Coronary artery bypass grafting is acknowledged as a major clinical approach for treatment of severe coronary artery atherosclerotic heart disease. This procedure typically requires autologous small-diameter vascular grafts. However, the limited availability of the donor vessels and associated trauma during tissue harvest underscore the necessity for artificial arterial alternatives. Herein, decellularized bovine intercostal arteries were successfully fabricated with lengths ranging from 15 to 30 cm, which also closely match the inner diameters of human coronary arteries. These decellularized arterial grafts exhibited great promise following poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) grafting from the inner surface. Such surface modification endowed the decellularized arteries with superior mechanical strength, enhanced anticoagulant properties and improved biocompatibility, compared to the decellularized bovine intercostal arteries alone, or even those decellularized grafts modified with both heparin and vascular endothelial growth factor. After replacement of the carotid arteries in rabbits, all surface-modified vascular grafts have shown good patency within 30 days post-implantation. Notably, strong signal was observed after α-SMA immunofluorescence staining on the PMPC-grafted vessels, indicating significant potential for regenerating the vascular smooth muscle layer and thereby restoring full structures of the artery. Consequently, the decellularized bovine intercostal arteries surface modified by PMPC can emerge as a potent candidate for small-diameter artificial blood vessels, and have shown great promise to serve as viable substitutes of arterial autografts.

The recellularization of tissues after decellularization is a relatively new technology in the field of tissue engineering (TE). Decellularization involves removing cells from a tissue or organ, leaving only the extracellular matrix (ECM). This can then be recellularized with new cells to create functional tissues or organs. The first significant mention of recellularization in decellularized tissues can be traced to research conducted in the early 2000s. One of the landmark studies in this field was published in 2008 by Ott, where researchers demonstrated the recellularization of a decellularized rat heart with cardiac cells, resulting in a functional organ capable of contraction. Since then, other important studies have been published. These studies paved the way for the widespread application of recellularization in TE, demonstrating the potential of decellularized ECM to serve as a scaffold for regenerating functional tissues. Thus, although the concept of recellularization was initially explored in previous decades, these studies from the 2000s marked a major turning point in the development and practical application of the technology for the recellularization of decellularized tissues. The article reviews the historical advances and limitations in organ recellularization in TE over the last two decades.

Chronic respiratory diseases often necessitate lung transplantation due to irreversible damage. Organ engineering offers hope through stem cell-based organ generation. However, the crucial sterilization step in scaffold preparation poses challenges. This study conducted a systematic review of studies that analysed the extracellular matrix (ECM) conditions of decellularised lungs subjected to different sterilisation processes. A search was performed for articles published in the PubMed, Web of Sciences, Scopus, and SciELO databases according to the PRISMA guidelines. Overall, five articles that presented positive results regarding the effectiveness of the sterilisation process were selected, some of which identified functional damage in the ECM. Was possible concluded that regardless of the type of agent used, physical or chemical, all of them demonstrated that sterilisation somehow harms the ECM. An ideal protocol has not been found to be fully effective in the sterilisation of pulmonary scaffolds for use in tissue and/or organ engineering.

Host remodeling of decellularized extracellular matrix (dECM) material through the appropriate involvement of immune cells is essential for achieving functional organ/tissue regeneration. As many studies have focused on the role of macrophages, only few have evaluated the role of regulatory T cells (Tregs) in dECM remodeling. In this study, we used a mouse model of traumatic muscle injury to determine the role of Tregs in the constructive remodeling of vascular-derived dECM. According to the results, a certain number of Tregs could be recruited after dECM implantation. Notably, using anti-CD25 to reduce the number of Tregs recruited by the dECM was significantly detrimental to material remodeling based on a significant reduction in the number of M2 macrophages. In addition, collagen and elastic fibers, which maintain the integrity and mechanical properties of the material, rapidly degraded during the early stages of implantation. In contrast, the use of CD28-SA antibodies to increase the number of Tregs recruited by dECM promoted constructive remodeling, resulting in a decreased inflammatory response at the material edge, thinning of the surrounding fibrous connective tissue, uniform infiltration of host cells, and significantly improved tissue remodeling scores. The number of M2 macrophages increased whereas that of M1 macrophages decreased. Moreover, Treg-conditioned medium further enhanced material-induced M2 macrophage polarization in vitro. Overall, Treg is an important cell type that influences constructive remodeling of the dECM. Such findings contribute to the design of next-generation biomaterials to optimize the remodeling and regeneration of dECM materials.

The paper highlights how significant characteristics of liver can be modeled in tissue-engineered constructs using unconventional scaffolds. Hepatic lobular organization and metabolic zonation can be mimicked with decellularized plant structures with vasculature resembling a native-hepatic lobule vascular arrangement or silk blend scaffolds meticulously designed for guided cellular arrangement as hepatic patches or metabolic activities. The functionality of hepatocytes can be enhanced and maintained for long periods in naturally fibrous structures paving way for bioartificial liver development. The phase I enzymatic activity in hepatic models can be raised exploiting the microfibrillar structure of paper to allow cellular stacking creating hypoxic conditions to induce in vivo-like xenobiotic metabolism. Lastly, the paper introduces amalgamation of carbon-based nanomaterials into existing scaffolds in liver tissue engineering.
Unconventional scaffolds have the potential to meet the current challenges in liver tissue engineering- loss of hepatic morphology and functions over long-term culture, absence of native-like cell-cell and cell-matrix interactions, organization of hepatocytes into lobular structures exhibiting metabolic variations-which hinder pharmaceutical analysis, regenerative therapies and artificial organ development. Paper with cellulose microfibril network develops cellular aggregates with hypoxic conditions that influence enzymes of xenobiotic metabolism proving to be a better scaffold for hepatotoxicity testing compared with conventional monolayers in tissue culture plates. Decellularized plant stems provide already-built vasculature to be exploited for the development of intricate vessel networks that exist in hepatic lobules aiding in regenerative medicine for hepatic pathologies. Fibrous plant structures are excellent materials for the immobilization of hepatocytes and improve albumin secretion enabling their use in bioartificial liver development. Biomimicry of metabolic zonation in hepatic lobules can be achieved with perfusion culture using silk blend scaffolds with varying proportions of the liver matrix that orchestrate cellular function. The mechanical properties of silk allow the fabrication of structures that resemble liver anatomy to generate native-like hepatic lobules. Nanomaterials have immense potential as a component of composite material development for scaffolds to achieve improved predictive ability in pharmacokinetics. Most of these unconventional scaffolds have the added advantage of being readily available, accessible, affordable and sustainable for liver tissue engineering applications. Conclusively, the shift of attention away from conventional scaffolds poses a promising future in the field of tissue engineering.

Severe injuries to skeletal muscles, including cases of volumetric muscle loss (VML), are linked to substantial tissue damage, resulting in functional impairment and lasting disability. While skeletal muscle can regenerate following minor damage, extensive tissue loss in VML disrupts the natural regenerative capacity of the affected muscle tissue. Existing clinical approaches for VML, such as soft-tissue reconstruction and advanced bracing methods, need to be revised to restore tissue function and are associated with limitations in tissue availability and donor-site complications. Advancements in tissue engineering (TE), particularly in scaffold design and the delivery of cells and growth factors, show promising potential for regenerating damaged skeletal muscle tissue and restoring function. This article provides a brief overview of the pathophysiology of VML and critiques the shortcomings of current treatments. The subsequent section focuses on the criteria for designing TE scaffolds, offering insights into various natural and synthetic biomaterials and cell types for effectively regenerating skeletal muscle. We also review multiple TE strategies involving both acellular and cellular scaffolds to encourage the development and maturation of muscle tissue and facilitate integration, vascularization, and innervation. Finally, the article explores technical challenges hindering successful translation into clinical applications.

Small-diameter vascular grafts (SDVGs) are severely lacking in clinical settings. Therefore, our study investigates a new source of biological vessels-bovine and porcine decellularized intercostal arteries (DIAs)-as potential SDVGs. We utilized a combination of SDS and Triton X-100 to perfuse the DIAs, establishing two different time protocols. The results show that perfusing with 1% concentrations of each decellularizing agent for 48 h yields DIAs with excellent biocompatibility and mechanical properties. The porcine decellularized intercostal arteries (PDIAs) we obtained had a length of approximately 14 cm and a diameter of about 1.5 mm, while the bovine decellularized intercostal arteries (BDIAs) were about 29 cm long with a diameter of approximately 2.2 mm. Although the lengths and diameters of both the PDIAs and BDIAs are suited for coronary artery bypass grafting (CABG), as the typical diameter of autologous arteries used in CABG is about 2 mm and the grafts required are at least 10 cm long, our research indicates that BDIAs possess more ideal mechanical characteristics for CABG than PDIAs, showing significant potential. Further enhancements may be necessary to address their limited hemocompatibility.

The umbilical cord is a material that enhances regeneration and is devoid of age-related changes in the extracellular matrix (ECM). The aim of this work was to develop a biodegradable scaffold from a decellularized human umbilical cord (UC-scaffold) to heal full-thickness wounds. Decellularization was performed with 0.05% sodium dodecyl sulfate solution. The UC-scaffold was studied using morphological analysis methods. The composition of the UC-scaffold was studied using immunoblotting and Fourier transform infrared spectroscopy. The adhesion and proliferation of mesenchymal stromal cells were investigated using the LIVE/DEAD assay. The local reaction was determined by subcutaneous implantation in mice (n = 60). A model of a full-thickness skin wound in mice (n = 64) was used to assess the biological activity of the UC-scaffold. The proposed decellularization method showed its effectiveness in the umbilical cord, as it removed cells and retained a porous structure, type I and type IV collagen, TGF-β3, VEGF, and fibronectin in the ECM. The biodegradation of the UC-scaffold in the presence of collagenase, its stability during incubation in hyaluronidase solution, and its ability to swell by 1617 ± 120% were demonstrated. Subcutaneous scaffold implantation in mice showed gradual resorption of the product in vivo without the formation of a dense connective tissue capsule. Epithelialization of the wound occurred completely in contrast to the controls. All of these data suggest a potential for the use of the UC-scaffold.

The uterine tube extracellular matrix is a key component that regulates tubal tissue physiology, and it has a region-specific structural distribution, which is directly associated to its functions. Considering this, the application of biological matrices in culture systems is an interesting strategy to develop biomimetic tubal microenvironments and enhance their complexity. However, there are no established protocols to produce tubal biological matrices that consider the organ morphophysiology for such applications. Therefore, this study aimed to establish region-specific protocols to obtain decellularized scaffolds derived from porcine infundibulum, ampulla, and isthmus to provide suitable sources of biomaterials for tissue-engineering approaches. Porcine uterine tubes were decellularized in solutions of 0.1% SDS and 0.5% Triton X-100. The decellularization efficiency was evaluated by DAPI staining and DNA quantification. We analyzed the ECM composition and structure by optical and scanning electronic microscopy, FTIR, and Raman spectroscopy. DNA and DAPI assays validated the decellularization, presenting a significative reduction in cellular content. Structural and spectroscopy analyses revealed that the produced scaffolds remained well structured and with the ECM composition preserved. YS and HEK293 cells were used to attest cytocompatibility, allowing high cell viability rates and successful interaction with the scaffolds. These results suggest that such matrices are applicable for future biotechnological approaches in the reproductive field.

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