Fabrication of 3D Biomimetic Smooth Muscle Using Magnetic Induction and Bioprinting for Tissue Regeneration.

Smooth muscles play a vital role in peristalsis, tissue constriction, and relaxation but lack adequate self-repair capability for addressing extensive muscle defects. Engineering scaffolds have been broadly proposed to repair the muscle tissue. However, efforts to date have shown that those engineered scaffolds focus on cell alignment in 2-dimension (2D) and fail to direct muscle cells to align in 3D area, which is irresolvable to remodel the muscle architecture and restore the muscle functions like contraction and relaxation. Herein, we introduced an iron oxide (Fe3O4) filament-embedded gelatin (Gel)-silk fibroin composite hydrogel in which the oriented Fe3O4 self-assembled and functioned as micro/nanoscale geometric cues to induce cell alignment growth. The hydrogel scaffold can be designed to fabricate aligned or anisotropic muscle by combining embedded 3D bioprinting with magnetic induction to accommodate special architectures of muscular tissues in the body. Particularly, the bioprinted muscle-like matrices effectively promote the self-organization of smooth muscle cells (SMCs) and the directional differentiation of bone marrow mesenchymal stem cells (BMSCs) into SMCs. This biomimetic muscle accelerated tissue regeneration, enhancing intercellular connectivity within the muscular tissue, and the deposition of fibronectin and collagen I. This work provides a novel approach for constructing engineered biomimetic muscles, holding significant promise for clinical treatment of muscle-related diseases in the future.

Analysis of the CPZ/Wnt4 osteogenic pathway for high-bonding-strength composite-coated magnesium scaffolds through transcriptomics.

Magnesium (Mg)-based scaffolds are garnering increasing attention as bone repair materials owing to their biodegradability and mechanical resemblance to natural bone. Their effectiveness can be augmented by incorporating surface coatings to meet clinical needs. However, the limited bonding strength and unclear mechanisms of these coatings have impeded the clinical utility of scaffolds. To address these issues, this study introduces a composite coating of high-bonding-strength polydopamine-microarc oxidation (PDA-MHA) on Mg-based scaffolds. The results showed that the PDA-MHA coating achieved a bonding strength of 40.56 ± 1.426 MPa with the Mg scaffold surface, effectively enhancing hydrophilicity and controlling degradation rates. Furthermore, the scaffold facilitated bone regeneration by influencing osteogenic markers such as RUNX-2, OPN, OCN, and VEGF. Transcriptomic analyses further demonstrated that the PDA-MHA/Mg scaffold upregulated carboxypeptidase Z expression and activated the Wnt-4/ß-catenin signaling pathway, thereby promoting bone regeneration. Overall, this study demonstrated that PDA can synergistically enhance bone repair with Mg scaffold, broadening the application scenarios of Mg and PDA in the field of biomaterials. Moreover, this study provides a theoretical underpinning for the application and clinical translation of Mg-based scaffolds in bone tissue engineering endeavors.

Fullerene Derivatives for Tumor Treatment: Mechanisms and Application.

Fullerenes hold tremendous potential as alternatives to conventional chemotherapy or radiotherapy for tumor treatment due to their abilities to photodynamically kill tumor cells, destroy the tumor vasculature, inhibit tumor metastasis and activate anti-tumor immune responses, while protecting normal tissue through antioxidative effects. The symmetrical hollow molecular structures of fullerenes with abundant C=C bonds allow versatile chemical modification with diverse functional groups, metal clusters and biomacromolecules to synthesize a wide range of fullerene derivatives with increased water solubility, improved biocompatibility, enhanced photodynamic properties and stronger targeting abilities. This review introduces the anti-tumor mechanisms of fullerenes and summarizes the most recent works on the functionalization of fullerenes and the application of fullerene derivatives in tumor treatment. This review aims to serve as a valuable reference for further development and clinical application of anti-tumor fullerene derivatives.

Highly sensitive microfluidic sensor using integrated optical fiber and real-time single-cell Raman spectroscopy for diagnosis of pancreatic cancer.

Pancreatic cancer is notoriously lethal due to its late diagnosis and poor patient response to treatments, posing a significant clinical challenge. This study introduced a novel approach that combines a single-cell capturing platform, tumor-targeted silver (Ag) nanoprobes, and precisely docking tapered fiber integrated with Raman spectroscopy. This approach focuses on early detection and progression monitoring of pancreatic cancer. Utilizing tumor-targeted Ag nanoparticles and tapered multimode fibers enhances Raman signals, minimizes light loss, and reduces background noise. This advanced Raman system allows for detailed molecular spectroscopic examination of individual cells, offering more practical information and enabling earlier detection and accurate staging of pancreatic cancer compared to conventional multicellular Raman spectroscopy. Transcriptomic analysis using high-throughput gene screening and transcriptomic databases confirmed the ability and accuracy of this method to identify molecular changes in normal, early, and metastatic pancreatic cancer cells. Key findings revealed that cell adhesion, migration, and the extracellular matrix are closely related to single-cell Raman spectroscopy (SCRS) results, highlighting components such as collagen, phospholipids, and carotene. Therefore, the SCRS approach provides a comprehensive view of the molecular composition, biological function, and material changes in cells, offering a novel, accurate, reliable, rapid, and efficient method for diagnosing and monitoring pancreatic cancer.

A nomogram model based on SII, AFR, and NLR to predict infectious complications of laparoscopic hysterectomy for cervical cancer.

BACKGROUND: This study aimed to investigate the potential risk factors associated with postoperative infectious complications following laparoscopic hysterectomy for cervical cancer and to develop a prediction model based on these factors. METHODS: This study enrolled patients who underwent selective laparoscopic hysterectomy for cervical cancer between 2019 and 2024. A multivariate regression analysis was performed to identify independent risk factors associated with postoperative infectious complications. A nomogram prediction model was subsequently constructed and evaluated using R software. RESULTS: Out of 301 patients were enrolled and 38 patients (12.6%) experienced infectious complications within one month postoperatively. Six variables were independent risk factors for postoperative infectious complications: age ≥ 60 (OR: 3.06, 95% confidence interval (CI): 1.06-8.79, P = 0.038), body mass index (BMI) ≥ 24.0 (OR: 3.70, 95%CI: 1.4-9.26, P = 0.005), diabetes (OR: 2.91, 95% CI: 1.10-7.73, P = 0.032), systemic immune-inflammation index (SII) ≥ 830 (OR: 6.95, 95% CI: 2.53-19.07, P < 0.001), albumin-to-fibrinogen ratio (AFR) < 9.25 (OR: 4.94, 95% CI: 2.02-12.07, P < 0.001), and neutrophil-to-lymphocyte ratio (NLR) ≥ 3.45 (OR: 7.53, 95% CI: 3.04-18.62, P < 0.001). Receiver operator characteristic (ROC) curve analysis indicated an area under the curve (AUC) of this nomogram model of 0.928, a sensitivity of 81.0%, and a specificity of 92.1%. CONCLUSIONS: The nomogram model, incorporating age, BMI, diabetes, SII, AFR, and NLR, demonstrated strong predictive capabilities for postoperative infectious complications following laparoscopic hysterectomy for cervical cancer.

Polydimethylsiloxane enabled triple-action water-resistant coating with desirable relaxation rate in clear aligner.

Clear aligners undergo rapid stress relaxation in warm, moist oral environments, compromising therapeutic effectiveness and longevity of treatment. To develop an innovative multilayer composite material with improved stability and reduced stress release, we have engineered an innovative coating characterized by the surface aggregation of polydimethylsiloxane (PDMS), which imparts a pronounced hydrophobic effect. In addition, the chemically and physically cross-linked structure of the coating reduces the free volume created by molecular chain rearrangement owing to the presence of water molecules, thereby minimizing water penetration into the coating. Concurrently, the coating's internal structure is enriched with numerous polar functional groups to capture water molecules that penetrate into the inside of the coating. Through combination of these mechanisms, water molecules are effectively sequestered, thereby impeding their penetration into the polyethylene terephthalate glycol (PETG) substrate. The impact of the polydimethylsiloxane content on the triple-action water-resistance mechanisms was thoroughly examined using attenuated total reflection (ATR)-Fourier transform infrared (FTIR), water absorption rate, water swelling rate, and X-ray photoelectron spectroscopy. The low surface energy cross-linked polyurethane coating is applied to the polyethylene terephthalate glycol (PETG) substrate to create a novel composite material with specific mechanical properties and reduced stress relaxation. The composite material remains stable in simulated oral environment with linear swelling rate of 0.58 % upon water absorption. Additionally, the stress release rate of the composite material within 336 h is notably lower (23.64 %) than that of PETG (62.29 %).

Bioprinted biomimetic hydrogel matrices guiding stem cell aggregates for enhanced chondrogenesis and cartilage regeneration.

Articular cartilage tissue has limited self-repair capabilities, with damage frequently progressing to irreversible degeneration. Engineered tissues constructed through bioprinting and embedded with stem cell aggregates offer promising therapeutic alternatives. Aggregates of bone marrow mesenchymal stromal cells (BMSCs) demonstrate enhanced and more rapid chondrogenic differentiation than isolated cells, thus facilitating cartilage repair. However, it remains a key challenge to precisely control biochemical microenvironments to regulate cellular adhesion and cohesion within bioprinted matrices simultaneously. Herein, this work reports a bioprintable hydrogel matrix with high cellular adhesion and aggregation properties for cartilage repair. The hydrogel comprises an enhanced cell-adhesive gelatin methacrylate and a cell-cohesive chitosan methacrylate (CHMA), both of which are subjected to photo-initiated crosslinking. By precisely adjusting the CHMA content, the mechanical stability and biochemical cues of the hydrogels are finely tuned to promote cellular aggregation, chondrogenic differentiation and cartilage repair implantation. Multi-layer constructs encapsulated with BMSCs, with high cell viability reaching 91.1%, are bioprinted and photo-crosslinked to support chondrogenic differentiation for 21 days. BMSCs rapidly form aggregates and display efficient chondrogenic differentiation both on the hydrogels and within bioprinted constructs, as evidenced by the upregulated expression of Sox9, Aggrecan and Collagen 2a1 genes, along with high protein levels. Transplantation of these BMSC-laden bioprinted hydrogels into cartilaginous defects demonstrates effective hyaline cartilage repair. Overall, this cell-responsive hydrogel scaffold holds immense promise for applications in cartilage tissue engineering.

Construction methods and biomedical applications of PVA-based hydrogels.

Polyvinyl alcohol (PVA) hydrogel is favored by researchers due to its good biocompatibility, high mechanical strength, low friction coefficient, and suitable water content. The widely distributed hydroxyl side chains on the PVA molecule allow the hydrogels to be branched with various functional groups. By improving the synthesis method and changing the hydrogel structure, PVA-based hydrogels can obtain excellent cytocompatibility, flexibility, electrical conductivity, viscoelasticity, and antimicrobial properties, representing a good candidate for articular cartilage restoration, electronic skin, wound dressing, and other fields. This review introduces various preparation methods of PVA-based hydrogels and their wide applications in the biomedical field.

The occurrence and development mechanisms of esophageal stricture: state of the art review.

BACKGROUND: Esophageal strictures significantly impair patient quality of life and present a therapeutic challenge, particularly due to the high recurrence post-ESD/EMR. Current treatments manage symptoms rather than addressing the disease's etiology. This review concentrates on the mechanisms of esophageal stricture formation and recurrence, seeking to highlight areas for potential therapeutic intervention. METHODS: A literature search was conducted through PUBMED using search terms: esophageal stricture, mucosal resection, submucosal dissection. Relevant articles were identified through manual review with reference lists reviewed for additional articles. RESULTS: Preclinical studies and data from animal studies suggest that the mechanisms that may lead to esophageal stricture include overdifferentiation of fibroblasts, inflammatory response that is not healed in time, impaired epithelial barrier function, and multimethod factors leading to it. Dysfunction of the epithelial barrier may be the initiating mechanism for esophageal stricture. Achieving perfect in-epithelialization by tissue-engineered fabrication of cell patches has been shown to be effective in the treatment and prevention of esophageal strictures. CONCLUSION: The development of esophageal stricture involves three stages: structural damage to the esophageal epithelial barrier (EEB), chronic inflammation, and severe fibrosis, in which dysfunction or damage to the EEB is the initiating mechanism leading to esophageal stricture. Re-epithelialization is essential for the treatment and prevention of esophageal stricture. This information will help clinicians or scientists to develop effective techniques to treat esophageal stricture in the future.

An oxidized dextran-composite self-healing coated magnesium scaffold reduces apoptosis to induce bone regeneration.

Self-healing coatings have shown promise in controlling the degradation of scaffolds and addressing coating detachment issues. However, developing a self-healing coating for magnesium (Mg) possessing multiple biological functions in infectious environments remains a significant challenge. In this study, a self-healing coating was developed for magnesium scaffolds using oxidized dextran (OD), 3-aminopropyltriethoxysilane (APTES), and nano-hydroxyapatite (nHA) doped micro-arc oxidation (MHA), named OD-MHA/Mg. The results demonstrated that the OD-MHA coating effectively addresses coating detachment issues and controls the degradation of Mg in an infectious environment through self-healing mechanisms. Furthermore, the OD-MHA/Mg scaffold exhibits antibacterial, antioxidant, and anti-apoptotic properties, it also promotes bone repair by upregulating the expression of osteogenesis genes and proteins. The findings of this study indicate that the OD-MHA coated Mg scaffold possessing multiple biological functions presents a promising approach for addressing infectious bone defects. Additionally, the study showcases the potential of polysaccharides with multiple biological functions in facilitating tissue healing even in challenging environments.

Cation-crosslinkedκ-carrageenan sub-microgel medium for high-quality embedded bioprinting.

Three-dimensional (3D) bioprinting embedded within a microgel bath has emerged as a promising strategy for creating intricate biomimetic scaffolds. However, it remains a great challenge to construct tissue-scale structures with high resolution by using embedded 3D bioprinting due to the large particle size and polydispersity of the microgel medium, as well as its limited cytocompatibility. To address these issues, novel uniform sub-microgels of cell-friendly cationic-crosslinked kappa-carrageenan (κ-Car) are developed through an easy-to-operate mechanical grinding strategy. Theseκ-Car sub-microgels maintain a uniform submicron size of around 642 nm and display a rapid jamming-unjamming transition within 5 s, along with excellent shear-thinning and self-healing properties, which are critical for the high resolution and fidelity in the construction of tissue architecture via embedded 3D bioprinting. Utilizing this new sub-microgel medium, various intricate 3D tissue and organ structures, including the heart, lungs, trachea, branched vasculature, kidney, auricle, nose, and liver, are successfully fabricated with delicate fine structures and high shape fidelity. Moreover, the bone marrow mesenchymal stem cells encapsulated within the printed constructs exhibit remarkable viability exceeding 92.1% and robust growth. Thisκ-Car sub-microgel medium offers an innovative avenue for achieving high-quality embedded bioprinting, facilitating the fabrication of functional biological constructs with biomimetic structural organizations.

Axial assembly of AuNR for tumor theranostics via Zn2+-GSH chelation induced degradation of AuNR@ZIF-8 heterostructures.

Tumor microenvironment responsive photothermal ablation is a noninvasive and accurately targeted approach for cancer therapy. Herein, an intracellular directional assembly strategy for enhanced photothermal therapy (PTT) was realized by using ZIF-8 encapsulated Au nanorod (AuNR) heterostructure as the precursor of photothermal convertible material. The ZIF-8 shell selectively degraded in tumor cells upon the chelation between GSH and Zn2+, while the as-formed Zn(SG) connected the released AuNR in end-to-end fashion. The coating of ZIF-8 shell significantly improves the stability and targeting of AuNR, and the released Zn2+ shielded the GSH binding site on the lateral side of AuNR, increased the plasmonic coupling efficiency of AuNR assembly geometer. This design enabled atomic-economical, efficient and low-side effect targeted photothermal therapy through the effective integration of heterostructures.

Flexible Organic Photovoltaic-Powered Hydrogel Bioelectronic Dressing With Biomimetic Electrical Stimulation for Healing Infected Diabetic Wounds.

Electrical stimulation (ES) is proposed as a therapeutic solution for managing chronic wounds. However, its widespread clinical adoption is limited by the requirement of additional extracorporeal devices to power ES-based wound dressings. In this study, a novel sandwich-structured photovoltaic microcurrent hydrogel dressing (PMH dressing) is designed for treating diabetic wounds. This innovative dressing comprises flexible organic photovoltaic (OPV) cells, a flexible micro-electro-mechanical systems (MEMS) electrode, and a multifunctional hydrogel serving as an electrode-tissue interface. The PMH dressing is engineered to administer ES, mimicking the physiological injury current occurring naturally in wounds when exposed to light; thus, facilitating wound healing. In vitro experiments are performed to validate the PMH dressing's exceptional biocompatibility and robust antibacterial properties. In vivo experiments and proteomic analysis reveal that the proposed PMH dressing significantly accelerates the healing of infected diabetic wounds by enhancing extracellular matrix regeneration, eliminating bacteria, regulating inflammatory responses, and modulating vascular functions. Therefore, the PMH dressing is a potent, versatile, and effective solution for diabetic wound care, paving the way for advancements in wireless ES wound dressings.

FOXD1 expression-based prognostic model for uveal melanoma.

FOXD1, a new member of the FOX transcription factor family, serves as a mediator and biomarker for cell reprogramming. But its contribution to prognosis of uveal melanoma (UVM) is unclear. This study demonstrated that FOXD1 might promote tumor growth and invasion, because FOXD1 expression was negatively correlated with overall survival, progression-free survival, and disease-specific survival in UVM patients. This conjecture was verified in cell culture with human uveal melanoma cell line (MUM2B) as model cells. Additionally, the biological mechanisms of FOXD1 based on FOXD1-related genomic spectrum, molecular pathways, tumor microenvironment, and drug treatment sensitivity were examined using The Cancer Genome Atlas (TCGA) database, aiming to reasonably explain why FOXD1 leads to poor prognosis of UVM. On these bases, a novel tumor prognostic model was established using the FOXD1-related immunomodulators TMEM173, TNFRSF4, TNFSF13, and ULBP1, which will enable the stratification of disease seriousness and clinical treatment for patients.

Engineered muscle from micro-channeled PEG scaffold with magnetic Fe3O4 fixation towards accelerating esophageal muscle repair.

Engineered scaffolds are used for repairing damaged esophagus to allow the precise alignment and movement of smooth muscle for peristalsis. However, most of these scaffolds focus solely on inducing cell alignment through directional apparatus, often overlooking the promotion of muscle tissue formation and causing reduced esophageal muscle repair effectiveness. To address this issue, we first introduced aligned nano-ferroferric oxide (Fe3O4) assemblies on a micropatterned poly(ethylene glycol) (PEG) hydrogel to form micro-/nano-stripes. Further modification using a gold coating was found to enhance cellular adhesion, orientation and organization within these micro-/nano-stripes, which consequently prevented excessive adhesion of smooth muscle cells (SMCs) to the thin PEG ridges, thereby effectively confining the cells to the Fe3O4-laid channels. This architectural design promotes the alignment of the cytoskeleton and elongation of actin filaments, leading to the organized formation of muscle bundles and a tendency for SMCs to adopt synthetic phenotypes. Muscle patches are harvested from the micro-/nano-stripes and transplanted into a rat esophageal defect model. In vivo experiments demonstrate the exceptional viability of these muscle patches and their ability to accelerate the regeneration of esophageal tissue. Overall, this study presents an efficient strategy for constructing muscle patches with directional alignment and muscle bundle formation of SMCs, holding significant promise for muscle tissue regeneration.

Biological importance of human amniotic membrane in tissue engineering and regenerative medicine.

The human amniotic membrane (hAM) is the innermost layer of the placenta. Its distinctive structure and the biological and physical characteristics make it a highly biocompatible material in a variety of regenerative medicine applications. It also acts as a supply of bioactive factors and cells, which indicate the advantages over other tissues. In this review, we firstly discussed the biological properties of hAM-derived cells in vivo or in vitro, along with their stemness of markers, pointing out a promising source of stem cells for regenerative medicine. Then, we systematically summarized current knowledge on the collection, preparation, preservation, and decellularization of hAM, as well as their characteristics helping to improve the understanding of applications in tissue engineering. Finally, we highlighted the recent advances in which hAM has undergone additional modifications to achieve an adequate perspective of regenerative medicine applications. More investigations are required in utilizing appropriate modifications to enhance the therapeutic effectiveness of hAM in the future.

Platelet Rich Plasma Loaded Multifunctional Hydrogel Accelerates Diabetic Wound Healing via Regulating the Continuously Abnormal Microenvironments.

Continuous oxidative stress and cellular dysfunction caused by hyperglycemia are distinguishing features of diabetic wounds. It has been a great challenge to develop a smart dressing that can accelerate diabetic wound healing through regulating abnormal microenvironments. In this study, a platelet rich plasma (PRP) loaded multifunctional hydrogel with reactive oxygen species (ROS) and glucose dual-responsive property is reported. It can be conveniently prepared with PRP, dopamine (DA) grafted alginate (Alg-DA), and 6-aminobenzo[c][1,2]oxaborol-1(3H)-ol (ABO) conjugated hyaluronic acid (HA-ABO) through ionic crosslinks, hydrogen-bond interactions, and boronate ester bonds. The hydrogel possesses injectability, moldability, tissue adhesion, self-healing, low hemolysis, and hemostasis performances. Its excellent antioxidant property can create a low oxidative stress microenvironment for other biological events. Under an oxidative stress and/or hyperglycemia state, the hydrogel can degrade at an accelerated rate to release a variety of cytokines derived from activated blood platelets. The result is a series of positive changes that are favorable for diabetic wound healing, including fast anti-inflammation, activated macrophage polarization toward M2 phenotype, promoted migration and proliferation of fibroblasts, as well as expedited angiogenesis. This work provides an efficient strategy for chronic diabetic wound management and offers an alternative for developing a new-type PRP-based bioactive wound dressing.

VDVM: An automatic vertebrae detection and vertebral segment matching framework for C-arm X-ray image identification.

BACKGROUND: C-arm fluoroscopy, as an effective diagnosis and treatment method for spine surgery, can help doctors perform surgery procedures more precisely. In clinical surgery, the surgeon often determines the specific surgical location by comparing C-arm X-ray images with digital radiography (DR) images. However, this heavily relies on the doctor's experience. OBJECTIVE: In this study, we design a framework for automatic vertebrae detection as well as vertebral segment matching (VDVM) for the identification of vertebrae in C-arm X-ray images. METHODS: The proposed VDVM framework is mainly divided into two parts: vertebra detection and vertebra matching. In the first part, a data preprocessing method is used to improve the image quality of C-arm X-ray images and DR images. The YOLOv3 model is then used to detect the vertebrae, and the vertebral regions are extracted based on their position. In the second part, the Mobile-Unet model is first used to segment the vertebrae contour of the C-arm X-ray image and DR image based on vertebral regions respectively. The inclination angle of the contour is then calculated using the minimum bounding rectangle and corrected accordingly. Finally, a multi-vertebra strategy is applied to measure the visual information fidelity for the vertebral region, and the vertebrae are matched based on the measured results. RESULTS: We use 382 C-arm X-ray images and 203 full length X-ray images to train the vertebra detection model, and achieve a mAP of 0.87 in the test dataset of 31 C-arm X-ray images and 0.96 in the test dataset of 31 lumbar DR images. Finally, we achieve a vertebral segment matching accuracy of 0.733 on 31 C-arm X-ray images. CONCLUSIONS: A VDVM framework is proposed, which performs well for the detection of vertebrae and achieves good results in vertebral segment matching.

Stem-loop RT-qPCR system for multiplex miRNA profiling and its application in wound healing-specific biomarker identification.

MiRNAs are biomarkers widely used in research but their clinical application is still challenging due to their low expression levels. Current methods for miRNA detection involve separate transcription and quantification for each target, which is costly and unsuitable for large sample sizes. This study provides a strategy for designing and screening miRNA-specific stem-loop reverse transcription (RT) primers, which enable the simultaneous transcription of three miRNAs and U6, and the concurrent detection of miRNA and U6 in the same transcript using TaqMan probes labeled with different dyes. The strategy was successfully employed to establish multiplex RT-PCR and dual-quantitative PCR (qPCR) quantification systems for 21 differentially expressed miRNAs during wound healing. The corresponding system can accurately quantify the cell culture samples containing miR-7a-5p mimic, miR-7a-5p inhibitor, or negative control. In summary, our results demonstrate that this strategy could efficiently accomplish the design, screening, and analysis of stem-loop RT primers for multiplex miRNA detection. Compared with the commercially customized miRNA assay kits, our system showed a higher degree of automation, more accurate qPCR assay capabilities, and lower assay costs, which could provide practical value for clinical diagnosis.

Repairing gastric ulcer with hyaluronic acid/extracellular matrix composite through promoting M2-type polarization of macrophages.

The treatment of gastric ulcer and perforation using synthetic and biomaterials has been a clinical challenge. In this work, a drug-carrying layer of hyaluronic acid was combined with a gastric submucosal decellularized extracellular matrix called gHECM. The regulation of macrophage polarization by the extracellular matrix's components was then investigated. This work proclaims how gHECM responds to inflammation and aids in the regeneration of the gastric lining by altering the phenotype of surrounding macrophages and stimulating the body's whole immune response. In a nutshell, gHECM promotes tissue regeneration by changing the phenotype of macrophages around the site of injury. In particular, gHECM reduces the production of pro-inflammatory cytokines, decreases the percentage of M1 macrophages, and further encourages differentiation of macrophage subpopulation to the M2 phenotype and the release of anti-inflammatory cytokines, which could block the NF-κB pathway. Activated macrophages are capable of immediately delivering through spatial barriers, modulating the peripheral immune system, influencing the inflammatory microenvironment, and ultimately promoting the recovery of inflammation and healing of ulcers. They contribute to the secreted cytokines that act on local tissues or enhance the chemotactic ability of macrophages through paracrine secretion. In this study, we focused on the immunological regulatory network of macrophage polarization to further develop the mechanisms behind this process. Nevertheless, the signaling pathways involved in this process need to be further explored and identified. We think that our research will encourage more investigation into how the decellularized matrix affects immune modulation and will help the decellularized matrix perform better as a new class of natural biomaterials for tissue engineering.