Abstract A common strategy to deliver bioactive factor-loaded microparticles in a defect site for tissue engineering applications has been to encapsulate the microparticles in a secondary, space-filling, carrier to prevent them from escaping the site of interest. However, there has been growing interest in harnessing microparticles to form granular hydrogels that are composed solely of microparticles. In our lab, thiolated gelatin microparticles (GMPSH) have recently been shown to be a promising carrier for the controlled release of charge-modified peptides via electrostatic interactions. This delivery platform could be employed as a building block to fabricate bioactive granular hydrogels. Thus, the main objective was to develop a GMPSH-based granular hydrogel delivery platform for the controlled release of charge-modified bioactive peptides. We successfully fabricated granular hydrogels using GMPSH via confined swelling, without the need for interparticle crosslinking. GMPSH were loaded with a charge-modified model osteogenic peptide, enabling sustained peptide release from the granular hydrogel for up to 21 days under enzymatic conditions. Importantly, charge modification of the model osteogenic peptide did not adversely affect cell function. These results demonstrate the potential of GMPSH-based granular hydrogels as versatile, controlled release platforms in the field of tissue engineering and drug delivery.
Implant-associated infection remains a critical challenge for orthopedic implants, particularly for bioinert polyetheretherketone (PEEK), which also requires improved osteogenic support. Here, we developed a heterostructured surface on PEEK by coupling a graphite-like layer with a defect-rich TaOx nanoarray. The graphite-like layer promoted uniform TaOx nanoarray formation and may facilitate interfacial electronic coupling, while the TaOx nanoarray showed polarity-dependent and interface-limited charge-transport behavior in model electrical tests. Upon bacterial contact, the heterostructure produced a bacteria-associated 3,3',5,5'-tetramethylbenzidine (TMB) oxidative response and markedly decreased bacterial ATP levels, leading to broad-spectrum antibacterial performance. Thermal annealing attenuated defect-associated TaOx states and weakened antibacterial activity, supporting the involvement of defect-related interfacial states in the antibacterial process. Meanwhile, Ta/H-PEEK supported osteoblast proliferation and osteogenic differentiation in vitro and promoted peri-implant bone formation in vivo. The surface also reduced early bacterial burden in a rat infection model. Collectively, this work demonstrates a heterostructure-based PEEK surface strategy to integrate antibacterial activity with osteogenic compatibility.
Hematoma formation represents one of the earliest biological events during bone healing after bone injury or biomaterial implantation, a process that involves coagulation, provisional matrix formation, innate immune activation and early adaptive immune signaling. During this stage, the hematoma is rapidly infiltrated by neutrophils, monocytes/macrophages, dendritic cells and lymphocytes, which collectively construct the initial osteoimmune microenvironment that modulates subsequent angiogenesis, osteogenesis and osseointegration. Therefore, a systematic elucidation of the hematoma formation process and the regulatory factors governing hematoma behavior provides an important foundation for designing immunomodulatory bone implants. However, most current research has focused primarily on the modulation of macrophages by surface characteristics, relying heavily on simplified in vitro monoculture systems, with limited in vivo temporal characterization of the intact hematoma microenvironment. Insufficient investigation of other immune cells and the regulation of hematomas limits our in-depth understanding of the interplay between hematomas and immunity. This review focuses on the hematoma as a spatiotemporally regulated immune niche and summarizes how material-derived biophysical cues, including surface topography, porosity, wettability and mechanical stiffness, may influence hematoma evolution and the downstream establishment of the osteoimmune microenvironment. This review also discusses the current challenges and future research directions in unraveling the complex material-hematoma-immunity axis, aiming to provide a conceptual framework for the development of translationally relevant immunomodulatory biomaterials for both physiological and pathological bone repair.
Biphasic calcium phosphate (BCP)/poly(methyl methacrylate) (PMMA) bone cement is an effective fixation material for bone tissue regeneration but has drawbacks, including poor hydrophilicity and low biological activity. To overcome these drawbacks, we present a novel human hair keratin-modified BCP/PMMA (KBP) composite. In this study, the influence of human hair keratin on the setting properties, mechanical strength, hydrophilicity, in vitro bioactivity and in vivo biocompatibility of KBP bone cement was investigated. Results show that incorporation of human hair-derived keratin improves the setting properties and hydrophilicity of bone cement, as reflected by a 16% reduction in contact angle, 80% increase in water absorption, 21% increase in porosity and 6% decrease in maximum setting temperature. The modification also improved mesenchymal stem cell viability by 15% and enhanced osteogenic differentiation. The keratin-based composite markedly promoted bone repair in a Sprague-Dawley rat bone defect model, with bone mineral density elevated by 17% and bone volume fraction increased by 15%. In vivo studies further demonstrated that KBP is nontoxic, nonpyrogenic and nonsensitizing, underscoring its potential as a safe and effective alternative for bone tissue repair. In summary, human hair keratin-modified bone cement is a promising candidate for orthopedic clinical applications.
Abstract Foam dressings are vital for exuding wounds, yet antibacterial modification remains challenging and relies heavily on cytotoxic silver compounds. To address these challenges, in this study we developed a process for the antibacterial modification of polyurethane foam dressings using hyperbranched polylysine. The modification process consisted of a simple five-step procedure (soaking–drying–reacting–washing–drying) that did not compromise the foam's intrinsic properties, including hydrophilicity, pore structure, and mechanical performance. The optimized modified foam achieved above 99.9% killing of both methicillin-resistant Staphylococcus aureus and Escherichia coli under experimental conditions, competitive to the commercial silver-containing dressing. The HBPL-modified foam dressings also exhibited Grade 0 cytotoxicity and a hemolysis ratio below 1%, showing good biosafety far better than that of silver dressings. In an infected burn wound model in vivo, the modified foam dressings achieved complete wound closure within 21 d, similar to that of silver dressing. More importantly, the healing quality was significantly improved, including enhanced inflammation resolution, angiogenesis, and collagen remodeling. Given the convenience of operation and the success of modification, the method to prepare antibacterial foam dressings proposed here has great potential for applications in real world.
Abstract Targeted delivery and low toxicity are key considerations in the development of nanomaterials. Herein, we report a strategy to realize accumulation of antibacterial gold nanoparticles (GNPs) in the lungs via regulating particle size. We prepare two types of 3-amino-1,2,4-triazole-5-thiol (ATT)-modified GNPs (A-GNPs) with distinct sizes: small A-GNPs (A-sGNPs) and large A-GNPs (A-lGNPs). The A-sGNPs preferentially accumulate in the lungs, instead of in the liver or kidneys. This targeting ability lowered their toxicity to the liver and kidneys. In contrast, the A-lGNPs exhibit the opposite distribution profile. The A-GNPs especially A-sGNPs show potent antibacterial effects against multidrug-resistant (MDR) Gram-negative bacteria. In a mouse model of pneumonia induced by MDR Pseudomonas aeruginosa (P.a), A-sGNPs achieve a 100% bacterial clearance rate in lung tissue and a 100% animal survival rate, demonstrating ideal therapeutic effects and low systemic toxicity in a size-dependent manner. Our work paves the way for developing nanomaterials with improved bioactivity and ameliorated side effects by tuning particle size, offering broad potential for biomedical applications.
Abstract Skeletal muscle is a highly organized tissue composed of densely packed, uniaxially aligned myofibers that enable directional force generation and normal motor function. Although skeletal muscle has robust endogenous regenerative capacity, this response is overwhelmed by volumetric muscle loss (VML), which heals through fibrosis and scarring rather than functional regeneration, causing permanent structural and functional deficits. Current treatments, including autologous muscle transfer, remain limited by donor-site morbidity, restricted tissue availability, and incomplete restoration of muscle form and function. Thus, a major knowledge gap remains: the lack of an implantable, scalable construct capable of recapitulating native muscle architecture, mechanics, and function. Skeletal muscle regenerative engineering (SMRE), which integrates suitable cell sources, advanced biomaterials, and biomimetic fabrication strategies, offers a promising approach to address this gap. Hydrogels are particularly attractive for SMRE because of their high water content, muscle-like viscoelasticity, tunable properties, and compatibility with biochemical functionalization and diverse fabrication methods. Herein, we critically review hydrogel-based SMRE strategies for engineering myo-mimetic skeletal muscle constructs, including cell sources, hydrogel systems, anisotropic organization cues, and fabrication methods. We further examine key translational barriers, including vascularization, immune response, cell maturation, scalability, and manufacturing reproducibility, and outline actionable future directions for clinical translation.
The myocardium is a highly organized, multilayered anisotropic tissue in which the extracellular matrix (ECM) provides structural guidance for cardiomyocyte alignment, enabling synchronized contraction and efficient electrical conduction. Following myocardial infarction (MI), however, this intricate architecture and electrical integrity are severely disrupted, leading to impaired cardiac function and limited self-repair capacity. Consequently, engineering bio-inspired, multi-strata electroactive scaffolds capable of mimicking the essential architectural and physiological properties of natural heart tissue represents a vital strategy for successful cardiac repair. In this study, we constructed a biomimetic oriented nanofiber-reinforced conductive cardiac patch by integrating dopamine-polypyrrole (DA-PPy) with a GelMa hydrogel matrix. In vitro, the presence of multi-strata oriented nanofibers conferred directional electrical properties to the hydrogel while orchestrating the orderly arrangement of cardiomyocytes. This architecture ensured that cellular alignment followed the fiber axis within each layer, displaying a seamless transition across the stacked interfaces. In a rat MI model, the implanted cardiac patch exhibited remarkable therapeutic effects, including significant improvement of cardiac function, attenuation of ventricular wall thinning and fibrosis, reduced cardiomyocyte apoptosis and oxidative stress, and enhanced angiogenesis within the infarcted region. Furthermore, seeding cardiomyocytes onto the cardiac patch before implantation further amplified these reparative outcomes. Taken together, this work highlights the indispensable nature of re-establishing both the ECM's structural integrity and its electrical properties to foster myocardial regrowth, while positioning our biomimetic conductive cardiac patch as a highly viable therapeutic modality for MI intervention.
To address the clinical challenge of difficult bone defect healing in osteoporosis patients, this study developed a functional delivery system based on a thermosensitive hydrogel loaded with epoxomicin (CS-βGP@10Epoxomicin). This system possesses injectability and body-temperature-triggered in situ gelation properties, overcoming the poor targeting and potential complications associated with systemic drug administration, while achieving dual anti-inflammatory and osteoclast-inhibitory effects within the local bone defect microenvironment. In vitro experiments confirmed its ability to significantly reduce the expression of inflammatory cytokines and osteoclast-related factors. In an ovariectomized (OVX) mouse femoral defect model, local application of this hydrogel significantly increased bone mineral density (BMD) at the defect site by 53.47% compared to the OVX group and downregulated the expression of the inflammatory cytokine interleukin-1 beta (IL-1β) by 27.37%. The system maintained favorable biocompatibility while effectively inhibiting the activation of the nuclear factor kappa-B (NF-κB) signaling pathway, alleviating inflammatory responses and suppressing osteoclast differentiation. Transcriptomic analysis of a public dataset further supported the central role of the NF-κB pathway in the pathological microenvironment of osteoporosis. In summary, this study establishes an intelligent localized delivery strategy that integrates targetability, safety and therapeutic efficacy, providing a potential solution for the local treatment of osteoporotic bone defects.
Abstract Traditional in vivo degradation assessments for resorbable medical devices face challenges due to extreme durations, high costs, and a lack of criteria for reaching tissue-response steady states. This study investigates a 3D-printed PCL/β-TCP bone grafting scaffold by designing a model that correlates multi-stage in vitro accelerated degradation with in vivo implantation across a full 25-month timeline. This integrated approach allows for a systematic evaluation of safety and efficacy by overlapping key degradation stages. Results identified a distinct three-phase degradation pattern; the scaffold provided robust bone regeneration and maintained mechanical support for 18 months, exhibiting excellent osseointegration and biocompatibility throughout. Significantly, the correlation model identified a "risk peak" regarding safety and functionality during degradation. By utilizing this concept to evaluate tissue compatibility, the study provides the experimental evidence necessary to establish "tissue-response homeostasis." Ultimately, this research proposes a novel evaluation strategy rooted in homeostasis principles, significantly improving the reliability of long-term degradation predictions. It establishes an efficient performance validation pathway for clinical scenarios like alveolar bone repair and offers vital guidance for the development of regulatory systems for similar resorbable medical devices.
Embolic microspheres are important for the interventional treatment of solid tumors, but it is a dilemma for microspheres to keep sufficient strength and resilience. Herein, we propose a strategy to fabricate core-shell poly(vinyl alcohol) microspheres with gradient crosslinking (GCL) on an industrial scale to solve the dilemma. The synthesized GCL microspheres exhibit superior mechanical characteristics in comparison to the homogeneous microspheres and the conventional core-shell microspheres produced by standard one-step and two-step methods, respectively. An in vitro model is conducted to assess the distribution in the vascular network and migration over time of three microspheres. The GCL microspheres possess optimal strength and flexibility, facilitating distal vascular embolization and reducing the risk of microsphere migration over time. The performances are validated in vivo with the porcine renal model in large animal experiments. Clinical trials addressing liver cancer further confirm the embolic efficacy and safety of the GCL microspheres in humans. The relationship between mechanical properties and embolic efficiency offers valuable insights for the development of other embolic agents in the formulism of interventional therapy.
Abstract Tissue filling represents an effective strategy for correcting facial contour irregularities and eliminating facial wrinkles. In recent years, silica-based biomaterials have emerged as promising candidates for the development of novel tissue fillers, owing to their superior physical support and bioactivity. In this study, an injectable skin tissue filler (Col-SiO2) is developed by combining silica microspheres (SiO2, 20-45 μm) with biocompatible collagen hydrogel. The SiO2 microspheres in Col-SiO2 filler are capable of offering a spherical configuration for physical support and gradually releasing bioactive SiO32- ions, thereby simultaneously enabling wrinkle filling and inducing collagen regeneration. The Col-SiO2 filler shows appropriate mechanical injectability (injection force < 5 N) owing to its shear-thinning property, meeting the practical requirements for clinical application. Furthermore, the Col-SiO2 filler can effectively promote the proliferation, migration and collagen secretion of human skin fibroblasts cells (HSFs). Most importantly, the Col-SiO2 filler can induce collagen regeneration in vivo and maintain long-term filling stability, achieving superior subcutaneous filling and collagen deposition effects compared to hydroxyapatite (HAP)- and polymethyl methacrylate (PMMA)-based tissue fillers. Overall, the SiO2 microspheres offer a novel and effective strategy for developing skin tissue fillers aimed at wrinkle smoothing and collagen regeneration.
Abstract A PTMC coating with the embedding of polyphenols/ebselen was proposed to construct on the AZ31 alloy, with the aim of surface modification on cardiovascular stents. Ebselen (Ebs) can endow the coating with the ability of catalytically releasing nitric oxide while polyphenols impart stable corrosion resistance to the coating by complexing with metal ions. In vitro corrosion resistance tests showed that icorr of AZ31-P/2.5% Ebs (8.91 × 10−8 A/cm2) is two orders of magnitude lower than that of AZ31 (6.16 × 10−6 A/cm2). During the 10-day immersion in PBS, the impedance modulus value of AZ31-P/2.5%Ebs was consistently higher than that of the other samples. AZ31-P/1%Ebs coating released least amount of H2 (0.315 mL) and the pH value (∼7.5) maintained almost constant during the 360 hours immersion. During a 30-day immersion, the NO catalytic release rates of AZ31-P/2.5%Ebs remained within the range of 3.5-0.9&cenveo_unknown_entity_wingdings2_F0CD;10−10 mol/cm2/min. The biological evaluation results showed that the AZ31-P/2.5%Ebs exhibits anticoagulant, endothelial cell growth promotion and smooth muscle proliferation inhibition functions. This coating strategy effectively slowed down the degradation rate of the magnesium substrate, and achieved multiple functions, which is of great significance for the surface design of magnesium-based vascular stents.
Abstract Methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds present a significant clinical challenge due to persistent inflammation and impaired tissue regeneration. Here, we developed an IR780SS-engineered hydrogel with a hydrogen-bond-regulated network for infected wound treatment. In this system, IR780SS serves not only as a NIR photosensitizer, but also as an active component that interacts with the hydrogel matrix through hydrogen bonding, hydrophobic interactions, and π-π stacking. These interactions improve the stability and dispersion of IR780SS within the hydrogel and help preserve its photoactivity. Under 808 nm NIR irradiation, the hydrogel generates mild local hyperthermia and abundant ROS, producing antibacterial effects through combined action of PTT and PDT mechanisms. This treatment disrupts bacterial membranes and induces severe oxidative damage inside bacterial cells, leading to the near-complete elimination of drug-resistant bacteria. In a MRSA-infected wound model, rapid bacterial clearance promoted the transition from the inflammatory phase to the proliferative phase and resulted in a wound closure rate of 85.6% on day 11. Histological and immunofluorescence analyses further confirmed improved tissue repair, including enhanced re-epithelialization, angiogenic responses, and collagen remodeling, as evidenced by increased cytokeratin 14 (CK14) and smooth muscle actin (α-SMA) expression, together with more organized collagen deposition. These results suggest that integrating IR780SS into a hydrogen-bonded hydrogel not only enables effective antibacterial phototherapy but also facilitates functional wound reconstruction, providing valuable insight into the clinical development of regenerative dressings for MRSA-infected wounds.
Abstract Organoids provide physiologically relevant platforms for disease modeling and drug screening, but their performance depends critically on the extracellular matrix (ECM). Matrigel, the current standard, suffers from undefined composition, batch-to-batch variability, and limited tunability. We engineered a photo-crosslinkable hyaluronic acid-collagen (HA-collagen) composite hydrogel using riboflavin-mediated blue-light activation and examined how the collagen-to-HA ratio modulates physicochemical and biological properties. Storage modulus scaled with HA content (Col4HA1: 156 Pa; Col3HA1: 216 Pa; Col2HA1: 824 Pa vs 6 Pa for Matrigel), and organoid formation efficiency was inversely correlated with stiffness: Col2HA1 yielded significantly fewer organoids than Matrigel, whereas Col4HA1 fell within a mechanically permissive range and supported organoid formation comparable to Matrigel. Col4HA1 retained 48.6 ± 2.3% of its mass throughout the 14-day organoid culture period, whereas Matrigel underwent complete degradation by day 10. Organoids in Col4HA1 maintained stemness (Lgr5, Sox9) and differentiation markers (Villin), avoided stress-associated lysozyme elevation, and preserved E-cadherin/β-catenin junctions and epithelial polarity. Critically, Col4HA1 sustained stable Lgr5 expression across passages, whereas Matrigel showed passage-dependent Lgr5 elevation indicative of hyperproliferative drift. The photo-crosslinkable HA-collagen hydrogel offers a chemically defined, tunable, and reproducible Matrigel alternative for intestinal organoid research and regenerative-medicine applications.
Abstract The geometric configuration of prosthetic aortic valve is a key determinant of its mechanical response and associated hemodynamics during the cardiac cycle. In this work, high-fidelity fluid–structure interaction (FSI) analysis is conducted to provide physical insight into the effects of geometry on valve design. We integrate the data from the Doppler experiments and the Windkessel model for the inlet velocity and outlet pressure conditions, respectively. The arbitrary Lagrangian–Eulerian (ALE) method is employed to address the two-way interaction between hyperelastic leaflets undergoing periodic large deformation and the surrounding blood flow. The effects of leaflet aspect ratio (AR) and blood non-Newtonian properties on mechanical performance are systematically investigated. The FSI analysis shows that increasing AR elevates von Mises stress, wall shear stress (WSS), blood velocity magnitude, transvalvular pressure gradient (TPG), and regurgitation fraction (RF), while reducing geometric orifice area (GOA). These trends are opposite to the results from pure structural mechanical analysis. As AR increases from 0.86 to 1.26, the maximum von Mises stress increases by 58.66%, whereas GOA decreases by 71.54%. For the AR = 1.26 valve, the jet deviates from the centerline toward the lower vessel wall during peak systole and the subsequent deceleration phase, resulting in asymmetric deformation.
Abstract Despite the widespread use of various bone repair materials, ideal scaffolds with excellent cell adhesion and satisfactory osteogenesis are still urgently needed for bone defect regeneration. The self-assembling peptide RADA16‑I hydrogel has been widely used for bone defect repair owing to its excellent biocompatibility and favorable cytocompatibility, yet its application is limited by insufficient osteogenesis and weak cell adhesion. In this study, a novel peptide RADA16‑TRSAW was designed by conjugating the positively charged osteogenic short peptide TRSAW to RADA16‑I via solid-phase synthesis. TRSAWmax (mixture of RADA16‑TRSAW and RADA16‑I as 1:1) carried net positive charge, maintained stable a β‑sheet secondary structure, retained self-assembly capability, and readily formed a hydrogel in PBS. The resulting hydrogel showed a microstructure and rheological properties similar to those of RADA16‑I hydrogel, suitable for cell growth, but with significantly enhanced cell adhesion owing to cationic arginine residues. RNA‑seq confirmed the upregulation of adhesion-related genes and pathways. Moreover, TRSAWmax exhibited excellent biocompatibility, promoted hMSC osteogenic differentiation through the Src‑Erk pathway in vitro, and demonstrated superior osteogenic capability in vivo. This work provides a highly adhesive and osteogenic peptide hydrogel candidate for accelerating bone tissue regeneration.
Skin fibrosis is a pathological process characterized by excessive extracellular matrix (ECM) deposition and tissue remodeling following chronic injury or inflammation. Current treatments remain limited, highlighting the need for more effective therapeutic strategies. Tissue-engineered hydrogels (TEHs) have emerged as promising platforms for fibrosis intervention due to their biocompatibility and tunable physicochemical properties. This review summarizes recent advances in TEH-based approaches for skin fibrosis, with a focus on the design of smart hydrogels. Unlike conventional scaffolds, smart hydrogels can sense pathological changes in the fibrotic microenvironment and respond to disease-associated cues, including pH changes, elevated reactive oxygen species (ROS), enzymatic activity and mechanical alterations. These adaptive systems enable controlled cargo delivery and local microenvironment regulation. We further discuss multifunctional hydrogel platforms incorporating bioactive molecules, nucleic acids and nanomaterials to modulate key fibrotic pathways. Finally, we highlight current challenges in clinical translation and future perspectives for developing safer and more effective responsive hydrogel therapies for skin fibrosis.
Bacterial infection remains a major barrier to effective wound healing by disrupting immune homeostasis, sustaining chronic inflammation and impairing tissue regeneration. Herein, we present a green, sustainable strategy for fabricating antibacterial, immunomodulatory bioactive granular hydrogels (GHs) for infected wound regeneration. An amino-alcohol ether prepolymer (MP) was first synthesized via epoxy-amine click chemistry and subsequently complexed with the natural polyphenol tannic acid (TA), thereby triggering phase-separation-driven supramolecular self-assembly into GHs without additional crosslinkers. To elucidate the polymer assembly mechanism and identify the bioactive concentration threshold, agarose was introduced as a fourth component to construct A/MP@TA GHs. The results showed that increasing the agarose content progressively transformed the granular architecture into a sheet-like network, whereas A/MP@TA3, which represents the lowest agarose ratio that preserves the granular morphology, exhibited potent antibacterial and antioxidant activities and enhanced fibroblast migration. In a bacteria-infected wound, A/MP@TA3 still markedly accelerated wound closure while promoting collagen deposition and angiogenesis. Mechanistically, sustained TA release reprogrammed the microenvironment by activating the KEAP1/Nrf2/HO-1 and suppressing NF-κB signaling, thereby driving macrophage polarization toward a pro-regenerative M2 phenotype. This work establishes a simple, cost-effective and environmentally friendly platform for fabricating multifunctional hydrogel dressings and provides a biomaterial-based strategy for remodeling the immune microenvironment.
Although hydrophobic drugs demonstrate the promising therapeutic efficacy for peripheral artery disease in vitro, their in vivo performance is often hindered by low bioavailability due to inherent hydrophobicity. To address this, an injectable, self-healing and curcumin-sustained-release hydrogel (CGP hydrogel) using a gelatin/polyvinyl alcohol hydrogel (GP hydrogel) was developed. The CGP hydrogel effectively preserved the DPPH radical-scavenging activity of curcumin at room temperature. Meanwhile, in the murine hindlimb ischemia model, a single intramuscular injection of CGP following femoral artery ligation significantly improved the motor function of the ischemic limb compared to curcumin suspension. This superior therapeutic outcome is attributed to the sustained release of curcumin from the CGP hydrogel. Mechanistically, we found that CGP, but not GP, inhibited the expression of Atp6v0d2 in ischemic skeletal muscle cells and suppressed ischemia-induced autophagy. The inhibition of autophagy may mitigate tissue and cellular necrosis and promote the expression of Myogenin. Furthermore, CGP reduced the expression of pro-fibrotic factors such as Tgfb1 and Ctgf and prevented skeletal muscle fibrosis. In summary, the CGP hydrogel, through its sustained release of curcumin, inhibits ischemia-induced autophagy, alleviates necrosis and fibrosis in skeletal muscle tissue and preserves motor function in the ischemic limb.
