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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

Type 1 diabetes (T1D) is caused by autoimmune-mediated destruction of pancreatic β-cells, resulting in insulin deficiency. While islet transplantation presents a potential therapeutic approach, its clinical application is impeded by limited donor availability and the risk of immune rejection. This study proposes an innovative islet encapsulation strategy that utilizes decellularized porcine pancreatic extracellular matrix (pECM) as the sole biomaterial to engineer bioactive, immunoprotective microcapsules. Rat islets were encapsulated within pECM-based microcapsules using the electrospray technology and were compared to conventional alginate-based microcapsules in terms of viability, function, and response to hypoxic stress. The pECM microcapsules maintained a spherical morphology, demonstrating mechanical robustness, and preserving essential ECM components (collagen I/IV, laminin, fibronectin). Encapsulated islets exhibited sustained viability and superior insulin secretion over a two-week period compared to alginate controls. The expression of key β-cell transcription factors (PDX1, MAFA) and structural integrity were preserved. Under hypoxic conditions, pECM microcapsules significantly reduced islet apoptosis, improved structural retention, and promoted functional recovery, likely due to antioxidant and ECM-derived cues inherent to the pECM. In vivo transplantation in immunocompetent mice confirmed the biocompatibility of pECM microcapsules, with minimal immune responses, stable insulin/glucagon expression, and no adverse systemic effects. These findings position pECM-based microencapsulation as a promising strategy for creating immunoprotective, bioactive niches for xenogeneic islet transplantation, with the potential to overcome current limitations in cell-based diabetes therapy. Full article

Porcine small intestinal submucosa (SIS) extracellular matrix (ECM) has emerged as a widely researched biological scaffold in regenerative medicine. This meta-analysis examines 205 peer-reviewed studies published from 1993 to 2025, emphasizing the biochemical composition, decellularization techniques, biomedical applications, and validation methods associated with SIS-ECM. Findings reveal a dominant focus on wound healing and cardiovascular repair, reflecting the scaffold’s mechanical adaptability and bioactivity. Research has evolved from basic compositional analyses to complex, application-specific investigations that incorporate in vivo models and functional outcome measures. Decellularization methods vary significantly, trending toward hybrid, multi-step protocols that preserve ECM integrity while ensuring cellular clearance. While the results are encouraging, a notable transparency issue persists, with only a third of studies providing full methodological details, which restricts reproducibility. Frequently utilized validation methods encompass mechanical testing, histology, DNA quantification, and growth factor retention. This review emphasizes the critical requirement for standardized guidelines in preparation and reporting to guarantee the safe and effective clinical application of SIS-ECM. Through continuous refinement and collaboration among various disciplines, SIS-ECM has the potential to serve as a next-generation scaffold for a range of regenerative uses. 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

Skin trauma, especially chronic trauma, poses a significant clinical challenge, often leading to severe disability or even death. Traditional treatment methods exhibit several limitations in terms of efficacy, material availability, and biocompatibility. The development of decellularized extracellular matrices (dECMs) has led to revolutionary progress in this field. These materials retain the bioactive components of the natural extracellular matrix (ECM) and, combined with their excellent physical structure, promote wound healing. Preclinical studies have demonstrated that dECM-based dressings can enhance the re-epithelialization rate by 20–50% and shorten the healing cycle of chronic wounds by 40%. This article systematically reviews the application of dECM in wound repair. First, it outlines the pathophysiology of wound healing, focusing on the mechanisms by which key ECM components promote wound healing. Next, it classifies decellularized materials and proposes material design schemes for different types of damage. Finally, the limitations of current dECM-based wound treatments and future research directions are discussed. This review aims to provide a theoretical framework and technical reference for researchers in related fields, promoting the widespread application of dECM materials for skin trauma treatment. Full article

Postoperative adhesions (POAs) are a common and often serious complication following abdominal and gynecologic surgeries, leading to infertility, chronic pain, and bowel obstruction. To address these outcomes, the development of anti-adhesion barriers using biocompatible materials has emerged as a key area of biomedical research. This article presents a comprehensive overview of clinically relevant natural and synthetic biomaterials explored for POA prevention, emphasizing their degradation behavior, barrier integrity, and translational progress. Natural biopolymers—such as collagen, gelatin, fibrin, silk fibroin, and decellularized extracellular matrices—are discussed alongside polysaccharides, including alginate, chitosan, and carboxymethyl cellulose, focusing on their structural features and biological functionality. Synthetic polymers, including polycaprolactone (PCL), polyethylene glycol (PEG), and poly(lactic-co-glycolic acid) (PLGA), are also examined for their tunable degradation profiles (spanning days to months), mechanical robustness, and capacity for drug incorporation. Recent innovations, such as bioprinted and electrospun dual-layer membranes, are highlighted for their enhanced anti-fibrotic performance in preclinical studies. By consolidating current material strategies and fabrication techniques, this work aims to support informed material selection while also identifying key knowledge gaps—particularly the limited comparative data on degradation kinetics, inconsistent definitions of ideal mechanical properties, and the need for more research into cell-responsive barrier systems. 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

Objective: To evaluate early and midterm outcomes of cryopreserved aortic homograft implantation in pediatric patients undergoing aortic valve and root replacement. Methods: A retrospective analysis was conducted on 36 pediatric patients aged 2 to 7 years who underwent cryopreserved aortic homograft implantation between January 2016 and December 2024. Indications included complex congenital aortic valve disease, annular hypoplasia, failed Ross procedure, and infective endocarditis. The standard root replacement technique was used under moderate hypothermic cardiopulmonary bypass. Postoperative outcomes were analyzed, including early complications, mortality, echocardiographic parameters, and long-term graft performance. Statistical analyses included the use of chi-square test, the Mann–Whitney U test, and Spearman correlation. Results: There was no 30-day mortality. One patient (2.8%) experienced late mortality at year 3, and two patients (5.6%) underwent reoperation at years 4 and 7 due to root aneurysm and severe regurgitation, respectively. Early postoperative echocardiography showed satisfactory hemodynamic performance with a mean gradient of 8.4 ± 3.2 mmHg. At 5-year follow-up, 92.9% of grafts maintained normal function. Conclusions: Cryopreserved homografts provide a safe and effective option for pediatric aortic valve replacement in the early and midterm period. However, potential late complications such as structural degeneration or root dilation necessitate long-term surveillance. Advances in decellularized grafts may improve future durability and integration. Full article

This study assessed the impact of implanting mononuclear stem cells and Wharton’s Jelly (WJ), either separately or together, on left ventricular dysfunction following myocardial infarction in Wistar rats. Functional and histopathological parameters were analyzed, and a rat model of left anterior descending coronary artery ligation was used. Treatments included an intramyocardial injection of 0.9% sodium chloride (control, n = 14), decellularized WJ (n = 12), bone marrow-derived mononuclear cells (BMMC) (n = 12), and bone marrow-derived mononuclear cells (BMMC) combined with WJ (n = 15). Echocardiography assessed the left ventricular function and ejection fraction over four weeks. Histological and immunohistochemical analyses with anti-factor VIII evaluated angiogenesis and collagen types I and III. The results showed no statistically significant effect on ventricular remodeling 30 days post-acute myocardial infarction (AMI). Moreover, the infarct area was significantly smaller in the BMMC + WJ group compared to the control group, suggesting a potential benefit in reducing myocardial scarring. BMMC + WJ therapy demonstrated potential for functional improvement and infarct size reduction 30 days post-infarction. Further studies are needed to confirm its therapeutic benefits. Full article

This study aimed to synthesize and characterize cassava starch-based (S) scaffolds functionalized with decellularized extracellular matrix (dECM) and isosorbide dinitrate (ISDN) for wound healing. The scaffolds were synthesized via the casting method and evaluated for physicochemical, mechanical, and morphological properties, as well as ISDN release and hemocompatibility. Swelling and degradation tests revealed a biphasic behavior, with high water absorption followed by controlled degradation. The ISDN release followed a biphasic pattern, fitting the Korsmeyer–Peppas model. Hemolysis tests confirmed biocompatibility, with hemolysis levels below 2%. Among the formulations, the scaffold containing 12.5% ECM and 40 mg ISDN exhibited optimal mechanical stability, controlled drug release, and biocompatibility. These findings suggest that starch/ECM/ISDN scaffolds hold potential for wound healing applications. Further studies should focus on in vivo evaluation and cytotoxicity assessments to confirm their clinical applicability. 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

Type 1 diabetes mellitus (T1DM) involves the destruction of pancreatic β-cells, requiring ongoing insulin therapy. A promising alternative for management is pancreatic islet transplantation, or the bioartificial pancreas. Here, we examine the primary implantation sites for the bioartificial pancreas, highlighting their anatomical, physical, and immunological characteristics in the context of T1DM treatment. Traditionally used for islet transplantation, the liver promotes metabolic efficiency due to portal drainage; however, it presents issues such as hypoxia and inflammatory responses. The omentum offers excellent vascularization but has limited capacity for subsequent transplants. The renal subcapsular space is advantageous when combined with kidney transplants; however, its use is limited due to low vascularization. The subcutaneous space is notable for its accessibility and lower invasiveness, although its poor vascularization poses significant challenges. These challenges can be mitigated with bioengineering strategies. The gastrointestinal submucosa provides easy access and good vascularization, which makes it a promising option for endoscopic approaches. Additionally, the intrapleural space, which remains underexplored, offers benefits such as increased oxygenation and reduced inflammatory response. Selecting the ideal site for bioartificial pancreas implantation should balance graft support, complication reduction, and surgical accessibility. Bioengineered devices and scaffolds can address the limitations of traditional sites and enhance T1DM management. 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