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Background The regeneration and repair of articular cartilage remains a major challenge for clinicians and scientists due to the poor intrinsic healing of this tissue. Since cartilage injuries are often clinically irregular, tissue-engineered scaffolds that can be easily molded to fill cartilage defects of any shape that fit tightly into the host cartilage are needed. Method In this study, bone marrow mesenchymal stem cell (BMSC) affinity peptide sequence PFSSTKT (PFS)-modified chondrocyte extracellular matrix (ECM) particles combined with GelMA hydrogel were constructed. Results In vitro experiments showed that the pore size and porosity of the solid-supported composite scaffolds were appropriate and that the scaffolds provided a three-dimensional microenvironment supporting cell adhesion, proliferation and chondrogenic differentiation. In vitro experiments also showed that GelMA/ECM-PFS could regulate the migration of rabbit BMSCs. Two weeks after implantation in vivo, the GelMA/ECM-PFS functional scaffold system promoted the recruitment of endogenous mesenchymal stem cells from the defect site. GelMA/ECM-PFS achieved successful hyaline cartilage repair in rabbits in vivo, while the control treatment mostly resulted in fibrous tissue repair. Conclusion This combination of endogenous cell recruitment and chondrogenesis is an ideal strategy for repairing irregular cartilage defects. Graphical Abstract

The tissue‐specific heart decellularized extracellular matrix (hdECM) demonstrates a variety of therapeutic advantages, including fibrosis reduction and angiogenesis. Consequently, recent research for myocardial infarction (MI) therapy has utilized hdECM with various delivery techniques, such as injection or patch implantation. In this study, a novel approach for hdECM delivery using a wet adhesive paintable hydrogel is proposed. The hdECM‐containing paintable hydrogel (pdHA_t) is simply applied, with no theoretical limit to the size or shape, making it highly beneficial for scale‐up. Additionally, pdHA_t exhibits robust adhesion to the epicardium, with a minimal swelling ratio and sufficient adhesion strength for MI treatment when applied to the rat MI model. Moreover, the adhesiveness of pdHA_t can be easily washed off to prevent undesired adhesion with nearby organs, such as the rib cages and lungs, which can result in stenosis. During the 28 days of in vivo analysis, the pdHA_t not only facilitates functional regeneration by reducing ventricular wall thinning but also promotes neo‐vascularization in the MI region. In conclusion, the pdHA_t presents a promising strategy for MI treatment and cardiac tissue regeneration, offering the potential for improved patient outcomes and enhanced cardiac function post‐MI. The heart decellularized extracellular matrix (hdECM) is one well‐known factor for the myocardial infarction (MI) regeneration. Here, a novel hdECM delivery method using paintable hydrogel with no size or shape limitations on application is shown. It exhibits stable wet cardiac tissue adhesion that is easily regulated with a simple treatment. Moreover, it demonstrates angiogenesis and MI regeneration abilities upon in vivo implantation.

The incidence of liver diseases is high worldwide. Many factors can cause liver fibrosis, which in turn can lead to liver cirrhosis and even liver cancer. Due to the shortage of donor organs, immunosuppression, and other factors, only a few patients are able to undergo liver transplantation. Therefore, how to construct a bioartificial liver that can be transplanted has become a global research hotspot. With the rapid development of three-dimensional (3D) bioprinting in the field of tissue engineering and regenerative medicine, researchers have tried to use various 3D bioprinting technologies to construct bioartificial livers in vitro. In terms of the choice of bioinks, liver decellularized extracellular matrix (dECM) has many advantages over other materials for cell-laden hydrogel in 3D bioprinting. This review mainly summarizes the acquisition of liver dECM and its application in liver 3D bioprinting as a bioink with respect to availability, printability, and biocompatibility in many aspects and puts forward the current challenges and prospects.

The extracellular matrix regulates cell survival, proliferation, and differentiation. In vitro two-dimensional cell experiments are typically performed on a plastic plate or a substrate of a single extracellular matrix constituent such as collagen or calcium phosphate. As these approaches do not include extracellular matrix proteins or growth factors, they fail to mimic a complex cell microenvironment. The cell-derived matrix is an alternative platform for better representing the in vivo microenvironment in vitro. Standard decellularization of a cell-derived matrix is achieved by combining chemical and physical methods. In this study, we compared the decellularization efficacy of several methods: ammonium hydroxide, sodium dodecyl sulfate (SDS), or Triton X-100 with cold or heat treatment on a matrix of Saos-2 cells. We found that the protocols containing SDS were cytotoxic during recellularization. Heat treatment at 47 °C was not cytotoxic, removed cellular constituents, inactivated alkaline phosphatase activity, and maintained the levels of calcium deposition. Subsequently, we investigated the differentiation efficiency of a direct bone coculture system in the established decellularized Saos-2 matrix, an inorganic matrix of calcium phosphate, and a plastic plate as a control. We found that the decellularized Saos-2 cell matrix obtained by heat treatment at 47 °C enhanced osteoclast differentiation and matrix mineralization better than the inorganic matrix and the control. This simple and low-cost method allows us to create a Saos-2 decellularized matrix that can be used as an in vivo-like support for the growth and differentiation of bone cells.

The skin, as the body's largest organ, plays vital protective and regulatory roles, making it a key target in regenerative medicine. However, current skin models often lack patient specificity and fail to recapitulate native extracellular matrix (ECM) composition, limiting their clinical relevance. This study presents a 3D‐bioprinted skin model using a patient‐derived decellularized ECM (pddECM) bioink combined with keratin‐alginate (KA) bioink, mimicking native skin architecture and function. The pddECM supports high viability of human dermal fibroblasts (HDFs), promoting collagen I production and robust ECM remodeling, while the KA bioink enhances basal keratinocyte activation and cornification. The construct exhibits improved cell migration and angiogenesis, contributing to effective tissue integration and reduced hypoxic stress. Cytokine profiling reveals upregulation of ICAM‐1 and complement C5, which are associated with enhanced keratinocyte motility and rapid matrix remodeling, while downregulation of pro‐inflammatory cytokines (IL‐4 and IL‐8) suggests a favorable, fibrosis‐suppressive environment. In vivo, GelMA and GelMA+pddECM scaffolds accelerated wound closure without local or systemic toxicity, preserving dermal thickness and inducing migrating epidermal tongue (MET) expression. This patient‐specific, bioactive skin model holds strong potential as a next‐generation platform for personalized wound healing, drug screening, and high‐fidelity skin grafting in translational tissue engineering. This study presents a patient‐specific skin model using autologous cells, decellularized dermal ECM, and keratin–alginate bioinks. The model supports cell compatibility, collagen deposition, and epidermal differentiation within a biomimetic ECM environment.  It enhances angiogenesis while reducing pro‐fibrotic cytokines, creating a regenerative niche. In vivo results confirm its biocompatibility and wound healing potential, demonstrating its promise for personalized skin substitutes in regenerative medicine.

Idiopathic pulmonary fibrosis can be caused by different factors, including accumulation of pathological extracellular matrix (ECM) with abnormal composition, stiffness, and architecture in the lung tissue. We studied the effect of ECM produced by lung fibroblasts of healthy mice or mice with bleomycin-induced pulmonary fibrosis on the process of endothelialto- mesenchymal transition, one of the main sources of effector myofibroblasts in fibrosis progression. Despite stimulation of spontaneous and TGFβ-1-induced differentiation of fibroblasts into myofibroblasts by fibrotic ECM, the appearance of α-SMA, the main marker of myofibroblasts, and its integration in stress fibrils in endotheliocytes were not observed under similar conditions. However, the expression of transcription factors SNAI1 and SNAI2/Slug and the production of components of fibrotic ECM (specific EDA-fibronectin splice form and collagen type I) were increased in endotheliocytes cultured on fibrotic ECM. Endothelium also demonstrated increased cell velocity in the models of directed cell migration. These data indicate activation of the intermediate state of the endothelial-to-mesenchymal transition in endotheliocytes upon contact with fibrotic, but not normal stromal matrix. In combination with the complex microenvironment that develops during fibrosis progression, it can lead to the replenishment of myofibroblasts pool from the resident endothelium.

Poor fiber orientation and mismatched bone–ligament interface fusion have plagued the regeneration of periodontal defects by cell‐based scaffolds. A 3D bioprinted biomimetic periodontal module is designed with high architectural integrity using a methacrylate gelatin/decellularized extracellular matrix (GelMA/dECM) cell‐laden bioink. The module presents favorable mechanical properties and orientation guidance by high‐precision topographical cues and provides a biochemical environment conducive to regulating encapsulated cell behavior. The dECM features robust immunomodulatory activity, reducing the release of proinflammatory factors by M1 macrophages and decreasing local inflammation in Sprague Dawley rats. In a clinically relevant critical‐size periodontal defect model, the bioprinted module significantly enhances the regeneration of hybrid periodontal tissues in beagles, especially the anchoring structures of the bone–ligament interface, well‐aligned periodontal fibers, and highly mineralized alveolar bone. This demonstrates the effectiveness and feasibility of 3D bioprinting combined with a dental follicle‐specific dECM bioink for periodontium regeneration, providing new avenues for future clinical practice. A biomimetic and functional periodontal module is developed using the methacrylate gelatin/decellularized extracellular matrix bioink by employing a 3D bioprinting approach. The module simulates natural anatomical complexity and biochemical microenvironment, and exhibits strong biological induction activity. Well‐aligned periodontal fibers, highly mineralized alveolar bone, as well as satisfactory bone–ligament interface integration are achieved after 3 months of implantation in vivo.

Over the past decade, organoids have emerged as a prevalent and promising research tool, mirroring the physiological architecture of the human body. However, as the field advances, the traditional use of animal or tumor-derived extracellular matrix (ECM) as scaffolds has become increasingly inadequate. This shift has led to a focus on developing synthetic scaffolds, particularly hydrogels, that more accurately mimic three-dimensional (3D) tissue structures and dynamics in vitro. The ECM–cell interaction is crucial for organoid growth, necessitating hydrogels that meet organoid-specific requirements through modifiable physical and compositional properties. Advanced composite hydrogels have been engineered to more effectively replicate in vivo conditions, offering a more accurate representation of human organs compared to traditional matrices. This review explores the evolution and current uses of decellularized ECM scaffolds, emphasizing the application of decellularized ECM hydrogels in organoid culture. It also explores the fabrication of composite hydrogels and the prospects for their future use in organoid systems.

Brain decellularized extracellular matrix (ECM) can be an attractive scaffold capable of mimicking the native ecosystem of the central nervous system tissue. We studied the in vitro response of neural cultures exposed to region-specific brain decellularized ECM scaffolds from three distinct neuroanatomical sections: cortex, cerebellum and remaining areas. First, each brain region was evaluated with the isotropic fractionator method to understand the cellular composition of the different cerebral areas. Second, the cerebral regions were subjected to the decellularization process and their respective characterization using molecular, histological, and ultrastructural techniques. Third, the levels of neurotrophic factors in the decellularized brain scaffold were analyzed. Fourth, we studied the region-specific brain decellularized ECM as a mimetic platform for the maturation of PC12 cells, as a unidirectional model of differentiation. Finally, in vitro studies were carried out to evaluate the cell recovery capacity of brain decellularized ECM under stroke-mimetic conditions. Our results show that region-specific brain decellularized ECM can serve as a biomimetic scaffold capable of promoting the growth of neural lineage cells and, in addition, it possesses a combination of structural and biochemical signals (e.g., neurotrophic factors) that are capable of inducing cell phenotypic changes and promote viability and cell recovery in a stroke/ischemia model in vitro.

[Display omitted] Decellularized extracellular matrix (d-ECM) serves as an ideal scaffold for constructing artificial ovaries, a promising approach to fertility preservation for patients experiencing premature ovarian failure. The biomechanical properties of d-ECM are crucial for the development and maturation of follicles. However, there is no standardized or comprehensive framework for evaluating the various decellularization methods proposed in the literature. In this study, we developed a novel decellularization protocol for porcine ovaries using liquid nitrogen and hypertonic saline methods, comparing its effectiveness against conventional chemical and enzymatic techniques through histological analysis, quantitative assessments and biomechanical testing. Histological analyses demonstrated that our d-ECM protocols effectively removed cellular and nuclear materials (at least 95% reduction) while preserving the structural integrity of elastin and collagen fibers (maximum 15% reduction). Furthermore, tensile testing results indicated that the novel decellularization methods using liquid nitrogen and hypertonic saline retained mechanical properties most similar to those of the fresh group. Our findings expand the evaluation of decellularization techniques by incorporating the biomechanical properties of d-ECM. Additionally, we provide valuable insights for enhancing decellularization methods and identifying optimal scaffolds for artificial ovaries.