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Bone tissue engineering addresses the limitations of autologous resources and the risk of allograft disease transmission in bone diseases. In this regard, engineered three-dimensional (3D) models emerge as biomimetic alternatives to natural tissues, replicating intracellular communication. Moreover, the unique properties of super-paramagnetic iron oxide nanoparticles (SPIONs) were shown to promote bone regeneration via enhanced osteogenesis and angiogenesis in bone models. This study aimed to investigate the effects of SPION on both osteogenesis and angiogenesis and characterized a co-culture of Human umbilical vein endothelial cells (HUVEC) and MG-63 cells as a model of bone microtissue. HUVECs: MG-63s with a ratio of 4:1 demonstrated the best results among other cell ratios, and 50 μg/mL of SPION was the optimum concentration for maximum survival, cell migration and mineralization. In addition, the data from gene expression illustrated that the expression of osteogenesis-related genes, including osteopontin, osteocalcin, alkaline phosphatase, and collagen-I, as well as the expression of the angiogenesis-related marker, CD-31, and the tube formation, is significantly elevated when the 50 μg/mL concentration of SPION is applied to the microtissue samples. SPION application in a designed 3D bone microtissue model involving a co-culture of osteoblast and endothelial cells resulted in increased expression of specific markers related to angiogenesis and osteogenesis. This includes the design of a novel biomimetic model to boost blood compatibility and biocompatibility of primary materials while promoting osteogenic activity in microtissue bone models. Moreover, this can improve interaction with surrounding tissues and broaden the knowledge to promote superior-performance implants, preventing device failure., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

One of the goals of tissue engineering and regenerative medicine is restoring primary living tissue function by manufacturing a 3D microenvironment. One of the main challenges is protecting implanted non-autologous cells or tissues from the host immune system. Cell encapsulation has emerged as a promising technique for this purpose. It involves entrapping cells in biocompatible and semi-permeable microcarriers made from natural or synthetic polymers that regulate the release of cellular secretions. In recent years, droplet-based microfluidic systems have emerged as powerful tools for cell encapsulation in tissue engineering and regenerative medicine. These systems offer precise control over droplet size, composition, and functionality, allowing for creating of microenvironments that closely mimic native tissue. Droplet-based microfluidic systems have extensive applications in biotechnology, medical diagnosis, and drug discovery. This review summarises the recent developments in droplet-based microfluidic systems and cell encapsulation techniques, as well as their applications, advantages, and challenges in biology and medicine. The integration of these technologies has the potential to revolutionise tissue engineering and regenerative medicine by providing a precise and controlled microenvironment for cell growth and differentiation. By overcoming the immune system's challenges and enabling the release of cellular secretions, these technologies hold great promise for the future of regenerative medicine.

Spinal cord injury, traumatic brain injury, and neurosurgery procedures usually lead to neural tissue damage. Self-assembled peptide (SAP) hydrogels, a type of innovative hierarchical nanofiber-forming peptide sequences serving as hydrogelators, have emerged as a promising solution for repairing tissue defects and promoting neural tissue regeneration. SAPs possess numerous features, such as adaptable morphologies, biocompatibility, injectability, tunable mechanical stability, and mimicking of the native extracellular matrix. This review explores the capacity of neural cell regeneration and examines the critical aspects of SAPs in neuroregeneration, including their biochemical composition, topology, mechanical behavior, conductivity, and degradability. Additionally, it delves into the latest strategies involving SAPs for central or peripheral neural tissue engineering. Finally, the prospects of SAP hydrogel design and development in the realm of neuroregeneration are discussed., (© 2024 Wiley‐VCH GmbH.)

This study aimed to improve the mechanical and biological properties of alginate-based hydrogels. For this purpose, in-situ forming hydrogels were prepared by dual crosslinking of Alginate (Alg)/Oxidized Alginate (OAlg)/Silk Fibroin (SF) through simultaneous ionic gelation using CaCO 3 -GDL and Schiff-base reaction. The resulting hydrogels were characterized by FTIR, SEM, compressive modulus, and rheological tests. Compared to the physically-crosslinked alginate hydrogel, the compressive modulus of dual-crosslinked Alg/OAlg/SF hydrogel increased from 28 to 67 kPa, due to the covalent imine bond formation. Then, MTT and DAPI staining assays were performed to demonstrate the biocompatibility of hydrogel. Furthermore, the differentiation potential of bone marrow mesenchymal stem cells encapsulated in hydrogel scaffolds to bone tissue was tested by ALP activity, Alizarin Red staining, and real-time PCR. The overall results showed the potential of Alginate/Oxidized Alginate/Silk Fibroin hydrogel scaffold for bone tissue engineering applications., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Tissue engineering is considered as a promising tool for remodeling the native cells microenvironment. In the present study, the effect of alginate hydrogel and collagen microspheres integrated with extracellular matrix components were evaluated in the decrement of apoptosis in human pancreatic islets., Materials/methods: For three-dimensional culture, the islets were encapsulated in collagen microspheres, containing laminin and collagen IV and embedded in alginate scaffold for one week. After that the islets were examined in terms of viability, apoptosis, genes and proteins expression including BAX, BCL2, active caspase-3, and insulin. Moreover, the islets function was evaluated through glucose-induced insulin and C-peptide secretion assay. In order to evaluate the structure of the scaffolds and the morphology of the pancreatic islets in three-dimensional microenvironments, we performed scanning electron microscopy., Results: Our findings showed that the designed hydrogel scaffolds significantly improved the islets viability using the reduction of activated caspase-3 and TUNEL positive cells., Conclusions: The reconstruction of the destructed matrix with alginate hydrogels and collagen microspheres might be an effective step to promote the culture of the islets., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Chronic liver diseases affect thousands of lives throughout the world every year. The shortage of liver donors for transplantation has been the main driving force to employ alternative methods such as liver tissue engineering (LTE) in fabricating a three-dimensional transplantable liver tissue or enhancing cell delivery techniques alleviating the need for liver donors. LTE consists of three components, cells, ECM (extracellular matrix), and signaling molecules, which we discuss the first and second. The three most common cell sources used in LTE are human and animal primary hepatocytes, and stem cells for different applications. Two major categories of ECM are used to mimic the microenvironment of these cells, named scaffolds and microbeads. Scaffolds have been made by numerous methods with a wide range of synthetic and natural biomaterials. Cell encapsulation has also been utilized by many polymeric biomaterials. To investigate their functions, many properties have been discussed in the literature, such as biochemical, geometrical, and mechanical properties, in both of these categories. Overall, LTE shows excellent potential in assisting hepatic disorders. However, some challenges exist that prevent the practical use of it clinically, making LTE an ongoing research subject in the scientific society.

Congenital and acquired valvular heart diseases (VHDs) are significant causes of mortality worldwide. With valve replacement being the primary solution for VHD, current options display shortcomings, including calcification, thrombogenicity, and hemodynamic alteration, leading to repetitive surgeries. Tissue engineering, however, has shown great potential for fabricating heart valves (HVs) with fewer complications. Here, a series of inks are developed, combining poly(vinyl alcohol), gelatin, and carrageenan for 3D printing of tissue‐engineered heart valves (TEHVs). The inks/hydrogels are investigated to characterize their physico‐chemical, morphological, mechanical, and rheological characteristics. In vitro and in vivo biocompatibility, immune response, hemolysis, and thrombogenicity of the inks/hydrogels are also evaluated. Moreover, in vitro hydrodynamics of the TEHVs under physiological conditions are reported. Inks demonstrate mechanical characteristics comparable to native leaflets. Subcutaneous implantation reveals that the hydrogels do not induce chronic inflammation and can undergo remodeling. In vitro hemocompatibility assessments of the hydrogels show minimal hemolysis with low thrombogenicity. Different sizes and types of HVs are successfully printed with high fidelity in the air. In vitro hydrodynamic assessment confirms that the TEHVs can withstand aortic conditions. Altogether, the 3D‐printed TEHVs can be a promising alternative for valve replacement to solve the problems associated with the current options. [ABSTRACT FROM AUTHOR]

Angiogenesis is a vital step in tissue regeneration. Hence, the current study aimed to prepare oxidized dextran (Odex)/collagen (Col)‐hydrogels with laminin (LMN), as an angiogenic extracellular matrix (ECM) component, for promoting human umbilical vein endothelial cell (HUVEC) proliferation and function. Odex/Col scaffolds were constructed at various concentrations and temperatures. Using oscillatory rheometry, scanning electron microscopy (SEM), and cell viability testing, the scaffolds were characterized, and then HUVEC proliferation and function was compared with or without LMN. The gelation time could be modified by altering the Odex/Col mass ratio as well as the temperature. SEM showed that Odex/Col hydrogels had a more regular three‐dimensional (3D) porous structure than the Col hydrogels. Moreover, HUVECs grew faster in the Col scaffold (12 mg/mL), whereas the Odex (30 mg/mL)/Col (6 mg/mL) scaffold exhibited the lowest apoptosis index. Furthermore, the expression level of vascular endothelial growth factor (VEGF) mRNA in the group without LMN was higher than that with LMN, and the Odex (30 mg/mL)/Col (6 mg/mL) scaffold without LMN had the highest VEGF protein secretion, allowing the cells to survive and function effectively. Odex/Col scaffolds, with or without LMN, are proposed as a tissue engineering construct to improve HUVEC survival and function for angiogenesis. [ABSTRACT FROM AUTHOR]

Fingolimod as a useful drug in nerve regeneration is a promising candidate for promoting axonal regeneration by positively affecting neonatal and adult Schwann cells. Nerve tissue engineering show a novel practical approach by recruiting the scientific methods for creating neural extracellular matrix. In this study, fingolimod was incorporated in polylactic‐co‐glycolic acid and then, an electrospun scaffold composed of polyurethane (PU), polycaprolactone (PCL) and gelatin polymers containing different amount of encapsulated fingolimod (0.01%, 0.02%, and 0.03%) were fabricated. The morphology and microstructure of each scaffold were assessed by scanning electron microscopy (SEM). The physicochemical properties of scaffolds including Fourier transform infrared spectroscopy, mechanical properties, water contact angle, and degradation test were evaluated. MTT assay and also SEM were utilized for the investigation of cell viability and adhesion. The results showed that the mean fiber diameter of scaffold was increased from 151 ± 31 to 243 ± 68 nm followed by increase of fingolimod. Young's modulus was showed all scaffold had in the expected range for nerve tissues. Cell viability assessment proved that PU/PCL/Gel/0.01% fingolimod had a higher cell survival among other groups. The results suggest that PU/PCL/gelatin scaffolds loading from 0.01 fingolimod can be a suitable candidate for peripheral nerve regeneration. [ABSTRACT FROM AUTHOR]

Stem cells exist as normal cells in embryonic and adult tissues. In recent years, scientists have spared efforts to determine the role of stem cells in treating many diseases. Stem cells can self-regenerate and transform into some somatic cells. They would also have a special position in the future in various clinical fields, drug discovery, and other scientific research. Accordingly, the detection of safe and low-cost methods to obtain such cells is one of the main objectives of research. Jaw, face, and mouth tissues are the rich sources of stem cells, which more accessible than other stem cells, so stem cell and tissue engineering treatments in dentistry have received much clinical attention in recent years. This review study examines three essential elements of tissue engineering in dentistry and clinical practice, including stem cells derived from the intra- and extra-oral sources, growth factors, and scaffolds. [ABSTRACT FROM AUTHOR]

Along with providing an environment for cell attachment and proliferation, a tissue engineering scaffolds should possess physical and mechanical properties that would fit the target tissue. The present study aimed to manipulate physico-mechanical properties of polyacrylamide/gelatin hydrogels using response surface method-central composite design (RSM-CCD) to reach a scaffold with defined properties. On this demand, mixtures of gelatin and acrylamide (AAm) monomer were used to prepare semi-interpenetrating hydrogels by free radical polymerization of AAm. Selected variables for statistical modeling were chosen to be weight ratios of monomer/crosslinker, monomer/gelatin, and monomer/initiator. The desired responses were compressive modulus, compressive strength, and swelling. Results showed that desired responses could be tailored by varying these parameters with the highest impact for monomer/crosslinker ratio. The swelling ratio of hydrogels was in the range of 947–1654%, while the modulus varied between 5 and 35 kPa. The cyclic compressive test showed the durability of hydrogels under cyclic loadings. Finally, the results of cell attachment and cytocompatibility analyses indicated that the hydrogels were completely biocompatible and enhanced cell attachment. Thus, these hydrogels could potentially be used as tissue engineering scaffolds for load-bearing organs, including muscle and cartilage, or could be used for in vitro differentiation of stem cells using mechanical clues. [ABSTRACT FROM AUTHOR]

Studying the profile of micro RNAs (miRs) elucidated the highest expressed miRs in hepatic differentiation. In this study, we investigated to clarify the role of three embryonic overexpressed miRs (miR-106a, miR-574-3p and miR-451) during hepatic differentiation of human umbilical cord derived mesenchymal stem cells (UC-MSCs). We furthermore, aimed to explore whether overexpression of any of these miRs alone is sufficient to induce the differentiation of the UC-MSCs into hepatocyte-like cells. UC-MSCs were transfected either alone or together with miR-106a, miR-574-3p and miR-451 and their potential hepatic differentiation and alteration in gene expression profile, morphological changes and albumin secretion ability were investigated. We found that up-regulation of any of these three miRs alone cannot induce expression of all hepatic specific genes. Transfection of each miR alone, led to Sox17, FoxA2 expression that are related to initiation step of hepatic differentiation. However, concurrent ectopic overexpression of three miRs together can induce UC-MSCs differentiation into functionally mature hepatocytes. These results show that miRs have the capability to directly convert UC-MSCs to a hepatocyte phenotype in vitro. [ABSTRACT FROM AUTHOR]

Appropriate selection of suitable materials and methods is essential for scaffolds fabrication in tissue engineering. The major challenge is to mimic the structure and functions of the extracellular matrix (ECM) of the native tissues. In this study, an optimized 3D structure containing poly(3-hydroxybutyrate) (P3HB), multiwalled carbon nanotubes (MCNTs) and curcumin (CUR) was created by electrospinning a novel biomimetic scaffold. CUR, a natural anti-inflammatory compound, has been selected as a bioactive component to increase the biocompatibility and reduce the potential inflammatory reaction of electrospun scaffolds. The presence of CUR in electrospun scaffolds was confirmed by 1H NMR and Fourier-transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) revealed highly interconnected porosity of the obtained 3D structures. Addition of up to 20 wt% CUR has enhanced mechanical properties of the scaffolds. CUR has also promoted in vitro bioactivity and hydrolytic degradation of the electrospun nanofibers. The developed P3HB-MCNT composite scaffolds containing 20 wt% of CUR revealed excellent in vitro cytocompatibility using mesenchymal stem cells and in vivo biocompatibility in rat animal model study. Importantly, the reduced inflammatory reaction in the rat model after 8 weeks of implantation has also been observed for scaffolds modified with CUR. Overall, newly developed P3HB-MCNTs-CUR electrospun scaffolds have demonstrated their high potential for tissue engineering applications. [ABSTRACT FROM AUTHOR]