Search Results (424)

Advancements in bioinks and three-dimensional (3D) printing and bioprinting have significantly advanced cardiovascular tissue engineering by enabling the fabrication of biomimetic cardiac and vascular constructs. Traditional 3D printing has contributed to the development of acellular scaffolds, vascular grafts, and patient-specific cardiovascular models that support surgical planning and biomedical applications. In contrast, 3D bioprinting has emerged as a transformative biofabrication technology that allows for the spatially controlled deposition of living cells and biomaterials to construct functional tissues in vitro. Bioinks—derived from natural biomaterials such as collagen and decellularized matrix, synthetic polymers such as polyethylene glycol (PEG) and polycaprolactone (PCL), or hybrid combinations—have been engineered to replicate extracellular environments while offering tunable mechanical properties. These formulations ensure biocompatibility, appropriate mechanical strength, and high printing fidelity, thereby maintaining cell viability, structural integrity, and precise architectural resolution in the printed constructs. Advanced bioprinting modalities, including extrusion-based bioprinting (such as the FRESH technique), droplet/inkjet bioprinting, digital light processing (DLP), two-photon polymerization (TPP), and melt electrowriting (MEW), enable the fabrication of complex cardiovascular structures such as vascular patches, ventricle-like heart pumps, and perfusable vascular networks, demonstrating the feasibility of constructing functional cardiac tissues in vitro. This review highlights the respective strengths of these technologies—for example, extrusion’s ability to print high-cell-density bioinks and MEW’s ultrafine fiber resolution—as well as their limitations, including shear-induced cell stress in extrusion and limited throughput in TPP. The integration of optimized bioink formulations with appropriate printing and bioprinting platforms has significantly enhanced the replication of native cardiac and vascular architectures, thereby advancing the functional maturation of engineered cardiovascular constructs. Full article

The tumor microenvironment (TME) has a substantial impact on the progression of gastric cancer. Collagen, the most abundant protein in the extracellular matrix (ECM), forms a dense physical barrier that regulates anti-tumor immunity in the TME. It is a significant regulator of the signaling pathways of cancer cells, which are responsible for migration, proliferation, and metabolism. ECM proteins, particularly remodeling enzymes and collagens, can be modified to increase stiffness and alter the mechanical properties of the stroma. This, in turn, increases the invasive potential of tumor cells and resistance to immunotherapy. Given the dynamic nature of collagen, novel therapeutic strategies have emerged that target both collagen biosynthesis and degradation, processes that are essential for addressing ECM stiffening. This review delineates the upregulation of the expression and deposition of collagen, as well as the biological functions, assembly, and reorganization that contribute to the dissemination of this aggressive malignancy. Furthermore, the review emphasizes the importance of creating 3D in vitro models that incorporate innovative biomaterials that avoid the difficulties of traditional 2D culture in accurately simulating real-world conditions that effectively replicate the distinctive collagen microenvironment. Ultimately, it investigates the use of decellularized ECM-derived biomaterials as tumor models that are designed to precisely replicate the mechanisms associated with the progression of stomach cancer. Full article

The combination of scaffold materials and bioactive factors is a promising strategy for promoting bone defect repair in tissue engineering. Previous studies have shown that osteoglycin (OGN) is highly expressed in the bone repair process using deer antler as an animal model of bone defects. It suggests that OGN may be a key active component involved in the bone repair process. The aim of this study was to investigate whether deer OGN (dOGN) could effectively promote bone regeneration. We successfully expressed dOGN using the E. coli pET30a system and evaluated its biological activity through cell proliferation and migration assays. At a concentration of 5 μg/mL, dOGN significantly promoted cell proliferation and migration. We then incorporated dOGN onto decellularized antler cancellous bone (DACB) scaffolds and assessed their osteogenic potential both in vitro and in vivo. The results indicated that dOGN loading enhanced cell proliferation, adhesion, and osteogenic activity. In vivo experiments confirmed that the dOGN-DACB scaffold significantly improved bone regeneration compared to DACB alone. This study demonstrates that dOGN-loaded DACB scaffolds hold great potential for clinical applications in treating critical-sized bone defects by mimicking the rapid regenerative properties of deer antlers. Full article

Tissue engineering is a growing field with multidisciplinary players in cell biology, engineering, and medicine, aiming to maintain, restore, or enhance functions of tissues and organs. The extracellular matrix (ECM) plays fundamental roles in tissue development, maintenance, and repair, providing not only structural support, but also critical biochemical and biomechanical cues that regulate cell behavior and signaling. Although its specific composition varies across different tissue types and developmental stages, matrix molecules influence various cell functional properties in every tissue. Given the importance of ECM in morphogenesis, tissue homeostasis, and regeneration, ECM-based bioscaffolds, developed through tissue engineering approaches, have emerged as pivotal tools for recreating the native cellular microenvironment. The aim of this study is to present the main categories of these scaffolds (i.e., natural, synthetic, and hybrid), major fabrication techniques (i.e., tissue decellularization and multidimensional bioprinting), while highlighting the advantages and disadvantages of each category, focusing on biological activity and mechanical performance. Scaffold properties, such as mechanical strength, elasticity, biocompatibility, and biodegradability are essential to their function and integration into host tissues. Applications of ECM-based bioscaffolds span a range of engineering and regenerative strategies, including cartilage, bone, cardiac tissue engineering, and skin wound healing. Despite promising advances, challenges remain in standardization, scalability, and immune response modulation, with future directions directed towards improving ECM-mimetic platforms. Full article

The treatment of type 1 diabetes through pancreatic islet transplantation faces significant limitations, including donor organ shortages and poor islet survival due to post-transplantation loss of extracellular matrix support and inadequate vascularization. Developing biocompatible scaffolds that mimic the native islet microenvironment could substantially improve transplantation outcomes. This study aimed to create and evaluate decellularized (DCL) matrices from porcine organs as potential platforms for islet transplantation. Porcine lung and pancreatic tissues were decellularized using four different protocols combining detergents (Triton X-100, SDS and SDC) with optimized incubation times. The resulting matrices were characterized through DNA quantification and histological staining (H&E and Van Gieson). Islet viability was assessed in vitro using Live/Dead staining after 3 and 7 days of culture on the matrices. In vivo biocompatibility was evaluated by implanting matrices into rat omentum or peritoneum, with histological analysis at 1-, 4-, and 8 weeks post-transplantation. Protocols 3 (for lung tissue) and 4 (for pancreas tissue) demonstrated optimal decellularization efficiency with residual DNA levels below 8%, while preserving the collagen and elastin networks. In vitro, islets cultured on decellularized lung matrix had maintained 95% viability by day 7, significantly higher than the controls (60%) and pancreatic matrix (83%). The omentum showed superior performance as an implantation site, exhibiting minimal inflammation and fibrosis compared to the peritoneum sites throughout the 8-week study period. These findings establish DCL as a promising scaffold for islet transplantation due to its superior preservation of ECM components and excellent support of islet viability. This work provides a significant step toward developing effective tissue-engineered therapies for diabetes treatment. Full article

Tracheal defects have been the focus of research since the 19th century, but reconstructing this complex structure remains challenging. Identifying a safe, effective tracheal substitute is a key goal of surgery. This integrative review explores current tracheal substitutes and tissue engineering techniques. Data were collected from June 2024 to March 2025 from electronically available databases. Articles published between 2015 and 2025 were selected using the individualized protocol for each database. After screening 190 articles, 82 were excluded, and 108 were reviewed, with 100 meeting the final inclusion criteria. Recent substitutes include three-dimensional synthetic grafts made from polycaprolactone and copolyamide with thermoplastic elastomer, thermoplastic polyurethane and polylactic acid. Additionally, models using decellularized and recellularized tracheal matrix scaffolds and bioprinting techniques are being developed. Comparative studies of synthetic grafts and tracheal scaffolds, as well as cell self-aggregation methods to create tracheal analogues, are discussed. Advances in hybrid approaches combining synthetic polymers with extracellular matrix components aim to improve biocompatibility and functional integration. The importance of selecting appropriate preclinical animal models, such as goats, is also highlighted for translational relevance. Further research is required to refine protocols, overcome challenges related to vascularization and immune response, and ensure the development of clinically viable, long-lasting tracheal substitutes. Full article

Neural stem cells (NSCs) are crucial components of the nervous system, primarily located in the subventricular zone (SVZ) and subgranular zone (SGZ). The SVZ neural stem cell niche (NSCN) is a specialized microenvironment where growth factors and extracellular matrix (ECM) components collaborate to regulate NSC self-renewal and differentiation. Despite its importance, our understanding of the SVZ remains incomplete due to the inherent challenges of animal research, particularly given the tissue’s dynamic nature. To address these limitations, we developed a proof-of-concept, dynamic, and tissue-specific 3D organotypic SVZ model to reduce reliance on animal models. This static 3D organotypic model integrates a region-specific decellularized ECM derived from the SVZ, mimicking the native NSCN and supporting mouse-derived ependymal cells (ECs), radial glial cells (RGCs), astrocytes, and NSCs. To further improve physiological relevance, we incorporated a dynamic microfluidic culture system (SVZonChip), replicating cerebrospinal fluid (CSF) flow as observed in vivo. The resulting SVZonChip platform, combining region-specific ECM proteins with dynamic culture conditions, provides a sustainable and reproducible tool to minimize animal model use. It holds significant promise for studying SVZ-related diseases, such as congenital hydrocephalus, stroke, and post-stroke neurogenesis, while advancing translational research and enabling personalized medicine protocols. Full article

The mammary gland is a modified sweat gland responsible for milk production. It is affected by diseases that reduce animals’ quality of life, consequently leading to economic losses in livestock. With advancements in tissue bioengineering and regenerative medicine, studying the extracellular matrix (ECM) of the bovine mammary gland can improve our understanding of its physiology and the processes that affect it. This knowledge could also enable the development of sustainable therapeutic alternatives for both the dairy production chain and human oncology research. A common approach in regenerative medicine is decellularization, a process that removes all cells from tissue while preserving its architecture and ECM components for subsequent recellularization. The success of recellularization depends on obtaining immunologically compatible scaffolds and using appropriate cell culture sources and methods to ensure tissue functionality. However, tissue culture technology still faces challenges due to specific requirements and high costs. Here, we review the literature on biomaterials and tissue engineering, providing an overview of the ECM of the bovine mammary gland and advances in its bioengineering, with a focus on regenerative medicine for bovine species. The methodology employed consists of a structured search of scientific databases, including PubMed, Google Scholar, and SciELO, using specific keywords related to tissue engineering and the bovine mammary gland. The selection criteria prioritized peer-reviewed articles published between 2002 and 2025 that demonstrated scientific relevance and contributed to the understanding of bovine mammary gland bioengineering. Although research on this topic has advanced, vascularization, tissue maturation, and scalability remain key barriers to widespread application and economic viability. Full article

Tissue substitution and graft transplantation are currently the best treatment options for patients suffering from severe heart diseases. However, the limited availability of donors and the restricted durability of tissues applied in cardiovascular treatments result in a constraint on applicability and a suboptimal therapeutic approach that is still not fully resolved. There are multiple ways to preserve heart tissue grafts, and the choice of method is solely dependent upon the nature and complexity of the tissue and the length of storage. The conventional cold storage method provides the base to nearly all of the preservation protocols for short- and long-term storage. Short-term storage methods frequently rely on designing preserving solutions to protect the graft against warm and cold ischemia at the temperature above freezing point. As ice-nucleation is the major notorious phenomenon during graft preservation, the modern era of research is focusing on developing ice-free preservation techniques, termed vitrification. However, despite the promising outcomes of vitrification, there are several recognized hurdles required to be overcome to build a biobank of heart grafts for an extended period of time. Besides tissue deterioration due to extreme cold temperature, there is another extreme phenomenon of tissue rejection mainly caused by the presence of cellular antigens. The modern approach of decellularization has the potential to minimize the chances of tissue rejection by removing the cells and providing a structural support and sustained biochemical signal via keeping the extracellular matrix of the graft intact. In conclusion, both nano-warming and decellularization are the leading approaches that have great potential to store the graft tissue in its optimal form via keeping its viability safe for a longer time and extending its applicability. This review article outlines a variety of approaches for the preservation and bioengineering of tissue to fulfill the need for the availability of on-shelf long-lasting grafts both in clinical and laboratory setups. Full article

Squid skin decellularized dermal matrix (SADM) is gaining attention in tissue engineering and regenerative medicine due to its mimicking of the extracellular matrix property. Hence, SADM was used to investigate mimicking the microenvironment of cellular growth, inducing cellular infiltration and angiogenesis, and facilitating the repair of acute craniofacial wounds. For this, tissue regeneration membranes from squid skin were prepared by decolorization, degreasing and decellularisation methods. The effect of SADM in guiding bone tissue regeneration was evaluated using the rabbit skull bone defect model. SEM images of SADM had a bilayer membrane architecture characterized by a reticulated porous structure on one side and a dense, non-porous surface on the opposite side. Notably, the water absorption capacity of SADM was approximately eight times higher than its weight, exhibiting a porosity of 58% and a peak average tensile stress of 10.43 MPa. Additionally, simulations of tissue fluid degradation indicated a degradation rate of 70.42% and 88.33% on days 8 and 12, respectively. Following 4 and 8 weeks of animal studies focused on repairing cranial bone defects in rabbits, the findings demonstrated that SADM served as an effective barrier against fibrous connective tissue, promoted the proliferation of osteoblasts, and supported bone regeneration. This was confirmed through micro-CT imaging, and sections were stained with senna solid green. In summary, SADM is capable of directing cell infiltration and bone tissue formation, modulating the expression and secretion of inflammatory and skin repair-related factors, thereby enhancing tissue healing. Full article

Vascularized composite allotransplantation (VCA) has emerged as a robust alternative for addressing anatomically complex defects but requires a toxic lifelong immunosuppressive regimen. Tissue engineering offers the promise of creating recipient-specific alternative grafts using a decellularization and recellularization approach. In this article, we establish a reliable protocol for human face decellularization by immersion as a new tool in the development of engineered graft alternatives for reconstructive surgery. Three cadaveric face grafts were immersed in 1% sodium dodecyl sulfate for 216 h followed by 1% Triton X-100 for 48 h, without perfusion through the pedicle. We determined that decellularization was successfully accomplished for three facial specimens as confirmed by histological evaluation and quantification of DNA content. The extracellular components including collagen, glycosaminoglycans, elastin, and matrix-bound growth factors were preserved. Vascular architecture did not show significant differences between native and decellularized grafts as imaged by X-ray angiography. The mechanical strength of the grafts was not altered after decellularization. We also showed that the decellularized grafts were biocompatible in vitro and in vivo allowing cell engraftment. As a result, we have successfully developed a protocol to yield a clinical size decellularized graft suitable for generating a recellularized, potentially non-immunogenic graft for facial reconstruction. Full article

Tendons connect animal skeletons to skeletal muscles, playing a crucial role in weight-bearing and maintaining motor functions. After decellularization, tendon extracellular matrix (tECM) retains the physicochemical characteristics similar to those of native tendons. This has made tECM a promising biomaterial in the fields of tissue engineering and regenerative medicine in recent years. This paper summarizes the origin, structure, and ECM components of animal tendons, reviews decellularization methods, and discusses recent advancements in the research and applications of decellularized tendons. Furthermore, it explores future development trends of xenogeneic decellularized tendon materials, aiming to provide a reference for fundamental research and the development of biomaterials related to decellularized tendons. Full article

The field of reconstructive surgery faces significant challenges in addressing limb loss and disfigurement, with current organ preservation methods limited by short storage times. Decellularization offers a promising solution for generating engineered alternatives for reconstructive surgery by removing cellular material while preserving the extracellular matrix (ECM) and providing scaffolds for tissue regeneration. In this study, we developed a robust protocol for decellularizing whole digits from long-term freezer storage, achieving the successful removal of cellular material with intact ECM. Digit angiography confirmed the preservation of vascular integrity, facilitating future perfusion for recellularization. Quantitative analysis revealed significantly lower DNA content in decellularized tissues, indicating effective decellularization. Furthermore, extracellular matrix analysis showed the preservation of collagen, elastin, and glycosaminoglycans (GAGs) contents. Histological examination confirmed the reduction in cellularity and maintenance of tissue architecture in decellularized digits. Mechanical strength testing of decellularized digit tendons proved consistent with that of native digits. Our findings highlight the potential of decellularized digits as versatile platforms for tissue engineering and regenerative medicine. Moving forward, further optimization of protocols and collaborative efforts are essential for translating these findings into clinical practice, offering innovative solutions for reconstructive surgery and limb transplantation. Full article

Bone tissue engineering aims to restore lost bone and create an environment conducive to new bone formation. To address this challenge, we developed a novel biomimetic hydrogel that combines maleic anhydride–modified type I collagen (ColME) with maleic anhydride–modified demineralized and decellularized porcine bone matrix particles (mDBMp), forming a composite ColME–mDBMp (CMB) hydrogel. Chemical modification of collagen resulted in a high degree of substitution, thereby enhancing its photocrosslinkability. Integration of mDBMp into the ColME hydrogel via photocrosslinking resulted in enhanced physiological stability, reduced shrinkage, and improved mechanical strength compared to gelatin methacrylate (GelMA)-based hydrogels. Moreover, mineralization of the CMB hydrogel promoted the formation of pure hydroxyapatite (HAp) crystals, providing superior stiffness while maintaining ductility relative to GelMA-based hydrogels. In vitro, human bone marrow mesenchymal stem cells (hBMSCs) encapsulated in CMB hydrogels exhibited enhanced proliferation, cell–matrix interactions, and osteogenic differentiation, as evidenced by increased calcium deposition and histological analysis. These results demonstrate that the CMB hydrogel, enriched with extracellular matrix (ECM) components, shows considerable promise over current GelMA-based hydrogels for bone tissue engineering. Full article

Dupuytren’s contracture belongs to a group of fibrotic diseases that have similar mechanisms but lack effective treatment and prevention options. The excessive accumulation of connective tissue in Dupuytren’s disease leads to palmar fibrosis that results in contracture deformities. The present study aimed to investigate how the tissue microenvironment in Dupuytren’s contracture affects the phenotypic differentiation of macrophages, which leads to an inflammatory response and the development of chronicity in fibrotic disease. We utilized a decellularization-based method combined with proteomic analysis to identify shifts in extracellular matrix composition and the surrounding tissue microenvironment. We found that the expression of several matricellular proteins, such as MFAP4, EFEMP1 (fibulin-3), and ANGPTL2, was elevated in Dupuytren’s tissue. We show that, in response to the changes in the extracellular matrix of Dupuytren’s contracture, macrophages regulate the fibrotic process by cytokine production, promote myofibroblast differentiation, and increase the fibroblast migration rate. Moreover, we found that the extracellular matrix of Dupuytren’s contracture directly supports the macrophage-to-myofibroblast transition, which could be another contributor to Dupuytren’s disease pathogenesis. Our results suggest that interactions between macrophages and the extracellular matrix should be considered as targets for novel fibrotic disease treatment and prevention strategies in the future. Full article