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Biological scaffolds are plagued by poor biomechanical properties and untimely degradation. These limitations have yet to be addressed without compromising their biocompatibility. It is desirable to avoid inflammation and have degradation with concomitant host collagen deposition or even site-appropriate in situ regeneration for the successful outcome of an implanted biological scaffold. This work aims to achieve this by utilizing a biocompatible method to modify acellular scaffolds by impregnating alkaline-catalyzed citric acid (CA) cross-linking between the extracellular matrix proteins and silk fibroin (SF)/SF-gelatin (SFG) blends. Combinatorial detergent decellularization was employed to prepare a decellularized porcine liver scaffold (DPL). After proving the decellularization efficiency, the scaffold underwent modification by vacuum impregnation with CA containing SF (SF100DPL) and SFG blends (SFG5050DPL and SFG3070DPL) following pre-cross-linking, drying, and post-cross-linking. The subsequent strength augmentation was demonstrated by significant improvement in tensile strength from 2.4 ± 0.4 MPa (DPL) to, 3.8 ± 0.7 MPa (SF100DPL), 3.4 ± 0.7 MPa (SFG5050DPL), and 3.5 ± 0.2 MPa (SFG3070DPL); Young's modulus from 8.7 ± 1.8 MPa (DPL) to 20 ± 1.9 MPa (SF100DPL), 13.3 ± 2.6 MPa (SFG5050DPL), and 16 ± 1.2 MPa (SFG3070DPL); and suture retention strength from 0.9 ± 0.08 MPa (DPL) to 2.3 ± 0.2 MPa (SF100DPL), 2.8 ± 1.2 MPa (SFG5050DPL), and 2.6 ± 0.9 MPa (SFG3070DPL). The degradation resistance of the modified scaffolds was also markedly improved. Being cytocompatible, its ability to incite tolerable inflammatory and immune responses was confirmed by rat subcutaneous implantation for 14, 30, and 90 days, in terms of inflammatory cell infiltration, neoangiogenesis, and in vitro cytokine release to assess B-cell and T-cell activation. Such ECM composite scaffolds with appropriate strength and biocompatibility offer great promise in soft tissue repair applications such as skin grafting.

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Skin aging, a complex physiological process characterized by alterations in skin structure and function, seriously affects human life. Collagen holds considerable potential in aging skin treatment, while animal-derived collagen poses risks of pathogen transmission. Self-assembled peptides have garnered increasing attention in creating collagen mimetic materials; however, previous reported self-assembled peptides rely on vulnerable non-covalent interactions or lack the capability of controlling morphology and incorporating functional motifs, limiting their ability to mimic collagen structure and function. We have herein created a controllable tyrosine-rich triblock peptide system capable of self-assembling into robust collagen mimetic bioscaffolds for rejuvenating aging skin. Through ruthenium-mediated crosslinking, these peptides self-assemble into well-defined nanospheres or collagen-mimetic scaffolds, precisely regulated by the triple-helical structure and tyrosine distribution. The self-assembled collagen mimetic scaffolds exhibit outstanding resistances to various solvents and pH conditions. The integrin-binding motif has been incorporated into the triple helical block without disrupting their assembly, while endowing them with superior bioactivities, effectively promoting cell adhesion and proliferation. In vivo studies demonstrated their efficacy in treating photoaging skin by accelerating collagen regeneration and activating fibroblasts. The self-assembled tyrosine-rich triblock peptides represent a versatile system for creating robust collagen mimetic biomaterials, providing great potential in skin rejuvenation and tissue regeneration.

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INTRODUCTION: Decellularized extracellular matrix (ECM) bioscaffolds have emerged as a promising three-dimensional (3D) model, but so far there are no data concerning their use in radiobiological studies. MATERIAL AND METHODS: We seeded two well-known radioresistant cell lines (HMV-II and PANC-1) in decellularized porcine liver-derived scaffolds and irradiated them with both high- (Carbon Ions) and low- (Photons) Linear Energy Transfer (LET) radiation in order to test whether a natural 3D-bioscaffold might be a useful tool for radiobiological research and to achieve an evaluation that could be as near as possible to what happens in vivo. RESULTS: Biological scaffolds provided a favorable 3D environment for cell proliferation and expansion. Cells did not show signs of dedifferentiation and retained their distinct phenotype coherently with their anatomopathological and clinical behaviors. The radiobiological response to high LET was higher for HMV-II and PANC-1 compared to the low LET. In particular, Carbon Ions reduced the melanogenesis in HMV-II and induced more cytopathic effects and the substantial cell deterioration of both cell lines compared to photons. CONCLUSIONS: In addition to offering a suitable 3D model for radiobiological research and an appropriate setting for preclinical oncological analysis, we can attest that bioscaffolds seemed cost-effective due to their ease of use, low maintenance requirements, and lack of complex technology.

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Traditional decellularized bioscaffolds possessing intact vascular networks and unique architecture have been extensively studied as conduits for repairing nerve damage. However, they are limited by the absence of electrical conductivity, which is crucial for proper functioning of nervous tissue. This study focuses on investigating decellularized umbilical cord arteries by applying coatings of graphene oxide (GO) and reduced graphene oxide (RGO) to their inner surfaces. This resulted in a homogeneous GO coating that fully covered the internal lumen of the arteries. The results of electrical measurements demonstrated that the conductivity of the scaffolds could be significantly enhanced by incorporating RGO and GO conductive sheets. At a low frequency of 0.1 Hz, the electrical resistance level of the coated scaffolds decreased by 99.8% with RGO and 98.21% with GO, compared with uncoated scaffolds. Additionally, the mechanical properties of the arteries improved by 24.69% with GO and 32.9% with RGO after the decellularization process. The GO and RGO coatings did not compromise the adhesion of endothelial cells and promoted cell growth. The cytotoxicity tests revealed that cell survival rate increased over time with RGO, while it decreased with GO, indicating the time-dependent effect on the cytotoxicity of GO and RGO. Blood compatibility evaluations showed that graphene nanomaterials did not induce hemolysis but exhibited some tendency toward blood coagulation.

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In the process of tissue engineering, several types of stresses can influence the outcome of tissue regeneration. This outcome can be understood by designing hydrogels that mimic this process and studying how such hydrogel scaffolds and cells behave under a set of stresses. Here, a hydrogel formulation is proposed to create biomimetic scaffolds suitable for fibroblast cell culture. Subsequently, we examine the impact of external stresses on fibroblast cells cultured on both solid and porous hydrogels. These stresses included mechanical tension and altered-gravity conditions experienced during the 83rd parabolic flight campaign conducted by the European Space Agency. This study shows distinct cellular responses characterized by cell aggregation and redistribution in regions of intensified stress concentration. This paper presents a new biomimetic hydrogel that fulfills tissue-engineering requirements in terms of biocompatibility and mechanical stability. Moreover, it contributes to our comprehension of cellular biomechanics under diverse gravitational conditions, shedding light on the dynamic cellular adaptations versus varying stress environments.

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Spinal cord injury (SCI) is a devastating neurological disorder, leading to loss of motor or somatosensory function, which is the most challenging worldwide medical problem. Re-establishment of intact neural circuits is the basis of spinal cord regeneration. Considering the crucial role of electrical signals in the nervous system, electroactive bioscaffolds have been widely developed for SCI repair. They can produce conductive pathways and a pro-regenerative microenvironment at the lesion site similar to that of the natural spinal cord, leading to neuronal regeneration and axonal growth, and functionally reactivating the damaged neural circuits. In this review, we first demonstrate the pathophysiological characteristics induced by SCI. Then, the crucial role of electrical signals in SCI repair is introduced. Based on a comprehensive analysis of these characteristics, recent advances in the electroactive bioscaffolds for SCI repair are summarized, focusing on both the conductive bioscaffolds and piezoelectric bioscaffolds, used independently or in combination with external electronic stimulation. Finally, thoughts on challenges and opportunities that may shape the future of bioscaffolds in SCI repair are concluded.

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Objective: To explore and construct a 3D bone remodeling research model displaying stability, repeatability, and precise simulation of the physiological and biochemical environment in vivo. Methods: In this study, 3D bioprinting was used to construct a bone reconstruction model. Sodium alginate (SA), hydroxyapatite (HA) and gelatin (Gel) were mixed into hydrogel as scaffold material. The osteoblast precursor cells MC3T3-E1 and osteoclast precursor cells RAW264.7 were used as seed cells, which may or may not be separated by polycarbonate membrane. The cytokines osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) were used to induce cell differentiation. The function of scaffolds in the process of bone remodeling was analyzed by detecting the related markers of osteoblasts (alkaline phosphatase, ALP) and osteoclasts (tartrate resistant acid phosphatase, TRAP). Results: The scaffold showed good biocompatibility and low toxicity. The surface morphology aided cell adhesion and growth. The scaffold had optimum degradability, water absorption capacity and porosity, which are in line with the conditions of biological experiments. The effect of induced differentiation of cells was the best when cultured alone. After direct contact between the two types of cells at 2D or 3D level, the induced differentiation of cells was inhibited to varying degrees, although they still showed osteogenesis and osteoclast. After the cells were induced by indirect contact culture, the effect of induced differentiation improved when compared with direct contact culture, although it was still not as good as that of single culture. On the whole, the effect of inducing differentiation at 3D level was the same as that at 2D level, and its relative gene expression and enzyme activity were higher than that in the control group. Hence the scaffold used in this study could induce osteogenesis as well as osteoclast, thereby rendering it more effective in inducing new bone formation. Conclusion: This method can be used to construct the model of 3D bone remodeling mechanism.

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Introduction: Biomaterials currently utilized for the regeneration of myocardial tissue seem to associate with certain restrictions, including deficiency of electrical conductivity and sufficient mechanical strength. These two factors play an important role in cardiac tissue engineering and regeneration. The contractile property of cardiomyocytes depends on directed signal transmission over the electroconductive systems that happen inside the innate myocardium. Because of their distinctive electrical behavior, electroactive materials such as graphene might be used for the regeneration of cardiac tissue. Methods: In this review, we aim to provide deep insight into the applications of graphene and graphene derivative-based hybrid polymeric scaffolds in cardiomyogenic differentiation and cardiac tissue regeneration. Results: Synthetic biodegradable polymers are considered as a platform because their degradation can be controlled over time and easily functionalized. Therefore, graphene-polymeric hybrid scaffolds with anisotropic electrical behavior can be utilized to produce organizational and efficient constructs for macroscopic cardiac tissue engineering. In cardiac tissue regeneration, natural polymer based-scaffolds such as chitosan, gelatin, and cellulose can provide a permissive setting significantly supporting the differentiation and growth of the human induced pluripotent stem cells -derived cardiomyocytes, in large part due to their negligible immunogenicity and suitable biodegradability. Conclusion: Cardiac tissue regeneration characteristically utilizes an extracellular matrix (scaffold), cells, and growth factors that enhance cell adhesion, growth, and cardiogenic differentiation. From the various evaluated electroactive polymeric scaffolds for cardiac tissue regeneration in the past decade, graphene and its derivatives-based materials can be utilized efficiently for cardiac tissue engineering.

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Approximately 50% of the adult global population is projected to suffer from some form of metabolic disease by 2050, including metabolic syndrome and diabetes mellitus. At the same time, this trend indicates a potential increase in the number of patients who will be in need of implant-supported reconstructions of specific bone regions subjected to inflammatory states. Moreover, physiological conditions associated with dysmetabolic subjects have been suggested to contribute to the severity of bone loss after bone implant insertion. However, there is a perspective evidence strengthening the hypothesis that custom-fabricated bioengineered scaffolds may produce favorable bone healing effects in case of altered endocrine or metabolic conditions. This perspective review aims to share a comprehensive knowledge of the mechanisms implicated in bone resorption and remodelling processes, which have driven researchers to develop metallic implants as the cobalt-chromium (Co-Cr) bioscaffolds, presenting optimized geometries that interact in an effective way with the osteogenetic precursor cells, especially in the cases of perturbed endocrine or metabolic conditions.

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Tumor recurrence and a lack of bone-tissue integration are two critical concerns in the surgical treatment of osteosarcoma. Thus, an advanced multifunctional therapeutic platform capable of simultaneously eliminating residual tumor cells and promoting bone regeneration is urgently needed for efficient osteosarcoma treatment. Herein, to thoroughly eliminate tumors and simultaneously promote bone regeneration, an intelligent multifunctional therapeutic scaffold has been engineered by integrating microwave-responsive zeolitic imidazolate framework 8 (ZIF-8) nanomaterials loaded with a chemotherapeutic drug and an immune checkpoint inhibitor onto 3D-printed titanium scaffolds. The constructed scaffold features distinct microwave-thermal sensitization and tumor microenvironment-responsive characteristics, which can induce tumor immunogenic death by microwave hyperthermia and chemotherapy. Orthotopic implantation of the nanocomposite scaffold results in an enhanced immune response against osteosarcoma that may effectively inhibit tumor recurrence through synergistic immunotherapy. During long-term implantation, the zinc ions released from the degradation of ZIF-8 can induce the osteogenic differentiation of stem cells. The porous structure and mechanical properties of the 3D-printed titanium scaffolds provide a structural microenvironment for bone regeneration. This study provides a paradigm for the design of multifunctional microwave-responsive composite scaffolds for use as a therapy for osteosarcoma, which could lead to improved strategies for the treatment of the disease.

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Tendon wounds are a worldwide health issue affecting millions of people annually. Due to the characteristics of tendons, their natural restoration is a complicated and lengthy process. With the advancement of bioengineering, biomaterials, and cell biology, a new science, tissue engineering, has developed. In this field, numerous ways have been offered. As increasingly intricate and natural structures resembling tendons are produced, the results are encouraging. This study highlights the nature of the tendon and the standard cures that have thus far been utilized. Then, a comparison is made between the many tendon tissue engineering methodologies proposed to date, concentrating on the ingredients required to gain the structures that enable appropriate tendon renewal: cells, growth factors, scaffolds, and scaffold formation methods. The analysis of all these factors enables a global understanding of the impact of each component employed in tendon restoration, thereby shedding light on potential future approaches involving the creation of novel combinations of materials, cells, designs, and bioactive molecules for the restoration of a functional tendon.

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Skin tissue engineering possesses great promise in providing successful wound injury and tissue loss treatments that current methods cannot treat or achieve a satisfactory clinical outcome. A major field direction is exploring bioscaffolds with multifunctional properties to enhance biological performance and expedite complex skin tissue regeneration. Multifunctional bioscaffolds are three-dimensional (3D) constructs manufactured from natural and synthetic biomaterials using cutting-edge tissue fabrication techniques incorporated with cells, growth factors, secretomes, antibacterial compounds, and bioactive molecules. It offers a physical, chemical, and biological environment with a biomimetic framework to direct cells toward higher-order tissue regeneration during wound healing. Multifunctional bioscaffolds are a promising possibility for skin regeneration because of the variety of structures they provide and the capacity to customise the chemistry of their surfaces, which allows for the regulated distribution of bioactive chemicals or cells. Meanwhile, the current gap is through advanced fabrication techniques such as computational designing, electrospinning, and 3D bioprinting to fabricate multifunctional scaffolds with long-term safety. This review stipulates the wound healing processes used by commercially available engineered skin replacements (ESS), highlighting the demand for a multifunctional, and next-generation ESS replacement as the goals and significance study in tissue engineering and regenerative medicine (TERM). This work also scrutinise the use of multifunctional bioscaffolds in wound healing applications, demonstrating successful biological performance in the in vitro and in vivo animal models. Further, we also provided a comprehensive review in requiring new viewpoints and technological innovations for the clinical application of multifunctional bioscaffolds for wound healing that have been found in the literature in the last 5 years.

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Engineered bio-scaffolds for wound healing provide an attractive treatment option for tissue engineering and traumatic skin injuries since they can reduce dependence on donors and promote faster repair through strategic surface engineering. Current scaffolds present limitations in handling, preparation, shelf life, and sterilization options. In this study, bio-inspired hierarchical all-carbon structures comprising carbon nanotube (CNT) carpets covalently bonded to flexible carbon fabric have been investigated as a platform for cell growth and future tissue regeneration applications. CNTs are known to provide guidance for cell growth, but loose CNTs are susceptible to intracellular uptake and are suspected to cause in vitro and in vivo cytotoxicity. This risk is suppressed in these materials due to the covalent attachment of CNTs on a larger fabric, and the synergistic benefits of nanoscale and micro-macro scale architectures, as seen in natural biological materials, can be obtained. The structural durability, biocompatibility, tunable surface architecture, and ultra-high specific surface area of these materials make them attractive candidates for wound healing. In this study, investigations of cytotoxicity, skin cell proliferation, and cell migration were performed, and results indicate promise in both biocompatibility and directed cell growth. Moreover, these scaffolds provided cytoprotection against environmental stressors such as Ultraviolet B (UVB) rays. It was seen that cell growth could also be tailored through the control of CNT carpet height and surface wettability. These results support future promise in the design of hierarchical carbon scaffolds for strategic wound healing and tissue regeneration applications.

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Aging is a complex, multifaceted degenerative process characterized by a progressive accumulation of macroscopic and microscopic modifications that cause a gradual decline of physiological functions. During the last few years, strategies to ease and counteract senescence or even rejuvenate cells and tissues were proposed. Here we investigate whether young cell secretome-derived extracellular vesicles (EVs) ameliorate the cellular and physiological hallmarks of aging in senescent cells. In addition, based on the assumption that extracellular matrix (ECM) provides biomechanical stimuli, directly influencing cell behavior, we examine whether ECM-based bio-scaffolds, obtained from decellularized ovaries of young swine, stably maintain the rejuvenated phenotype acquired by cells after exposure to young cell secretome. The results obtained demonstrate that young cells release EVs endowed with the ability to counteract aging. In addition, comparison between young and aged cell secretomes shows a significantly higher miR-200 content in EVs produced using fibroblasts isolated from young donors. The effect exerted by young cell secretome-derived EVs is transient, but can be stabilized using a young ECM microenvironment. This finding indicates a synergistic interaction occurring among molecular effectors and ECM-derived stimuli that cooperate to control a unique program, driving the cell clock. The model described in this paper may represent a useful tool to finely dissect the complex regulations and multiple biochemical and biomechanical cues driving cellular biological age.

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Burns are a widespread global public health traumatic injury affecting many people worldwide. Non-fatal burn injuries are a leading cause of morbidity, resulting in prolonged hospitalization, disfigurement, and disability, often with resulting stigma and rejection. The treatment of burns is aimed at controlling pain, removing dead tissue, preventing infection, reducing scarring risk, and tissue regeneration. Traditional burn wound treatment methods include the use of synthetic materials such as petroleum-based ointments and plastic films. However, these materials can be associated with negative environmental impacts and may not be biocompatible with the human body. Tissue engineering has emerged as a promising approach to treating burns, and sustainable biomaterials have been developed as an alternative treatment option. Green biomaterials such as collagen, cellulose, chitosan, and others are biocompatible, biodegradable, environment-friendly, and cost-effective, which reduces the environmental impact of their production and disposal. They are effective in promoting wound healing and reducing the risk of infection and have other benefits such as reducing inflammation and promoting angiogenesis. This comprehensive review focuses on the use of multifunctional green biomaterials that have the potential to revolutionize the way we treat skin burns, promoting faster and more efficient healing while minimizing scarring and tissue damage.

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Inflammatory reactions resulting from spinal cord injury cause significant secondary damage. Microglial cells activate CD4+ T cells via major histocompatibility complex class II (MHCII) molecules. The activated T cells lead to neural tissue damage and demyelination at early stages of spinal cord injury. Control of the inflammatory response may attenuate the injury process. In this study, we compared gene expression in human microglia grown on soy protein-collagen hybrid scaffolds versus collagen scaffolds. Differentially expressed genes (DEGs) were subjected to gene ontology (GO) and pathway enrichment assays. Among down-regulated genes, the "antigen processing and presentation" pathway shows enrichment, primarily due to the down-regulation of MHCII molecules. The DEGs in this pathway show enrichment of binding sites for several transcription factors, with CIITA and IRF8 being the top candidates. The down-regulation of MHCII along with the significant enrichment of the GO term "focal adhesion" among the up-regulated genes helps explain the higher motility of microglial cells on the hybrid scaffold compared with that on the collagen scaffold. Up-regulated genes associated with "focal adhesion" include DNM2, AHNAK, and HYOU1, which have been previously implicated in increased cell motility. Overall, our study indicates that the use of hybrid scaffolds containing soy protein and collagen may modulate the immune response of wounded neural tissue.

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BACKGROUND: Matrix-induced chondrogenesis (MIC) is a promising treatment option for critical-size cartilage lesions of the knee; however, there exists substantial heterogeneity in the choice of acellular scaffold matrix for MIC cartilage repairs. HYPOTHESIS: The choice of acellular matrix will not affect patient outcomes after MIC cartilage repair procedures, and the addition of concentrated bone marrow aspirate (cBMA) will improve short-term patient outcomes regardless of matrix choice. STUDY DESIGN: Meta-analysis; Level of evidence, 4. METHODS: Studies were stratified by matrix type: multilayered, single layered, and gel based. Continuous outcomes were analyzed with pairwise meta-analysis using the inverse variance model with random effects applied. Binary outcomes were analyzed as pooled proportions in a single-arm fashion; after which, reconstruction of relative risks (RRs) with confidence intervals was performed using the Katz logarithmic method. RESULTS: A total of 876 patients were included: 469 received multilayered bioscaffolds; 238, gel-based scaffolds; and 169, single-layered scaffolds. The mean age of patients was 36.2 years (95% CI, 33.9 to 38.4), while the mean lesion size was 3.91 cm2 (95% CI, 3.40 to 4.42). The weighted mean follow-up was 23.8 months (95% CI, 20.1 to 27.6). Multilayered bioscaffolds were most effective at improving visual analog scale scores (P = .03; weighted mean difference [WMD], -4.44 [95% CI, -4.83 to -4.06]; P < .001). There were significantly lower risks of incomplete defect filling for gel-based scaffolds when compared with multilayered scaffolds (RR, 0.78 [95% CI, 0.69 to 0.88]; P < .001) and single-layered scaffolds (RR, 0.58 [95% CI, 0.41 to 0.81]; P = .001). Augmentation with cBMA further improved clinical scores across all scaffolds, with significant improvements in Tegner score (P = .02), while decreasing incomplete defect filling rates as well. There was significantly greater improvement in visual analog scale scores (P = .01) for single-layered scaffolds with cBMA augmentation (WMD, -4.88 [95% CI, -5.38 to -4.37]; P < .001) as compared with single-layered scaffolds without cBMA augmentation (WMD, -4.08 [95% CI, -4.46 to -3.71]; P < .001). All significant improvements were below their respective minimum clinically important differences. CONCLUSION: While cartilage repair with acellular scaffolds provides significant improvements in pain and function for patients, there is insufficient clinical evidence to suggest which scaffold material is the most superior in influencing such improvements. The enhancement of cartilage repair procedures with cBMA may provide further functional improvements and improve defect filling; however, more long-term evidence is required to evaluate the effects.

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Aging is defined as a complex, multifaceted degenerative process that causes a gradual decline of physiological functions and a rising mortality risk with time. Stopping senescence or even rejuvenating the body represent one of the long-standing human dreams. Somatic cell nuclear transfer as well as cell reprogramming have suggested the possibility to slow or even reverse signs of aging. We exploited miR-200 family ability to induce a transient high plasticity state in human skin fibroblasts isolated from old individuals and we investigated whether this ameliorates cellular and physiological hallmarks of senescence. In addition, based on the assumption that extracellular matrix (ECM) provides biomechanical stimuli directly influencing cell behavior, we examine whether ECM-based bio-scaffolds, obtained from decellularized ovaries of young swine, stably maintain the rejuvenated phenotype acquired by cells after miR-200 exposure. The results show the existence of multiple factors that cooperate to control a unique program, driving the cell clock. In particular, miR-200 family directly regulates the molecular mechanisms erasing cell senescence. However, this effect is transient, reversible, and quickly lost. On the other hand, the use of an adequate young microenvironment stabilizes the miR-200-mediated rejuvenating effects, suggesting that synergistic interactions occur among molecular effectors and ECM-derived biomechanical stimuli. The model here described is a useful tool to better characterize these complex regulations and to finely dissect the multiple and concurring biochemical and biomechanical cues driving the cell biological clock.

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The impact of magnetic fields on cellular function is diverse but can be described at least in part by the radical pair mechanism (RPM), where magnetic field intervention alters reactive oxygen species (ROS) populations and downstream cellular signaling. Here, cellular migration within three-dimensional scaffolds was monitored in an applied oscillating 1.4 MHz radiofrequency (RF) magnetic field with an amplitude of 10 µT and a static 50 µT magnetic field. Given that cellular bioenergetics can be altered based on applied RF magnetic fields, this study focused on a magnetic field configuration that increased cellular respiration. Results suggest that RF accelerated cell clustering and elongation after 1 day, with increased levels of clustering and cellular linkage after 7 days. Cell distribution analysis within the scaffolds revealed that the clustering rate during the first day was increased nearly five times in the RF environment. Electron microscopy provided additional topological information and verified the development of fibrous networks, with a cell-derived matrix (CDM) visualized after 7 days in samples maintained in RF. This work demonstrates time-dependent cellular migration that may be influenced by quantum biology (QB) processes and downstream oxidative signaling, enhancing cellular migration behavior.

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This review focuses on the advancements in additive manufacturing techniques that are utilized for fabricating bioceramic scaffolds and their characterizations leading to bone tissue regeneration. Bioscaffolds are made by mimicking the human bone structure, material composition, and properties. Calcium phosphate apatite materials are the most commonly used scaffold materials as they closely resemble live bone in their inorganic composition. The functionally graded scaffolds are fabricated by utilizing the right choice of the 3D printing method and material combinations to achieve the requirement of the bioscaffold. To tailor the physical, mechanical, and biological properties of the scaffold, certain materials are reinforced, doped, or coated to incorporate the functionality. The biomechanical loading conditions that involve flexion, torsion, and tension exerted on the implanted scaffold are discussed. The finite element analysis (FEA) technique is used to investigate the mechanical property of the scaffold before fabrication. This helps in reducing the actual number of samples used for testing. The FEA simulated results and the experimental result are compared. This review also highlights some of the challenges associated while processing the scaffold such as shrinkage, mechanical instability, cytotoxicity, and printability. In the end, the new materials that are evolved for tissue engineering applications are compiled and discussed.

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