NIH 3T3 Fibroblast Cells Research Articles

Tackling the Problem of Tendon Adhesions: Physical Barriers Prepared from α-Amino Acid-Based Poly(ester amide)s

In this work, electrospun membranes of α-amino acid based poly(ester amide)s (AAA-PEAs) from L-alanine (PEA_ala) or L-phenylalanine (PEA_phe) were successfully prepared to be used as physical barriers in the orthopedic field. Also, blends of these two polymers were used in different weight ratios (25:75, 50:50 and 75:25) to obtain physical barriers with different properties. All membranes had a suitable pore size to prevent fibroblast infiltration, and their porosity and permeability values were in a range that allowed the passage of nutrients. The membrane made from a blend of 25%wt of PEA_ala and 75% wt of PEA_phe showed the highest value of swelling capacity, suggesting a higher lubricant feature. The same membrane suffered a more pronounced degradation, as evidenced by the in vitro enzymatic degradation tests. All membranes showed suitable toughness values, a crucial property with regard to application. In vitro cytotoxicity tests performed with a NIH3T3 fibroblast cell line revealed decreased cell viability after 7 days, suggesting that these membranes are not ideal substrates to promote fibroblast adhesion and proliferation. These membranes as physical barriers represent a significant advance in the field given the limited literature on electrospun AAA-PEAs and their use to prevent tendon adhesion.

A Comparative Study on Centella Asiatica‐Mediated Green Synthesis of Silver and Copper Oxide Nanoparticles: Implications for Wound Healing

AbstractConventional wound dressings often lack efficient antimicrobial properties and may exhibit limited bio‐compatibility, necessitating the development of advanced solutions for effective wound healing. Green synthesis of nanoparticles opens the door to a strategy that is efficient in terms of pharmaceutical biotechnology, besides being nontoxic and eco‐friendly. In the present study, Centella asiatica leaf extract conjugated with silver nanoparticles and copper oxide nanoparticles are synthesized and their bioactivity is compared. Gas chromatography mass spectrometry (GC‐MS) results show 4‐butoxy‐1‐Butanol, Phthalic acid, and 2‐propyldecan‐1‐ol as major phytochemicals in Centella asiatica. The green‐synthesized silver nanoparticles (Ag‐NPs) and copper oxide nanoparticles (CuO‐NPs) are characterized using transmission electron microscopy (TEM), X‐ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). TEM results confirm the circular morphology for Ag‐NPs and elliptical structures for CuO‐NPs, whereas energy dispersive x‐ray (EDX) spectrum confirms the presence of Cu and Ag in their respective samples. XRD spectrum confirms that both the nanoparticles exhibit high crystallinity. Both nanoparticles demonstrate satisfactory radical scavenging activity as confirmed by the 2,2‐Diphenyl‐1‐picrylhydrazyl (DPPH) assay. CuO‐NPs exhibit greater antibacterial activity against Escherichia coli (E. coli) and Methicillin‐resistant Staphylococcus aureus (MRSA) in comparison to the Ag‐NPs evident from the clear zone of inhibition obtained. In conclusion, green synthesized CuO‐NPs prove to have enhanced wound healing activity in the NIH3T3 fibroblast cells than Ag‐NPs.

Biocompatible hydrogel coating on single living cells through visible light-induced polymerization.

Visible light-mediated photocatalysis leads to the efficient hydrogel coating of individual mammalian cells, functionalized with biocompatible anchor molecules tagged with fluorescein serving as a trifecta: photocatalyst, initiator, and fluorophore. NIH3T3 fibroblast cells are encapsulated within hydrogel shells of poly(ethylene glycol) diacrylate (PEGDA) and N-vinylpyrrolidone without any noticeable decrease in cell viability.

Red and NIR light-triggered enhancement of anticancer and antibacterial activities of dinuclear Co(II)-catecholate complexes.

Photoactive complexes of bioessential 3d metals, activable within the phototherapeutic window (650-900 nm), have gained widespread interest due to their therapeutic potential. Herein, we report the synthesis, characterization, and light-enhanced anticancer and antibacterial properties of four new dinuclear Co(II) complexes: [Co(phen)(cat)]2 (Co-1), [Co(dppz)(cat)]2 (Co-2), [Co(phen)(esc)]2 (Co-3), and [Co(dppz)(esc)]2 (Co-4). In these complexes, phen (1,10-phenanthroline) and dppz (dipyrido[3,2-a:2',3'-c]phenazine) act as neutral N,N-donor ligands, while cat2- and esc2- serve as O,O-donor catecholate ligands derived from catechol (1,2-dihydroxybenzene) and esculetin (6,7-dihydroxy coumarin). Their high-spin paramagnetic nature and dimeric identity in solution were confirmed by magnetic susceptibility, UV-visible, emission, and mass spectral data. Co-1-Co-4 exhibited an absorption band within the 600-850 nm range, originating from a charge transfer transition. The electrically neutral complexes demonstrated sufficient solution stability both in the dark and under irradiated conditions. The dppz complexes Co-2 and Co-4 exhibited notable toxicity towards A549 lung carcinoma cells, with potency increasing significantly under brief (5 min) exposure to 660 nm (red) and 808 nm (NIR) laser light (IC50 ∼ 8.9 to 14.9 μM). Notably, their toxicity towards normal NIH-3T3 fibroblast cells was minimal. Cellular assays highlighted that the induced cell death followed an apoptotic pathway, primarily due to mitochondrial damage. Co-2 and Co-4 also demonstrated significant antibacterial potency against Gram-(+) S. aureus and Gram-(-) P. aeruginosa, with effectiveness significantly enhanced upon 808 nm laser irradiation (MIC ∼ 15-142 μM). The increase in the anticancer and antibacterial efficacies was attributed to the generation of cytotoxic singlet oxygen (1O2) species upon red/NIR light exposure. Notably, 808 nm NIR irradiation produced more pronounced effects compared to 660 nm. This study is the first to report on cobalt complexes exhibiting red and NIR light-triggered enhancement of antibacterial and anticancer activities, illuminating the path for the development of long-wavelength absorbing cobalt complexes with enhanced therapeutic efficacy.

Improving Stability and Mechanical Strength of Electrospun Chitosan-Polycaprolactone Scaffolds Using Genipin Cross-linking for Biomedical Applications.

Electrospun nanofiber scaffolds have become vital in biomedical applications due to their high surface area and tunable properties. Chitosan (CS) is widely used, but its rapid degradation limits its effectiveness. This study addresses this limitation by blending CS with polycaprolactone (PCL) and applying genipin cross-linking to enhance its stability and mechanical properties. Scanning electron microscopy indicated a uniform morphology of the electrospun fibers, and further, the crystallinity of the scaffolds before and after cross-linking is verified. Fourier-transform infrared spectroscopy is used to analyze the chemical structure, identifying the presence of trifluoroacetic acid residues in the as-spun fibers. These residues are successfully eliminated through neutralization and cross-linking, which are critical for enhancing stability and cell viability in in-vitro studies. Mechanical testing revealed that cross-linked CS+PCL scaffolds exhibit a 350% increase in tensile strength compared to pure CS, and zeta potential reaches the favorable for cell development -26.27mV. The cytotoxicity assay results with murine NIH 3T3 fibroblast cells indicate the suitability of CS+PCL scaffolds for targeted tissue engineering and wound healing. This work establishes the potential for fine-tuning scaffold properties to create stable, functional, and biocompatible substrates for extended biomedical use.

Pirin does not bind to p65 or regulate NFκB-dependent gene expression but does modulate cellular quercetin levels.

Pirin is a non-heme iron binding protein with a variety of proposed functions including serving as a co-activator of p65 NFκB and quercetinase activity. We report here, failure to confirm pirin's primary proposed mechanism, binding of Fe(III)-pirin and p65. Analytical size exclusion chromatography (SEC) and fluorescence polarization (FP) studies did not detect an interaction. We also found no effects of pirin on TNFα-activated p65-regulated gene transcription using mouse embryonic fibroblasts (MEFs) from a pirin knockout mouse and a pirin knockdown NIH3T3 fibroblast cell line. TNFα - activated p65 response gene mRNA was neither increased nor decreased in cells with loss of pirin compared to wildtype cells. Furthermore, pirin immunofluorescence in NIH3T3 fibroblasts showed primarily a cytoplasmic localization, not nuclear as in most previous studies. This was confirmed by cell fractionation analysis. Pirin did show colocalization with the endoplasmic reticulum (ER) marker protein disulfide-isomerase (PDI) as well as cyotoplasmic labeling. We confirmed pirin's quercetinase activity in biochemical assays and demonstrated competitive inhibition by the pirin inhibitor CCG-257081. Cellular quercetin levels in cells exposed to quercetin in vitro were increased by knockdown of pirin or by treatment with pirin inhibitors. Since pirin is localized to ER and flavanols are protective of ER stress, we investigated whether pirin knockdown altered ER stress signaling but did not find any effect of pirin knockdown on ER stress response genes. Our results challenge the dominant model of pirin's function (NFκB regulation) but confirm its quercetinase activity with implications for the mechanisms of pirin binding small molecules.

Methylglyoxal impairs human dermal fibroblast survival and migration by altering RAGE-hTERT mRNA expression in vitro

Fibroblasts are native residents in dermal layer of human skin which are important for dermal regeneration and essential during cutaneous wound healing by releasing inflammatory markers and actively migrate to close an open wound. Premature skin ageing due to methylglyoxal (MGO) has recently caught the attention considering its potential to accelerate the emergence of skin ageing signs, however previous studies were only focused in primary neonatal dermal fibroblast and NIH3t3 fibroblast cell line. Therefore, thorough investigation is required to study the impact of MGO on primary human dermal fibroblast isolated from adult subject (HDFa). In our experiments, short exposure of MGO was observed to induced significant reductions in cell viability at concentrations of 7.5, 10, 12.5, 15, and 17.5 mM (p < 0.005) after 3 hours of treatment. The cellular death of HDFa at 10, 12.5 and 15 mM of MGO were also marked by increased in intracellular ROS level, indicating the involvement of oxidative stress-induced death in these cells. We also observed enlarge scratch areas of cells exposed with 7.5 and 10 mM MGO compared to control after 26 hours, thereby suggesting a decline in cell migration and viability in this group. We propose the increased ROS as the consequence of AGE-RAGE activation which was marked by significant elevation of RAGE mRNA on cells exposed to 10 mM MGO. Our data also suggest the occurrence of DNA damage events via ROS-induced oxidation or mediated by decline in hTERT mRNA expression.

The Photocleavable Protein PhoCl-Based Dynamic Hydrogels.

Dynamic protein hydrogels have attracted increasing attention owing to their tunable physiochemical and mechanical properties, customized functionality, and biocompatibility. Among the different types of dynamic hydrogels, photoresponsive hydrogels are of particular interest. Here, we report the engineering of a photoresponsive protein hydrogel by using the photocleavable protein PhoCl. We employed the well-developed SpyTag and SpyCatcher chemistry to engineer PhoCl-containing covalently cross-linked hydrogels. In the hydrogel network, PhoCl, which can be cleaved into two fragments upon violet irradiation, is employed as a dynamic structural motif to regulate the cross-linking density of the hydrogel network. The resultant PhoCl-containing hydrogels showed photoresponsive viscoelastic properties. Upon violet irradiation, the PhoCl hydrogels soften, leading to an irreversible reduction in the storage moduli. However, no gel-sol transition was observed. Leveraging this light-induced stiffness change, we employed this hydrogel as a cell culture substrate to investigate the mechanobiological response of NIH-3T3 fibroblast cells. Our results showed that 3T3 cells can change their morphologies in response to the stiffness change of the PhoCl hydrogel substrate dynamically, rendering PhoCl-based hydrogels a useful substrate for other mechanobiological studies.

Gallic acid functionalized silk fibroin/gelatin composite wound dressing for enhanced wound healing

As the incidence of chronic wounds increases, the requirements for wound dressings are rising. The specific aim of this study is to propose a novel gallic acid (GA) functionalized silk fibroin (SF) and gelatin (Gel) composite wound dressing in which GA is used as an antibacterial and wound healing substance. Via electrospinning, SF, Gel, and GA mixed solutions could be conveniently fabricated into a composite nanofiber mat (SF-Gel-GA), consisting of uniform fibers with an average diameter around 134.57 ± 84 nm. The internal mesh structure of SF-Gel-GA provides sufficient drug loading capacity, proper moisture permeability, and proper degradation rate. SF-Gel-GA presents excellent biocompatibility. NIH-3T3 fibroblast cells could adhere and spread stably on the SF-Gel-GA surface with slightly promoted proliferation. In the presence of SF-Gel-GA, the growth of both Gram-positive and Gram-negative bacteria, includingStaphylococcus aureusandPseudomonas aeruginosa, is significantly inhibited in both plate and suspension cultures. A cutaneous excisional mouse wound model proves the efficient ability of SF-Gel-GA to promote wound healing. Compared with pure SF dressing and commercial Tegaderm Hydrocolloid3Mdressing, the wound closure rate with SF-Gel-GA treatment is significantly improved. The histological assessments further demonstrate SF-Gel-GA could facilitate collagen deposition, neovascularization, and epithelialization at wound sites to promote wound healing. In conclusion, a novel SF-Gel-GA composite wound dressing with efficient wound healing activities have been developed for chronic wound treatment with broad healing potential.

Quercetin suppresses pyroptosis in mouse fibroblasts by inhibiting the NLRP3/caspase-1/GSDMD pathway

To investigate whether quercetin inhibits pyroptosis of mouse fibroblast NIH-3T3 cells by regulating the NLRP3/caspase-1/GSDMD signaling pathway. NIH-3T3 cells were treated with quercetin or MCC950 (a specific inhibitor of NLRP3) before stimulation with lipopolysaccharide (LPS) and ATP to induce cell pyroptosis. The optimal quercetin concentration and duration were screened using the CCK-8assay after testing various concentrations and times. Morphological changes of the treated cells was observed, and the levels of IL-18 and IL-1β in the cell culture supernatant were detected with ELISA; the protein expressions of NLRP3, cleaved caspase-1, and GSDMD-N and the mRNA levels of NLRP3, caspase-1 and GSDMD were detected using Western blotting and qRT-PCR. The changes in cell pyroptosis were examined with TUNEL staining and LDH release assay. The CCK-8 assay indicated that 24-hour treatment with 20 μmol/L quercetin yielded the most favorable results. LPS and ATP stimulation of NIH-3T3 cells induced obvious swelling, cell membrane rupture and leakage of cell contents, significantly increased IL-18 and IL-1β levels, and enhanced protein expressions of NLRP3, cleaved caspase-1 and GSDMD-N and mRNA levels of NLRP3, caspase-1 and GSDMD. LPS and ATP stimulation also caused a significant increment of TUNEL-positive cell counts and LDH release in NIH-3T3 cells. Treatment with quercetin or MCC950 significantly reduced cell pyroptosis induced by LPS and ATP, lowered the concentrations of IL-18 and IL-1β, decreased the expression levels of NLRP3, caspase-1/cleaved caspase-1, GSDMD/GSDMD-N, and reduced the number of TUNEL-positive cells and LDH release. Quercetin suppresses pyroptosis of mouse fibroblasts stimulated with LPS and ATP and reduces secretion of inflammatory cytokines by inhibiting the NLRP3/caspase-1/GSDMD pathway.

Cell spheroid viscoelasticity is deformation-dependent

Tissue surface tension influences cell sorting and tissue fusion. Earlier mechanical studies suggest that multicellular spheroids actively reinforce their surface tension with applied force. Here we study this open question through high-throughput microfluidic micropipette aspiration measurements on cell spheroids to identify the role of force duration and spheroid deformability. In particular, we aspirate spheroid protrusions of mice fibroblast NIH3T3 and human embryonic HEK293T homogeneous cell spheroids into micron-sized capillaries for different pressures and monitor their viscoelastic creep behavior. We find that larger spheroid deformations lead to faster cellular retraction once the pressure is released, regardless of the applied force. Additionally, less deformable NIH3T3 cell spheroids with an increased expression level of alpha-smooth muscle actin, a cytoskeletal protein upregulating cellular contractility, also demonstrate slower cellular retraction after pressure release for smaller spheroid deformations. Moreover, HEK293T cell spheroids only display cellular retraction at larger pressures with larger spheroid deformations, despite an additional increase in viscosity at these larger pressures. These new insights demonstrate that spheroid viscoelasticity is deformation-dependent and challenge whether surface tension truly reinforces at larger aspiration pressures.

Synergistic Bactericidal Effect of Zn2+ Ions and Reactive Oxygen Species Generated in Response to Either UV or X-ray Irradiation of Zn-Doped Plasma Electrolytic Oxidation TiO2 Coatings.

Zn-containing TiO2-based coatings with Na, Ca, Si, and K additives were obtained by plasma electrolytic oxidation (PEO) of Ti in order to achieve an effective and broad bactericidal protection without compromising biocompatibility. A protocol has been developed for cleaning the coating surface from electrolyte residues, ensuring the preservation of the microstructure and composition of the surface layer. Using high-resolution transmission electron microscopy, three characteristic microstructural zones in the PEO-Zn coating are well documented: zone 1 with a TiO2-based nanocrystalline structure, zone 2 with an amorphous structure, and zone 3 around pores with an amorphous-nanocrystalline structure. The excellent cytocompatibility of PEO-Zn samples was confirmed by three different methods: monitoring the proliferation of MC3T3-E1 cells, assessing the viability of sheep osteoblast cells using calcein-AM staining and fluorescence microscopy, and incubation with spheroids based on primary osteoblast cells and mouse embryonic fibroblast NIH3T3 cells. The PEO-Zn coatings absorb >60% of the incident light over the UV and Vis-NIR spectral ranges. After 24 h, the PEO-Zn coatings completely inactivate four types of strains: Gram-positive Staphylococcus aureus CSA154 and ATCC29213 and Gram-negative Escherichia coli K261 and U20, and also prevent E. coli U20 and K261 biofilm formation. The superior antibacterial activity is associated with the synergistic effect of Zn2+ ions in safe concentration and reactive oxygen species (ROS) generated in response to either UV irradiation or soft short-term X-ray irradiation. The X-ray irradiation-induced ROS formation by a PEO coating is reported for the first time. The enhanced bactericidal activity after X-ray irradiation compared to UV illumination is attributed to the more intense ROS generation in the first few hours. The results obtained significantly expand the possibilities of using PEO coatings on the surfaces of titanium implants.

Engineered bacterial cellulose-based Ag nanoparticles/g-C3N4/Eucalyptus extract nanocomposites for wound dressing: In vitro evaluation

Engineered bacterial cellulose-based Ag nanoparticles/g-C3N4/Eucalyptus extract nanocomposites for wound dressing: In vitro evaluation

Formation of Zwitterionic and Self-Healable Hydrogels via Amino-yne Click Chemistry for Development of Cellular Scaffold and Tumor Spheroid Phantom for MRI.

In situ-forming biocompatible hydrogels have great potential in various medical applications. Here, we introduce a pH-responsive, self-healable, and biocompatible hydrogel for cell scaffolds and the development of a tumor spheroid phantom for magnetic resonance imaging. The hydrogel (pMAD) was synthesized via amino-yne click chemistry between poly(2-methacryloyloxyethyl phosphorylcholine-co-2-aminoethylmethacrylamide) and dialkyne polyethylene glycol. Rheology analysis, compressive mechanical testing, and gravimetric analysis were employed to investigate the gelation time, mechanical properties, equilibrium swelling, and degradability of pMAD hydrogels. The reversible enamine and imine bond mechanisms leading to the sol-to-gel transition in acidic conditions (pH ≤ 5) were observed. The pMAD hydrogel demonstrated potential as a cellular scaffold, exhibiting high viability and NIH-3T3 fibroblast cell encapsulation under mild conditions (37 °C, pH 7.4). Additionally, the pMAD hydrogel also demonstrated the capability for in vitro magnetic resonance imaging of glioblastoma tumor spheroids based on the chemical exchange saturation transfer effect. Given its advantages, the pMAD hydrogel emerges as a promising material for diverse biomedical applications, including cell carriers, bioimaging, and therapeutic agent delivery.

Evaluating some &lt;i&gt;in vitro&lt;/i&gt; bioactivities of ethanol extract from &lt;i&gt;Ageratum conyzoidesin&lt;/i&gt; L. leaves collected in Vietnam in supporting skin wound treatment

Ageratum conyzoides L. is widely used for the treatment of skin wound in some communities in Asia, Africa, and South America, including in Vietnam. In this study, we demonstrated that the 70% ethanol extract of A. conyzoides L. leaves collected in Bidoup National Park, Nui Ba, Lam Dong, Vietnam had some properties that would be advantageous for the treatment of skin wounds. Firstly, we found that the extract contained 64.9±2.58 mgGAE/gE polyphenols and 79.33±1.03 mgQE/gE flavonoids, and had antioxidant activity with the IC50 of 131.74±2.67 µg/mL. This extract was also proven to have antimicrobial activities against some pathogenic bacteria, including S. aureus, P. aeruginosa, E. faecalis, and E. coli. We also demonstrated that this extract could inhibit the generation of nitric oxide in LPS-activated Raw 264.7 cells, indicating its in vitro anti-inflammatory activity. And finally, for the first time, we found that the ethanol extract of A. conyzoides leaves could promote the proliferation of fibroblast NIH-3T3 cell line. All together, these findings support the traditional use of this plant in skin wound treatment.

Xanthan gum and chitosan polyelectrolyte hydrogels with self-reinforcement of Zn+2 for wound dressing applications

Xanthan gum and chitosan polyelectrolyte hydrogels with self-reinforcement of Zn+2 for wound dressing applications

Comparative bioactivity assessment of bixin pigment and associated phytochemicals extracted from annatto seeds using conventional and green solvents.

Nutraceuticals, that include food ingredients and bioactives from natural products, confer physiological health benefits and protection against chronic diseases. Annatto is a tropical shrub grown in Central and South America and parts of India. Its seeds are rich in the edible carotenoid-derived apocarotenoid pigment, bixin, which is used as a natural colorant in food, textiles, and cosmetics, and is now gaining attention for its potential health-promoting attributes. Here, we compared a green solvent (ethyl lactate) based extraction of bixin and associated metabolites in annatto seeds (crushed and seed coat) with two other conventional solvents (acetone and acid-base). Bixin was characterized in the extracts using UV-visible- and FTIR-spectroscopy and thin-layer chromatography. The bixin-containing solvent extracts were then profiled for other co-existing metabolites using GC-MS analysis, which were found to be sesquiterpenes, terpenes, terpenoids, phytosterols, and tocotrienols. Their bioactivity was evaluated based on antioxidant and wound-healing efficacies and compared with pure bixin, using NIH-3T3 fibroblast cells in-vitro. Pure bixin, as well as the annatto solvent extracts, showed strong antioxidant and wound healing properties, wherein pure bixin and green solvent extract (ethyl lactate coat) exhibited higher levels of antioxidant activity, achieving 46.00% and 44.60% reduction in MDA levels, respectively, as well as enhanced wound-healing activity, with 54.09% and 53.60% wound closure within 24 h. The green solvent extracts of annatto seeds revealed: (a) differential bioactive profiles in annatto seeds (crushed and seed coat) in comparison with other solvents, and (b) strong antioxidant and wound healing properties. Thus, ethyl lactate extraction shows strong potential for sustainable environmental friendly production of functional foods/nutraceuticals from annatto seeds.

Chitosan films synthesized via thiol-ene click chemistry: Toward safe and versatile platforms for packaging, cosmetics and biomedical applications

Chitosan films synthesized via thiol-ene click chemistry: Toward safe and versatile platforms for packaging, cosmetics and biomedical applications

Epigallocatechin-3-gallate-synthesized gold nanoparticles modulate reactive oxygen species and antioxidant parameters in brain and heart tissues using a chicken embryo model

Epigallocatechin-3-gallate-synthesized gold nanoparticles modulate reactive oxygen species and antioxidant parameters in brain and heart tissues using a chicken embryo model

Enhancing cellular behavior in repaired tissue via silk fibroin-integrated triboelectric nanogenerators

Triboelectric nanogenerators (TENGs) have emerged as a promising approach for generating electricity and providing electrical stimuli in medical electronic devices. Despite their potential benefits, the clinical implementation of TENGs faces challenges such as skin compliance and a lack of comprehensive assessment regarding their biosafety and efficacy. Therefore, further research is imperative to overcome these limitations and unlock the full potential of TENGs in various biomedical applications. In this study, we present a flexible silk fibroin-based triboelectric nanogenerator (SFB-TENG) that features an on-skin substrate and is characterized by excellent skin compliance and air/water permeability. The range of electrical output generated by the SFB-TENG was shown to facilitate the migration and proliferation of Hy926, NIH-3T3 and RSC96 cells. However, apoptosis of fibroblast NIH-3T3 cells was observed when the output voltage increased to more than 20 V at a frequency of 2 Hz. In addition, the moderate electrical stimulation provided by the SFB-TENG promoted the cell proliferation cycle in Hy926 cells. This research highlights the efficacy of a TENG system featuring a flexible and skin-friendly design, as well as its safe operating conditions for use in biomedical applications. These findings position TENGs as highly promising candidates for practical applications in the field of tissue regeneration.