Histological assessment of thermal damage in porcine muscle induced by monopolar electrosurgical cutting devices during manual and robotic testing.

Surgical cutting with electrosurgical tools facilitates tissue dissection and vessel sealing, preventing blood loss. The extent of tissue necrosis due to temperature elevations is dependent on the cutting technique, device design, coating properties and power settings, but the influence of these parameters is not fully understood. Here we conduct a comprehensive comparative analysis of thermal damage comparing (1) manual user-controlled and robotic electrosurgical cutting approaches for (2) varying electrodes and coatings, and power settings.

Altered extracellular matrix and mechanotransduction gene expression in rat bone tissue following long-term estrogen deficiency.

Osteoporosis is primarily associated with bone loss, but changes in bone tissue matrix composition and osteocyte mechanotransduction have also been identified. However, the molecular mechanisms underlying these changes and their relation to bone loss are not fully understood. The objectives of this study were to (1) conduct comprehensive temporal gene expression analyses on cortical bone tissue from ovariectomized rats, with a specific focus on genes known to govern matrix degradation, matrix production, and mechanotransduction, and (2) correlate these findings with bone mass, trabecular and cortical microarchitecture, and mineral and matrix composition.

A mechanobiological model of bone metastasis reveals that mechanical stimulation inhibits the pro-osteolytic effects of breast cancer cells.

Bone is highly susceptible to cancer metastasis, and both tumor and bone cells enable tumor invasion through a "vicious cycle" of biochemical signaling. Tumor metastasis into bone also alters biophysical cues to both tumor and bone cells, which are highly sensitive to their mechanical environment. However, the mechanobiological feedback between these cells that perpetuate this cycle has not been studied.

Computational Investigation of Vessel Injury Due to Catheter Tracking During Transcatheter Aortic Valve Replacement.

Catheter reaction forces during transcatheter valve replacement (TAVR) may result in injury to the vessel or plaque rupture, triggering distal embolization or thrombosis. In vitro test methods represent the arterial wall using synthetic proxies to determine catheter reaction forces during tracking, but whether they can account for reaction forces within the compliant aortic wall tissue in vivo is unknown. Moreover, the role of plaque inclusions is not well understood.

Instrumental in Surgery: A Narrative Review on Energy-based Surgical Cutting Devices and Surgical Smoke.

Objective: To provide an informed understanding of existing energy-based surgical cutting technologies and aerosol-generating surgical procedures. We provide a perspective on the future innovation and research potential in this space for the benefit of surgeons, physicians, engineers, and researchers alike.

Background: Surgery is a treatment for many medical conditions, the success of which depends on surgical cutting instruments that enable surgeons to conduct surgical procedures for tissue cutting and manipulation.

Mechanoregulation may drive osteolysis during bone metastasis: A finite element analysis of the mechanical environment within bone tissue during bone metastasis and osteolytic resorption.

Metastatic bone disease occurs in 70-80% of advanced breast cancer patients and bone tissue is accepted to have attractive physical properties that facilitate cancer cell attraction, adhesion, and invasion. Bone cells also facilitate tumour invasion by biochemical signalling and through resorption of the bone matrix (osteolysis), which releases factors that further stimulate tumour cell activity. The evolving mechanical environment during tumour invasion might play an important role in these processes, as the activity of both bone and cancer cells is regulated by mechanical cues.

Temporal and spatial changes in bone mineral content and mechanical properties during breast-cancer bone metastases.

Cancer cells favour migration and metastasis to bone tissue for 70-80 % of advanced breast cancer patients and it has been proposed that bone tissue provides attractive physical properties that facilitate tumour invasion, resulting in osteolytic and or osteoblastic metastasis. However, it is not yet known how specific bone tissue composition is associated with tumour invasion. In particular, how compositional and nano-mechanical properties of bone tissue evolve during metastasis, and where in the bone they arise, may affect the overall aggressiveness of tumour invasion, but this is not well understood.

Osteocytes and Estrogen Deficiency.

Purpose Of Review: Postmenopausal osteoporosis reduces circulating estrogen levels, which leads to osteoclast resorption, bone loss, and fracture. This review addresses emerging evidence that osteoporosis is not simply a disease of bone loss but that mechanosensitive osteocytes that regulate both osteoclasts and osteoblasts are also impacted by estrogen deficiency.

Recent Findings: At the onset of estrogen deficiency, the osteocyte mechanical environment is altered, which coincides with temporal changes in bone tissue composition.

Estrogen withdrawal alters cytoskeletal and primary ciliary dynamics resulting in increased Hedgehog and osteoclastogenic paracrine signalling in osteocytes.

Estrogen deficiency during post-menopausal osteoporosis leads to osteoclastogenesis and bone loss. Increased pro-osteoclastogenic signalling (RANKL/OPG) by osteocytes occurs following estrogen withdrawal (EW) and is associated with impaired focal adhesions (FAs) and a disrupted actin cytoskeleton. RANKL production is mediated by Hedgehog signalling in osteocytes, a signalling pathway associated with the primary cilium, and the ciliary structure is tightly coupled to the cytoskeleton.

The effect of marrow secretome and culture environment on the rate of metastatic breast cancer cell migration in two and three dimensions.

Metastasis is responsible for over 90% of cancer-related deaths, and bone is the most common site for breast cancer metastasis. Metastatic breast cancer cells home to trabecular bone, which contains hematopoietic and stromal lineage cells in the marrow. As such, it is crucial to understand whether bone or marrow cells enhance breast cancer cell migration toward the tissue.

Mechanical stimuli and matrix properties modulate cancer spheroid growth in three-dimensional gelatin culture.

Most patients who succumb to cancer have metastases to bone that contribute to their death. Cancer cells that metastasize to bone are regularly subjected to mechanical stimuli that may affect their proliferation, growth and protein expression. Understanding why some cancer cells thrive in this environment could provide insight into new approaches to prevent or treat metastasis to bone.

ROCK-II inhibition suppresses impaired mechanobiological responses in early estrogen deficient osteoblasts.

Mechanobiological responses by osteoblasts are governed by downstream Rho-ROCK signalling through actin cytoskeleton re-arrangements but whether these responses are influenced by estrogen deficiency during osteoporosis remains unknown. The objective of this study was to determine alterations in the mechanobiological responses of estrogen-deficient osteoblasts and investigate whether an inhibitor of the Rho-ROCK signalling can revert these changes. MC3T3-E1 cells were pre-treated with 10 nM 17-β estradiol for 7 days and further cultured with or without estradiol for next 2 days.

Comparison of Surgical Smoke Generated During Electrosurgery with Aerosolized Particulates from Ultrasonic and High-Speed Cutting.

"Surgical smoke" is an airborne by-product of electrosurgery comprised of vapour and suspended particles. Although concerns exist that exposure may be harmful, there is a poor understanding of the smoke in terms of particle size, morphology, composition and biological viability. Notably, it is not known how the biological tissue source and cutting method influence the smoke.

A Novel 3D Osteoblast and Osteocyte Model Revealing Changes in Mineralization and Pro-osteoclastogenic Paracrine Signaling During Estrogen Deficiency.

Recent studies have revealed that the mechanobiological responses of osteoblasts and osteocytes are fundamentally impaired during estrogen deficiency. However, these two-dimensional (2D) cell culture studies do not account for biophysical cues. Thus, the objectives of this study are to (1) develop a three-dimensional (3D) osteoblast and osteocyte model integrated into a bioreactor and (2) apply this model to investigate whether estrogen deficiency leads to changes in osteoblast to osteocyte transition, mechanosensation, mineralization, and paracrine signaling associated with bone resorption by osteoclasts.

Administration of Human Non-Diabetic Mesenchymal Stromal Cells to a Murine Model of Diabetic Fracture Repair: A Pilot Study.

Individuals living with type 1 diabetes mellitus may experience an increased risk of long bone fracture. These fractures are often slow to heal, resulting in delayed reunion or non-union. It is reasonable to theorize that the underlying cause of these diabetes-associated osteopathies is faulty repair dynamics as a result of compromised bone marrow progenitor cell function.

Alterations in osteocyte mediated osteoclastogenesis during estrogen deficiency and under ROCK-II inhibition: An in vitro study using a novel postmenopausal multicellular niche model.

This study sought to derive an enhanced understanding of the complex intracellular interactions that drive bone loss in postmenopausal osteoporosis. We applied an in-vitro multicellular niche to recapitulate cell-cell signalling between osteocytes, osteoblasts and osteoclasts to investigate (1) how estrogen-deficient and mechanically loaded osteocytes regulate osteoclastogenesis and (2) whether ROCK-II inhibition affects these mechanobiological responses. We report that mechanically stimulated and estrogen-deficient osteocytes upregulated RANKL/OPG and M-CSF gene expression, when compared to those treated with 10 nM estradiol.

A Developmental Engineering-Based Approach to Bone Repair: Endochondral Priming Enhances Vascularization and New Bone Formation in a Critical Size Defect.

There is a distinct clinical need for new therapies that provide an effective treatment for large bone defect repair. Herein we describe a developmental approach, whereby constructs are primed to mimic certain aspects of bone formation that occur during embryogenesis. Specifically, we directly compared the bone healing potential of unprimed, intramembranous, and endochondral primed MSC-laden polycaprolactone (PCL) scaffolds.

Bone Mineral Is More Heterogeneously Distributed in the Femoral Heads of Osteoporotic and Diabetic Patients: A Pilot Study.

Osteoporosis is associated with systemic bone loss, leading to a significant deterioration of bone microarchitecture and an increased fracture risk. Although recent studies have shown that the distribution of bone mineral becomes more heterogeneous because of estrogen deficiency in animal models of osteoporosis, it is not known whether osteoporosis alters mineral distribution in human bone. Type 2 diabetes mellitus (T2DM) can also increase bone fracture risk and is associated with impaired bone cell function, compromised collagen structure, and reduced mechanical properties.

Integrins in Osteocyte Biology and Mechanotransduction.

Purpose Of Review: Osteocytes are the main mechanosensitive cells in bone. Integrin-based adhesions have been shown to facilitate mechanotransduction, and therefore play an important role in load-induced bone formation. This review outlines the role of integrins in osteocyte function (cell adhesion, signalling, and mechanotransduction) and possible role in disease.

Estrogen deficiency impairs integrin αβ-mediated mechanosensation by osteocytes and alters osteoclastogenic paracrine signalling.

The integrin αβ has been shown to play an important role in osteocyte mechanotransduction. It has been reported that there are fewer β integrin-containing cells in osteoporotic bone cells. Osteocytes cultured in vitro under estrogen deficient conditions demonstrate altered mechanotransduction.

An in vitro model quantifying the effect of calcification on the tissue-stent interaction in a stenosed aortic root.

Transcatheter Aortic Valves rely on the tissue-stent interaction to ensure that the valve is secured within the aortic root. Aortic stenosis presents with heavily calcified leaflets and it has been proposed that this calcification also acts to secure the valve, but this has never been quantified. In this study, we developed an in vitro calcified aortic root model to quantify the role of calcification on the tissue-stent interaction.

The impact of implantation depth of the Lotus™ valve on mechanical stress in close proximity to the bundle of His.

It has been proposed that inappropriate positioning of transcatheter aortic valves (TAVs) is associated with procedural complications and decreased device durability. Second-generation TAVs allow for repositioning giving greater control over the final deployment position. However, the impact of positioning on the tissue surrounding these devices needs to be better understood, in particular for the interleaflet triangle in which the conductance system (bundle of His) resides.

Investigating the interplay between substrate stiffness and ligand chemistry in directing mesenchymal stem cell differentiation within 3D macro-porous substrates.

Dimensionality can have a profound impact on stiffness-mediated differentiation of mesenchymal stem cells (MSCs). However, while we have begun to understand cellular response when encapsulated within 3D substrates, the behavior of cells within macro-porous substrates is relatively underexplored. The goal of this study was to determine the influence of macro-porous topographies on stiffness-mediated differentiation of MSCs.

A coupled diffusion-fluid pressure model to predict cell density distribution for cells encapsulated in a porous hydrogel scaffold under mechanical loading.

Tissue formation within tissue engineering (TE) scaffolds is preceded by growth of the cells throughout the scaffold volume and attachment of cells to the scaffold substrate. It is known that mechanical stimulation, in the form of fluid perfusion or mechanical strain, enhances cell differentiation and overall tissue formation. However, due to the complex multi-physics environment of cells within TE scaffolds, cell transport under mechanical stimulation is not fully understood.

In silico study of bone tissue regeneration in an idealised porous hydrogel scaffold using a mechano-regulation algorithm.

Mechanical stimulation, in the form of fluid perfusion or mechanical strain, enhances osteogenic differentiation and overall bone tissue formation by mesenchymal stems cells cultured in biomaterial scaffolds for tissue engineering applications. In silico techniques can be used to predict the mechanical environment within biomaterial scaffolds, and also the relationship between bone tissue regeneration and mechanical stimulation, and thereby inform conditions for bone tissue engineering experiments. In this study, we investigated bone tissue regeneration in an idealised hydrogel scaffold using a mechano-regulation model capable of predicting tissue differentiation, and specifically compared five loading cases, based on known experimental bioreactor regimes.