Mechanical stress regulates various biological processes in cells, tissues, and organs as well as contributes to the pathogenesis of various diseases. The retina is subjected to mechanical stress ...imposed by intraocular pressure as well as by retinal hemorrhage and edema. Responses to mechanical stress have been studied in retinal pigment epithelial cells and Müller cells of the retina, with the former cells having been found to undergo a stress-induced increase in the expression of vascular endothelial growth factor (VEGF), which plays a key role in physiological and pathological angiogenesis in the retina. We here examined the effects of stretch stimulation on the expression of angiogenic factors in cultured human Müller cells. Reverse transcription and quantitative PCR analysis revealed that expression of the VEGF-A gene was increased by such stimulation in Müller cells, whereas that of the angiopoietin 1 gene was decreased. An enzyme-linked immunosorbent assay showed that stretch stimulation also increased VEGF secretion from these cells. Expression of the transcription factor HIF-1α (hypoxia-inducible factor–1α) was increased at both mRNA and protein levels by stretch stimulation, and the HIF-1α inhibitor CAY10585 prevented the effects of mechanical stress on VEGF-A gene expression and VEGF secretion. Furthermore, RNA-sequencing analysis showed that the expression of angiogenesis-related pathway genes was upregulated by stretch stimulation. Our results thus suggest that mechanical stress induces VEGF production in Müller cells in a manner dependent on HIF-1α, and that HIF-1α is therefore a potential therapeutic target for conditions such as diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion.
•Mechanical stress regulates VEGF expression and ANG1 expression in Müller cells.•Their mechanisms depend on the upward regulation of HIF1α.•VEGF expression is increased by HIF1α expression.•ANG1 expression is decreased by HIF1α expression.•HIF1α is a potential therapeutic target for AMD and other conditions.
Chronic diabetic wounds are a significant global healthcare challenge. Current strategies, such as biomaterials, cell therapies, and medical devices, however, only target a few pathological features ...and have limited efficacy. A powerful platform technology combining magneto‐responsive hydrogel, cells, and wireless magneto‐induced dynamic mechanical stimulation (MDMS) is developed to accelerate diabetic wound healing. The hydrogel encapsulates U.S. Food and Drug Administration (FDA)‐approved fibroblasts and keratinocytes to achieve ∼3‐fold better wound closure in a diabetic mouse model. MDMS acts as a nongenetic mechano‐rheostat to activate fibroblasts, resulting in ∼240% better proliferation, ∼220% more collagen deposition, and improved keratinocyte paracrine profiles via the Ras/MEK/ERK pathway to boost angiogenesis. The magneto‐responsive property also enables on‐demand insulin release for spatiotemporal glucose regulation through increasing network deformation and interstitial flow. By mining scRNAseq data, a mechanosensitive fibroblast subpopulation is identified that can be mechanically tuned for enhanced proliferation and collagen production, maximizing therapeutic impact. The “all‐in‐one” system addresses major pathological factors associated with diabetic wounds in a single platform, with potential applications for other challenging wound types.
An “all‐in‐one” platform combining magneto‐responsive hydrogel, cells, and wireless magneto‐induced dynamic mechanical stimulation is developed for diabetic wound healing. It encapsulates fibroblasts and keratinocytes for superior wound closure, with enhanced cell proliferation, extracellular microenvironment production, and neo‐vascularization, suggesting potential applicability to diabetic ulcer. Plus, leveraging scRNAseq data, a mechanosensitive fibroblast subpopulation is identified for further therapeutic impact.
•Air stream-based mechanical stimulation significantly inhibited stem elongation in tomato seedlings.•Stem elongation inhibition is predominantly affected by the air velocity.•Stem elongation ...inhibition is not affected by the air stream application frequency.•The dose-response relationship between air velocity and the extent of stem elongation inhibition follows a sigmoidal curve trend with a defined stimulus threshold and stimulus saturation point.
Stem elongation control is a fundamental requirement for the production of high-quality seedlings in terms of plant compactness and stability. It is known that stem elongation of seedlings can be inhibited by mechanical stimulation. In this study, a custom-built air stream applicator was used to apply intermittent stimuli to tomato (Solanum lycopersicum cv. ‘Romello’). Tomato plants were cultivated under greenhouse conditions for 21 days and then exposed to intermittent air stimuli at different air stream application frequencies (8, 24, 40, 56, 72 and 80 d−1) and different air stream velocities (0.7 – 6.0 m s−1) for 14 days. Tomato plants responded with an inhibition of stem elongation of approximately 31% compared to the untreated control, without a systematic dose-response relationship related to application frequency. In contrast, stem elongation inhibition was significantly affected by air velocity, with a sigmoid dose-response relationship with negligible effects up to 2.0 m s−1, followed by a steep increase in the reduction effect up to 4.7 m s−1 and a fading of the effect at 36 % reduction for air velocities beyond that. Dry mass of leaves, stems, and petioles was reduced by approximately 10%, 41%, and 19%, respectively, after 14 days of treatment at a gradually increasing air velocity from 3.5 m s−1 at day 0 to 6.1 m s−1 at day 14 and an application frequency of 8 d−1. Root dry mass was less affected by the air stream application, but showed a slight tendency to decrease compared to control plants.
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Background: To investigate whether hysteroscopic endometrial mechanical stimulation improves pregnancy outcomes in patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection ...(ICSI). Methods: We conducted a systematic search in electronic databases including PubMed, Embase, Cochrane Library, Web of Science from their inception to Feb 20th, 2021, as well as a manual search. All publications on the impact of hysteroscopic endometrial mechanical stimulation on IVF/ICSI outcomes were retrieved. Two reviewers independently screened the retrieved studies using stringent inclusion and exclusion criteria; data were subsequently extracted, and risk of bias was assessed. Meta-analysis of the selected studies was performed using Revman 5.3. Results: Eight studies involving 1494 patients were eligible for inclusion, including 5 randomized controlled trials and 3 prospective non-randomized simultaneous controlled experimental studies. We found that compared with the control group, hysteroscopic endometrial mechanical stimulation effectively increased live birth rate risk ratio (RR) = 2.15, 95% confidence interval (CI) (1.78, 2.60), p < 0.00001 and clinical pregnancy rate RR = 1.95, 95% CI (1.28, 2.98), p = 0.002, and also decreased abortion rate RR = 0.54, 95% CI (0.35, 0.86), p = 0.009. Subgroup analyses revealed that, hysteroscopic endometrial mechanical stimulation administered in the luteal phase in patients undergoing their first IVF/ICSI cycle was associated with significantly higher live birth rate and clinical pregnancy rate, as well as a significantly lower abortion rate. Discussion: Endometrial mechanical stimulation may improve live birth rate, clinical pregnancy rate and reduce abortion rate in patients with normal hysteroscopic findings who are undergoing IVF/ICSI. The benefits may be even greater if this therapy is given in the luteal phase and in patients who are in their first IVF/ICSI cycle. However, due to the limited quantity and quality of the included studies and variable stimulation methods, these findings should be interpreted with caution, and more high-quality studies are needed to confirm this conclusion.
The study is aimed to assess the role of Ca10(PO4)6(OH)2 (HAp) and Zn3(PO4)2 (ZnP) bioceramics respectively as powder reinforcement and coating agent for magnesium alloys. The nano-sized HAp powder ...was synthesised and Mg-2Mn-1.5Zn (MZ21) and Mg-2Mn-1.5Zn/1HAp (MZ21/HAp) metal matrix nanocomposites were developed using vacuum-assisted stir casting process in Ar-SF6 protected environment. The chemical conversion coatings of ZnP were prepared on fabricated composites using Teflon lined stainless steel with zinc phosphate-based reaction solution. X-ray diffraction was used to assess the interaction of Mn and Zn on Mg crystal lattice. Microstructural observations were made using optical and scanning electron microscopy with energy dispersive X-ray spectroscopy. Mechanical properties were determined using tensile, hardness and dynamic mechanical analysis. Tensile yield and ultimate strengths of the MZ21 (60.31 ± 0.24 MPa, 142.83 ± 18.40 MPa) and MZ21/HAp (73.41 ± 2.24 MPa, 139.65 ± 16.16 MPa) showed a two-fold increase compared to pure Mg (30.36 ± 2.66 MPa, 73 ± 5.74 MPa). In-vitro studies indicated 10 % and 59 % improvement in cell viability, and 60 % and 33 % reduction in hemolysis rate respectively for MZ21 and MZ21/HAp by employing ZnP, and its bioactivity resulted in increased cell attachment. The effectiveness of the material was biomechanically evaluated and analysed using finite element approach. The results indicated that the developed composites reduced the mechanically shielded region and could provide enhanced healing in transverse tibial shaft fracture.
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•Surface coatings of Zn3(PO4)2 were prepared using twin-step hydrothermal method•Improved cell viability and bioactivity of ZnP in increased cell attachment•Significant rise in yield strengths with combined SSH effect of Mn and Zn solutes•Enhancement of biomechanical stimulus level in tibia transverse fracture
•Compact, easy-to-use, tunable stretch bioreactor.•Validation tests confirmed the bioreactor accuracy, repeatability and reliability.•Biological tests demonstrated bioreactor suitability for cardiac ...tissue engineering applications.•Cyclic stretch promoted human cardiac progenitor cells differentiation towards adult cardiac myocytes.
Physical stimuli are crucial for the structural and functional maturation of tissues both in vivo and in vitro. In tissue engineering applications, bioreactors have become fundamental and effective tools for providing biomimetic culture conditions that recapitulate the native physical stimuli. In addition, bioreactors play a key role in assuring strict control, automation, and standardization in the production process of cell-based products for future clinical application. In this study, a compact, easy-to-use, tunable stretch bioreactor is proposed. Based on customizable and low-cost technological solutions, the bioreactor was designed for providing tunable mechanical stretch for biomimetic dynamic culture of different engineered tissues. In-house validation tests demonstrated the accuracy and repeatability of the imposed mechanical stimulation. Proof of concepts biological tests performed on engineered cardiac constructs, based on decellularized human skin scaffolds seeded with human cardiac progenitor cells, confirmed the bioreactor Good Laboratory Practice compliance and ease of use, and the effectiveness of the delivered cyclic stretch stimulation on the cardiac construct maturation.
The aim of osteochondral tissue engineering is to achieve the complex, functional and three-dimensional tissue regeneration under well defined, controlled and reproducible conditions in vitro. To ...achieve tissue-engineered products in vitro that incorporate rapidly in vivo with healthy tissue, it is essential to develop high-performance cell/scaffold culture systems that mimic the dynamics of the in vivo environment. Bioreactors could provide specific physicochemical culture environment, suitable mechanical stimulation and controlled condition for the development of osteochondral constructs in vitro. This review highlighted the multifunction of bioreactor in tissue engineering, and presented microenvironment and biomechanics of native osteochondral tissue, to illustrate the necessity of establishing osteochondral constructs by bioreactor. Then, we especially emphasized the advantages and limitations of various bioreactors. Furthermore, we systematically summarized and discussed the development of bioreactor-based production systems for bone, cartilage and osteochondral tissue engineering in recent years. Finally, we made a simple conclusion and offered perspectives of bioreactor‐based osteochondral tissue engineering. This review aims to serve as a reference for incorporating bioreactor strategies which could provide mechanical stimulation and physicochemical culture environment into the osteochondral construct culture regimens.
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•Emphasizing advantage of bioreactor as high-performance cell/scaffold culture systems.•Comprehensively analyzing the characteristics of various bioreactors.•Systematically discussing the development of bioreactor-based osteochondral construction.•Proposing future perspectives to acquire better bioreactor-based osteochondral constructs.
Native and engineered tissue development are regulated by the integrative effects of multiple microenvironmental stimuli. Microfabricated bioreactor array platforms can efficiently dissect ...cue-response networks, and have recently integrated critical 2D and 3D mechanical stimulation for greater physiological relevance. However, a limitation of these approaches is that assessment of tissue functional properties is typically limited to end-point analyses. Here we report a new deformable membrane platform with integrated strain sensors that enables mechanical stretching or compression of 3D cell-hydrogel arrays and simultaneous measurement of hydrogel construct stiffness in situ. We tested the ability of the integrated strain sensors to measure the evolution of the stiffness of cell-hydrogel constructs for two cases. First, we demonstrated in situ stiffness monitoring of degradable poly (ethylene glycol)-norbornene (PEG-NB) hydrogels embedded with mesenchymal stromal cells (MSCs) and cultured with or without cyclic tensile stimulation for up to 15 days. Whereas statically-cultured hydrogels degraded and softened throughout the culture period, mechanically-stimulated gels initially softened and then recovered their stiffness corresponding to extensive cell network and collagen production. Second, we demonstrated in situ measurement of compressive stiffening of MSC-seeded PEG-NB gels cultured statically under osteogenic conditions, corresponding to increased mineralization and cellularization. This measurement technique can be generalized to other relevant bioreactor and organ-on-a-chip platforms to facilitate online, non-invasive, and high-throughput functional analysis, and to provide insights into the dynamics of engineered tissue development that are otherwise not available.
Mechanobiological study of chondrogenic cells and multipotent stem cells for articular cartilage tissue engineering (CTE) has been widely explored. The mechanical stimulation in terms of wall shear ...stress, hydrostatic pressure and mechanical strain has been applied in CTE in vitro. It has been found that the mechanical stimulation at a certain range can accelerate the chondrogenesis and articular cartilage tissue regeneration. This review explicitly focuses on the study of the influence of the mechanical environment on proliferation and extracellular matrix production of chondrocytes in vitro for CTE. The multidisciplinary approaches used in previous studies and the need for in silico methods to be used in parallel with in vitro methods are also discussed. The information from this review is expected to direct facial CTE research, in which mechanobiology has not been widely explored yet.
•Air stream-based mechanical stimulation results in a stunted and compact phenotype of tomato.•Leaf and stem sink strength are promoted at the expense of dry mass accumulation to petioles.•Increased ...leaf density is associated with higher net carbon assimilation rates maintaining biomass productivity.
Plant responses to mechanical stimulation have a great potential for growth control of ornamentals plants and vegetable seedlings and is a major requirement to ensure plant compactness and stability. 21 days old tomato (Solanum lycopersicum cv. ‘Romello’) plants were exposed to regularly applied mechanical stimuli for 14 days by applying of a defined air stream through a custom-built air stream applicator. Air stream application gradually reduced total plant leaf area by 14% and promoted radial growth relative to internode length compared to the untreated control, resulting in a more compact and stable plant phenotype, which was also related to an increased stem dry matter content of the air stream-treated plants. The reduction in total plant leaf area was compensated for the translocation of proportionally more assimilates to light-harvesting tissues and to stems at the expense of dry mass accumulation in petioles. Total stem, leaf and root dry mass of air stream-treated plants were unaffected. The specific leaf area of the air stream treated plants was reduced compared to the control, resulting in an increased relative leaf greenness and consequently in an 8% higher net carbon assimilation rates on average compared to the control. Thereby, air stream-treated plants were able to maintain overall biomass accumulation at the same level as the control. Leaf transpiration rate of air stream treated plants was not markedly affected in the long-term. The technique presented should be easily transferable to other plants, such as ornamentals where the application of chemical plant growth regulators is still the most common technique for plant growth control.
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