulating microvascular network at the infarcted myocardium. In addition, the GMA@OSM possesses effective reactive oxygen species-scavenging capacity and can facilitate electrophysiological repair of myocardium with ionic conductivity. In vitro and in vivo studies indicate that the multifunctional GMA@OSM ECPs form well-developed collateral circulation with infarcted myocardium to protect cardiomyocytes and improve cardiac function. Overall, this study highlights the potential of a multifunctional platform for developing collateral circulation, which can lead to an effective therapeutic strategy for repairing myocardial infarction.

Accurate and rapid detection of Cardiac Troponin I (CTnI) is essential for the early diagnosis and timely management of myocardial infarction (MI). However, conventional detection methods relying on antigen-antibody interactions often face challenges such as high costs and lengthy procedures. Novel detection methods based on antigen-aptamer interactions offer a potentially superior alternative. Nevertheless, the performance of antigen-aptamer sensors is typically compromised by the unstable structure of aptamers, resulting in limited sensitivity and inconsistent specificity in CTnI detection. To address these issues, we have developed an innovative aptamer structure to construct a paper-based sensor comprising a paper electrode and a CTnI aptamer detection module. The paper electrode employs PEDOT:PSS to uniformly distribute single-walled carbon nanotubes (SWCNTs) at high concentrations on filter paper. The detection module utilizes modified CTnI aptamers with a continuous (AT)5 sequence in the anchor domain to enhance stable immobilization on SWCNTs without chemical reactions. We discovered that incorporating appropriate 18-atom hexa-ethylene glycol spacers (Sp18) between the protein-capture and anchor domains of the aptamers can improve the sensitivity of the current response for CTnI detection. Through the optimization of annealing temperature and duration, the paper sensor Aps3-CTnI-PS@CP, which integrates (AT)5 and three Sp18 into the aptamer, demonstrated enhanced sensitivity and specificity for CTnI detection. When applied to clinical samples, Aps3-CTnI-PS@CP exhibited a favorable receiver operating characteristic (ROC) curve, with an area under the curve (AUC) of 0.982, a sensitivity of 0.917, and a specificity of 0.945 for CTnI detection. This performance correlates strongly with traditional chemiluminescence immunoassay (CLIA) assays used in clinical settings. The straightforward fabrication process and minimal batch-to-batch variability make Aps3-CTnI-PS@CP a promising candidate for clinical aptamer-based CTnI detection.

It is urgent for patients with chronic kidney disease (CKD) to develop a robust and facile therapy for effective control of serum phosphate and reasonable regulation of gut microbiota, which are aiming to prevent cardiovascular calcification and reduce cardiovascular complications. Here, bioinspired by intestinal microstructures, we developed biomimetic wrinkled prebiotic-containing microspheres with enhanced intestinal retention and absorption for reducing hyperphosphatemia and vascular calcification of CKD model rats. The resultant CSM@5 microspheres exhibited favorable phosphate binding capacity in vitro and could effectively reduce serum concentration of phosphorous in vivo. Through increasing the beneficial bacteria and decreasing the harmful bacteria in the intestinal tract, these prebiotic microspheres can modulate intestinal microbiota and then ameliorate vascular calcification notably. This feasible and robust approach may offer a potential and effective strategy for the treatment of hyperphosphatemia of CKD and prevention of its cardiovascular complications.

Although elastic cardiac patches have demonstrated efficacy in alleviating ventricular wall stress and restoring cardiac function following myocardial infarction (MI), the mechanistic basis governing their therapeutic effects remains incompletely elucidated. In this study, three distinct acellular hydrogel patches with tailored elastic moduli were fabricated, namely soft (1.61 kPa), mechano-matching (16.82 kPa, corresponding to the moduli of native adult myocardium), and rigid (602.61 kPa). These patches were implanted in a rat model of MI to evaluate their therapeutic potential. Among the three groups, the mechano-matching hydrogel patch exhibited superior performance, significantly improving cardiac function (with left ventricular ejection fraction [LVEF] elevated by 15.89 %, p = 0.002), reducing infarct size by 14.49 % (p < 0.001), mitigating myocardial fibrosis, and attenuating cardiomyocyte apoptosis. To dissect the underlying mechanism, an in vitro cyclic stretch model mimicking the in vivo myocardial mechanical microenvironment was established. Results revealed that hydrogels with moderate stiffness (16.82 kPa) transduced mechanical cues to promote nuclear translocation of Yes-associated protein (YAP) in cardiomyocytes. This key mechanotransduction event upregulated the expression of anti-apoptotic protein Bcl-2, thereby suppressing cardiomyocyte apoptosis. Notably, this study uncovers a previously unelucidated mechanistic paradigm by which moderate mechanical stimuli, matching the intrinsic stiffness of native myocardium, confer cardioprotection specifically through activation of the YAP-Bcl-2 signaling axis. Furthermore, it establishes that acellular biomaterials can exclusively harness their intrinsic mechanical properties to reverse pathological myocardial remodeling post-MI, without relying on cellular components or bioactive molecules. This finding provides strategy guided by mechanobiology for cardiac regeneration, substantially enhancing the clinical translatability of acellular cardiac patches.

The treatment of volumetric muscle loss (VML) is still a major clinical challenge. Integration of native striated muscle organigrams and electromechanical coupling cues may be an effective strategy for repairing structural and functional injuries in muscle tissue. Here, we developed a biomimetic muscle patch integrating hierarchical microstructures with electromechanically coupled materials for VML treatment. This scaffold design not only organizes myofibroblasts into mature muscle tissues with well-defined structures, but also integrates the local electrical environment by generating electrical stimulation in situ. Notably, the hierarchical structure is able to facilitate the internal network integration of the material, greatly enhancing its overall electromechanical coupling properties. The results of implanting the muscle patch into VML animals showed that the patch was able to promote VML repair by accelerating myogenic maturation and regulating related biological processes such as electromechanical coupling and skeleton remodeling. Thus, this strategy that combine hierarchical microstructures with electromechanical coupling properties is expected to contribute to the development of muscle tissue engineering.

Redox imbalance resulting from NAD+ [nicotinamide adenine dinucleotide (oxidized form)] depletion and NADH (reduced form of NAD+) accumulation is a conserved hallmark of both aging and myocardial infarction (MI), promoting cellular senescence and limiting the efficacy of regenerative therapies. Despite several NADH oxidase (NOX)-mimetic nanozymes having been reported, their therapeutic utility in aging and cardiovascular repair remains largely unexplored. Here, we present a vanadium-based nanozyme (MXene-TA) that mimics bacterial NOX activity, catalytically oxidizing NADH to restore NAD+ and directly fixing redox imbalance. In aged (24-month-old) mice, systemic MXene-TA administration restored NAD+/NADH homeostasis and reduced senescence markers (p16, p21, γH2AX, and SASP) in the heart, liver, and spleen, yet this effect was not observed in the lungs or kidneys, indicating organ-specific redox susceptibility. In a rat MI model, local injection of MXene-TA into the infarcted myocardium reprogrammed metabolism, activated NAD+-dependent pathways, attenuated oxidative damage in cardiomyocytes, decreased infarct area, and enhanced myocardial function. To further enhance stem cell retention and function, we embedded MXene-TA and adipose-derived stem cells (ADSCs) into a pH-responsive, conductive hydrogel that mimics cardiac mechanical and electrical properties. This platform extended ADSC survival beyond 4 weeks (versus 1 week in controls) and further improved cardiac repair. Together, these findings uncover the therapeutic potential of NOX-mimetic nanozymes in aging and ischemic heart disease and introduce a redox-regulating hydrogel system that addresses both oxidative stress and stem cell integration for effective myocardial repair.

C-C chemokine receptor type 2 (CCR2-) cardiac-resident macrophages (CCR2- cRMs) are known to promote cardiac repair after myocardial infarction (MI). However, the substantial depletion and slow recovery of CCR2- cRMs pose significant barriers in cardiac recovery. Here, we construct a functional conductive cardiac patch (CCP) that can provide exogenously elastic conductive microenvironment and induce endogenously reparative microenvironment mediated by CCR2- cRMs for MI repair. This CCP exhibits suitable mechanical properties, conductivity, and high water retention, reminiscent of natural myocardium, which can actively engage in modulating CCR2- cRM renewal and their cell crosstalk. The functional CCP can promote the expression of Connexin43 between CCR2- cRMs and cardiomyocytes (CMs) and regulate paracrine signaling to activate epicardial cell epithelial-to-mesenchymal transition (EMT) toward endothelial cells using rat and Wt1CreERT2 transgenic lineage tracing mice. Overall, this study provides a promising strategy to construct a synergistic reparative microenvironment for MI repair.

Background Assembled delivery systems (ADS) are a novel drug delivery technology that has emerged in biomedical engineering in recent years. By integrating molecular self-assembly with intelligent functional materials, ADS enables efficient delivery of drugs, genes, and bioactive substances. Compared to conventional delivery systems, ADS offer advantages such as tunable structure, controllable function, and precise responsiveness, demonstrating great potential in targeted therapy, tissue regeneration, and disease diagnosis. However, systematic conceptualization and in-depth research on ADS remain limited. Aim of review This review aims to clarify the fundamental principles, functional characteristics, and multidisciplinary applications of ADS. It elucidates their material design, self-assembly mechanisms, and delivery strategies, emphasizes core advantages of ADS, and outlines current challenges and future directions. It provides theoretical support and technical pathways for developing intelligent, efficient, and personalized ADS, accelerating their translation from laboratory research to clinical application. Key scientific concepts of review The core principle of ADS lies in the synergistic integration of molecular self-assembly and stimulus-responsive smart materials, enabling the rational design of carriers with precise structure–function relationships for the intelligent delivery of bioactive agents. Key advantages of ADS include precise targeting through multi-level strategies, intelligent responsiveness, multimodal synergy, enhanced biocompatibility, and flexible engineering. Representative breakthroughs have been achieved in drug delivery, tissue engineering, and gene editing. Furthermore, the convergence of ADS with emerging technologies, such as artificial intelligence and microfluidics, offers a strategic pathway toward next-generation systems that are efficient, intelligent, and highly precise, establishing new paradigms for biomedical applications.