Search Results (17)

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

Background/Objectives: Angiogenesis is the multistep process of the formation of new blood vessels. It is beneficial in scenarios that require tissue repair and regeneration, such as wound healing, bone fracture repair, and recovery from ischemic injuries like stroke, where new blood vessel formation restores oxygen and nutrient supply to damaged areas. Extremely low-frequency electromagnetic stimulation (ELF-EMS), which involves electromagnetic fields in the frequency range of 0–300 Hz, have been shown to reduce ischemic stroke volume by improving cerebral blood flow and recovery effects that are dependent on eNOS. Based on previous results, we herein explore the effects of ELF-EMS treatment (13.5 mT/10 and 60 Hz) on the activation of angiogenic processes in vitro in homeostatic conditions. Methods: Using human microvascular endothelial cells (HMEC-1), we studied cell proliferation, migration, and tube formation in vitro, as well as nitric oxide production and the effect of calcium and nitric oxide (NO) on these processes. Moreover, blood vessel formation was studied using a chicken chorioallantoic membrane (CAM) assay. Results: Our results showed that ELF-EMS increases proliferation, tube formation, and both the migration and transmigration of these cells, the latter of which was mediated via NO. In turn, calcium inhibition decreased ELF-EMF-induced NO production. Furthermore, ELF-EMS significantly increased blood vessel formation in the CAM assay. Conclusions: Our results indicated that ELF-EMS exposure (13.5 mT/10 and 60 Hz) significantly induces angiogenesis in vitro and in ovo, underscoring its potential application in the treatment of conditions characterized by insufficient blood supply. Full article

Background and Objectives: Vascular endothelial growth factor (VEGF) is a protein which stimulates the formation of new blood vessels, playing a crucial role in processes such as wound healing and tumor growth. Methods: This study investigated the effects of VEGF on cell viability and osteogenic differentiation in mesenchymal stem cell (MSC) spheroids. Stem cell spheroids were fabricated using concave microwells and cultured with VEGF at concentrations of 0, 0.01, 0.1, 1, and 10 ng/mL. Morphological assessments were conducted on days 1, 3, 5, and 7, while cell viability was evaluated using the LIVE/DEAD assay and Cell Counting Kit-8. Alkaline phosphatase activity (ALP) and calcium deposition were measured to assess osteogenic differentiation, and qPCR was used to analyze osteogenic marker expression. Results: The spheroids maintained their shape across all VEGF concentrations, with the largest diameter being at 0.01 ng/mL on day 1, which decreased over time. Cell viability was highest at 0.01 ng/mL VEGF, while calcium deposition peaked at 0.1 ng/mL. Osteogenic markers, including RUNX2, osteocalcin, and COL1A1, showed significant upregulation at 1 ng/mL VEGF. Conclusions: These results suggest that VEGF enhances early osteogenic differentiation in MSC spheroids, indicating its potential for bone repair and tissue regeneration. VEGF could be applied in clinical settings for bone healing, fracture repair, and regenerative dentistry treatments. Full article

Silver nanoparticles (NPs) have become highly promising agents in the field of biomedical science, offering wide therapeutic potential due to their unique physicochemical properties. The unique characteristics of silver NPs, such as their higher surface-area-to-volume ratio, make them ideal for a variety of biological applications. They are easily processed thanks to their large surface area, strong surface plasmon resonance (SPR), stable nature, and multifunctionality. With an emphasis on the mechanisms of action, efficacy, and prospective advantages of silver NPs, this review attempts to give a thorough overview of the numerous biological applications of these particles. The utilization of silver NPs in diagnostics, such as bioimaging and biosensing, as well as their functions in therapeutic interventions such as antimicrobial therapies, cancer therapy, diabetes treatment, bone repair, and wound healing, are investigated. The underlying processes by which silver NPs exercise their effects, such as oxidative stress induction, apoptosis, and microbial cell membrane rupture, are explored. Furthermore, toxicological concerns and regulatory issues are discussed, as well as the present difficulties and restrictions related to the application of silver NPs in medicine. Full article

Inflammation is a vital defense mechanism, creating hostile conditions for pathogens, preventing the spread of tissue infection and repairing damaged tissues in humans and animals. However, when inflammation resolution is delayed or compromised as a result of its misregulation, the process proceeds from the acute phase to chronic inflammation, leading to the development of various chronic illnesses. It is proven that redox balance disturbances and oxidative stress are among major factors inducing NF-κB and leading to over-inflammation. Therefore, the anti-inflammatory properties of various natural antioxidants have been widely tested in various in vitro and in vivo systems. Accumulating evidence indicates that silymarin (SM) and its main constituent silibinin/silybin (SB) have great potential as an anti-inflammation agent. The main anti-inflammatory mechanism of SM/SB action is attributed to the inhibition of TLR4/NF-κB-mediated signaling pathways and the downregulated expression of pro-inflammatory mediators, including TNF-α, IL-1β, IL-6, IL-12, IL-23, CCL4, CXCL10, etc. Of note, in the same model systems, SM/SB was able to upregulate anti-inflammatory cytokines (IL-4, IL-10, IL-13, TGF-β, etc.) and lipid mediators involved in the resolution of inflammation. The inflammatory properties of SM/SB were clearly demonstrated in model systems based on immune (macrophages and monocytes) and non-immune (epithelial, skin, bone, connective tissue and cancer) cells. At the same time, the anti-inflammatory action of SM/SB was confirmed in a number of in vivo models, including toxicity models, nonalcoholic fatty liver disease, ischemia/reperfusion models, stress-induced injuries, ageing and exercising models, wound healing and many other relevant model systems. It seems likely that the anti-inflammatory activities of SM/SB are key elements on the health-promoting properties of these phytochemicals. Full article

Wound healing is a complex process of repair that involves the interaction between different cell types and involves coordinated interactions between intracellular and extracellular signaling. Bone Marrow Mesenchymal Stem Cells (BMSCs) based and acellular amniotic membrane (AM) therapeutic strategies with the potential for treatment and regeneration of tissue. We aimed to evaluate the involvement of paracrine effects in tissue repair after the flap skin lesion rat model. In the full-thickness flap skin experiment of forty Wistar rats: A total of 40 male Wistar rats were randomized into four groups: group I: control (C; n = 10), with full-thickness lesions on the back, without (BMSCs) or AM (n = 10); group II: injected (BMSCs; n = 10); group III: covered by AM; group IV–injected (AM + BMSCs; n = 10). Cytokine levels, IL-1, and IL-10 assay kits, superoxide dismutase (SOD), glutathione reductase (GRs) and carbonyl activity levels were measured by ELISA 28th day, and TGF-β was evaluated by immunohistochemical, the expression collagen expression was evaluated by Picrosirius staining. Our results showed that the IL-1 interleukin was higher in the control group, and the IL-10 presented a higher mean when compared to the control group. The groups with BMSCs and AM showed the lowest expression levels of TGF-β. SOD, GRs, and carbonyl activity analysis showed a predominance in groups that received treatment from 80%. The collagen fiber type I was predominant in all groups; however, the AM + BMSCs group obtained a higher average when compared to the control group. Our findings suggest that the AM+ BMSCs promote skin wound healing, probably owing to their paracrine effect attributed to the promotion of new collagen for tissue repair. Full article

Although chronic inflammation inhibits bone healing, the healing process is initiated by an inflammatory phase. In a well-tuned sequence of molecular events, pro-inflammatory cytokines are secreted to orchestrate the inflammation response to injury and the recruitment of progenitor cells. These events in turn activate the secretion of anti-inflammatory signaling molecules and attract cells and mediators that antagonize the inflammation and initiate the repair phase. Sulfated glycosaminoglycanes (sGAG) are known to interact with cytokines, chemokines and growth factors and, thus, alter the availability, duration and impact of those mediators on the local molecular level. sGAG-coated polycaprolactone-co-lactide (PCL) scaffolds were inserted into critical-size femur defects in adult male Wistar rats. The femur was stabilized with a plate, and the defect was filled with either sGAG-containing PCL scaffolds or autologous bone (positive control). Wound fluid samples obtained by microdialysis were characterized regarding alterations of cytokine concentrations over the first 24 h after surgery. The analyses revealed the inhibition of the pro-inflammatory cytokines IL-1β and MIP-2 in the sGAG-treated groups compared to the positive control. A simultaneous increase of IL-6 and TNF-α indicated advanced regenerative capacity of sGAG, suggesting their potential to improve bone healing. Full article

Induced pluripotent stem cell (iPSC) derived mesenchymal stem cells (iMSCs) represent a promising source of progenitor cells for approaches in the field of bone regeneration. Bone formation is a multi-step process in which osteogenesis and angiogenesis are both involved. Many reports show that the secretome of mesenchymal stromal stem cells (MSCs) influences the microenvironment upon injury, promoting cytoprotection, angiogenesis, and tissue repair of the damaged area. However, the effects of iPSC-derived MSCs secretome on angiogenesis have seldom been investigated. In the present study, the angiogenic properties of IFN-γ pre-conditioned iMSC secretomes were analyzed. We detected a higher expression of the pro-angiogenic genes and proteins of iMSCs and their secretome under IFN-γ and hypoxic stimulation (IFN-H). Tube formation and wound healing assays revealed a higher angiogenic potential of HUVECs in the presence of IFN-γ conditioned iMSC secretome. Sprouting assays demonstrated that within Coll/HA scaffolds, HUVECs spheroids formed significantly more and longer sprouts in the presence of IFN-γ conditioned iMSC secretome. Through gene expression analyses, pro-angiogenic genes (FLT-1, KDR, MET, TIMP-1, HIF-1α, IL-8, and VCAM-1) in HUVECs showed a significant up-regulation and down-regulation of two anti-angiogenic genes (TIMP-4 and IGFBP-1) compared to the data obtained in the other groups. Our results demonstrate that the iMSC secretome, pre-conditioned under inflammatory and hypoxic conditions, induced the highest angiogenic properties of HUVECs. We conclude that pre-activated iMSCs enhance their efficacy and represent a suitable cell source for collagen/hydroxyapatite with angiogenic properties. Full article

Mast cells (MCs) are bone marrow-derived cells capable of secreting many active molecules, ranging from the mediators stored in specific granules, some of which have been known about for several decades (histamine, heparin), to small molecules produced immediately upon stimulation (membrane lipid derivatives, nitric oxide), to a host of constitutively secreted, multifunctional cytokines. With the aid of a wide array of mediators, the activated MCs control the key events of inflammation and therefore participate in the regulation of local immune response. On the basis of the structure, origin, principal subtypes, localization and function of these cells, their involvement in injury repair is therefore to be considered in acute and chronic conditions, respectively. The importance of MCs in regulating the healing processes is underscored by the proposed roles of a surplus or a deficit of their mediators in the formation of exuberant granulation tissue (such as keloids and hypertrophic scars), the delayed closure or dehiscence of wounds and the transition of acute to chronic inflammation. Full article

Inflammatory lung disorders (ILDs) are one of the world’s major reasons for fatalities and sickness, impacting millions of individuals of all ages and constituting a severe and pervasive health hazard. Asthma, lung cancer, bronchiectasis, pulmonary fibrosis acute respiratory distress syndrome, and COPD all include inflammation as a significant component. Microbe invasions, as well as the damage and even death of host cells, can cause and sustain inflammation. To counteract the negative consequences of irritants, the airways are equipped with cellular and host defense immunological systems that block the cellular entrance of these irritants or eliminate them from airway regions by triggering the immune system. Failure to activate the host defense system will trigger chronic inflammatory cataracts, leading to permanent lung damage. This damage makes the lungs more susceptible to various respiratory diseases. There are certain restrictions of the available therapy for lung illnesses. Vitamins are nutritional molecules that are required for optimal health but are not produced by the human body. Cholecalciferol (Vitamin D) is classified as a vitamin, although it is a hormone. Vitamin D is thought to perform a function in bone and calcium homeostasis. Recent research has found that vitamin D can perform a variety of cellular processes, including cellular proliferation; differentiation; wound repair; healing; and regulatory systems, such as the immune response, immunological, and inflammation. The actions of vitamin D on inflammatory cells are dissected in this review, as well as their clinical significance in respiratory illnesses. Full article

Pearl powder is a well-known traditional Chinese medicine for a variety of indications from beauty care to healthcare. While used for over a thousand years, there has yet to be an in-depth understanding and review in this area. The use of pearl powder is particularly growing in the biomedical area with various benefits reported due to the active ingredients within the pearl matrix itself. In this review, we focus on the emerging biomedical applications of pearl powder, touching on applications of pearl powder in wound healing, bone repairing, treatment of skin conditions, and other health indications. Full article

Nanofibers are considered versatile materials with remarkable potential in tissue engineering and regeneration. In addition to their extracellular matrix-mimicking properties, nanofibers can be functionalized with specific moieties (e.g., antimicrobial nanoparticles, ceramics, bioactive proteins, etc.) to improve their overall performance. A novel approach in this regard is the use of enzymes immobilized onto nanofibers to impart biocatalytic activity. These nanofibers are capable of carrying out the catalysis of various biological processes that are essential in the healing process of tissue. In this review, we emphasize the use of biocatalytic nanofibers in various tissue regeneration applications. Biocatalytic nanofibers can be used for wound edge or scar matrix digestion, which reduces the hindrance for cell migration and proliferation, hence displaying applications in fast tissue repair, e.g., spinal cord injury. These nanofibers have potential applications in bone regeneration, mediating osteogenic differentiation, biomineralization, and matrix formation through direct enzyme activity. Moreover, enzymes can be used to undertake efficient crosslinking and fabrication of nanofibers with better physicochemical properties and tissue regeneration potential. Full article

Calcium phosphate (CaP) materials do not always induce ectopic vascularization and bone formation; the reasons remain unclear, and there are active discussions of potential roles for post-implantation hematoma, circulating immune and stem cells, and pericytes, but studies on adipose-derived stem cells (AMSCs) in this context are lacking. The rough (average surface roughness R_a = 2–5 µm) scaffold-like CaP coating deposited on pure titanium plates by the microarc oxidation method was used to investigate its subcutaneous vascularization in CBA/CaLac mice and in vitro effect on cellular and molecular crosstalk between human blood mononuclear cells (hBMNCs) and AMSCs (hAMSCs). Postoperative hematoma development on the CaP surface lasting 1–3 weeks may play a key role in the microvessel elongation and invasion into the CaP relief at the end of the 3rd week of injury and BMNC migration required for enhanced wound healing in mice. Satisfactory osteogenic and chondrogenic differentiation but poor adipogenic differentiation of hAMSCs on the rough CaP surface were detected in vitro by differential cell staining. The fractions of CD73⁺ (62%), CD90⁺ (0.24%), and CD105⁺ (0.41%) BMNCs may be a source of autologous circulating stem/progenitor cells for the subcutis reparation, but allogenic hBMNC participation is mainly related to the effects of CD4⁺ T cells co-stimulated with CaP coating on the in vitro recruitment of hAMSCs, their secretion of angiogenic and osteomodulatory molecules, and the increase in osteogenic features within the period of in vivo vascularization. Cellular and molecular crosstalk between BMNCs and AMSCs is a model of effective subcutis repair. Rough CaP surface enhanced angio- and osteogenic signaling between cells. We believe that preconditioning and/or co-transplantation of hAMSCs with hBMNCs may broaden their potential in applications related to post-implantation tissue repair and bone bioengineering caused by microarc CaP coating. Full article

Bone remodeling and repair require osteogenic cells to reach the sites that need to be rebuilt, indicating that stimulation of osteoblast migration could be a promising osteoanabolic strategy. We showed that purified δ-tocotrienol (δ-TT, 10 μg/mL), isolated from commercial palm oil (Elaeis guineensis) fraction, stimulates the migration of both MC3T3-E1 osteoblast-like cells and primary human bone marrow mesenchymal stem cells (BMSC) as detected by wound healing assay or Boyden chamber assay respectively. The ability of δ-TT to promote MC3T3-E1 cells migration is dependent on Akt phosphorylation detected by Western blotting and involves Wnt/β-catenin signalling pathway activation. In fact, δ-TT increased β-catenin transcriptional activity, measured using a Nano luciferase assay and pretreatment with procaine (2 µM), an inhibitor of the Wnt/β-catenin signalling pathway, reducing the wound healing activity of δ-TT on MC3T3-E1 cells. Moreover, δ-TT treatment increased the expression of β-catenin specific target genes, such as Osteocalcin and Bone Morphogenetic Protein-2, involved in osteoblast differentiation and migration, and increased alkaline phosphatase and collagen content, osteoblast differentiation markers. The ability of δ-TT to enhance the recruitment of BMSC, and to promote MC3T3-E1 differentiation and migratory behavior, indicates that δ-TT could be considered a promising natural anabolic compound. Full article

In contrast to the general belief that regeneration is a rare event, mainly occurring in simple organisms, the ability of regeneration is widely distributed in the animal kingdom. Yet, the efficiency and extent of regeneration varies greatly. Humans can recover from blood loss as well as damage to tissues like bone and liver. Yet damage to the heart and brain cannot be reversed, resulting in scaring. Thus, there is a great interest in understanding the molecular mechanisms of naturally occurring regeneration and to apply this knowledge to repair human organs. During regeneration, injury-activated immune cells induce wound healing, extracellular matrix remodeling, migration, dedifferentiation and/or proliferation with subsequent differentiation of somatic or stem cells. An anti-inflammatory response stops the regenerative process, which ends with tissue remodeling to achieve the original functional state. Notably, many of these processes are associated with enhanced glycolysis. Therefore, peroxisome proliferator-activated receptor (PPAR) β/δ—which is known to be involved for example in lipid catabolism, glucose homeostasis, inflammation, survival, proliferation, differentiation, as well as mammalian regeneration of the skin, bone and liver—appears to be a promising target to promote mammalian regeneration. This review summarizes our current knowledge of PPARβ/δ in processes associated with wound healing and regeneration. Full article