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Electrospinning has been used for the fabrication of extracellular matrix (ECM)-mimicking fibrous scaffolds for several decades. Electrospun fibrous scaffolds provide nanoscale/microscale fibrous structures with interconnecting pores, resembling natural ECM in tissues, and showing a high potential to facilitate the formation of artificial functional tissues. In this review, we summarize the fundamental principles of electrospinning processes for generating complex fibrous scaffold geometries that are similar in structural complexity to the ECM of living tissues. Moreover, several approaches for the formation of three-dimensional fibrous scaffolds arranged in hierarchical structures for tissue engineering are also presented.

Cartilage tissue is under extensive investigation in tissue engineering and regenerative medicine studies because of its limited regenerative potential. Currently, many scaffolds are undergoing scientific and clinical research. A key for appropriate scaffolding is the assurance of a temporary cellular environment that allows the cells to function as in native tissue. These scaffolds should meet the relevant requirements, including appropriate architecture and physicochemical and biological properties. This is necessary for proper cell growth, which is associated with the adequate regeneration of cartilage. This paper presents a review of the development of scaffolds from synthetic polymers and hybrid materials employed for the engineering of cartilage tissue and regenerative medicine. Initially, general information on articular cartilage and an overview of the clinical strategies for the treatment of cartilage defects are presented. Then, the requirements for scaffolds in regenerative medicine, materials intended for membranes, and methods for obtaining them are briefly described. We also describe the hybrid materials that combine the advantages of both synthetic and natural polymers, which provide better properties for the scaffold. The last part of the article is focused on scaffolds in cartilage tissue engineering that have been confirmed by undergoing preclinical and clinical tests.

Chronic liver damage leads to pathological accumulation of ECM proteins (liver fibrosis). Comprehensive characterization of the human ECM molecular composition is essential for gaining insights into the mechanisms of liver disease. To date, studies of ECM remodeling in human liver diseases have been hampered by the unavailability of purified ECM. Here, we developed a decellularization method to purify ECM scaffolds from human liver tissues. Histological and electron microscopy analyses demonstrated that the ECM scaffolds, devoid of plasma and cellular components, preserved the three-dimensional ECM structure and zonal distribution of ECM components. This method has been then applied on 57 liver biopsies of HCV-infected patients at different stages of liver fibrosis according to METAVIR classification. Label-free nLC-MS/MS proteomics and computation biology were performed to analyze the ECM molecular composition in liver fibrosis progression, thus unveiling protein expression signatures specific for the HCV-related liver fibrotic stages. In particular, the ECM molecular composition of liver fibrosis was found to involve dynamic changes in matrix stiffness, flexibility and density related to the dysregulation of predominant collagen, elastic fibers and minor components with both structural and signaling properties. This study contributes to the understanding of the molecular bases underlying ECM remodeling in liver fibrosis and suggests new molecular targets for fibrolytic strategies.

Tissue engineering aims to develop bionic scaffolds as alternatives to autologous vascular grafts due to their limited availability. This study introduces a novel wet-electrospinning fabrication technique to create small-diameter, uniformly aligned tubular scaffolds. By combining this innovative method with conventional electrospinning, a bionic tri-layer scaffold that mimics the zonal structure of vascular tissues is produced. The inner and outer layers consist of PCL/Gelatin and PCL/PLGA fibers, respectively, while the middle layer is crafted using PCL through Wet Vertical Magnetic Rod Electrospinning (WVMRE). The scaffold’s morphology is analyzed using Scanning Electron Microscopy (SEM) to confirm its bionic structure. The mechanical properties, degradation profile, wettability, and biocompatibility of the scaffold are also characterized. To enhance hemocompatibility, the scaffold is crosslinked with heparin. The results demonstrate sufficient mechanical properties, good wettability of the inner layer, proper degradability of the inner and middle layers, and overall good biocompatibility. In conclusion, this study successfully develops a small-diameter tri-layer tubular scaffold that meets the required specifications.

The extracellular matrix (ECM) has pleiotropic effects, ranging from cell adhesion to cell survival. In tissue engineering, the use of ECM and ECM-like scaffolds has separated the field into two distinct areas—scaffold-based and scaffold-free. Scaffold-free techniques are used in creating reproducible cell aggregates which have massive potential for high-throughput, reproducible drug screening and disease modeling. Though, the lack of ECM prevents certain cells from surviving and proliferating. Thus, tissue engineers use scaffolds to mimic the native ECM and produce organotypic models which show more reliability in disease modeling. However, scaffold-based techniques come at a trade-off of reproducibility and throughput. To bridge the tissue engineering dichotomy, we posit that finding novel ways to incorporate the ECM in scaffold-free cultures can synergize these two disparate techniques.

Osteochondral tissue engineering has shown an increasing development to provide suitable strategies for the regeneration of damaged cartilage and underlying subchondral bone tissue. For reasons of the limitation in the capacity of articular cartilage to self‐repair, it is essential to develop approaches based on suitable scaffolds made of appropriate engineered biomaterials. The combination of biodegradable polymers and bioactive ceramics in a variety of composite structures is promising in this area, whereby the fabrication methods, associated cells and signalling factors determine the success of the strategies. The objective of this review is to present and discuss approaches being proposed in osteochondral tissue engineering, which are focused on the application of various materials forming bilayered composite scaffolds, including polymers and ceramics, discussing the variety of scaffold designs and fabrication methods being developed. Additionally, cell sources and biological protein incorporation methods are discussed, addressing their interaction with scaffolds and highlighting the potential for creating a new generation of bilayered composite scaffolds that can mimic the native interfacial tissue properties, and are able to adapt to the biological environment.

Cell culture and cell scaffold engineering have previously developed in two directions. First can be ‘static into dynamic’, with proven effects that dynamic cultures have benefits over static ones. Researches in this direction have used several mechanical means, like external vibrators or shakers, to approximate the dynamic environments in real tissue, though such approaches could only partly address the issue. Second, can be ‘2D into 3D’, that is, artificially created three-dimensional (3D) passive (also called ‘static’) scaffolds have been utilized for 3D cell culture, helping external culturing conditions mimic real tissue 3D environments in a better way as compared with traditional two-dimensional (2D) culturing. In terms of the fabrication of 3D scaffolds, 3D printing (3DP) has witnessed its high popularity in recent years with ascending applicability, and this tendency might continue to grow along with the rapid development in scaffold engineering. In this review, we first introduce cell culturing, then focus 3D cell culture scaffold, vibration stimulation for dynamic culture, and 3DP technologies fabricating 3D scaffold. Potential interconnection of these realms will be analyzed, as well as the limitations of current 3D scaffold and vibration mechanisms. In the recommendation part, further discussion on future scaffold engineering regarding 3D vibratory scaffold will be addressed, indicating 3DP as a positive bridging technology for future scaffold with integrated and localized vibratory functions.

The three‐dimensional (3D) multicellular platforms prepared by cells or biomaterials have been widely applied in biomedical fields for the regeneration of complex tissues, the exploration of cell crosstalk, and the establishment of tissue physiological and pathological models. Compared with the traditional 2D culture methods, the 3D multicellular platforms are easier to adjust the components and structures of extracellular matrix (ECM) because of the synthesis of ECM by cells and the use of biomaterials. Moreover, the 3D multicellular platforms also can customize the cell distribution and precisely design micro and macro structures of the systems. Based on these typical advantages of 3D multicellular platforms and their increasingly important position in the biomedical field, this review summarizes the present 3D multicellular platforms. Herein, current 3D multicellular platforms are divided into two major types: scaffold‐free and scaffold‐based 3D multicellular platforms. The specific characteristics and applications of different types of 3D multicellular platforms are thoroughly introduced to help readers understand how different models affect and regulate cell behaviors and inspire researchers on how to select and design suitable 3D multicellular platforms according to different application scenarios. The three‐dimensional (3D) multicellular platforms are becoming increasingly important in biomedical research. It is particularly important to have a correct and comprehensive understanding of these important tools for biomedical research. This review introduces two major types of 3D multicellular platforms: scaffold‐free and scaffold‐based multicellular platforms. Furthermore, their applicability and limitations to different biomedical research are highlighted.

Additive manufacturing has been used to develop a variety of scaffold designs for clinical and industrial applications. Mechanical properties (i.e., compression, tension, bending, and torsion response) of these scaffolds are significantly important for load-bearing orthopaedic implants. In this study, we designed and additively manufactured porous metallic biomaterials based on two different types of triply periodic minimal surface structures (i.e., gyroid and diamond) that mimic the mechanical properties of bone, such as porosity, stiffness, and strength. Physical and mechanical properties, including compressive, tensile, bending, and torsional stiffness and strength of the developed scaffolds, were then characterised experimentally and numerically using finite element method. Sheet thickness was constant at 300 μm, and the unit cell size was varied to generate different pore sizes and porosities. Gyroid scaffolds had a pore size in the range of 600–1200 μm and a porosity in the range of 54–72%, respectively. Corresponding values for the diamond were 900–1500 μm and 56–70%. Both structure types were validated experimentally, and a wide range of mechanical properties (including stiffness and yield strength) were predicted using the finite element method. The stiffness and strength of both structures are comparable to that of cortical bone, hence reducing the risks of scaffold failure. The results demonstrate that the developed scaffolds mimic the physical and mechanical properties of cortical bone and can be suitable for bone replacement and orthopaedic implants. However, an optimal design should be chosen based on specific performance requirements.

In recent years, one of the main goals of cartilage tissue engineering has been to find appropriate scaffolds for hyaline cartilage regeneration, which could serve as a matrix for chondrocytes or stem cell cultures. The study presents three types of scaffolds obtained from a blend of polyethersulfone (PES) and polyurethane (PUR) by a combination of wet-phase inversion and salt-leaching methods. The nonwovens made of gelatin and sodium chloride (NaCl) were used as precursors of macropores. Thus, obtained membranes were characterized by a suitable structure. The top layers were perforated, with pores over 20 µm, which allows cells to enter the membrane. The use of a nonwoven made it possible to develop a three-dimensional network of interconnected macropores that is required for cell activity and mobility. Examination of wettability (contact angle, swelling ratio) showed a hydrophilic nature of scaffolds. The mechanical test showed that the scaffolds were suitable for knee joint applications (stress above 10 MPa). Next, the scaffolds underwent a degradation study in simulated body fluid (SBF). Weight loss after four weeks and changes in structure were assessed using scanning electron microscopy (SEM) and MeMoExplorer Software, a program that estimates the size of pores. The porosity measurements after degradation confirmed an increase in pore size, as expected. Hydrolysis was confirmed by Fourier-transform infrared spectroscopy (FT-IR) analysis, where the disappearance of ester bonds at about 1730 cm−1 wavelength is noticeable after degradation. The obtained results showed that the scaffolds meet the requirements for cartilage tissue engineering membranes and should undergo further testing on an animal model.