Electrospun scaffold micro-architecture induces an activated transcriptional phenotype within tendon fibroblasts. Bulk RNA-seq data.
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ABSTRACT:
PROVIDER: PRJNA785809 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17111300_1.fastq.gz | Fastqsanger.gz | |||
| SRR17111300_2.fastq.gz | Fastqsanger.gz | |||
| SRR17111253_1.fastq.gz | Fastqsanger.gz | |||
| SRR17111253_2.fastq.gz | Fastqsanger.gz | |||
| SRR17111254_1.fastq.gz | Fastqsanger.gz |
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Project description:Biomaterial augmentation of surgically repaired rotator cuff tendon tears aims to improve the high failure rates (~40%) of traditional repairs. Biomaterials that can alter cellular phenotypes through the provision of microscale topographical cues are now under development. We aimed to systematically evaluate the effect of topographic architecture on the cellular phenotype of fibroblasts from healthy and diseased tendons. Electrospun polydioxanone scaffolds with fiber diameters ranging from 300 to 4000 nm, in either a highly aligned or random configuration, were produced. Healthy tendon fibroblasts cultured for 7 days on scaffolds with highly aligned fibers demonstrated a distinctive elongated morphology, whilst those cultured on randomly configured fibers demonstrated a flattened and spread morphology. The effect of scaffold micro-architecture on the transcriptome of both healthy and diseased tendon fibroblasts was assessed with bulk RNA-seq. Both healthy (n=3) and diseased tendon cells (n=3) demonstrated a similar transcriptional response to architectural variants. Gene set enrichment analysis revealed that large diameter (≥ 2000 nm) aligned scaffolds induced an upregulation of genes involved in cellular replication and a downregulation of genes defining inflammatory responses and cell adhesion. Similarly, PDPN and CD248, markers of inflammatory or ‘activated’ fibroblasts, were downregulated during culture of both healthy and diseased fibroblasts on aligned scaffolds with large (≥ 2000 nm) fiber diameters. In conclusion scaffold architectures resembling that of disordered type III collagen, typically present during the earlier phases of wound healing, resulted in tendon fibroblast activation. Conversely, scaffolds mimicking aligned diameter collagen I fibrils, present during tissue remodelling, did not activate tendon derived fibroblasts. This has implications for the design of scaffolds used during rotator cuff repair augmentation.
2021-12-05 | GSE190085 | GEO
Project description:Many surgical tendon repairs fail despite advances in surgical materials and techniques. Tendon repair failure can be partially attributed to the tendon’s poor intrinsic healing capacity and the repurposing of sutures from use in other tissues. Electrospun materials show promise as a biological scaffold to support endogenous tendon repair, but their relatively low tensile strength has limited their clinical translation. It is hypothesized that combining electrospun fibres with a stronger material may improve the suture’s mechanical properties while retaining biophysical cues necessary to encourage cell-mediated repair. This paper describes the production of a hybrid electrospun-extruded suture with a sheath of submicron electrospun fibres and a core of melt-extruded fibres. The porosity and tensile strength of this hybrid suture is compared to an electrospun-only braided suture and clinically used sutures Vicryl and PDS. Bioactivity is assessed by measuring the adsorbed serum proteins on electrospun and melt-extruded filaments using mass spectrometry. Human hamstring tendon fibroblast attachment and proliferation was quantified and compared between the hybrid and control sutures. Combining an electrospun sheath with melt-extruded cores created a hybrid braid with increased tensile strength (70.1±0.3N) compared to an electrospun only suture (12.9±1N, p<0.0001). The hybrid suture had a similar force at break to clinical sutures, but lower stiffness and stress. The Young’s modulus was 772.6±32Mpa for the hybrid suture, 1693.0±69Mpa for PDS, and 3838.0±132MPa for Vicryl, p<0.0001. Hybrid sutures had lower overall porosity than electrospun-only sutures (40±4% and 60±7%, respectively, p=0.0018) but had a significantly larger overall porosity and average pore diameter compared to surgical sutures. There were similar clusters of adsorbed proteins on electrospun and melt-extruded filaments, which were distinct from PDS. Tendon fibroblast attachment on hybrid and electrospun sutures was significantly higher than on clinical sutures (hybrid 28±7%; electrospun 24±7%; Vicryl 10±5%; PDS 2±0.1%, p<0.0001). Cell proliferation was significantly higher on hybrid and electrospun sutures compared to on clinical sutures. Overall, this study demonstrated that a bioactive suture with increased tensile strength and lower stiffness could be produced by adding a core of 10um melt-extruded fibres to a sheath of electrospun fibres. In contrast to currently used sutures, the hybrid sutures promoted a bioactive response: serum proteins adsorbed, and fibroblasts attached, survived, grew along the sutures, and adopted appropriate morphologies.
2024-05-23 | PXD045312 | Pride
Project description:Biomaterial augmentation of surgically repaired rotator cuff tendon tears aims to improve the high failure rates (∼40%) of traditional repairs. Biomaterials that can alter cellular phenotypes through the provision of microscale topographical cues are now under development. We aimed to systematically evaluate the effect of topographic architecture on the cellular phenotype of fibroblasts from healthy and diseased tendons. Electrospun polydioxanone scaffolds with fiber diameters ranging from 300 to 4000 nm, in either a highly aligned or random configuration, were produced. Healthy tendon fibroblasts cultured for 7 days on scaffolds with highly aligned fibers demonstrated a distinctive elongated morphology, whilst those cultured on randomly configured fibers demonstrated a flattened and spread morphology. The effect of scaffold micro-architecture on the transcriptome of both healthy and diseased tendon fibroblasts was assessed with bulk RNA-seq. Both healthy (n = 3) and diseased tendon cells (n = 3) demonstrated a similar transcriptional response to architectural variants. Gene set enrichment analysis revealed that large diameter (≥2000 nm) aligned scaffolds induced an upregulation of genes involved in cellular replication and a downregulation of genes defining inflammatory responses and cell adhesion. Similarly, PDPN and CD248, markers of inflammatory or "activated" fibroblasts, were downregulated during culture of both healthy and diseased fibroblasts on aligned scaffolds with large (≥2000 nm) fiber diameters. In conclusion scaffold architectures resembling that of disordered type III collagen, typically present during the earlier phases of wound healing, resulted in tendon fibroblast activation. Conversely, scaffolds mimicking aligned diameter collagen I fibrils, present during tissue remodelling, did not activate tendon derived fibroblasts. This has implications for the design of scaffolds used during rotator cuff repair augmentation.
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Project description:Tendons and ligaments are important biological structures in both humans and animals. They are part of dense connective tissue and are crucial to the functioning of the musculoskeletal system. However, they are commonly damaged due to age-related wear and tear, trauma or sports related incidents, which can lead to severe immobility for the individual and can lead to injury of other tissues and development of degenerative joint disease such as osteoarthritis. Tissue engineering can offer great potential in the treatment of tendon and ligament injury by seeking a biological replacement with fully regenerated autologenous tissue. This approach commonly involves an artificial ECM (scaffold) on which cell can proliferate and differentiate with subsequent new tissue generation. Fibrin is a natural scaffold with no expected toxic degradation or inflammatory reaction and can be used as an autologous scaffold for fibroblast from connective tissue to create a three dimensional structure. The purpose of this study was to compare the proteomic differences between native tendon, ligament and 3D tissue engineered tendon and ligament fibrin constructs.
2016-06-27 | PXD003094 | Pride
Project description:Background: Tendon is a major component of musculoskeletal system connecting the muscles to the bone. Tendon injuries are very common orthopedics problems leading to impeded motion. Up to now, there still lacks effective treatments for tendon diseases. Methods: Tendon stem/progenitor cells (TSPCs) were isolated from the patellar tendons of SD rats. The expression levels of genes were evaluated by quantitative RT-PCR. Immunohistochemistry staining was performed to confirm the presence of tendon markers in tendon tissues. Bioinformatics analysis of data acquired by RNA-seq was used to find out the differentially expressed genes. Rat patellar tendon injury model was used to evaluate the effect of U0126 on tendon injury healing. Biomechanical testing was applied to evaluate the mechanical properties of newly formed tendon tissues. Results: In this study, we have shown that ERK inhibitor U0126 rather PD98059 could effectively increase the expression of tendon-related genes and promote the tenogenesis of TSPCs in vitro. To explore the underlying mechanisms, RNA sequencing was performed to identify the molecular difference between U0126-treated and control TSPCs. The result showed that GDF6 was significantly increased by U0126, which is an important factor of the TGFβ superfamily regulating tendon development and tenogenesis. In addition, NBM (nonwoven-based gelatin/polycaprolactone membrane) which mimics the native microenvironment of the tendon tissue was used as an acellular scaffold to carry U0126. The results demonstrated that when NBM was used in combination with U0126, tendon healing was significantly promoted with better histological staining outcomes and mechanical properties. Conclusion: Taken together, we have found U0126 promoted tenogenesis in TSPCs through activating GDF6, and NBM loaded with U0126 significantly promoted tendon defect healing, which provides a new treatment for tendon injury.
2022-12-10 | GSE190685 | GEO
Project description:We have reported that loss of Tnmd leads to inferior early tendon repair characterized by fibrovascular scaring and therefore hypothesized that its lack will persistently cause deficient repair during later stages. Tnmd knockout (Tnmd-/-) and wild-type (WT) animals were subjected to complete Achilles tendon surgical transection followed by end-to-end suture. Lineage tracing revealed a reduction in tendon-lineage cells marked by ScleraxisGFP, but an increase in alpha smooth muscle actin myofibroblasts in Tnmd-/- tendon scars. At the proliferative stage, more pro-inflammatory M1 macrophages and larger collagen II cartilaginous template were detected in this group. At the remodeling stage, histological scoring revealed lower repair quality in the injured Tnmd-/- tendons, which was coupled with higher HO quantified by micro-CT. Tendon biomechanical properties were compromised in both groups upon injury, however we identified an abnormal stiffening of non-injured Tnmd-/- tendons, which possessed higher static and dynamic E-moduli. Pathologically thicker and abnormally shaped collagen fibrils were observed by TEM in Tnmd-/- tendons and this together with augmented HO resulted in diminished running capacity of Tnmd-/- mice. These novel findings demonstrate that Tnmd plays a protecting role against trauma-induced endochondral HO and can inspire the generation of novel therapeutics to accelerate repair.
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Project description:Rotator cuff tears are the most common conditions in sports medicine and attract increasing attention. Scar tissue healing at the tendon-bone interface results in a high rate of retears, making it a major challenge to enhance the healing of the rotator cuff tendon-bone interface. Biomaterials currently employed for tendon-bone healing in rotator cuff tears still exhibit limited efficacy. 3D printing, a promising technology, enables the customization of scaffold shapes and properties. Bone marrow mesenchymal stem cells (BMSCs) have multi-differentiation potential and valuable immunomodulatory effects. Basic fibroblast growth factor (bFGF), known for its role in proliferation, has been reported to promote osteogenesis. These properties make them applicable in tissue engineering. In this study, we developed a 3D-printed PCL scaffold loaded with bFGF and BMSCs (PCLMF) to restore the tendon-bone interface and regulate the local inflammatory microenvironment. The PCLMF scaffolds significantly improved the biomechanical strength, histological score, and local bone mineral density at regenerated entheses at 2 weeks post-surgery and achieved optimal performance at 8 weeks. Furthermore, PCLMF scaffolds facilitated BMSC osteogenic differentiation and suppressed adipogenic differentiation both in vivo and in vitro. In addition, RNA-seq showed that PCLMF scaffolds could regulate macrophage polarization and inflammation through the MAPK pathway. The implanted scaffold demonstrated excellent biocompatibility and biosafety. Therefore, this study proposes a promising and practical strategy for enhancing tendon-bone healing in rotator cuff tears.
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Project description:Tendon from young and old donors was used for RNA-Seq analysis. The aim of the study was to identify differentially expressed tendon transcripts in ageing in order to to characterize molecular mechanisms associated with age-related changes in tendon.
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