Single nucleus and spatial transcriptomic profiling of healthy human hamstring tendon.

The molecular and cellular basis of health in human tendons remains poorly understood. Among human tendons, hamstring tendon has markedly low pathology and can provide a prototypic healthy tendon reference. The aim of this study was to determine the transcriptomes and location of all cell types in healthy hamstring tendon.

Overcoming barriers to single-cell RNA sequencing adoption in low- and middle-income countries.

The advent of single-cell resolution sequencing and spatial transcriptomics has enabled the delivery of cellular and molecular atlases of tissues and organs, providing new insights into tissue health and disease. However, if the full potential of these technologies is to be equitably realised, ancestrally inclusivity is paramount. Such a goal requires greater inclusion of both researchers and donors in low- and middle-income countries (LMICs).

A Hybrid Electrospun-Extruded Polydioxanone Suture for Tendon Tissue Regeneration.

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 other clinical applications. Electrospun materials show promise as a biological scaffold to support endogenous tendon repair, but their relatively low tensile strength has limited their clinical translation.

A roadmap for delivering a human musculoskeletal cell atlas.

Advances in single-cell technologies have transformed the ability to identify the individual cell types present within tissues and organs. The musculoskeletal bionetwork, part of the wider Human Cell Atlas project, aims to create a detailed map of the healthy musculoskeletal system at a single-cell resolution throughout tissue development and across the human lifespan, with complementary generation of data from diseased tissues. Given the prevalence of musculoskeletal disorders, this detailed reference dataset will be critical to understanding normal musculoskeletal function in growth, homeostasis and ageing.

Cellular characterisation of advanced osteoarthritis knee synovium.

Objectives: Osteoarthritis (OA) is increasingly recognised as a whole joint disease, with an important role for synovium. However, the repertoire of immune cells and fibroblasts that constitute OA synovium remains understudied. This study aims to characterise the cellular composition of advanced OA synovium and to explore potential correlations between different cell types and patient demographics or clinical scores.

Manufacture of Soft-Hard Implants from Electrospun Filaments Embedded in 3D Printed Structures.

Rotator cuff tendon tears are common injuries of the musculoskeletal system that often require surgical repair. However, re-tearing following repair is a significant clinical problem, with a failure rate of up to 40%, notably at the transition from bone to tendon. The development of biphasic materials consisting of soft and hard components, which can mimic this interface, is therefore promising.

Humanoid robots to mechanically stress human cells grown in soft bioreactors.

For more than 20 years, robotic bioreactor systems have facilitated the growth of tissue-engineered constructs using mechanical stimulation. However, we are still unable to produce functional grafts that can translate into clinical use. Humanoid robots offer the prospect of providing physiologically-relevant mechanical stimulation to grafts and implants which may expedite their clinical deployment.

evaluation of the response of human tendon-derived stromal cells to a novel electrospun suture for tendon repair.

Recurrent tears after surgical tendon repair remain common. Repair failures can be partly attributed to the use of sutures not designed for the tendon cellular niche nor for the promotion of repair processes. Synthetic electrospun materials can mechanically support the tendon whilst providing topographical cues that regulate cell behaviour.

Research perspectives-Pipelines to human tendon transcriptomics.

Tendon transcriptomics is a rapidly growing field in musculoskeletal biology. The ultimate aim of many current tendon transcriptomic studies is characterization of in vitro, ex vivo, or in vivo, healthy, and diseased tendon microenvironments to identify the underlying pathways driving human tendon pathology. The transcriptome interfaces between genomic, proteomic, and metabolomic signatures of the tendon cellular niche and the response of this niche to stimuli.

Tough Photo-Cross-Linked PCL-Hydroxyapatite Composites for Bone Tissue Engineering.

Acrylate-based photo-cross-linked poly(ε-caprolactone) (PCL) tends to show low elongation and strength. Incorporation of osteo-inductive hydroxyapatite (HAp) further enhances this effect, which limits its applicability in bone tissue engineering. To overcome this, the thiol-ene click reaction is introduced for the first time in order to photo-cross-link PCL composites with 0, 10, 20, and 30 wt % HAp nanoparticles.

Electrospun Scaffold Micro-Architecture Induces an Activated Transcriptional Phenotype within Tendon Fibroblasts.

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.

Interleukin-17 Cytokines and Receptors: Potential Amplifiers of Tendon Inflammation.

Interleukin (IL)-17A, a pro-inflammatory cytokine that is linked to the pathology of several inflammatory diseases, has been shown to be upregulated in early human tendinopathy and to mediate inflammatory and tissue remodelling events. However, it remains unclear which cells in tendons can respond to IL-17A, and how IL-17A, and its family members IL-17F and IL-17AF, can affect intracellular signalling activation and mRNA expression in healthy and diseased tendon-derived fibroblasts. Using well-phenotyped human tendon samples, we show that IL-17A and its receptors IL-17RA and IL-17RC are present in healthy hamstring, and tendinopathic and torn supraspinatus tendon tissue.

Loss of mutual protection between human osteoclasts and chondrocytes in damaged joints initiates osteoclast-mediated cartilage degradation by MMPs.

Osteoclasts are multinucleated, bone-resorbing cells. However, they also digest cartilage during skeletal maintenance, development and in degradative conditions including osteoarthritis, rheumatoid arthritis and primary bone sarcoma. This study explores the mechanisms behind the osteoclast-cartilage interaction.

Early development of a polycaprolactone electrospun augment for anterior cruciate ligament reconstruction.

Despite the clinical success of Anterior Cruciate Ligament reconstruction (ACLR) in some patients, unsatisfactory clinical outcomes secondary to graft failure are seen, indicating the need to develop new regeneration strategies. The use of degradable and bioactive textiles has the potential to improve the biological repair of soft tissue. Electrospun (ES) filaments are particularly promising as they have the ability to mimic the structure of natural tissues and influence endogenous cell behaviour.

Host-biomaterial interactions in mesh complications after pelvic floor reconstructive surgery.

Polypropylene (PPL) mesh is widely used in pelvic floor reconstructive surgery for prolapse and stress urinary incontinence. However, some women, particularly those treated using transvaginal PPL mesh placement for prolapse, experience intractable pain and mesh exposure or extrusion. Explanted tissue from patients with complications following transvaginal implantation of mesh is typified by a dense fibrous capsule with an immune cell-rich infiltrate, suggesting that the host immune response has a role in transvaginal PPL mesh complications through the separate contributions of the host (patient), the biological niche within which the material is implanted and biomaterial properties of the mesh.

Interleukin-17A Causes Osteoarthritis-Like Transcriptional Changes in Human Osteoarthritis-Derived Chondrocytes and Synovial Fibroblasts .

Increased interleukin (IL)-17A has been identified in joints affected by osteoarthritis (OA), but it is unclear how IL-17A, and its family members IL-17AF and IL-17F, can contribute to human OA pathophysiology. Therefore, we aimed to evaluate the gene expression and signalling pathway activation effects of the different IL-17 family members in chondrocytes and synovial fibroblasts derived from cartilage and synovium of patients with end-stage knee OA. Immunohistochemistry staining confirmed that IL-17 receptor A (IL-17RA) and IL-17RC are expressed in end-stage OA-derived cartilage and synovium.

Synovial fluid fingerprinting in end-stage knee osteoarthritis: a novel biomarker concept.

Aims: The lack of disease-modifying treatments for osteoarthritis (OA) is linked to a shortage of suitable biomarkers. This study combines multi-molecule synovial fluid analysis with machine learning to produce an accurate diagnostic biomarker model for end-stage knee OA (esOA).

Methods: Synovial fluid (SF) from patients with esOA, non-OA knee injury, and inflammatory knee arthritis were analyzed for 35 potential markers using immunoassays.

Rotator cuff repair with biological graft augmentation causes adverse tissue outcomes.

Background and purpose - Biological patches can be used to augment rotator cuff tendon repair in an attempt to improve healing and reduce rates of re-rupture. However, little is known about the in vivo tissue response to these patches. We assessed native rotator cuff tissue response after surgical repair and augmentation with 2 commercially available extracellular matrix (ECM) patches.

Histological evaluation of cellular response to a multifilament electrospun suture for tendon repair.

Background: Rotator cuff tendon repair in humans is a commonly performed procedure aimed at restoring the tendon-bone interface. Despite significant innovation of surgical techniques and suture anchor implants, only 60% of repairs heal successfully. One strategy to enhance repair is the use of bioactive sutures that provide the native tendon with biophysical cues for healing.

Histopathological and immunohistochemical evaluation of cellular response to a woven and electrospun polydioxanone (PDO) and polycaprolactone (PCL) patch for tendon repair.

We investigated endogenous tissue response to a woven and electrospun polydioxanone (PDO) and polycaprolactone (PCL) patch intended for tendon repair. A sheep tendon injury model characterised by a natural history of consistent failure of healing was chosen to assess the biological potential of woven and aligned electrospun fibres to induce a reparative response. Patches were implanted into 8 female adult English Mule sheep.